Adenoid cystic carcinoma. Analysis of fifty oral cases. Fifty cases of oral minor salivary gland adenoid cystic carcinoma (ACC) are analyzed and reported. Oral ACC frequently masquerades as a benign neoplasm, and in the majority of cases there is no pain or ulceration. The most common location is in the palate; a plea is made for incisional biopsy of all oral lesions suspected of salivary gland origin. Survival rates show a progressive decrease with time, and there were no survivors beyond 20 years. In this study, there was a positive correlation between duration of the lesion before diagnosis and the salvage rate, but no correlation was found with the size of the presenting lesion.


Resection therapy of malignant tumours of the shoulder girdle. Based on 30 resections in the shoulder region, operation techniques and results are precisely described with a view to curing and functioning. In the case of radical resections the rate of recurrences and cures in patients are the same as the rate of ablations. As the function of the hand is not impaired, this is a considerable advantage over amputations, although the cosmetic result of a resection may appear insufficient. In humerus resections bending contractures may frequently occur in the elbow joint and previous radiation may occasionally cause interior decubitus and exculceration. With an endoprosthetic replacement of the proximal humerous complications may be avoided, as experience with ceramic implants proved in 3 cases.


[Regulation of the biosynthesis of macromolecules of the intercellular corneal matrix]. The influence of a 1M CaCl2 extract and of a collagenase digest of corneal stroma of the biosynthesis of the macromolecules of corneal stroma was investigated. Calf corneas were incubated "in vitro" with radioactive tracers (14C-L-proline; 3H-D-glucosamine or 35SO4) in the presence or absence of the above extracts. After incubation the corneas are submitted to a fractional extraction in order to separate the major macromolecular fractions of the stroma. An increase in incorporation of all tracers is observed in the 1M CaCl2 (CTC), TCA and urea-extracts (containing resp. the diffusible macromolecules, proteoglycans, polymeric collagen and structural glycoproteins) in the presence of the macromolecular extracts and also with the collagenase-hydrolysate of cornea. These results show the existence of a stimulation of the biosynthesis of intracellular matrix macromolecules of the cornea by corneal extracts, probably through positive "feedback" type of mechanism.


[Stereological analysis of the degranulation and the contraction of platelets. Application to the ultrastructural study of thrombin induced excretion in vitro]. A stereological model, which provides quantitative information on the morphology of the platelet release reaction as isolated from platelet aggregation, was developed for the human platelets separated from blood by Mustard's procedure. Three morphologically defined spaces (granules, surface-connected canalicular system S.C.S., cytoplasm) were used to characterize platelet degranulation (with the variation of the volume density of the granules) and contraction (with the variation of the volume density of both granules and S.C.S.). This model was applied to the evaluation of ultrastructural changes associated with the thrombin-induced release reaction. Degranulation and contraction were associated in the platelets which had been allowed to release for 1,5 and 150 sec. Under conditions of the study, prostaglandins E1 (10(-7) M) inhibited both degranulation and contraction (p less than 0,001). Aspirin (10(-4) M) only inhibited contraction (p less than 0.01) and dibutyryl-AMPc (10(-4)) only inhibited granulation (p less than 0,001).


[Ultrastructure of the blood platelets in the newborn infant and in the young mongolian child. Study of 13 cases]. Blood platelets from infant and new born mongolians were examined and compared taking into consideration existing or non existing haematologic anomalies, such as transitory leucoblastosis with or without hyperthrombocytosis and acute leucosis without thrombopenia. These abnormalities were correlated with the analysis of control samples from haematologically normal new-born and premature children as well as samples from adult mongolian, patients with other chromosomal alterations (13-15, phi) and new-born or adults with thrombocytosis. The presence of dysmorphic platelets could be observed in variable degrees and numbers in all the mongolian samples. The characters of the morphologic abnormalities, constantly observed with variations due to pathological causes, denote either metabolic or structural thrombopathy.


[Herpes simplex virus in the saliva of immunosuppressed patients (author's transl)]. Attempts to isolate Herpes Simplex Virus (HSV) from the saliva of patients submitted to immunosuppressive drugs after renal transplantation were undertaken in the early part of the week following the graft. Results showed that the virus constantly appeared in the salvia of patients with serological positive tests to HSV. The presence of HSV was generally detected a few days before the appearance of the clinical disease.


Lipid accumulation in a hepatocellular carcinoma associated with hypoglycaemia. Four serial specimens over 18 months from a hepatocellular carcinoma associated with hypoglycaemia were studied by light microscopy. Ultrastructural study was possible for two of the specimens. Progressive fatty metamorphosis of the tumour cells was observed. The mechanism postulated was that of diversion of carbohydrate metabolism to lipogenesis due to enzyme disruption and dextrose infusion. The possibility of a defect in lipid transport was also considered.


Cystic diseases of the kidney in children. Many genetically determined cystic kidney disorders occur in children. Presenting manifestations related to the kidney include failure to thrive, abdominal enlargement or flank masses, progressive renal failure, or urinary tract infection. Radiological techniques often yield information helpful in establishing the type and extent of renal lesions. Cataloging the cystic renal disease in terms of genetic patterns, the involvement of liver or another organs, and the nature of the disorder of renal architecture is helpful in establishing the proper handling of affected children, and in genetic counseling.


Evidence for the involvement of adenosine 3',5'-cyclic monophosphate in fever genesis. In rabbit cerebrospinal fluid (CSF) during fever induced by endotoxins, myxoviruses, or endogenous pyrogen, concentrations of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and prostaglandin E (PGE) are about 2-fold higher in comparison to normal values. In endotoxin treated animals paracetamol reduced the fever reaction and both PGE and cyclic AMP levels. Administration of theophyllin together with endotoxin enhanced the fever reaction and cyclic AMP levels in CSF, but had no influence on stimulation of PGE synthesis. Following injection of PGE2 into the lateral cerebral ventricles increased cyclic AMP concentrations were found in CSF. The results suggest, that the pyrogenic effect of PGE is mediated by stimulation of cerebral cyclic AMP synthesis.


[Sexual side-effects of spironolactones. Possible mechanisms of their anti-androgen action]. Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women. The mechanism of action of the antiandrogenic effects has been studied in man and rat. Acute i.v. injection of potassium canrenoate into man results in a decrease of plasma testosterone, without any change of gonadotropins. This decrease might be due to an impaired testicular steroidogenesis. On the other hand, spirolactones have an antiandrogenic effect at the target cells level. They do not modify the prostate 5alpha-reductase activity; however, they do inhibit the binding of androgens to their receptors. Thus the spirolactones interact with both biosynthesis and peripheral action of androgens.


[Association of nephrotic syndrome and Hodgkin's disease. Role of the Epstein-Barr virus]. The clinical association between glomerulonephrtis (GN) and malignant hematological disease is very rare. We report, in a 24 years old male, the occurrence of an apparently idiopathic nephrotic syndrome with minimal change glomerular lesions. This GN was in fact closely related to the progression of a stage 2A of Hodgkin's disease, following an infectious mononucleosis contracted one year ago. The nephrotic syndrome responded well to the therapy by Prednisone and Chlorambucil, and the complete remission persisted after eradication of Hodgkin's disease and despite early treatment discontinuation. Renal vein thrombosis, renal amyloidosis and renal interstitial infiltration with malignant cells were ruled out. Immunofluorescent and electron microscopy examination of the renal biopsies were consistent with, but not demonstrative of, an immune complex nephritis. Because of the chronological succession of infectious mononucleosis, Hodgkin's disease, and GN, we are stressing the possible oncogenic and immunogenic role of the Epstein-Barr virus.


Viral infections that affect the fetus.

Viral infections that affect the fetus. Several viral infections besides rubella are known to cause fetal anomalies and disease. Cytomegalovirus, for example, may adversely affect the fetus in a number of ways. Either herpesvirus or hepatitis B virus is transmissible from mother to offspring. Viruses whose potential for fetal harm is less clear are those of varicella, mumps, and influenza.


Not-so-hyper hyperlipo-proteinemia and coronary artery disease. Atherosclerosis is the leading cause of death in the United States, and its prevention is now a primary goal of health care personnel. Knowledge of the early history of the disease, which would be particularly helpful in determing its pathogenesis, is still lacking. Studies are only now beginning to be directed at younger individuals without clinical evidence of disease. Hyperlipoproteinemia has been considered a definite risk factor for atherosclerosis for some years, but because of the difficulty involved in relating specific lipid abnormalities to the extent of atherosclerosis in a given patient, unequivocal proof of its role is lacking. Serum lipid and lipoprotein levels used to define hyperlipoproteinemia in the United States are derived from a system in which 95% of the population are regarded as having normal levels. The cut points are set far too high. Mild hyperlipoproteinemia is rampant in this country, as is coronary artery disease, and from the evidence now available, it seems reasonable to try to lower the incidence of the latter by reducing blood lipid levels of the entire population through dietary modification.


Histochemistry of hormonally active ovarian tumors. Thirty-five ovarian tumors were examined (7 granulosa-cell tumors, 2 thecomas, 4 dysgerminomas, 6 mucinous cystadenomas, 10 serous cystadenomas, 2 adenocarcinomas, 3 Krukenberg tumors and 1 early embryonic tumor). The granulosa-cell tumors showed high activity of alpha-glycerophosphate dehydrogenase, and the changed cells of their stroma--that of glucose-6 phosphate and isocitrate dehydrogenases. The activity of the latter enzymes was striking also in thecomas. Dysgerminomas showed high alkaline phosphatase, acid phosphatase and nonspecific esterase activities. The authors emphasize the role of stromal cells in the hormonal activity of ovarian neoplasms.


Electron microscopic findings in rat hypophysis after adrenalectomy and administration of ACTH. I. Adenohypophysis. Ultrastructural changes in the secretory lobe of rat hypophysis following bilateral adrenalectomy and a single subcutaneous administration of 1 i.u. of ACTH were studied. Both after adrenalectomy and ACTH administration, ultrastructural changes were found to appear exclusively in one type of secretory cells. After adrenalectomy, pictures were found in these cells indicative of increased synthesis of the secretory granulations. One hour after the administration of ACTH the ACTH-secreting cells showed features of decreased secretory activity.


Fibroadenoma of the female breast. Some epidemiologic surprises. In a study of 70 cases of fibroadenoma of the female breast, two ages of peak incidence were recorded, one of them in the late 20s to early 30s and a second in the late 40s to early 50s. At the time of diagnosis, the lesions usually were less than 3.0 cm in diameter. Almost two thirds of the tumors were situated in the lateral quadrants of the breast. Incidence of fibroadenoma was significantly higher among parous females tham among nulliparas. Review of family histories showed a remarkably high incidence of breast disease of all types in the mothers and sisters of the patients studied. An inordinately high proportion of patients under 40 years of age were nonwhite. Recurrences and multiple lesions were much more frequent in patients over 40. "Recurrences" are undoubtedly serial presentations of multicentric lesions.


Electron microscopic findings in rat hypophysis after adrenalectomy and administration of ACTH. II. Neurohypophysis. Electron-microscopic changes in the neural lobe of the rat hypophysis following adrenalectomy and a single administration of ACTH were studied. Twelve hours after adrenalectomy, a decrease in the amount of neurosecretory substances was observed, manifested by a small number of elementary granules of high electron density and, by the appearance of a great number of optically empty vesicles and masses of membrane-free material of low electron density. The increased secretion of neurosecretory substances after adrenalectomy seems to be related to the increased requirement of the organism for the ACTH-releasing factor. One hour after administration of ACTH, a picture was observed suggestive of the release of neurosecretory substances from the neural lobe fibers, which is probably connected with disturbances in the composition of blood electrolytes accompanying the excess of adrenocortical hormones.


Communication and cancer patients. A new form of immediate hospital discharge letter. We present the favourable response we have received from general practitioners to our 'immediate discharge letter' relating to cancer patients.


Hyperhidrosis and hypohidrosis.

Hyperhidrosis and hypohidrosis. Sweating has an important physiological function concerned with both temperature and fluid balance. Hypohidrosis is uncommon and rarely recognized by the patient. It usually represents damage to the central nervous system or peripheral nerves. Hyperhidrosis may be a feature of general medical diseases such as thyrotoxicosis and fevers. It may also be due to damage of the central of peripheral sympathetic nerves. Localized hyperhidrosis tends to occur on the palms, the soles, the axillae and, to a lesser extent, the face. Treatment of local hyperhidrosis with topical aluminium salts, or with topical or oral anticholinergics, may help some patients but surgery may be indicated in those with severe hyperhidrosis.


Functional incorporation of ganglioside into intact cells: induction of choleragen responsiveness. NCTC 2071 cells are unable to synthesize the monosialoganglioside GM1. When grown in chemically defined medium these cells contained no detectable GM1 and did not accumulate 3': 5'-cyclic AMP in response to choleragen. Incubation of the cells with [3H]GM1 permitted quantification of ganglioside uptake which was dependent on time and concentration of [3H]GM1 in the medium. Responsiveness to choleragen was demonstrated with binding of as few as 17,000 molecules of [3H]GM1 per cell; a maximal response was observed with 10(5) molecules per cell. With increasing cellular content of GM1, the rate of rise in intracellular cyclic AMP in response to choleragen was increased. With greater than 1 X 10(5) molecules of GM1 per cell, the delay between addition of choleragen and the cyclic AMP response was inversely proportional to choleragen concentration; less than 250 molecules of choleragen per cell caused a significant increase in cyclic AMP after 8 hr of incubation. Although the responsiveness of intact cells to choleragen was dependent on GM1, choleragen activation of adenylate cyclase in homogenates with 0.6 mM NAD was independent of added ganglioside. These observations are consistent with the view that exogenous ganglioside GM1 can be functionally integrated into the surface membrane of intact cells and serve as the choleragen receptor. Furthermore, although exogenous GM1 is required for choleragen responsiveness in intact cells, the ganglioside does not play an obligatory role in cell homogenates, where the surface receptor can presumably be bypassed.


Synthetic hexapeptide substrates and inhibitors of 3':5'-cyclic AMP-dependent protein kinase. The substrate specificity of the catalytic subunit of rabbit skeletal muscle 3': 5'-cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP: protein phosphotransferase) has been studied using the synthetic peptide Arg-Gly-Tyr-Ser-Leu-Gly corresponding to the sequence around serine 24, a phosphorylation site in reduced, carboxymethylated, maleylated (RCMM) chicken egg white lysozyme. This peptide served as a substrate for the enzyme and exhibited a 6-fold higher Vmax and a 100-fold higher Km than RCMM-lysozyme. Replacement of the arginine with glycine, histidine, or lysine resulted in a dramatic reduction in the Vmax. These results support the concept that arginine is an important residue in determining the substrate specificity of the protein kinase,  predominantly influencing the Vmax of the phosphorylation reaction. Two synthetic peptides in which serine was replaced by an alanine acted as competitive inhibitors of phosphorylation of the synthetic peptide substrate and RCMM-lysozyme.


Construction and propagation of a defective simian virus 40 genome bearing an operator from bacteriophage lambda. A 2400 base pair DNA segment containing the leftward operator (OL) of phage lambda was covalently joined in vitro to a fragment of simian virus 40 (SV40) DNA harboring the SV40 replication origin. The recombinant molecule was propagated in the presence of helper wild-type SV40 DNA in monkey kidney cells and partially cloned by an infectious center procedure. After propagation in monkey cells and purification, the hybrid DNA could be distinguished from wild-type SV40 DNA by its shortened length (about 80% that of SV40), specific hybridization to denatured lambda DNA immobilized on filters, specific affinity for lambda repressor, and preservation of a large part (about 2300 base pairs) of the lambda immunity region as determined by restriction nuclease cleavage patterns and electron microscopic heteroduplex analysis. These results indicate that defective SV40 replicons can serve as vectors for propagating foreign DNA in mammalian cells.


Distribution of envelope-specific and sarcoma-specific nucleotide sequences from different parents in the RNAs of avian tumor virus recombinants. The distribution of leukosis-virus- and sarcoma-virus-specific oligonucleotide sequences was investigated in the RNAs of viral recombinants selected for an envelope gene (env) from a leukosis parent and a sarcoma gene (src) from a sarcoma parent. For this purpose 20 to 30 RNase-T1-resistant oligonucleotides were chemically analyzed and mapped within the 10,000 nucleotides of each viral RNA relative to the 3'-poly(A) end. The resulting oligonucleotide maps were compared. Proceeding from the 3' to the 5' end, the maps of four recombinants contained: (i) in a segment of 2000 nucleotides, three to four src-specific oligonucleotides, so identified because they were shared only with the sarcoma parent; and (ii) in a segment of 8000 nucleotides, 20 oligonucleotides shared with the leukosis parent, of which six to seven were also shared with the sarcoma parent. Two other recombinants contained: (1) in a segment of 2000 (one) or 3000 (the other) nucleotides, three src-specific oligonucleotides; (ii) in a segment of 3000 (one) or 2000 (the other) nucleotides, five (one) or four (the other) oligonucleotides, all or some of which are env-specific, because they were shared with the leukosis parent; (iii) in a segment of 5000 nucleotides (both), 11 functionally unidentified sarcoma-virus-derived oligonucleotides, of which seven were also shared with the leukosis parent. The map locations of parental oligonucleotides were not changed in recombinants and all viral strains tested shared six to eight highly conserved oligonucleotides at equivalent map locations. The partial map -env-src-poly(A) emerged from the analyses of these recombinants.


Deficiency in histone acetylation in nontransforming host range mutants of polyoma virus. Histones H3 and H4 derived from transforming wild-type polyoma and simian virus 40 particles show extensive acetylation compared to the histones of the host cells. The same histone fractions derived from nontransforming host range mutants of polyoma virus fail to show this high degree of acetylation.


Two forms of simian-virus-40-specific T-antigen in abortive and lytic infection. Simian-virus-40-specific T-antigen was isolated by immunoprecipitation. From other studies we have proof that the T-antigen described in this work is coded by the viral DNA. The molecular weight estimated from electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels of T-antigen isolated from nonpermissive mouse cells in abortive infection is 86,000 and from permissive monkey cells in lytic infection is 82,000. The 86 kilodalton T-antigen is readily converted in vitro into an 82 kilodalton form by incubation with extracts from permissive monkey cells but not with extracts from nonpermissive mouse or hamster cells. This and the results of fingerprinting analysis of tryptic peptides suggest that T-antigen may be processed in permissive cells.


Integrated simian virus 40 sequences in transformed cell DNA: analysis using restriction endonucleases. The DNAs from five independent simian virus 40 (SV40) transformants of the BALB/c3T3 mouse cell line were digested with either the HpaII or the BamHI restriction endonuclease and the resulting fragments were fractionated by gel electrophoresis. The DNA fragments were denatured in situ in the gel and transferred to a membrane filter. Fragments containing viral DNA were detected by hybridization with high specific activity 32P-labeled SV40 complementary RNA (cRNA) synthesized in vitro. Each of the lines yielded a small number of fragments containing SV40 DNA and the fragments from each line were different. This observation shows that the structure of the integrated SV40 DNA and/or its location in the host DNA are different in each line.


Control of protein synthesis in reticulocyte lysates: effects of 3':5'-cyclic AMP, ATP, and GTP on inhibitions induced by hemedeficiency, double-stranded RNA, and a reticulocyte translationa inhibitor. Protein chain initiation in reticulocyte lysates is inhibited by (a) heme-deficiency, (b) low levels of double-stranded RNA, and (c) a purified translational inhibitor isolated from heme-deficient lysates. Previous studies have shown that the inhibitions produced by heme-deficiency and double-stranded RNA are prevented by 3': 5'-cyclic AMP, and that GTP, but not ATP, prevents the inhibition of heme-deficiency. In view of the recent finding that the inhibitor purified from heme-deficient lysates is associated with a protein kinase which appears to be involved in the mechanism of inhibition, the effects of cyclic AMP, GTP, and ATP on the three modes of inhibition were examines. In all three types of inhibition, cyclic AMP or GTP (a) prevents the onset of inhibition when added at zero time, and (b) restores protein synthesis in inhibited lysates. In contrast to these effects, ATP potentiates each inhibition, and blocks reversal of inhibition by cyclic AMP or GTP. On the basis of these and earlier findings, we propose that (a) these inhibitions involve the phosphorylation by protein kinases of the Met-tRNAf binding factor and/or a related site(s) on the 40S ribosomal subunit; and (b) cyclic AMP, GTP, and ATP exert their effects by their actions on this phosphorylation mechanism.


Transcription-translation and translation-messenger RNA decay coupling: separate mechanisms for different messengers. Antibiotics were used to inhibit protein synthesis at specific steps in the biosynthetic pathway. In this way, it was possible to study the coupling of protein synthesis to the accumulation of biologically active mRNA in T4-infected Escherichia coli. Functional mRNA for the phage enzymes deoxynucleotide kinase (EC 2.7.4.4; ATP: nucleoside monophosphate phosphotransferase or nucleosidemonophosphate kinase) and alpha-glucosyltransferase (EC 2.4.1.5; 1, 4-alpha-D-glucan: 1, 6-alpha-D-glucan 6-alpha-glucosyltransferase or dextrin dextranase) accumulated during inhibition of protein synthesis irrespective of the step in the synthesis of protein that was blocked. Under these conditions, however, the rate of mRNA synthesis for both enzymes was significantly inhibited. In contrast, the rate of degradation of these mRNAs was markedly dependent on the step in protein synthesis that was inhibited. That is, the site for mRNase action was different for each message. The most important step in protein synthesis required for the stability of deoxynucleotide kinase mRNA is the initiation step. A single ribosome bound to the 5' end of the deoxynucleotide kinase mRNA can stabilize the molecule. On the other hand, the initiation event does not seem to be important for stabilizing the alpha-glucosyltransferase mRNA. Instead, a high ribosome denisty on the alpha-glucosyltransferase messenger is required to achieve significant stability. Therefore, in studying messenger metabolism, it is important to focus on the functional stability of specific mRNAs instead of on total messenger since each mRNA can be metabolized differently.


Dephosphorylation of nonhistone proteins specifically alters the pattern of gene transcription in reconstituted chromatin. A nonhistone phosphatase devoid of detectable protease activity has been purified from nuclear sap by chromatography on DEAE-Sephadex. After linkage to an insoluble agarose matrix, this enzyme was used to dephosphorylate nonhistone proteins obtained from S-phase HeLa cells. Chromatin reconstituted with these dephosphorylated proteins exhibited roughly a 50% reduction in the overall number of initiation sites available for transcription when compared to controls. Specific measurements of transcription of histone genes with use of a complementary DNA probe showed that genes coding for histones are preferentially inhibited after nonhistone dephosphorylation. These results provide the first direct support for the theory that phosphorylation of nonhistone proteins is involved in regulating the availability of individual genes for transcription.


Cell surface protein partially restores morphology, adhesiveness, and contact inhibition of movement to transformed fibroblasts. We have isolated the major cell surface glycoprotein of chick embryo fibroblasts, CSP, and added it to a variety of transformed cells in vitro. The transformed cells become more elongated, often more flattened, and show increased adhesion to the substratum. Several transformed cell lines also align in striking parallel arrays. This alignment is characterized by a decrease in the amount of nuclear overlapping, probably indicating restoration of contact inhibition of movement. The morphological changes are antagonized by antibody to CSP. These effects of CSP are not associated with an elevation of cellular 3':5'-cyclic AMP. Moreover, the morphological reversion is not accompanied by an alteration in growth properties. Our results are consistent with a role for CSP in cell adhesion and morphology but not in growth control.


Erythroid cell differentiation: murine erythroleukemia cell variant with unique pattern of induction by polar compounds. The murine-virus-infected erythroleukemia cell system provides an opportunity to examine regulatory mechanisms controlling cytodifferentiation. A cloned cell line (DR10c3) resistant to the erythropoiesis-inducing effect of dimethylsulfoxide (Me2SO) was isolated from the Me2SO-sensitive line DS19. DR10c3 is characterized as follows: (1) the uptake of [3H]Me2SO is similar to that in DS19; (2) cell growth with and without Me2SO is similar to that of DS19; (3) resistance is relatively stable; (4) the karyotype of DR10c3 reveals an average loss of five chromosomes per cell, but is otherwise similar to that of DS19; (5) total protein and globin synthesis by cells cultured 4 days with or without Me2SO is similar to these syntheses in DS19 cultured without Me2SO; (6) virtually no globin mRNA is detectable after 3 days in Me2SO, as assayed both by RNA-complementary DNA hybridization and by the heterologous cell-free protein-synthesizing system; (7) other polar compounds, N-methylpyrrolidinone, 1-methyl-2-piperidone, N, N-dimethylacetamide, and N-methylacetamide, induce erythroid differentiation in DR10c3, and the accumulation of alpha- and beta-globin chains is indistinguishable from that in DS19; and (8) the concentration optima for induction of differentiation by all these compounds are identical for DR10c3 and DS19.


Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases. The parenteral administration of a single dose of 3-methylcholanthrene to rats caused an increase in the liver of the concentration of 3', 5'-cAMP and of the activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). These events were followed by an increased activity of ornithine decarboxylase (L-ornithine carboxy-lase, EC 4.1.1.17), the enzyme that controls the biosynthesis of polyamines. Finally, the activity of benzo[a]pyrene hydroxylase, as well as the amount of cytochrome P-448, was increased. Similarly, after the administration of phenobarbital, there was first an increase in the cAMP concentration and in the activity of cAMP-dependent protein kinase, then the induction of ornithine decarboxylase, and finally, an enhanced activity of ethylmorphine N-demethylase and an increased content of cytochrome P-450. These data suggest that the drug-induced processes in liver that increase the activities of the oxidative, and presumably other, drug-metabolizing enzymes include the following sequence of events: (1) increase in cAMP concentration and/or activation of cAMP-dependent protein kinase; (2) induction of ornithine decarboxylase; and, (3) induction of drug-metabolizing enzymes.


A differentiation stimulating factor induces cell sensitivity to 3':5'-cyclic AMP pulses in dictyostelium discoideum. During the first few hours of starvation, Dictyostelium discoideum amoebae excrete a macromolecule, probably a glycoprotein, which stimulates cell differentiation to aggregation competence. 3':5'-Cyclic AMP pulses, which mimic the chemotactic signal, and this factor (differentiation stimulating factor) are shown to exert a cooperative effect in inducing cell differentiation. Data suggest that the appearance of the factor determines the moment amoebae become responsive to cyclic AMP pulses.


Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in oxygen-enriched environment: preliminary report. Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate in an incubator containing 95% air, 5% CO2. In an incubator atmosphere enriched with oxygen, however, the normal fibroblasts are maintained without proliferation, while the Rous sarcoma virus-infected fibroblasts continue to proliferate. This suggests that a respiratory function may be involved in the regulation of proliferation of normal cells, and that neoplastic cells may proliferate autonomously because of a deficiency in this regulatory function.


Cotransfer of two linked human genes into cultured mouse cells. Two linked human genes which code for the expression of cytosol thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred via purified metaphase chromosomes from the human lymphoblastoid cell line WI-L2a, into mouse L-cells [B82 and LM(TK-)]. Both genes have previously been shown to be closely linked on the human chromosome E17, band q21-22. Coexpression of both human enzyme markers was detected in two out of eight gene transfer clones, whilst the remaining six clones contained only human cytosol thymidine kinase, as shown by electrophoretic techniques. A further 23 human enzyme markers corresponding to 15 different human chromosomes were found to be absent in these gene transfer clones. No human chromosome or chromosomal fragment could be detected by karyotype analyses. Some of the gene transfer clones rapidly lost the transferred donor material when grown in nonselective medium, whereas others expressed a stable phenotype under these conditions. Prolonged maintenance in selective medium favors the survival of gene transfer cells expressing a stable phenotype. Possibly these cells harbor the donor genes integrated into a recipient chromosome.


Human papilloma virus DNA: physical mapping and genetic heterogeneity. The molecular weight of three preparations of human papilloma virus DNA derived from different plantar warts was determined by agarose gel electrophoresis or electron microscopic contour length measurement. It was found to amount to approximately 4.9 X 10(6). Analysis of this DNA after sequential digestion by four different restriction endonucleases (EcoRI, Bam, Hind II, and Hind III) permitted physical mapping of the cleavage sites. Two of the three DNA preparations revealed an identical cleavage pattern, whereas the third one contained two additional cleavage sites.


Cyclic nucleotides, adenylate cyclase, and cyclic AMP phosphodiesterase in mammary glands from pregnant and lactating mice. In the mammary glands of mice, levels of cyclic AMP increased during pregnancy and then fell precipitously following parturition. In contrast, levels of cyclic GMP fell during the gestation period and then rose rapidly during the early days of lactation. Adenylate cyclase and cyclic AMP hohsphodiesterase activities were elevated during the pregnancy and lactation periods.


Detection of antibody to Varicella-Zoster virus by immune adherence hemagglutination. A serologic test for measurement of antibody to V-Z virus by immune adherence hemagglutination is described. Initial evaluation of the test has shown it to be highly sensitive, specific, rapid, and simple to perform. The V-Z antigen may be stored at -70 degrees, and the test could be performed in any routine serology laboratory.


Epiphyseal cartilage cyclic nucleotide phosphodiesterase: partial purification and kinetic characteristics of multiple enzymes. Partial purification of chicken epiphyseal PDE activity by centrifugation and column chromatography has defined two distinct peaks of PDE activity. The faster eluting peak (I) has a higher apparent Km for cyclic AMP than the slower eluting major peak (IIs and II). Peak I has greater activity towards cyclic AMP as a substrate than towards cyclic GMP but does use both substrates. Peak I is not inhibited by T-3 or indomethacin at physiological concentrations. Substrates studies demonstrate the presence of at least two overlapping PDE species in the major peak(IIs and II). There is suggestive evidence that indomethacin is a more potent inhibitor of peak IIs which can use either cyclic AMP or cyclic GMP as substrates, whereas T-3 is a more potent inhibitor of fractions eluting where the enzyme only has activity with cyclic AMP.


Serologic response to BK Virus following human infection with SV40. A small group of human volunteers given live SV40 virus, and who sero-converted to SV40, did not develop any heterologous antibody response to BK virus, even when BK antibody was demonstrated in preinfection sera. SV40 infection does not appear to contribute significantly to the patterns of BK antibody seen in human populations.


Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection. Since age-dependent diminished macrophage function has been related to the increased susceptibility of newborn mice to herpes simplex virus (HSV) infection, the effect of several agents which might activate macrophages or other cells involved in immunity was investigated. BCG, typhoid vaccine, brucella vaccine, levamisole, or staphage lysate were administered to newborn mice prior to challenge with HSV-2. Of these agents, only BCG, administered ip or id 6 days prior to challenge, was found to increase the survival rate of newborn mice. The possible use of BCG, alone or in combination with other modalities, for the prevention or treatment of neonatal HSV infections is discussed.


Early events in the lytic infection of primary mouse kidney cell culture with polyoma virus. The effect of various input multiplicities. Early polyoma (Py) virus-specific RNA synthesis was examined in cells infected with different concentrations of Py-virus. The effect of various multiplicities of infection (m.o.i.) on the rate of Py-RNA synthesis is different at 30 hr as compared to 65 hr. Thirty hours after infection at 27degrees, in the presence of 5-fluoro-2-deoxyuridine (FdU), an increase in input multiplicity was not associated with a quantitatively commensurate increase in the amount of virus-specific RNA synthesized. At 65 hr, the amount of viral RNA synthesized was roughly proportional to the number of infecting virus particles.


Hepatic carbamyl phosphate synthetase and ornithine transcarbamylase in mouse influenze A and influenze B infection. In mice infected with mouse-adapted influenza A/PR/8/34, hepatic carbamyl phosphate synthetase (CPS) activity was reduced to 88%, and ornithine transcarbamylase (OTC) was reduced to 83% of control values. In mice infected with mouse-adapted B/Lee/40, CPS activity was 98% was 94% of control values. These limited reductions in enzyme activity were attributed to a nonspecific debilitating effect of acute influenzal pneumonia. These findings suggest that the pronounced reduction of CPS and OTC activities reported in Reye's syndrome in man are not a general manifestation of the severity of influenza infection.


Cyclic AMP and central noradrenaline receptors: failure to activate diencephalic adrenergic feeding pathways. Intracranial injection of graded doses of dibutyryl 3',5'-cyclic adenosine monophosphoric acid (cAMP) at sites in the accumbens/stria terminalis nuclei of satiated rats elicited behavioural arousal and occasional convulsive episodes at higher doses, but failed to affect food consumption even in sites where injection of noradrenaline (65 nmol) consistently elicited increased feeding. Intracranial aminophylline (550 nmol) or dopamine (65 nmol) were also without effect on food consumption. This result does not support recent suggestions that cAMP serves as the second messenger in central noradrenergic motivational pathways.


Spontaneous behavior and sleep-wakefulness cycle in isolated and paired REM sleep deprived-marihuana treated rats. The correlation between marihuana-induced aggressive behavior and changes in the sleep-wakefulness cycle was studied in chronically implanted rats. Marihuana injection in non-REM deprived rats did not induce aggressiveness irrespective of the animals being caged in isolation or paired. During this procedure quantization of the sleep-awake cycle revealed that wakefulness was increased while slow wave and REM sleep were decreased, mainly in the paired animals. REM deprived-marihuana injected animals recorded in isolation behaved like the control solution-injected rats. They showed a large rebound of REM and were not aggressive at the end of the 8 hr sessions. Conversely, when these animals were paired during the recording periods, they remained continuously awake and showed numerous episodes of aggressiveness. These results suggest that the aggressiveness inducing properties of marihuana are related to the REM deprivation and to the increased environmental stimulation achieved by pairing the animals.


Cephalic angiotensin receptors mediating drinking to systemic angiotensin II. In rats implanted with cannulae to allow delivery of solutions to the cerebral ventricular system, pretreatment with 5 mug or 0.5 mug of saralasin acetate (Sar1 Ala8 Angiotensin II), an angiotensin II competitive analog, significantly attenuated drinking to subcutaneous (SC) injections of 500 mug of angiotensin II. However, pretreatment with either SC (5 mug or 20 mug) or with intravenous (5 mug) saralasin had no effect on drinking to SC angiotensin II (500 mug). Intracranial (IC) injections of 5 mug of saralasin had no effect on drinking in response to SC injections of 0.8 cc of a 10 percent NaCl solution and did not attenuate ingestion of a milk solution in a dessert test. On the basis of the specificity and the greater efficacy shown by IC saralasin in attenuating drinking to systemically applied angiotensin II, it was concluded that circulating angiotensin II reaches brain periventricular receptors which mediate drinking.


Hydroxyamino compounds produced by the oxidation of diamines with diamine oxidase in the presence of alcohol dehydrogenase. When the diamines putrescine, cadaverine, cystamine and lanthionamine are oxidized by purified pig kidney diamine oxidase in the presence of NADH and either liver or yeast crystalline alcohol dehydrogenase, NADH is oxidized. Chromatographic evidence obtained in the case of putrescine and cystamine indicates the production of the respective hydroxy-amino compound. In the case of cystamine, the product of the reaction is mercapto-ethanol-cysteamine mixed disulfide which may represent a biological source for the production of mercaptoethanol used for other reactions.


The influence of denervation of the maturation of the flight muscle of Periplaneta americana. The metathoracic musculature of the American cockroach Periplaneta americana was denervated by dissecting the nerves originating in the metathoracic ganglion on one side within 2 days after the last moult. The biochemical and morphological differences between normal and denervated musculature were followed two weeks later. Denervation completely prevents the gain in weight, protein content and cytochrome oxidase activity which occur in normal muscles during the two weeks after previous moulting. The content of phosphoarginine in the denervated muscle does not differ from the control muscle and is lower than in young muscles. The ability to resynthesize phosphoarginine postanaerobically is substantially lower in the denervated muscle than in control muscles, or in young muscles immediately after the last moult. The ultramicroscopic structure of the denervated muscle differs from that of the normal muscle: the mitochondria possess less cristae, the matrix between them appears less dense and the sarcoplasmatic reticulum is less developed. Thus the denervated muscle not only fails to mature, but also developes serious structural and biochemical disorders.


Effect of diazepam on the electroencephalographic pattern and vigilance of unanaesthetized and curarized rats with a chronic cobalt-gelatin focus. The author studied the effect of diazepam in doses of 1 and 3 mg/kg on rats with a chronic cortical cobalt-gelatin focus and implanted cortical and subcortical electrodes. Focal spike activity localized at the site of the focus and hypersynchronous generalized episodes of spikes (and waves) of 8--9/sec frequency were studied in the electroencephalogram and the main phases of vigilance (waking, telencephalic slow waves/SWS/and REM sleep) after diazepam were evaluated. The effect of diazepam on rats temporarily immobilized with tubocurarine was also evaluated. 1. Focal spike activity during sleep was mildly inhibited by diazepam. If present in the waking state, it was markedly inhibited. 2. The number of episodes diminished significantly after diazepam. The maximum decrease occurred 30--45 minutes after administering diazepam and after that they slowly recovered. 3. Diazepam did not inhibit alteration of the phases of vigilance, but there was an increase in the proportion of telencephalic sleep with large numbers of spidles of 12--14/sec frequency and the incidence of REM phases rose by 250--300%. 4. Diazepam brought no renewal of the episodes which disappeared from the waking EEG recording of rats with a chronic focus temporarily immobilized with tubocurarine. Its administration was followed mostly by sleep activity with spindles. 5. Despite certain effects in common (disappearance of episodes), the action of diazepam differs from that of barbiturates in many respects and is effected by different mechanisms.


Effect of adrenal glucocorticoids on beta-lipoprotein production by resected liver. The action of adrenal glucocorticoids on the level of liver beta-lipoprotein (LP) production was studied. Their effect was verified by studying LP synthesis and release from liver after the administration of various doses of glucocorticoids, after the administration of ACTH and in cases in which the effect of glucocorticoids was precluded by adrenalectomy (in vivo and in vitro). Adrenal glucocorticoids were found to limit triglyceride release in the form of beta-LP from the liver into the blood stream during the first 6 hours after partial hepatectomy (PHE). A direct study of beta-LP synthesis in the liver tissue showed that glucocorticoids inhibit liver lipid secretion by interfering with the process of beta-LP release by the liver rather than by influencing actual beta-LP synthesis in the liver.


Pregnancy interrupting effects of some bacterial toxins. Embryotoxic properties of Shigella dysenteriae and Clostridium perfringens toxins, of E. coli endotoxin, V. cholerase and E. coli enterotoxins were compared in mice. E. coli endotoxin has embryotoxic effects at all stages of pregnancy. E. coli enterotoxin V. cholerae enterotoxin and Shigella dysenteriae toxin are most effective mainly at earlier stages of pregnancy. Clostridium perfringens toxin has no embryotoxic effect.


Remediable neuromuscular disorders.

Remediable neuromuscular disorders. Generalized muscular weakness may develop from a variety of causes, and in many cases is reversible with appropriate treatment of the underlying disorder.


[Aspects of the value of humoral antibodies in encephalomyelitis of neuroallergic origin]. The importance of humoral antibodies formed in the course of neuroallergic diseases characterized by a cytergic type of reaction and especially in the course of experimental allergic encephalomyelitis (EAEM) is discussed, special attention being given to the importance of pathogenetic, immunodynamic, diagnostic, and therapeutic factors. The circulating antibodies of EAEM induced by cellular and humoral immunoprocesses are assumed to produce either intensifying or mitigating effects. Among the most important functions are the influence of immune globulins on the blood/brain boundary lesion, the gliotoxic and myelinotoxic effects, and the detection of a blockade of the intraneural transmission. The therapeutical effect to be discussed in the light of the protective effects of humoral antibodies is a mere conception in view of incompletely understood mechanisms including those governing the chronology and dynamics of immunoprocesses associated with multiple sclerosis, especially since the antigen-specific induction of tolerance appears to be far more essential.


The continuing care clinic: outpatient treatment of the chronically ill. The need for continuing care of chronic psychiatric patients within the community is a pressing problem that calls for development and testing of new treatment methods. This paper describes one such method, the Continuing Care Clinic, an outpatient program for chronic patients who have not responded well to other outpatient treatment approaches. The clinic's structure, treatment rationale and procedures, and clinical results over a 31/2-year period are described. Among specific treatment features discussed are the use of multiple therapists, focus on available personality strengths and on reality issues, and patient-staff group interaction as an adjunct to individual psychotherapy.


[Functional diencephalo-pituitary diagnosis by means of radioimmunoassay]. The Author, after mentionating the always increasing need of cooperation between the clinical activity and the laboratory research, stops considering the semeiological meaning of the radioimmunoassay of the pituitary hormones. However he worns against the limitations that such dosages present at the base line and the possible dissociation between immunological activity and biological activity. He describes then the dynamic tests able to determine variations of hormonal levels and makes his conclusions stating that the observation made during dynamic conditions may be of help to the clinical diagnosis.


[Technical notes and clinical use of radioimmunologic determination of plasma ACTH]. Particular aspects of plasma ACTH radioimmunoassay are examinated. The results obtained with this method in adrenocortical diseases (Addison's disease, Cushing's syndrome, congenital adrenal hyperplasia) are reported and clinical value in etiological diagnosis of Cushing's syndrome is outlined. Moreover the results obtained in other syndromes of endocrinologic interest (massive obesity, Turner's and Klinefelter's syndromes, Laurence-Moon-Biedl syndrome, true precocious puberty, primary hypothyroidism, hypopituitary dwarphism) are reported and discussed.


Gray scale ultrasonic investigation of focal defects on 99Tc sulphur colloid liver scanning. Radionuclide liver scanning, though a well established technique for the detection of normal liver tissue replacement, has yet to deliver a satisfactory isotope method for distinguishing the benign or malignant nature of a disclosed nonfunctioning area. The solid or cystic nature of focal areas of replacement can be shown by ultrasonic echography, so the malignancy of the area can be inferred. The complementary use of both techniques is recommended.


The effect of steroids on the extravascular distribution of radiographic contrast material and technetium pertechnetate in brain tumors as determined by computed tomography. The effect of dexamethasone on the accumulation of iothalamate and 99mTc pertechnetate in cerebral tumors was investigated in 6 patients over a five-month period. Patients were examined by x-ray (transmission) computed tomography (CT) and by radionuclide (emission) computed tomography (RCT) prior to and during a course of dexamethasone therapy. Stenosis diminished the degree of accumulation of both agents but did not change the boundaries of their distribution.


Studies of growth hormone secretion VIII. Effects of alpha,beta-methylene-ATP on prostglandin induced GH release and cyclic AMP accumlation in rat anterior pituitary glands. Alpha, beta-methylene-ATP, a competitive inhibitor of adenylate cyclase of liver and fat cell membrane preparations, caused a dose related inhibition of PGE1 and PGE2-induced cyclic AMP accumulation in rat anterior pituitary explants. At the same time, this ATP analog potentiated PGE1 and PGE2-promoted growth hormone secretion. The possible functional role of prostaglandins and cyclic nucleotides in the regulation of growth hormone secretion remains to be defined.


Hypothalamic and pituitary effects of prostaglandins on ACTH secretion. Various prostaglandins (PGs) were tested for their effects on ACTH secretion upon injection into the anterior pituitary, basomedial hypothalamus, basolateral hypothalamus, or a tail vein in anesthetized female rats. In some experiments, the PGs were injected in combination with a CRF preparation. The greatest effect seen was the stimulation of ACTH (and presumably CRF) secretion exerted at the basomedial hypothalamus. At the anterior pituitary, the PGs alone were without effect, but they did decrease the magnitude of the response to subsequent CRF.


Spectral changes in the respiratory chain of cerebral cortex slices. Correlation with the energy status of the tissue. Elevation of the media potassium concentration results in an immediate, but transient increase in the rate of respiration in cerebral cortex slices of the rat. As the respiratory burst decrease in intensity, a transient oxidation of the tissue respiratory intermediates is followed by a net reduction. The burst of respiration is accompanied by a large decrease in tissue ATP and phosphocreatine concentrations. ATP and phosphocreatine concentrations are essentially fully recovered within 5-6 min. The apparent increase in ATP hydrolysis during the peak of the respiratory response was not, however, accompanied by increases in the tissue content of ADP and 5'-AMP. Increased deamination of the adenine nucleotides is discussed as a possible mechanism in the large contraction of the total adenine pool observed during the course of the metabolic response to elevated potassium concentrations.


Genetic determination of aggressive behavior and brain cyclic AMP. Inbred mouse strains exhibit differences in brain cyclic AMP concentrations. In two mouse strains, we have shown that both the tendency for aggressive attack and high brain cyclic AMP content are inherited as recessive traits and that these traits maintain a close association in segregating generations.


17 alpha estradiol: separation of estrogen effect on collagen from other clinical and biochemical effects in man. In rodents the effect of 17alpha estradiol upon collagen is identical to that of 17beta estradiol, but the 17alpha estradiol effect upon uterine lining is 1/1000 that of 17beta estradiol. Both steroids reverse the effect of D-penicillamine on rodent skin collagen. Five human beings with the skin collagen changes associated with D-penicillamine were treated with 17alpha estradiol for three to six weeks. 17alpha estradiol caused no detectable changes in blood pressure, breast development, menstrual periods, serum liver enzymes, serum proteins, plasma growth hormone, insulin, serum clotting factors, serum triglycerides, serum copper or serum ceruloplasma. In contrast, 17alpha estradiol increased skin prolyl hydroxylase activity, increased soluble collagen content in the skin and increased urinary hydroxyproline excretion. These studies with 17alpha estradiol, point out a specificity difference between the various sites of estrogen action in human beings.


Androgenic effects on protein kinases and cyclic AMP-binding protein in the ventral prostate. Androgenic deprivation resulted in marked impairment of prostate weight and significant alterations in cytosolic and particulate protein kinase activities and cyclic AMP-binding capacity of this tissue. Whereas rats orchidectomized for 7 days exhibited significant enhancement in the specific activity of cytosolic cyclic AMP-dependent (73%) and -independent (45%) protein kinases as well as cyclic AMP-binding protein (196%), administration of testosterone (5.0 mg/100 g, i.m., 5 days) exerted little or no effect in reversing these responses. In contrast, when expressed as total enzyme activity per prostate, castration led to marked decreases in protein kinase activity assayed in the presence (87%) and absence of the cyclic nucleotide (91%). Likewise, the cyclic AMP-binding capacity of the soluble enzyme was depressed (77%) following androgenic deprivation. Although testosterone treatment for 3 days significantly reversed these effects, complete restoration was not achieved even after 5 days of androgen replacement therapy. Moreover, while exogenous cyclic AMP had no effect on protein kinase activity from crude nuclear preparations, the phosphorylation of endogenous nuclear substrates was dependent on androgenic status of the animals. Whereas castration produced decreases in the specific and total activity of prostatic particulate protein kinase as well as the cyclic AMP-binding protein, testosterone replenishment was effective in abolishing these alterations seen in orchidectomized rats. Data from the present study provide additional support to the concept that changes in cyclic AMP-adenylate cyclase-protein kinase system play an important role in the overall mechanism(s) by which male sex steroids exert their diverse anabolic effects on male accessory sex tissues.


Radial immuno-diffusion and serum-neutralisation techniques for the assay of antibodies to swine vesicular disease. Pig sera were assayed for antibodies to swine vesicular disease virus by (a) the radial immuno-diffusion technique combined with autoradiography and (by serum neutralisation tests. The former was more sensitive and was used for initial screening of sera while the latter was used to obtain estimates of titres of positive sera. In a survey of 1759 sera collected at slaughterhouses there were 14 significant titres from a total of seven premises situated in localities where the disease had been known to occur, and it was concluded that this did not indicate wither widespread undetected disease or the occurence of inapparent infection in the pig population.


The effect of enterotoxin of Clostridium welchii (perfringens) type A on fowls. Lethal doses of enterotoxin of Clostridium welchii (perfringens) type A injected intravenously into young fowls caused immediate lassitude, with partial recovery, followed by death seven to 35 h after inoculation. Lesions found were ascites, hydropericardium, oedema of the muscles, hepatic congestion, urate deposits on the peritoneum and the pericardium, and intestinal hyperaemia. Sublethal doses produced no clinical signs or lesion. The LD50 of this enterotoxin was 74-84 mug/kg of body weight.


[Familial amyloid neuropathy of Corino Andrade. Ultrastructural study of the peripheral nerve in 2 patients]. The authors describe two typical cases of Portuguese amyloid neuropathy in immigrants. One of the patients had been ill for only a short time while the other's condition had been developing over more than ten years. The first patient's neuropathy was characterized by a perforating ulcer of the foot and loss of sensation. The neurological disorder as well as the effect on general health were much more serious in the second patient. Neuro-muscular biopsy was carried out on each of these patients and revealed excessive endoneural amyloid and very severe lesions of nerve parenchyma mainly secondary to Wallerian degeneration. The results were compared with the few existing ultrastructural studies on the peripheral nerve in amyloid neuropathies.


[Subcutaneous and tendinous nodules in scleroderma. Apropos of 4 anatomo-clinical cases]. The authors have observed 3 cases of pure scleroderma and one case of scleroderma in which tendinous or subcutaneous nodular structures were present. To the author's knowledge, such nodules have never been described previously in cases of scleroderma. Their site and their histology identifies them as "rheumatoid" nodules and at the same time provides other valuable information. Scleroderma is thus, together with rheumatoid polyarthritis and lupus erythematosus, one of the possible causes of nodule formation, and the authors put forward the hypothesis that these nodules might represent one of the first lesions of the Thibierge and Weissenbach syndrome.


Transfer factor treatment of patients with multuple sclerosis. I. Preliminary report of changes in immunological parameters. In five patients with definite multiple sclerosis and lack of cell-mediated immunity to measles and parainfluenza virus antigens, various immunological parameters were studied before and during transfer factor treatment. The study showed that cell-mediated immunity to measles virus antigen, as evaluated by the leukocyte migration agarose test, could temporarily be restored, using repeated injections of transfer factor pooled from unselected, normal blood donors.


Changes in the surface of virus-induced cells recognized by cytotoxic T cells. I. Minimal requirements for lysis of ectromelia-infected P-815 cells. P-815 mastocytoma cells developed susceptibility to immune T-cell-mediated cytolysis shortly after infection by ectromelia virus. Intracellular viral replication and late protein synthesis seem to bu unnecessary events. Interference with early protein synthesis, however, inhibits the development of susceptibility to lysis. The important intracellular events necessary for subsequent cytolysis appear to occur within 1 hour of infection. Virus rendered non-infectious by ultraviolet irradiation but not by gamma irradiation is able to induce these changes. By determining the minimum and essential events of the infectious process which result in T-cell-mediated cytolysis, the task of establishing the molecular changes occurring in the target cell surface membrane necessary for immune T-cell recognition should be simplified.


Attempts to improve the early enzymatic diagnosis of coronary heart disease. Based on the hypothesis that beta lipoproteins have the ability to trap certain enzymes, an attempt was made to release these enzymes from the eventual beta lipoprotein blockade, by subjecting the serum to different processings such as: freezing-thawing (3 times), ultrasonation or treatment with Triton X100 or sodium desoxycholate. After the first two procedures an increase of serum LDH and alkaline phosphatase activities was observed in about half the sera investigated (normal and pathologic). In few cases of coronary heart disease (two out of 60), LDH activity reached a clearly pathologic level.


A reovirus-like agent (rotavirus) in gastroenteritis of children. Virus detection and serological studies. A reovirus-like agent (rotavirus) was detected in 26 children (44%) when fecal specimens from 59 children with acute gastroenteritis were examined by electron microscopy. No rotavirus was detected in the feces of 49 children with other diseases. Sera from the acute and the convalescent phase from 40 children with acute gastroenteritis and from 18 other patients were examined for antibodies against a bovine rotavirus by an indirect fluorescent antibody test. 26 of the patients with gastroenteritis (65%) developed antibodies during their disease, whereas none of the other patients showed a rise in antibody titre. The specimens were submitted to the laboratory from hospitalized children during the period January 1973 through March 1975. Most of the cases of rotavirus gastroenteritis occurred during late autumn and early winter among children between 0.5 and 3 years of age. It is concluded that electron microscopy is a sensitive diagnostic technique during the acute phase of the disease, and that the serological test with bovine rotavirus antigen served as a useful diagnostic tool.


Early diagnosis of virus-caused vesicular rashes by immunofluorescence on skin biopsies. I. Varicella, zoster and herpes simplex. The use of immunofluorescence (IF) for the rapid identification of varicella-zoster (V-Z) and herpes simplex (HS) antigen in frozen sections of biopsies of early non-vesicular skin lesions was investigated. Direct IF, using fluorescein- isothiocyanate- conjugated immuoglobulin (FITC Ig) of paired human anti-V-Z sera and FITC-conjugated negative and positive anti-V-Z-monkey Ig, yielded specific fluorescence of virus antigen in all 14 varicella cases investigated and in 10/11 zoster cases. In contrast, indirect IF, using paired human anti-zoster sera and a sheep anti-human Ig FITC, was not satisfactorily specific, since staining with the anti-human Ig FITC alone also yielded fluorescence of infected cells in some cases. In 6/8 cases of HS infection, specific fluorescence of virus antigen was obtained by direct IF, using FITC-conjugated negative and positive guinea-pig anti-HS Ig. Because of the often predominant distribution of virus antigen to the corium and the skin appendages, punch biopsies are apparently better than scraped material, at least in the prevesicular stage.


An estimate of the course of herpes simplex virus encephalitis. Serologic responses, physical findings, and survival were studied in 51 cases of proved (14 patients) or presumptive (37 patients) herpes simplex encephalitis occurring in North America between 1965 and 1972. On the basis of a statistical analysis of 16 serological parameters tested in both groups, presumptive cases are likely similar to definitive cases. Using this assumption, the following tentatives conclusions are possible. Complement-fixing antibodies may be more sensitive measures of rises in anti-herpes simplex virus antibodies than are conventional or complement-requiring neutralizing or passive hemagglutinating antibodies. Mortality in herpes simplex virus encephalitis may vary from 0 to 80% and may be predictable depending upon the occurrence of seizures, paralysis and coma. Coma seems to dictate the dour prognosis. When 51 cases of herpes simplex virus encephalitis reported in the literature by others between 1944 and 1972 were analyzed by this method, a comparably varied mortality was obtained. It did not appear that treatment with idoxuridine increased the likelihood of survival.


Cholera toxin induces pineal enzymes in culture. Addition of choleragen to rat pineal organ cultures caused a long-lasting stimulation of adenylate cyclase activity, and this was followed by increases in seroton N-acetyltransferase and cyclic adenosine monophosphate phosphodiesterase activities. These effects of choleragen were not blocked by the beta-adrenoceptor antagonist propranolol, but the increases in cyclic adenosine monophosphate phosphodiesterase and serotonin N-acetyltransferase activities could be prevented by the protein synthesis inhibitor cycloheximide. The results indicate that cholera toxin can mimic the induction of pineal enzymes that normally follows beta-adrenoceptor activation and suggest that increased cyclic adenosine monophosphate is a necessary and sufficient signal for such changes in enzyme activity.


Hepatoma induced by thorium dioxide.

Hepatoma induced by thorium dioxide. A 74-year-old man complained of anorexia and weight loss. Twenty-six years earlier he had received an injection of Thorotrast. A needle biopsy of the liver showed thorium dioxide granules and periportal fibrosis. On laparotomy, a hepatoma of the left lobe of the liver was discovered. Hepatic malignancy should be suspected in any patient with abnormal results of liver function tests, particularly an elevated level of alkaline phosphatase, who previously has had an injection of Thorotrast.


Technique of adrenalectomy for metastatic cancer of the breast. The transabdominal approach to adrenalectomy offers many advantages in the patient with metastatic cancer of the breast who is likely to respond to an ablative operation. Information derived in the course of laparotomy is important in planning for adjunctive chemotherapy, and oophorectomy can be carried out through the same incision when indicated. The vena cava can be plicated in patients who are considered to be at riak for thromboembolic phenomenom.


Management of optic neuritis.

Management of optic neuritis. To improve understanding and effectiveness of therapy in optic nerve disease, various causes of so-called optic neuritis should be identified when possible. The clinical characteristics of demyelinating optic neuropathy can be contrasted with those of ischemic optic neuropathy, nutritional optic neuropathy, true optic nerve inflammation (e.g., luetic), optic nerve infiltration with tumor, and compression neuropathy caused by adjacent tumor. Radiologic studies and other means of investigating patients with optic neuritis are reviewed. Arguments in favor of, and against, treatment of presumed demyelinating optic neuritis are presented along with representative corticosteroid treatment regimens. The natural tendency toward spontaneous improvement of optic neuritis makes the effect of treatment difficult to assess.


Localization of angiotensin converting enzyme (kininase II). I. Preparation of antibody-hemeoctapeptide conjugates. Antibodies to pig lung angiotensin converting enzyme (kininase II) were conjugated to a heme-octapeptide (8-microperoxidase, 8-MP) derived from cytochrome c. 8-MP, which has only one reactive amine, was coupled to antibody in a two-step procedure using a bifunctional active ester, bis-succinyl succinate. In the first-step, 8-MP-succinyl succinate, a stable compound which can be stored. In a second step, the remaining active ester was used for coupling to reactive amines of the antibody. The conjugate consists of 1.6-2.3 8-MP moieties per antibody. Using these procedures, the formation of complex polymers is avoided. Each molecule of conjugate possesses both immunoreactivity and peroxidatic activity. The conjugate has been used to localize angiotensin converting enzyme along the plasma membrane and associated caveolae of pig aortic endothelial cells in culture.


Localization of angiotensin converting enzyme (kininase II). II. Immunocytochemistry and immunofluorescence. The cellular and subcellular sites of angiotensin converting enzyme (kininase II) in lung tissue and endothelial cells in culture were examined by immunocytochemical and immunofluorescence techniques. Converting enzyme is capable of inactivating bradykinin and of converting angiotensin I to its potent lower homolog, angiotensin II. Immunocytochemistry at the electron microscope level used goat anti- (pig lung and angiotensin converting enzyme) coupled to 11-MP (11-microperoxidase) via glutaraldehyde or to 8-MP (8-microperoxidase) via a bifunctional active ester, bis-succinyl succinate. The latter conjugate, which does not contain complex polymers, has been characterized in detail in terms of immunoreactivity and peroxidase activity.


Cell remodeling in the fat body of an insect. The fat body of the Lepidopteran, Calpodes ethlius, undergoes major functional changes during larval-adult metamorphosis. These changes occur in conjunction with extensive cell remodeling - a process whereby one population of cellular organelles is destroyed and replaced by another during development. Fat body organelles including mitochondria, microbodies, and RER are destroyed on a massive scale shortly before pupation (Locke and Collins, 1965; Locke and McMahon, 1971) a new populations of each are regenerated shortly after emergence of the adult. In addition, protein, lipid and RNA reserves formed shortly before pupation and multivesicular bodies formed shortly before emergence are secreted into the haemocoel during the first few days of adult life. Electron microscopic studies using tracer techniques, cytochemical and enzyme localization procedures, and sterological analyses have been undertaken to determine the time course and mechanism of organelle regeneration and the fate of reserves stored in the fat body.


Effects of imipramine, nomifensine and d-amphetamine on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase. The three dissimilar structural antidepressant drugs, imipramine, nomifensine and d-amphetamine, were compared for their effects on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase. Three antidepressant drugs caused a dose-dependent inhibition on type B monoamine oxidase. Of the three drugs, imipramine had a most potent effect. Unlike d-amphetamine, both imipramine and nomifensine inhibited the cyclic AMP phosphodiesterase activity at concentrations more than 10(-4)M. No effect was observed below this concentration. All drugs seemed to have little or no effects on the partially purified dopamine-beta-hydroxylase activity. The weak inhibitory effects of nomifensine on these three enzymes may not be attributable to its antidepressant properties. Morphine had no effect on the three enzyme activities.


Synthesis of potential antiprogestogens. Acylated derivatives of 17 alpha-hydroxyprogesterone were prepared in order to test the hypothesis that dialkylamino alkyl moieties have the effect of transforming progestogens into antiprogestogens. This approach has been successful with certain estrogens. Compounds with other functional groups were synthesized to determine whether these might exert binding influence outside the area occupied by progesterone itself. The compounds were tested for competitive affinity against tritiated progesterone and receptor from rabbit uterus cytosol. The low affinity of all derivatives makes it unlikely that they would be active as antiprogestational agents.


Existence of receptors bound to endogenous estradiol in breast cancers of premenopausal and postmenopausal women. The amounts of free and occupied estrogen receptors were determined in cytosols and cellular (cytoplasmic + nuclear) extracts of 23 human breast cancers. In vivo undersaturation of the receptors was observed in all tumors. A positive correlation was found between the degree of saturation and the concentration of circulating estrogens in premenopausal women. The saturation of the sites was higher in cellular extracts than in cytosols, pointing to the existence of receptor-estradiol complexes bound to nuclei. Our results suggest that the absolute number of occupied receptors depends upon the level of available cytoplasmic receptors as well as upon the level of tissue estradiol.


Uterine estrogen receptor binding of catecholestrogens and of estetrol (1,3,5(10)-estratriene-3,15alpha,16alpha,17beta-tetrol). The binding affinities for the catecholestrogen metabolites of estradiol and of their methyl ethers for the rat uterine cytosol estrogen receptors were examined. Similarly the binding of the fetal estradiol metabolite, 15alpha-hydroxyestriol (estertrol) was also measured. All of the catecholestrogens showed binding affinities far in excess of their uterotrophic potency. This is different from estriol, the product of the alternative metabolic pathways and suggests that the direction of estradiol metabolism may have an important role in the modulation of estrogenic activity of the female sex hormone.


Water-soluble metabolites of the estrogens. Quantitation of C-18 tetrols in rat feces. Several radioactive estrogens possessing one, two and three hydroxyl groups were injected orally (and in the case of estrone sulfate also intraperitoneally) into adult male rats. The rats were either intact or had ligated or cannulated bile ducts. Two unconjugated estrogen tetrols together represented 21 - 87% of the total metabolites in the intact rat. One of the tetrols was 2-hydroxyestriol (estra-1,3,5(10)-triene-2,3,16alpha,17beta-tetrol); the other may be estra-1,3,5(10)-triene-2,3,6xi,17beta-tetrol but this was not confirmed. It is concluded that poly-hydroxylated estrogens represent a very large proportion of the previously unidentified water-soluble metabolites of the estrogens in the adult male rat.


Specific progesterone receptors in dimethylbenzanthracene (DMBA)-induced mammary tumors. Properties of a progesterone receptor present in the cytosol (105,000 xg supernatant) of dimethylbenzanthracene (DMBA)-induced mammary tumors were studied using the highly potent progestin [3H]R 5020 (17, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione). As shown by sucrose gradient analysis, specific binding of [3H] R 5020 is associated with components migrating at 7-8S and 4S. Low affinity binding of the synthetic progestin is eliminated by treatment with dextran-coated charcoal. [3H] R 5020 binding is highly progestin-specific since it is easily displaced by unlabelled norgestrel, R 5020 and progesterone while estradiol-17beta, dihydrotestosterone, testosterone, testosterone and diethylstilbestrol have much lower activity. Dexamethasone and cortisol have little, if any, effect on [3H] R 5020 binding.


A survey of hospital services for suicidal persons. A person who threatens or attempts suicide, arriving for treatment at any 1 of 10 hospitals serving a suburban area in the Bay Area of California, will be met with a variety of responses by different kinds of personnel, depending on the hospital to which he comes. In half of the hospitals, he could be subsequently discharged without psychiatric consultation of any kind. Follow-through on any outpatient referral would usually be left up to him. Although a few hospitals attend to the problem of suicidal persons in many important respects, other hospitals pay little attention to these same aspects. Because of the important role of the hospital in the prevention of suicide, it is recommended that the hospital's function in dealing with suicidal patients be better defined, extended, and made more consistent.


The value of amoebic serology in an area of low endemicity. One hundred sera from army patients who had had amoebiasis in the past and 113 sera from coloured immigrants attending a venereal diseases clinic were examined by four serological techniques. The indirect haemagglutination and the latex agglutination tests showed almost complete correlation; they are useful epidemiological tools but too sensitive and the antibodies on which they depend are too persistent for clinical use. The indirect fluorescent antibody test is a good clinical screening test, and in an area of low endemicity the gel diffusion precipitin test shows a close correlation with clinical disease.


In vitro sensitivity of Entamoeba histolytica to furazolidone and iodochlorhydroxyquin, separate and combined. Entamoeba histolytica trophozoites isolated in Robinson's medium from faeces containing cysts, transported from India, have been tested in vitro against the drugs furazolidone, iodochlorhydroxyquin, and both drugs combined as Dependal. Results show the levels at which drug action is significant and that interaction between the drugs occurs at two concentrations.


Pyridine nucleotide redox state and blood flow of the cerebral cortex following middle cerebral artery occlusion in the cat. Acute changes in the redox state of NADH in the cerebral cortex of cats were investigated following occlusion of the middle cerebral cortex (MCA) and were correlated with alterations of regional cerebral blood flow in the ischemic cortex determined autoradiographically. Arterial occlusion was accomplished via the transorbital approach. Cortical fluorescence and reflected light signals were recorded from the central MCA territory by means of a beam-splitting fluorometer, and a fluorescence signal corrected for alterations in intravascular hemoglobin was derived. Following arterial occlusion, there was a rapid increase in cortical NADH fluorescence, peaking within 30 to 70 seconds at 20% to 40% of full scale. This was followed by a slow linear decline in fluorescence over the next several minutes. The behavior of cortical NADH fluorescence was unaffected by replacement of the ambient air over the cortical surface with nitrogen. Mean regional blood flow values in the most ischemic gyri two to 15 minutes following arterial occlusion were 21% to 23% of the corresponding values in the opposite, nonischemic hemisphere. In individual animals, peak NADH fluorescence values following arterial occlusion correlated with the extent of blood flow reduction in the affected ischemic gyri (P less than 0.05).


Ileal conduit urinary diversion. Ten-year review. The experience with ileal conduit urinary diversion at Emory University and Affiliated Hospitals over a ten-year period is presented. Included in this review are patients with benign and malignant disease. The indications, technique, results, and complications of this type of urinary diversion are considered. Some differences between ileal conduit diversion of children and adults are discussed.


Aerobic and anaerobic flora in bladder urine of patients with indwelling urethral catheters. Twenty-five bladder urine specimens from 13 patients with long-standing indwelling catheters were obtained by percutaneous suprapubic needle aspiration to avoid contamination by extraneous flora and cultured aerobically and anaerobically. Twenty different species of organism were isolated from twenty-four positive specimens. The isolates were predominantly gram-negative aerobic or facultatively anaerobic bacilli, with occasional gram-positive aerobic cocci and yeasts. One patient had Clostridium perfringens and a Bifidobacterium and another had Veillonella and two species of Bifidobacterium. Both patients had four concomitant aerobic or facultative bacteria present. Anaerobic bacteria may therefore be found in the bladder urine of some patients with indwelling urethral catheters, but their role in the initiation and perpetuation of urinary tract infection in this setting remains unclear.


[Drug resistance and hormone dependence of a case of breast cancer]. A case of breast cancer was treated with mastectomy followed by cyclical combination chemotherapy with CMF for a year. In the course of chemotherapy cancer developed in the contralateral breast. Mastectomy was followed within two months by lung metastases. After ovariectomy the lung metastases cleared almost completely. The case shown how the hormone dependence of a breast cancer can remain unimpaired even after prolonged chemotherapy and notwithstanding its failure and secondly that amenorrhea due to chemotherapy need not mean endocrine failure of the ovary.


[Phosphatase activity of the neutrophils in acute appendicitis in children]. Phosphatase activity of neutrophils was studied in 342 patients directed to the hospital with the diagnosis of acute appendicitis, and in 56 healthy children. The index of phosphatase activity of neutrophils (IPAN) was found to be considerably increased in all forms of appendicitis in childhood. An intensity of the reaction depends on the form and terms, elapsed since the disease onset. The determination of IPAN in the complex with clinical findings could be utilized for the differential diagnosis purposes in investigation of patients suspected of acute appendicitis, while in the postoperative period - for estimating a gravity of the course and prognosis of the disease.


Practical aspects of equine virus abortion in the United Kingdom. The current knowledge of the clinical signs, epidemiology and pathogenesis of abortion due to the equid herpesvirus (EHV 1) is reviewed. The relationship between the respiratory and abortigenic forms of the disease is discussed as well as the low incidence of virus abortion in the UK compared to some other parts of the world. Some practical aspects of the disease as they affect stud management are considered including methods of diagnosis, prophylaxis and the necessary action to be taken to prevent spread of infection.


Effect of ceruloplasmin on Sendai virus multiplication in chorioallantoic membrane fragments. Three stages can be distinguished in the evolution of HA titer during Sendai virus multiplication in chorioallantoic membrane (CAM) fragments in relation to the age of CAM and conditions of inoculation and maintenance. Ceruloplasmin has an inhibitory effect on virus multiplication, more marked in the case of stationarily maintained CAM fragments and dependent on the relationship between the moment of ceruloplasmin addition and of virus inoculation. Maximum inhibition is achieved by inoculation of Sendai  virus (1 Ha u) after 4 1/2-hour preincubation with ceruloplasmin (5 x 10(-7)M). The experimental data plead for the formation of a virus-ceruloplasmin complex able to inhibit both penetration and release of virus synthesized in the cell.


Studies on the presence of viral antibodies in patients with various forms of malignant neoplasia. The study of viral antibodies in 6714 sera demonstrated that the level of antibodies to infectious viruses was the same in cancer patients as in controls. However, the patients with various forms of neoplasia showed a considerable percentage and high antibody levels to viruses with oncogenic potential for animals (adenovirus, SV40, Rous virus) or involved in human carcinogenesis (herpes virus).


[Transfer of the genetic information of oncornaviruses by means of tumor cell DNA]. The infection process was reproduced in the culture of chick embryonal cells by means of: a) DNA isolated from chick Rous sarcoma (Carr-Zilber strain); b) DNA from blood cells of chicks with myeloblastosis (strain A); c) DNA from Rous virus malignified (Prague strain) rat cells (XC). Antigenic properties of the virus, transfected with DNA from chick Rous sarcoma, would differ from the original parental strain (Carr-Zilber RSV), that evidences the possibility of a partial transfer of genetic information in transfection. A suggestion is made on four presumable variants of oncornaviruses transfection by means of tumor cells DNA.


[Ultrastructural characteristics of experimental tumors of the intestine]. Tumors of the rat large intestine induced by subcutaneous injection of 1,2-dimethylhydrazine were studied by the method of electron microscopy. Adenocarcinomas retained histiotypical differentiation and at the same time consisted mostly of cells with a low rate of differentiation. Just on the contrary, in mucous and signet-ring cell carcinomas the picture of an advanced cell differentiation was observed in a complete loss of organogeny. The greatest malignancy of neoplasms (signet-ring carcinoma), which cells are characterized by a high degree of cytological differentiation, is a manifestation of independence of tumor progression signs.


[Pancreas carcinoma in the rat (attempts at implantation)]. It is reported on the technique of transplantation of a carcinoma on the pancreas of the rat. As to the origin the malignoma used is a tumour induced by Methyl-Yellow and known as solid form of the Zajdela-hepatoma. Out of 50 transplantation experiments 48 were successful (96%). After continuous growth regional formations of metastases were observed. Death took place in the 3rd week after transgression of the borders of the organs under the picture of cachexia.


[Adenosine-3', 5' -monophosphate in amniotic fluid of normal and high-risk pregnancy (author's transl)]. Transfer of information by cyclic AMP (cAMP) is an important principle of hormonal regulation. The endocrine and metabolic changes during pregnancy may result from a changed cAMP metabolism. At the beginning of systematic investigations on this complex of problems we determined the cAMP content in 111 samples of amniotic fluid from 104 pregnant women without risk symptoms between the eleventh and fortieth week of pregnancy. Up to the 20th week of pregnancy the cAMP content of the amniotic fluid remains constant (5 - 15pmol/ml) and subsequently rises (40th week: 19 - 35pmol/ml). We compared the cAMP content of 27 amniotic fluid samples from 22 risk pregnancies with the normal range which was established in this way. Higher levels of cAMP were measured in the amniotic fluid of women with hypertonic toxemia of pregnancy, gestational diabetes and intrauterine malnutrition - especially in relation to the birth weight. The various possible interpretations for this behavior must be clarified by further investigations.


Transplacental effects of ethylnitrosourea precursors ethylurea and sodium nitrite in hamsters. Four simultaneous dosages of the ethylnitrosourea precursors, ethylurea and sodium nitrite, were administered intragastrically to pregnant hamsters at 100 mg/kg and 50 mg/kg respectively, from the 12-15th days of pregnancy. The treatment induced multiple neurogenic tumors of the peripheral nervous system in the offspring. Female progeny developed a greater incidence and multiplicity of peripheral nervous system tumors with significantly shorter latencies than males, thus establishing evidence that the tumors were age and sex dependent. The tumors presented varied morphological patterns and upon transplantation, grew regularly, exhibiting their malignant nature. The possible influence of estrogenic hormones on the development and growth of peripheral nervous system tumors and comparative aspects of the relationship between prenatal and postnatal carcinogenesis with regard to the ensuing tumor spectra as a consequence of exposure to the same chemical agent, are discussed.


Transplantable, STH-producing and diabetogenic pituitary adenoma of the BD IX-strain of rats. A chromophobic pituitary adenoma induced on BD IX-rats has been grafted on animals of the same strain. The transplanted tumour takes in 90-100%; it grows at a slow rate (in 7 months after grafting a weight of 7-20 g is attained). Tumour-bearing animals display gigantism and hypertrophy of adrenals; moreover, in 33% of cases, diabetes is observed. With non-diabetic animals, splenomegaly and marked leukocytosis are observed; immature white and red cells are present in the peripheral blood. Spontaneous regression of the tumour never occurs. After surgical removal, tumour regrowth and the formation of metastases are observed. Diabetes is characterised by pronounced hyperglycaemia, glucosuria, polyphagia and polydipsia. Histochemically, insulin cannot be detected in pancreas. Splenomegaly is never observed in diabetic animals. Transplanted adenoma frequently tends to stop growing. No recurrence is observable after extirpation. Spontaneous regression of the tumour sometimes occurs. Gigantism, hypertrophy of adrenals and diabetes are considered as consequences of growth hormone- and ACTH-secretion of the transplanted adenoma. At present the tumour is running in the 8th passage. It did not change its characteristics over a period of 5 years.


[Effect of the experimentally induced stress situation on the vascular wall in the rabbit]. DCS and ACTH causes an increasing cellular proliferation in the arterial wall of the rabbit. The combination of both shows only a small further increasing. The importance of these experiments is thought as an additional cause in the atherosclerotic vessel wall alteration.


[Aseptic necrosis of head of femur and disturbance of fat-metabolism type IIa after Fredrickson (author's transl)]. The history of aseptic necrosis of the head of femur is given. Following publication of osteonecrosis in hyperlipoproteinemia type IV after Fredrickson, now for the first time the relation between aseptic necrosis of the femoral head and the primary disturbance of fat metabolism type II is revealed. There exists a hypercholesterinemia, more exactly a hyperbeta-cholesterinemia. The subgroups type IIa and type IIb are explained. Type II is of particular importance since it produces early arteriosclerosis which demands early diagnosis, since this condition can be treated by drugs and diet. In the writers' opinion further differentiation of dys-and hyperlipidemiae in aseptic necrosis of the femoral head will enable us to define signs of disturbances of lipid metabolism. The group of "idiopathic" necroses of the femoral head will become steadily smaller. According to this basic concept the hypothesis might be put forward that this type of aseptic osteonecrosis is a late complication of a differentiated fat-metabolic disturbance.


[Cycloalkylsulfamic acids and their salts. i.v. (author's transl)]. The sodium salts of cis- and trans-2-methyl-cyclohexylsulfamic acid were synthesized and tasted. There is no difference in their degree of sweetness.


[Determination of sulphydryl and disulphide groups in proteins by amperometric titration. III. Investigation of the specifity of Ag+ ions for protein SH groups (author's transl)]. The specifity of Ag+ ions for protein SH groups has been questioned frequently, even though the amperometric titration with AgNO3 is one of the most common methods for the determination of SH groups in proteins. This is due to the fact, that the formation of silver complexes in the titration of cysteine causes a consumption of AgNO3 which is too high. In order to find out if this may be true in the case of proteins, in the present work select proteins with a well known content of SH and SS groups have been titrated amperometrically in tris buffer pH 7.4 with 0.001 M AgNO3. The proteins used were hemoglobin, bovine serum albumin, ovalbumin, lysozyme, pepsin, myoglobin, and cytochrome c. The direct and the indirect titrations of (a) native, (b) denatured, and (c) NaBH4 reduced proteins showed, that the expected consumption of AgNO3 was in no case exceeded. Therefore under the conditions used AgNO3 may be considered as a specific reagent for protein SH groups. High SH values as a result of the amperometric titration of proteins with silver nitrate, which have been published occasionally, may be due to incorrect estimation of the end point of the titration. The reducibility of SS groups depends on the kind of protein. Lysozyme and pepsin were already completely reduced at 23 degrees C, whereas bovine serum albumin needed 60 degrees C. The direct titration method was useful only in some cases for the detection of all SH groups originally present in the proteins or formed by reduction with NaBH4. On the other hand the indirect titration method gave maximum values, because the slowly reacting SH groups of proteins are also allowed to react and the resulting titration curves may be evaluated correctly.


Adrenocorticotropic hormone, glucose and displacement activities in pigeons. The possibility that displacement activities might be consequences of stress-induced humoral responses was investigated. Adrenocorticotropic hormone and glucose were injected into the brain ventricles of unrestrained domestic pigeons. ACTH leads to an increased frequency of yawning and headshaking and glucose to a decrease in arousal. It is concluded that these behavioural responses correspond partly with the displacement activities shown by birds. The role of the cerebrospinal fluid as a mediator of behaviourally active substances is discussed.


Hepatomegaly in Lusaka.

Hepatomegaly in Lusaka. Pattern of hepatomegaly in Lusaka is studied. It appears that toxic hepatitis, viral hepatitis, hepatoma, cirrhosis and schistomasis play a major part in our set up in producing hepatic pathology.


[Physico-chemical and serological study of agglutinogen 3 of B. pertussis]. Results of immunoelectrophoresis, gel-filtration and sedimentation analysis showed the preparation of agglutinogen 3 of B. pertussis to be homogenous. The principal physico-chemical characteristics of agglutinogen 3 (sedimentation constant, diffusion coefficient, molecular weight) were determined.


[The effect of schizophrenic patients serum on the activity of several leukocyte enzymes]. A study of the activity of leukocyte enzymes in the blood of patients with nuclear forms of schizophrenia (52 cases) and in patients with circular schizophrenia (22 cases) depicted the following conditions. In the group of malignant schizophrenia, irrespective of the stage of the disease and in the group of circular forms there was a definite drop in the activity of cytochromoxidase, succinatedehydrogenase and MAO, while as the activity of the ATP-ase and peroxidase was increased. Supplementary animal experiments in vitro and in vivo made it possible to assume that these changes are due to the so-called serum factor.


Oestradiol- and dihydrotestosterone receptors in normal and neoplastic human mammary tissue. Human mammary gland and tumours derived from it contain individual receptors for oestradiol) and for dihydrotestosterone. Analysis of 97 mammary cancers by agargel electrophoresis revealed a widely varying pattern of simultaneous occurrence in different concentration ratios (46), sole presence of oestradiol receptor (23) or dihydrotestosterone receptor (8) and absence of both receptors (18). The relevance of the results is discussed and the need for an extensive cooperative study is emphasized.


Electron microscopic observations on sputum in alveolar cell carcinoma. This paper reports the techniques and results from the use of electron microscopy to augment the routine cytopathologic study of cells in sputum. The material for study consisted of specimens of sputum taken from a 75 year old white woman. The patient later died three months after the beginning of radiotherapy for alveolar cell carcinoma of the lung. Light microscopy revealed a homogenous population of cells, obviously malignant, and interpreted as being derived from alveolar cell carcinoma. Electron microscopic study showed prominent microvilli, numerous mitochondria, multiple foci of well-developed Golgi apparatus, and several types of lysosomes. The ultrastructure of these cells resembled that which has been described for type II alveolar cells from the lung.


Inhibition o'f insulin release by cyproheptadine: effects on 3',5'-cyclic-AMP-content and 45Ca-accumulation of incubated mouse islets. Cyproheptadine (1, 10 and 100 muM) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 muM cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the beta-cell.


Eosinophilic granulocytes on the gastrocytogram. The presence of eosinophilic granulocytes in the gastrocytogram requires examination is not specific and has to be clarified by repeated examinations. The patient should be kept under constant gastrocytologic control, because in certain cases the appearance of eosinophilic granulocytes may accompany cancer.


Preparation of islets of Langerhans from rabbits and hamsters by the collagenase digestion technique. In this report we describe some modifications of the collagenase digestion technique for the preparation of pancreatic islets, that we have found helpful in preparing isolated islets of Langerhans from rabbits and hamsters. These modifications include disrupting the pancreatic acinar tissue by directly infiltrating it with Hanks' solution, periodically monitoring the progress of the collagenase digestion of the pancreatic tissue with the dissecting microscope, and purifying the islets by serial passage of the digested tissue through three Petri dishes containing Hanks' solution. This technique results in the successful isolation of the fragile and irregular rabbit islets as well as the isolation of the sturdier and more uniformly shaped hamster islets. The isolated respond to a glucose stimulus with an increase in radioimmunoassayable insulin secretion. We also describe a filtration technique for the preparation of isolated islets for histological examination. Isolated islets are retained on Millipore filters. The filters are then fixed, stained and mounted. Finally, we present realistic photographs of rabbit and hamster islets, as they appear under the dissecting microscope, during various stages of purification and isolation.