Highly reiterated sequences of SIMIANSIMIANSIMIANSIMIANSIMIAN. A 172-base pair segment of DNA that is repeated several million times in the genome of the African green monkey has been characterized. Sequence analysis revealed that the many repeats of this complex unit are not all identical but represent a set of closely related segments: Sequence divergence occurs at various positions in the segment in a nonrandom manner. The uncloned segment obtained from monkey DNA is compared with a cloned segment of the same DNA which was recombined into the genome of simian virus 40 during permissive infection.


Induction of stalk and spore cell differentiation by cyclic AMP in slugs of Dictyostelium discoideum. Multicellular masses of the cellular slime mold Dictyostelium discoideum, under conditions which ordinarily suppress cell differentiation, develop clusters of stalk cells and spore cells when implanted with Sephadex particles that had been soaked in 5 X 10(-3)M cyclic adenosine monophosphate (AMP). A possible relation exists between oxygen gradients, cyclic AMP gradients, and the pattern of morphogenesis and cell differentiation during fruiting.


(S)-9-(2,3-Dihydroxypropyl)adenine: an aliphatic nucleoside analog with broad-spectrum antiviral activity. (S)-9-(2,3-Dihydroxypropyl)adenine, a novel nucleoside analog, the sugar moiety of which is replaced by an aliphatic chain, inhibits the replication in vitro of several DNA and RNA viruses, including vaccinia, herpes simplex (types 1 and 2), measles, and vesicular stomatitis. It is also effective in vivo in reducing the mortality rate of mice inoculated intranasally with vesicular stomatitis virus.


The genome of simian virus 40.

The genome of simian virus 40. The nucleotide sequence of SV40 DNA was determined, and the sequence was correlated with known genes of the virus and with the structure of viral messenger RNA's. There is a limited overlap of the coding regions for structural proteins and a complex pattern of leader sequences at the 5' end of late messenger RNA. The sequence of the early region is consistent with recent proposals that the large early polypeptide of SV40 is encoded in noncontinguous segments of DNA.


Cytochrome c oxidase as the receptor molecule for chemoaccumulation (chemotaxis) of Euglena toward oxygen. Chemoaccumulation of Euglena gracilis toward oxygen was selectively inhibited, without concomitant effects on cell motility, by cyanide (10(-6) to 10(-4) molar) and carbon monoxide (5 x 10(-5) to 5 x 10(-4) molar). Above these concentrations, motility of the cell was imparied and the chemosensory response was inhibited. Azide did not affect chemoaccumulation even at 5 x 10(-3) molar. It is concluded that cytochrome a3 serves as the chemoreceptor molecule for oxygen-mediated behavioral responses in Euglena.


Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone. The intraventricular injection of methionine-enkephalin (50 to 100 micrograms) or [d-Ala2]-methionine-enkephalinamide (1.5 to 12 micrograms), a synthetic enkephalin analog resistant to enzyme degradation, caused a marked dose-dependent increase in dihydroxyphenylacetic acid and homovanillic acid concentrations in the rat striatum. The [d-Ala2] analog increased the accumulation of dopa in the striatum after aromatic amino acid decarboxylase inhibition, indicating that it increased dopamine synthesis. At the highest doses used both enkephalins failed to modify brain serotonin metabolism. The monolateral microinjection of the [d-Ala2]] analog (3 to 6 micrograms) into the caudate nucleus increased the concentration of dihydroxyphenylacetic acid in the injected side, whereas bilateral injection increased the concentration of this compound in both caudate nuclei and caused catalepsy. The stimulant effect of the [d-Ala2] analog on dopamine synthesis in the striatum persisted after destruction of striatal postsynaptic dopamine receptors with kainic acid. The biochemical and behavioral effects of enkephalins were prevented by naloxone, a specific narcotic antagonist. The results indicate that enkephalins stimulate dopamine synthesis by an action on opioid receptors localized on dopaminergic nerve terminals.


Chemotactic antibody.

Chemotactic antibody. Antibody of the immunoglobulin G class to herpes simplex virus and antibody of the immunoglobulin M class to sheep red blood cells were coupled to the synthetic peptide formylmethionylleucylphenylalanine (fMet-Leu-Phe), which is chemotactic for both mononuclear and polymorphonuclear leukocytes. The resulting molecules were chemotactic and retained their antigen-binding activity. When antibodies coupled to fMet-Leu-Phe were incubated with antigen, the resulting immune complexes were also chemotactic. Chemotactic antibody may provide a potent means of enhancing the migration of inflammatory cells to specific sites.


Imprinting behavior: pituitary-adrenocortical modulation of the approach response. Plasma corticosterone concentrations in newly hatched ducklings exposed to an imprinting model are inversely related to the strength of approach behavior. Injections of corticosterone before imprinting reduces following, whereas alpha1-10-adrenocorticotropin or antiserum to corticosterone augments following behavior. The sensitive period for imprinting may be regulated by changes in the pituitary-adrenocortical axis.


Collagenase immunolocalization in cultures of rheumatoid synovial cells. Cultures of rheumatoid synovial cells that have been enzymatically dissociated and are adherent to a culture vessel are morphologically heterogeneous. When these cells are cultured on a collagenous substrate for 2 to 6 days at 37 degrees C in serum-free medium, they produce collagenase. A monospecific antibody to human collagenase has localized the enzyme extracellularly around cytoplasmic extensions of dendritic cells and intracellularly within a few macrophage-like and fibroblast-like cells.


Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons. Barbiturate anesthetics, but not anticonvulsants, abolish the spontaneous activity of cultured spinal cord neurons; directly increase membrane conductance, an effect which is suppressed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and penicillin; and are more potent than anticonvulsants in augmenting GABA and depressing glutamate responses. Barbiturate anticonvulsants abolish picrotoxin-induced convulsive activity. These results indicate qualitative and quantitative differences between anesthetic and anticonvulsant barbiturates, which may explain their different clinical effects.


Common alcohol-related disorders: recognition and management. Appropriate medical treatment of alcoholics often falls between the clinical specialties of psychiatry, internal medicine, toxicology, and neurology. All physicians need to have a high index of suspicion for alcoholism, since the diagnosis of alcohol dependence is frequently overlooked. Especially when alcoholics are self-referred to nonmedical agencies, their medical complications may be inadequately treated or unrecognized. Common alcohol-related complications requiring treatment include: (1) clinicopathologic disorders, often associated with the gastroenterologic or cardiorespiratory systems, including alcoholic cirrhosis, (2) peripheral myoneural effects, (3) neuropsychiatric complications (delirium tremens, acute alcoholic hallucinosis, Korsakoff's psychosis, alcoholic dementia), and (4) psychosocial disability.


Adhesive arachnoiditis following lumbar myelography. Late sequelae (adhesive arachnoiditis) have been reported following myelography with the oily contrast medium (Pantopaque) and with the ionic water-soluble contrast media methiodal sodium (Abrodil, Conturex, Kontrast U) meglumine iothalamate (Conray Meglumine) and meglumine iocarmate (Bis-Conray, Dimer-X). Adhesive arachnoiditis has not yet been reported after the use of the nonionic water-soluble contrast medium metrizamide (Amipaque). Thus, this is considered the contrast medium of choice for lumbar myelography. Using the recommended dose of 10 ml with an iodine concentration of 170 mg/ml for this examination, adhesive arachnoiditis is unlikely to occur. Increased osmolality of spinal fluid after injection of contrast medium is related to increased frequency of arachnoiditis.


Lumbar myelography with amipaque.

Lumbar myelography with amipaque. In lumbar myelography, early side effects occur in about half the patients examined with modern water-soluble contrast media. At myelography with Amipaque (metrizamide) these reactions are usually minor, and serious adverse reactions are rare. In our own series of 650 consecutive lumbar myelographies with Amipaque there were no serious adverse effects. Minor adverse reactions occurred in 56% of the patients. Transient electroencephalogram (eeg) changes were seen in 14% of the patients, with only 5 patients showing paroxysmal spike activity. Adhesive arachnoiditis following lumbar myelography occurs significantly less often with Amipaque than with any other contrast medium. The properties of Amipaque provide excellent possibilities for detailed studies of all parts of the spinal subarachnoid space, and the medium constitutes a new and interesting aid for these investigations.


Localization of insulinomas and islet cell hyperplasias by pancreatic vein catheterization and insulin assay. Percutaneous transhepatic portal vein catheterization and transfemoral portal and caval catheterizations were performed under local anesthesia in five patients with symptoms of organic hypoglycemia. During the investigation, results of pancreatic phlebography revealed the pancreatic venous anatomy. Blood obtained from the celiac artery, caval branches and pancreatic veins was assayed for insulin by two different radioimmunoassay methods. Pathologically high, pancreatic arteriovenous insulin differences in two patients with insulinomas and in two patients with islet cell hyperplasia. In one of the patients with an insulinoma, one of the assays failed to detect the tumor insulin. This inconsistency still remains unexplained. Angiography revealed a pancreatic abnormality in only two patients. During operation, two of the tumors were found upon palpation and inspection. Pancreatic resections were performed according to the findings of pathologic hormone differences in all five patients. Immunocytochemistry revealed that three of the patients had insulin-producing tumors and two had local islet cell hyperplasia. Catheterizations performed two months postoperatively confirmed the radicality of the operation in all patients, with the possible exception of one patient. In one patient, a recurrance was detected by catheterization ten months postoperatively.


Inactivation of clinical isolates of Herpesvirus hominis, types 1 and 2, by chemical contraceptives. Two chemical contraceptives were examined for virucidal effects against four strains each of Herpesvirus hominis, type 2 and 1. Seven of the strains represented recent clinical isolates; one strain was a type 2 prototype. Either psermicide reduced the infectivities ofall eight viruses after contact for 10 minutes at room or body temperature. The new spermicide-germicide, compound A, produced an antiviral effect at the low concentration of 0.05%, whereas the commercially available Preceptin was effective at 5%, but not at 0.5%. The substantial loss of viral infectivity was due to direct inactivation of virus by the spermicides and was not secondary to cytotoxicity or induction of interferon in the cell cultures used for the assay. These in vitro findings hold primse for the interruption of the sexual transmission of H. hominis.


Circulating immune complexes in patients following clinically curative resection of colorectal cancer. Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.


Display of epicardial ischemia by reduced nicotamide adenine dinucleotide fluorescence photography, electron microscopy, and ST segment mapping. Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique of assessing myocardial ischemia, was correlated with ischemia as identified by ST segment mapping and electron microscopy (EM) in 25 Langdneorff perfused rabbit hearts following coronary occlusion. Nicotinamide adenine dinucleotide (NAD), a component of the intramitochondrial electron transport chain, becomes reduced during periods of ischemia (NADH). NADH fluoresces when excited by ultraviolet light. NAD does not. All three techniques were compared to assess their resolution of the "border zone" between ischemia and nonischemic myocardium. The border zone defined by NADH fluorescence is 0.1 mm or less. Areas of high NADH fluorescence invariably revealed ST segment elevation, whereas minimally fluorescent areas did not. St segment mapping yields a border zone of approximately 7 mm. Areas of high NADH fluorescence following 1 hour of ischemia displayed severe damage on EM as compared to matched controls. A zone of intermediate ultrastructural damage is identified in a 1 mm biopsy taken between fluorescent and nonfluorescent myocardium. This evidence confirms epicardial NADH fluorescence photography as an assay of myocardial ischemia. This high resolution technique delineates a border zone of narrow dimensions as compared with ST segment mapping.


Platelet aggregation and cyclic nucleotide phosphodiesterase activity in arteriosclerotic patients. Although roles of roles of cyclic AMP and cyclic GMP in platelets are though to be important on platelet aggregation, little information on their phosphodiesterase (PDE) is available. Cyclic AMP and cyclic GMP hydrolytic activities of platelets (cAMPPDE and cGMPPDE in platelets) and platelet aggregation by ADP and adrenaline were measured in 22 healthy volunteers, 26 arteriosclerotic patients and other 20 miscellaneous patients excluding vascular diseases. Activities of cAMPPDE and cGMPPDE of platelets were 2.37 +/- 0.52, 7.23 +/- 1.84 in the healthy, 2.50 +/- 0.85, 7.53 +/- 2.60 in the arteriosclerotics and 2.38 +/- 1.02, 6.98 +/- 2.59 pmol/min/10(7) platelets in the miscellaneous patients, respectively. No significant difference was observed among these three groups. Platelet aggregabilities also showed no significant difference. However, there was a significant inverse correlation between the aggregability by 1 microgram/ml of adrenaline and the PDE activities only in the arteriosclerotic patients. The correlation coefficient were-0.61 between the primary aggregation and cAMPPDE,-0.65 between the primary aggregation and cGMPPDE,-0.58 between the 5 min aggregation and cAMPPDE and -0.76 between the 5 min aggregation and cGMPPDE. The inverse correlation between platelet aggregation and cyclic nucleotide metabolism in circulating platelts of the arteriosclerotic patients may suggest that interaction of platelets with arteriosclerotiv vessel walls would produce a certain change in platelets.


The effect of mitomycin C on platelet aggregation and adenosine 3',5'-monophosphate metabolism. The effect of Mitomycin C on aggregation, adenosine 3',5'-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin C. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.


Investigations on the modification of postirradiation pancreatic lipase activity by some endo- or exogenic factors. Part I. The influence of some agonists of adrenergic system. The role of some agonists of the adrenergic system and inhibitors of phosphodiesterase activity in the modulation of the degree of lipase release from pancreatic granular fraction (zymogen and lysosomes) of control and X-ray irradiated rats was investigated. It was shown the decrease of the release of enzymatic activity under the influence of cyclic adenosine monophosphate (cAMP) and noradrenaline (NA) in the fractions from both investigated groups. Effects were dependent on the concentration used. Isoprenaline evoked opposite changes in control and irradiated specimens. In controls it facilitated the enzyme release when applied in smaller (10(-8)M) concentration. In granules from irradiated animals the decrease of enzyme release was noted under the influence of greater concentration (10(-6)M) of the drug. The action of papaverine was nearly similar in control and irradiated groups. The drug evoked the decrease or increase of enzyme release when applied in greater (10(-6)M) or smaller (10(-8)M) concentration respectively. Lipase release was markedly enhanced in controls by theophylline (both concentrations); in specimens from irradiated pancreas, however, no significant alterations were observed.


A simple technique to assess the total number of Onchocerca volvulus microfilariae in skin snips. A technique for the assessment of the total number of microfilariae in skin snips from onchocerciasis patients is described. For the digestion of the skin tissue the biopsies are incubated at room temperature for 24 hours in medium 199, containing 3 mg/ml collagenase and antibiotics. This process leaves the microfilariae unharmed. A comparative study of the emergence of the microfilariae in different media showed that only 20% of the total number were released after 30 minutes in distilled water. After 24 hours incubation in isotonic saline 80% were found.


Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies. 1. One-fifth to 1/4 of globin mRNA is untranslated sequence other than polyadenylic acid. 2. The untranslated sequences of mRNA vary markedly in their sequence and in their length. 3. Globin mRNAs demonstrate a marked bias in codon selection. 4. Viral mRNA shows a quite different pattern of codon selection; therefore, the selection of codons is not uniform for all mRNAs functioning in animal cells. 5. Elongated hemoglobin chains can be accounted for by frame-shift mutations, or point mutations within the normal termination codon. The additional amino acids are then coded for by sequences that are normally untranslated. 6. Certain hemoglobin deletion mutants occur at sites where there are partially reiterated sequences within the heomoglobin messenger RNA.


The immediate pressor response to saralasin: a measure of the degree of angiotensin II vascular receptor vacancy. (1) An immediate pressor response so saralasin, 10 microgram/kg/min, occurred in 52 of 57 (91%) hypertensive patients. (2) We propose that the amplitude of the immediate pressor response functions as an in vivo measure of the number of initially vacan angiotensin II vascular receptors. (3) The immediate pressor response to saralasin forecasts the subsequent sustained response, both of which are related to the renin-sodium profile. (4) The dual blood pressure responses to saralasin, immediate and sustained, make this drug useful for the pharmacological identification of high, normal, and low renin hypertensive patients as they are presently classified. (5) The ability of saralasin to elevate the BP immediately in most hypertensive patients shows the need for caution in its use. It is a safe drug from this standpoint if very small infusions (0.01-0.10 microgram/kg/min) are first tried in hypertensive patients whose PRA is unknown.


The immunoprophylaxis of of rotavirus infections in lambs. The effect of colostrum or serum feeding on subsequent rotavirus infections was investigated in neonatal gnotobiotic lambs. Immunity after feeding colostrum did not depend on absorption of passively acquired antibody into the circulation. Protection against clinical disease depended on the volume of colostrum ingested. The protection afforded by feeding serum was specific, since serum free of rotavirus antibody failed to confer protection. Immune serum fed at a rate of 2.5 ml per kg twice daily protected against rotavirus infection. Also, it was shown by intraperitoneal inoculation of immune serum that protection could occur in the absence of ingested antibody, presumably by transfer of antibody into the gut. The implications of these findings for immunoprophylaxis of rotavirus diarrhoea in lambs and calves are discussed.


Demonstration of argyrophil granules in small cell carcinoma of the lung. The Grimelius silver nitrate stain has enabled us to demonstrate the presence of tumor cells with argyrophil granules (argyrophil cells) in small cell carcinoma of the lung. Of the 22 tumors, 11 showed varying numbers of argyrophil cells. The occurrence of the cells differed in frequency among the subtypes of small cell carcinoma. The fusiform cell type showed the cells more frequently than the other types. Both tumors with numerous argyrophil cells belonged to the fusiform cell type. The number of positive cells seen under the light microscope did not correlate with the number of cells containing neurosecretory granules under the electron microscope, nor with the amount of either ACTH or serotonin in the tumor extracts. The demonstration of these cells in a pulmonary carcinoma may be of help in making correct histological diagnosis.


Ultrastructural aspects of corneal fibrous tissue in the Scheie syndrome. An ultrastructural study of the corneal fibrous tissue was performed in a case of Scheie's syndrome. Mucopolysaccharidosis deposits in keratocytes were observed as electron-clear and electron-dense inclusions. Modifications of the extracellular space included modifications of lamellar collagen organization and local hypertrophy of collagen bundles; presence of microfibrillar dense material isolating large irregular collagen fibers; and presence of fibrous long spacing type collagen fibers. The significance of these changes is discussed. This special form of collagen organization is supposed to appear in a modified microenvironment, that is the presence of an abnormal concentration of proteoglycans.


Virus-specific early RNA in 3T6 cells infected by a tsA mutant of polyoma virus. The accumulation of virus-specific early RNA in mouse 3T6 cells infected by wild type polyoma virus or by a tsA mutant, tsA25E, was measured by hybridization of cytoplasmic RNA to radiolabeled "early" strand polyoma DNA. Cells infected by the tsA25E mutant accumulated approximately 20 times more virus-specific early RNA during the early phase of lytic infection than did wild type-infected cells at both the permissive and the nonpermissive temperature under identical conditions of infection and hybridization. Cells infected by the tsA25E mutant at the permissive temperature continued to accumulate virus-specific early RNA during the late phase of infection after being shifted to the nonpermissive temperature to block further viral DNA replication. A mixed infection of cells by wild-type polyoma and tsA25E showed that the overproduction of early RNA by the tsA mutant alone could be suppressed by coinfection with the wild type. The results suggest that the A gene product of polyoma regulates transcription of early RNA, as has been suggested for SV40 (Reed et al., 1976) and that the wild-type A-gene product overcomes the effect of the temperature-sensitive A-gene product.


[Factors influencing the results of treating trophoblastic tumor patients]. To assess prognostic factors the author has analysed the clinical data on 127 patients, subjected to three variants of the treatment (chemotherapy - in 72, surgery+chemotherapy - in 34, surgery+chemotherapy+radiotherapy - in 21). The following factors have been examined: patients' age, a duration of the affection symptoms in relation to their pregnancy prior to the disease, issues of pregnancy preceding the disease, the size of the primary focus (the uterus), the degree of the process spread, the height of the CH level in diurnal urine before the treatment, the method of initial therapy. Based on the data obtained, it was demonstrated that aside of the tumor morphological structure and the extent of the process spread the results of the treatment are influenced by a sum of clinical signs of the disease, which shound in prognostication.


[Conservative operations in malignant I-stage ovarian tumors]. The remote results of conservative operations in 16 patients with malignant ovarian tumors stage I are reported and compared with the results of treatment following radical (38) and nonradical (45) operations. Two thirds of conservatively operated patients (unilateral adnexectomy) survived for more than 5 years, over 50% of patients showed a 10-year survival. It is emphasized that saving operative procedures should not be performed in the presence of the factors aggravating the prognosis (proliferation of the tumor capsule, adhesions, a ruptured tumor capsule).


[A preliminary report of "selective ultraviolet phototherapy" in psoriasis (author's transl)]. 35 patients with psoriasis were treated solely by UV irradiation using a Saalmann selective ultraviolet phototherapy lamp (SUP), a mercury lamp with increased emission between 310 and 320 nm. Irradiation four to five times weekly produced 90 to 100% improvement in 83% of the patients. Nineteen of the thus-treated patients showed complete clearing of the psoriatic lesions. The average duration of treatment was 4 weeks. These good results were maintained on a regimen of twice-weekly UV therapy.


[Use of collalytine for preparation of monolayer primary cell cultures]. Collalytine, a national preparation of collagenase effect, may be used for dispersion of different organs of cattle and human fetuses. Depending on the concentration and time of treatment, this preparation permits to produce monolayer cultures of histotypic or cytotypic nature.


[Hyperlipemic arthropathy in primary hyperlipoproteinemia]. In this paper a case of hyperlipaemic arthropathy with participation of the skin in primary hyperlipoproteinaemia type IIa after Fredrickson is described. The case in question is a clinical picture which is very rarely described. Questions of differential diagnosis and genesis are discussed. The prognosis is to be estimated favourably when the basic disease is recognized and treated. The genesis of the disease is not yet clear. With the help of literature several possibilities of the development are discussed.


[Polypous nonchromaffin paraganglioma of the stomach]. It is reported on the unusual position of a nonchromaffin paraganglioma in the stomach, which in gastroscopy imposed as polyp and was removed. On the basis of the light-microscopic picture, its behaviour during staining and the electronmicroscopic investigations the tumour is classified in the group of the paragangliomata. Since there are no unequivocal histological criteria of malignity, on account of the well-known slow growth of these tumour only the polyp is removed.


Carbohydrate composition of peripheral, cultured and leukaemic human lymphocyte plasma membranes. Plasma membranes isolated from peripheral blood lymphocytes of normal donors, lymphocytes from patients with chronic lymphatic leukaemia (CLL), a T cell and B cell line (MOLT-3 and RPMI-1788) were analysed and compared for total carbohydrate contents. T cells and peripheral blood lymphocytes contained the highest relative amounts of sialic acid and fucose, whereas chronic lymphatic leukaemic cells possessed the highest amounts of N-acetylgalactosamine and also more total cell surface carbohydrate. The Thomsen-Friedenreich antigen (TF) was detected serologically on membrane fractions by the use of anti-TF containing sera and specific lectins from Arachis hypogaea, Agaricus bisporus and Vicia graminea. The disaccharide beta-D-galactosyl(1-3)-N-acetyl-D-galactosamine is the immunogdominant carbohydrate group of the FT antigen and was detected as its reduced form, by gas chromatography, in all cells, thus correlating serological and analytical evidence. The haemagglutinating activity of the lectins and sera used was only inhibited by plasma membranes after the removal of sialic acid showong that the native form of this antigen is normally masked by sialic acid in CLL cells as well as normal lymphocytes.


[Mechanism of specific vaccine therapy in ocular herpes simplex]. The mechanism of specific vaccine therapy in herpetic eye disease was studied. The effectiveness of the therapy in the observation period of 3 to 8 years was established. In 71 (62%) of 114 patients relapses of the disease disappeared completely, in 32 (26%) became less frequent and in 11 (10%) their frequency did not change. The clinical course of relapses in all cases became milder. The vaccination courses given were shown not to influence the level of virusneutralizing antibody but to induce the appearance in the lacrimal fluid of immunoglobulins G and M and to increase considerably the level of IgA. The vaccint therapy enhanced the reactions of cell-mediated immunity which was manifested in increased specific blasttransformation of lymphocytes (up to 18%) and reduced the migrational capacity of leucocytes to inactivated antigen of herpesvirus. The effect of the vaccine persisted only for a few months. The immunological and clinical analyses showed that it was expedient to give vaccine in courses at 6--12-month intervals after an attack of herpes.


[Pathomorphology of experimental infection caused by powassan virus isolated in the Primorskiĭ Territory]. Pathomorphology of the infection caused by Powassan virus strains isolated in the Primorsky Kray was studied in white mice. The central nervous system of the animals sacrificed in the time course of the infectious process was studied by light and luminescent microscopy. Severe diffuse inflammatory-degenerative changes were found in the brain and spinal cord. Immunofluorescence revealed cytoplasmic localization of the virus antigen in neurons, glial and connective tissue cells.


[Aftercare of patients operated on for goiter (author's transl)]. Between 1966 to 1976 2122 patients underwent a partial thyroidectomy for goiter. All patients received special aftercare in the outpatient department of the hospital. Without hormonal substitution there were 5,9% relapses.


[Diseases of the lumbosacral portion of the peripheral nervous system (treatment and prevention)]. A critical analysis of modern literature and personal experience permits the author in a discussional aspect to speak on diagnosis formulation in patients with lesions of the sacrolumbar area of the peripheral nervous system. The paper contains detailed recommendations in relation to different forms of medicative therapy and prevention in this group of patients. The subsequent perspectives and further studies, as well as organizational questions are being discussed.


Purification and properties of pig kidney glutamate dehydrogenase. Glutamate dehydrogenase from pig kidney has been purified to homogeneity by means of affinity chromatography on matrix bound Cibacron Blue F3G-A and gel chromatography on Sepharose 6B. The enzyme exhibits allosteric properties with the substrates alpha-ketoglutarate, ammonium, and NADH, respectively. GTP is a strong inhibitor which strengthened the cooperative interactions between the ammonium binding sites. ADP as an activator relieves the inhibition by GTP. Like glutamate dehydrogenase from bovine liver, glutamate dehydrogenase from pig kidney shows the ability of self-association, too. The sedimentation coefficient increases from 13.5 S at 0.07 mg protein/ml to 19.4 S at 1.32 mg protein/ml. In the sodium dodecylsulphate gel electrophoresis the enzyme migrates as a single band with a molecular-weight at 51000.


[Determination, proprerties and postnatal development of galactokinase in the swine liver]. 1. Starting from the spectrophotometric method of Ballard optimal reaction conditions for measurements of galactokinase in piglet liver were systematically studied. These are (final conc. in the test): 100 mM triethanolamine-HCl buffer, 33 mM KCl, 16.5 mM NaF (inhibiting ATPase), 5 mM cysteine hydrochloride, 0.33 mM NADH2, 1 U pyruvate kinase and lactic dehydrogenase, 0.5 mM phosphoenolpyruvate, 1.5 mM galactose, 0.5 mM ATP and 1 mM MgCl2, final pH 7.5. 2. An optimal substrate concentration, a Mg: ATP-ratio of 2:1, pH-stability and addition of activators are important for the determination of galactokinase activity in the supernatant fraction of pig liver. 3. Using the optimized method galactokinase activity of pig liver in dependence on age, with particular reference to the perinatal period, was determined. 4. Galactokinase activity of liver of newborn piglets is 7 times that of adult pigs. In the suckling period the activity remains relatively constant at this high level and decreases remarkably immediately after weaning. 5. Galactokinase of liver of newborn piglets differs in kinetic properties (lower Km of ATP, higher maximal reaction velocity) from the enzyme of adult pigs, which is still insufficient to make sure the existence of two different forms of the enzyme.


[Repeated characterization, analysis of variance limitation and discrimination analysis classification of EEG-activity patterns in human sleep]. 1. To describe quantitatively and to deliminate nine EEG sleep patterns, mean values and standard deviations of abundances of the frequencies 0.8 ... 1.8 c/sec, 2...3.5 c/sec, 4...13c/sec, 14 to 17 c/sec, 18 to 22 c/sec, and 23 to 40 c/sec as well as of the average amplitudes in selected frequency ranges were calaculated and the distributions represented. 2. All nine EEG activity patterns could be separated by means of univariate and multivariate analyses of variance on the basis of all 28 as well as the 17 indispensable variables. 3. In the course of a stepwise reduction of variables within the framework of a linear discriminant analysis an optimal set of 17 variables was determined for the separation of the patterns, comprising: the percent quantity of the frequencies 0.8 ... 3.5 c/sec, 7 ... 9 c/sec and 18 to 40 c/sec as well as the average amplitudes in the frequency ranges 0.8 to 3.5 c/sec and 7.5 to 40 c/sec. 4. By linear regression analyses it could be shown that the sleep scording system used, can be reflected on an interval scale with the aid of discriminant functions; this can be achieved on the basis of the optimal set of variables as well as of the five most indispensable variables. 5. Finally the degree of the objectivity of the scoring procedures was demonstrated. Advantages and disadvantages of sleep scoring systems were discussed and possibilities of the utilization of results suggested, also in respect to the further development of the automatic recognition of EEG activity patterns.


Ethylmorphine-N-demethylation by liver homogenate of newborn and adult rats; Enzyme kinetics and age course of Vmax and Km1. Optimum incubation conditions for determination of ethylmorphine-N-demethylation with newborn and adult rat liver homogenate have been determined: 1 ml 1:20 liver homogenate in 1.15% KCl, 1 ml 0.1 M phosphate buffer with ethylmorphine, NADP, and glucose-6-P, final concentrations 10, 0.33 and 5 mM, respectively, no nicotinamide, no MgCl2, 1 ml 0.5 M phosphate buffer; 3 ml final volume, 20 min incubation time. With both age groups NADH increases the activity to the same extent. With NADPH, saturation could be achieved only with newborn liver, but not with adult liver homogenate. Postnatally, the activity increases about fivefold, with a break at the 10th day of life. The Lineweaver-Burk plot was linear with newborn liver homogenate, whereas for all other age groups the graphs showed an angle. Statistical analysis pointed out that a two-enzyme model fits the experimental data only insignificantly better than a one-enzyme model. From other experimental evidence and manifold reproduction without any exception of these results, however, it may be concluded that there are different monooxygenases which show different affinities towards one substrate (ethylmorphine) and which show different developmental patterns.


[Electron transport particles from beef-heart mitochondria as a test system for inhibitors of the respiratory chain]. Respiratory inhibitors exert a potentially biocidic action on all aerobic organisms. Therefore the systematic search for them and the elucidation of their mechanism of action is of great importance. The non-phosphorylating electron transfer particles (ETP) according to Crane et al. are a suitable test object for this aim. A standardized preparation of ETP from beef heart is described and characterized enzymatically. The ETP show a variety of advantages in comparison with other systems; their field of application is broad. Owing to the absence of bypasses of the respiration, particles from animals are more suitable than those from plants for the search for fungicides and herbicides which inhibit the respiratory chain. With relatively little expense, the two standard assay systems proposed (NADH oxidase and succinate-cytochrome c oxidoreductase) pick up with certainty all inhibitors of the main pathway of the respiratory chain; they are useful for screening studies. The system proposed is also suitable for the analysis of the exact site and the mechanism of action of respiratory inhibitors. Furthermore, ETP can be used to obtain parameters of the hydrophobicity of drugs as well as for toxicological studies.


Lack of correlation between adrenal cAMP and corticosteroidogenesis in the newborn rat. In 2 to 16-day-old rats subjected to heat, the adrenal content of cAMP did not increase in animals younger than 14 days of age, but serum corticosterone was significantly higher than control values at all ages except in 10 and 12-day-old animals. This would suggest that cAMP may not mediate the adrenal steroidogenic response to stress during the first post-natal week. This hypothesis is consistent with the fact that the administration of 0.195 and 0.785 mU ACTH to 2-day-old rats resulted in a significant increase in serum corticosterone without a rise in the adrenal content of cAMP. The stress-induced rise in serum corticosterone progressively diminishes during the first post-natal week before returning to its previous 2-day-old capacity by day 16.


Inverse effects of corticosterone and thyroxine on glucocorticoid binding sites in the anterior pituitary gland. The aim of this study was to determine whether pituitary glucocorticoid binding sites are under hormonal control. It was shown that corticosterone and thyroxine exerted antagonistic effects on both the transcortin-like component and true receptor present in the hypophysis: thyroid hormones, in contrast to glucocorticoids which exhibited opposite influence, increased maximum binding without affecting significantly the apparent association constant. Thus, it seems that the concentration of glucocorticoid binding sites is regulated by the glucocorticoid ligands, as well as by a different hormone. Moreover, a striking parallelism was found between plasma transcortin and pituitary transcotin-like capacity, argueing in favour of a plasma origin for this pituitary binder.


Treatment of pituitary dependent Cushing's syndrome with closed stereotactic radiosurgery by means of 60Co gamma radiation. Four patients with pituitary dependent Cushing's syndrome were treated with external irradiation to the pituitary using 60Co gamma irradiation given with a stereotactic technique. The size of the sella turcica was normal or slightly enlarged in all patients. The doses given varied between 7000 and 10 000 rad, and the observation time ranged between 14 and 20 months. Three of the patients showed complete clinical remission and one marked improvement. One patient developed ACTH insufficiency, while none developed insufficient secretion of other pituitary hormones. No complicants of the irradiation were observed.


Effects of bromocriptine on the hypothalamo-pituitary axis. The effects of bromocriptine on the secretion of prolactin, gonadotrophins, thyretrophin (TSH), corticotrophin (ACTH), somatotrophin (GH) and melanocyte-stimulating hormone (MSH) in mammals are presented and the sites and mode of action briefly discussed.


Studies on the influence of monoamines on the cerebrovascular response to arterial hypoxia. The cerebrovascular response to arterial hypoxia  was studied during blockade of the vascular dopamine receptors and during alpha-adrenergic receptor stimulation and blockade in anaesthetized dogs. Dopamine receptor blockade with pimozide or haloperidol invariably decreased the degree of hypoxic vasodilatation in the brain pointing to a functional role of dopamine in this situation. Alpha-receptor blockade did not change the response, while stimulation of these receptors decreased the dilatory response even in deep arterial hypoxia.


An ultrastructural study of chronic cadmium chloride-induced neuropathy. After the long-term exposure to cadmium chloride in drinking water, the Wistar rats developed peripheral polyneuropathy. The main lesion was of myelin degeneration. Ultrastructural examination of the roots and sciatic nerves revealed segmental demyelination beginning from the node of Ranvier. There was the active autophagocytosis of Schwann cells which contained a number of myelin remnants and dense bodies. There was, on the other hand, the evidence of remyelination with toxic damage, in which the thinner myelin sheaths and abnormal myelinations were observed with increase of Schwann cells containing rich ribosomes. Axoplasmic changes were minimal, but consisted of accumulation of glycogen particles which very often produced glycogenosomes in characteristic appearance with axoplasmal dysfunction.


Morphological studies of hamster brain cells transformed in vitro by a human papovavirus BK. The cytomorphology and cytogenesis of BK virus-transformed hamster brain cells (HBBK cells) were studied. HBBK cells with indistinct processes showed a tendency to epithelial arrangement as well as characteristics of malignant tumor cells in vitro, and developed long, delicate processes when cell growth was suppressed. Glial fibrillary acidic protein was demonstrated by immunofluorescence in the cytoplasm of almost all HBBK cells. The tumors arising in hamsters after subcutaneous inoculation of HBBK cells were classified as poorly differentiated gliomas. These findings suggest that selective transformation of glial cells in hamster brain cells by BK virus occurred.


Infantile neuroaxonal dystrophy. Schwann cell inclusion in the peripheral nerve. Abnormal Schwann cell inclusion is reported in biopsied peripheral nerve in a case of infantile neuroaxonal dystrophy. In addition to non-specific dystrophic changes of the axons, the Schwann cells contained several distinct bodies which were composed of stacks of irregularly disposed membranes; in some instances, transformed Schwann cell cytoplasm was distined with similar bodies. This change has not been reported on this condition and its significance is briefly discussed.


Mixed mesenchymal and neuroectodermal tumor of the cerebellum. An unusual cerebellar tumor composed of mixed mesenchymal and neuroectodermal elements in a 44 year old man is reported. The mesenchymal element is well-differentiated adipose tissue, whereas the neuroectodermal components exhibit a variety of medulloblastomatous, astrocytomatous, oligodendrogliomatous and ependymomatous areas. A possible origin of such unusual mixed neoplasms is briefly discussed.


Effects of the antidiuretic hormone, arginine vasotocin, theophylline, filipin and A23187 on cyclic AMP in isolated frog skin epithelium (Rana temporaria). A method for measuring cAMP in frog skin epithelium was developed. The epithelia were isolated after collagenase-treatment. cAMP was extracted by boiling water and the extract was purified on dry Al2O3. The change with time of the cAMP level after addition of arginine vasotocin (AVT) was studied. The hormone caused a rapid increase in cAMP level with a maximum after 3-5 min, whereafter the cAMP level declined. Incubation with AVT made the epithelia refractory to a second dose of AVT, which indicates that the decline in cAMP level was caused by a feedback mechanism and not by inactivation of the hormone. cAMP appeared evenly distributed in all cell-layers of the epithelia both before and after stimulation with AVT. Theophylline caused a rapid increase in the cAMP level, which remained elevated for at least 45 min. Addition of the ionophore A23187 or of filipin had no effect on the cAMP level. However, in the presence of theophylline, A23187 enhanced the cAMP level, whereas filipin had no effect. Therefore the involvement of cAMP in the action of A23187 has to be considered.


Urinary cyclic AMP and vasopressin excretion in rat strains selected for their alcohol intake. Urinary excretion of adenosine 3',5' -cyclic monophosphate (cAMP) and immunoreactive arginine vasopressin (AVP) were investigated after water loading and following ethanol loading in two rat strains selected for their voluntary ethanol intake. After ethanol loading ethanol preferring (AA) rats excreted more cAMP but less AVP than water preferring (ANA) rats. The results suggest that the strain difference in cAMP excretion is of renal origin and is not due to vasopressin or parathormone. Differences in the sympathetic nervous activity may be responsible for the difference in cAMP excretion.


Lymphatic dissemination of bone and soft tissue sarcomas: a lymphographic investigation. The series consisted of 132 patients, 61 with primary bone sarcomas and 71 with primary soft tissue sarcomas. The patients were all evaluated by lymphography. The investigation included both patients who had not yet been treated and patients with suspected or confirmed metastases. All tumour diagnoses were confirmed microscopically. The findings as regards dissemination were based on clinical examinations, laboratory tests, roentgen examinations and lymphographies. In some cases, lymph node biopsies and surgical observations were also used. A total of 151 lymphographies were performed and 281 follow-up films taken. Preoperative lymphography was performed using the technique introduced by Kinmonth. For postoperative lymphography on the stumps of amputated extremities, two simple but useful methods were developed, which are presented here. Changes in the lymphographic appearance of lymph node metastases, the occurrence of new metastases, and the results of treatment were assessed by survey films and repeat lymphography. The generally accepted criteria for metastasis were used as a basis for the analysis of the lymphographic findings. The results may be summarized as follows: 1. Incidence of lymphatic dissemination. Different sarcomas varied greatly in their clinical course, including the frequency of dissemination. The lymphatic involvement in the metastatic cases was as follows: Bone sarcomas: 16 out of 28 (Table 10); of these, 13 were to regional lymph nodes, 8 to distant nodes and 5 to both (Table 14). Soft tissue sarcomas: 24 out of 40 (Table 11). All 24 had metastases in regional nodes, and 8 in distant nodes as well (Table 15). The highest frequencies of lymphatic spread in the different metastasized tumours were found to be: Bone sarcomas: reticulosarcoma 100%, Ewing's sarcoma 50%, osteosarcoma 47%. Soft tissue sarcomas: rhabdomyosarcoma 100%, synovial sarcoma 80%, neurogenic sarcoma 78%, leiomyosarcoma 67%. 2. Time-relation between lymphatic and haematogenic dissemination; The tendency to metastasize first via the lymphatics or via the blood vessels varied. Half of the cases of Ewing's sarcoma and reticulosarcoma had evidence of lymphatic spread before blood-borne metastases were detected. In the osteosarcoma cases, however, lymphatic dissemination was always preceded by haematogenic spread (Table 12). In synovial sarcoma, rhabdomyosarcoma and neurogenic sarcoma, the first dissemination was more frequently lymphatic than haematogenic (Table 13). 3. Possible existence of special lymphographic features of sarcoma metastases. Only reticulosarcoma displayed special characteristics. The lymph node metastases of reticulosarcoma of bone had lymphographic appearances similar to those found in reticulosarcoma of soft tissue or lymph node origin (Fig. 12). The lymph node metastases of other primary bone and soft tissue sarcomas had no specific lymphographic features and were indistinguishable from carcinomatous metastases (Figs 7, 9, 13, 15, 18, 19, 20, 22, 23). 4...


Cytomegalovirus pneumonia after treatment with melphalan and prednisone. Report of a case. A patient with multiple myeloma had pancytopenia after treatment with melphalan and prednisone and died of an interstitial pneumonia. Post-mortem examinations showed cytomegalic cells in the lungs. Lung tissue showed a high titer of cytomegalovirus. Only when other causes have been ruled out by microbiologic, serologic, and histologic examinations should melphalan be believed to cause respiratory illness.


Effect of prostaglandins and some methyl derivatives on the ductus arteriosus. In vitro studies showed that PGF2a constricted the ductus arteriosus of newborn animals, whereas PGEs produced dilatation. The finding that constriction could also be produced by c-GMP and dilatation by c-AMP raised the possibility that the PGs might produce their effects by altering the relative proportions of cyclic nucleotides in the ductus wall. Results of experiments with inhibitors of PG synthesis and with drugs which are known to interfere with the degradation of c-GMP and c-AMP accorded with this hypothesis. Angiographic studies in neonatal piglets showed that PGEs and PGAs were potent dilators of the ductus. Prostaglandin action was confirmed in infants with congenital heart disease who were dependent on ductus patency for survival. In those patients, PGs proved to be an extremely useful tool. Experimental studies are in progress in the hope of finding a PGE analog, active by the oral route, which may be suitable for the long-term treatment of patients.


Bronchioloalveolar carcinoma: two clinical entities with one pathologic diagnosis. Bronchioloalveolar carcinoma may present with a variety of radiologic and clinical patterns. Two types of this primary carcinoma of the lung have been recognized: a solitary lesion and a diffuse form. Charts and radiographs of 61 cases of bronchioloalveolar carcinoma were reviewed as well as the pertinent literature. Our experience indicates that the localized form seldom, if ever, becomes diffuse and has a good prognosis following appropriate surgery (lobectomy or pneumonectomy). If the lesion is diffuse, death almost invariably results within 3 years. Based on available clinical information, we suggest that at least two primary tumors of the lung have the histologic pattern of bronchioloalveolar carcinoma: one of these tumors is diffuse and the other is solitary.


Opportunistic ocular infections.

Opportunistic ocular infections. Since corticosteroids were introduced, a steadily increasing number of opportunistic pathogens have been causing major disease in both systemically and locally compromised hosts. In ocular disease, the most common cause of compromise (and of infection with such opportunistic pathogens as the herpeviruses, many gram-negative bacteria, numerous fungi and Toxoplasma) is the topical use of corticosteroids and antibiotic-corticosteroid preparations. To avoid the damaging and sometimes blinding results of opportunistic infection, the use of these preparations should be carefully restricted.


Silica flour exposures in Ontario.

Silica flour exposures in Ontario. A total of 16 cases of silicosis are reported in Ontario plants where there was exposure to silica flour. Dust counts expressed as mppcf are shown for four of these plants taken over a period of 37 years. A relationship has been obtained experimentally to permit conversion of the counts to respirable mass concentrations. Based on the information obtained, a TLV of 0.05 mg/m3 for silica flour is proposed.


Vitamin B6 nutritional status of pellagrins and their leucine tolerance. Disturbances in tryptophan-nicotinamide adenine dinucleotide pathway, seen in pellagrins whose staple is sorghum have been ascribed to an amino acid imbalance caused by excess intake of leucine. Studies in normal human volunteers and in experimental animals have shown that administration of vitamin B6 will counteract some of the metabolic effects of leucine. In view of these observations, two clinical studies were conducted--one to investigate the vitamin B6 nutritional status of pellagrins and the other to determine whether plasma leucine clearance in pellagrins is different from that of normals. Vitamin B6 nutritional status of pellagrins was found to be far from satisfactory, as indicated by elevated levels of xanthurenic acid and kynurenic acid in urine after a tryptophan load and low plasma pyridoxal phosphate levels. Plasma leucine concentrations at 1, 2, and 4 hr after a leucine load were significantly higher in pellagrins than those in normals. Administration of 25 mg of vitamin B6, intramuscularly 30 min before leucine load significantly decreased plasma leucine concentration in pellagrins. However, the leucine concentration at 4th hr did not return to basal level. Administration of vitamin B6 10 TO 20 mg/day orally for 10 to 15 days normalized leucine tolerance in pellagrins. Data presented here suggest that when the diets contain excess leucine, additional amounts of vitamin B6 are required.


Marked elevation of serum angiotension-converting enzyme and hepatic fibrosis containing long-spacing collagen fibrils in type 2 acute neuronopathic Gaucher's disease. Serum angiotensin-converting enzyme in a patient with type 2 acute neuronopathic Gaucher's disease (242 nmol/min/ml) was 10.8 times higher than values for eight patients with other hereditary neurologic abnormalities (22.5 +/- 2.0) and 9.4 times higher than those for 12 patients with other diseases (25.7 +/- 2.6) (P less than 0.001). Serum lysozyme was not elevated in the patient with type 2 Gaucher's disease. These results indicate that elevated serum angiotensin-converting enzyme in an infant with neurologic involvement and hepatosplenomegaly is suggestive of the possibility of type 2 Gaucher's disease. Typical Gaucher's cells and fibrosis were observed by light and electron microscopy of the liver. An aspect hitherto unreported in Gaucher's disease or in the liver was that approximately 20% of the collagen fibrils were of the long-spacing type, with periodicity of 1,000 to 1,100 A and diameters of 900 to 1,500 A.


Fatal rotavirus gastroenteritis: an analysis of 21 cases. During the period of May 1972 to March 1977, twenty-one fatal cases of rotavirus acute gastroenteritis were recorded in the city of Toronto. The mean age of these subjects was approximately 1 year. Boys outnumbered girls by 12 to 9. Death occurred within three days of onset of symptoms in all cases. Sixteen of the subjects were profoundly dehydrated and had sodium levels (serum or vitreous humor) in excess of 150 mEq/liter. In 11 subjects, sodium values were greater than 160 mEq/liter. Although a physician was contacted in 16 instances, these infants still perished. We suggest that both language difficulties and the rapid rate of fluid depletion contributed significantly to the fatal outcome. At autopsy the bowel was often dilated and filled with fluid. Postmortem autolysis precluded an accurate histological assessment of the small bowel mucosa.


Massive upper gastrointestinal hemorrhage from a granular cell tumor of the stomach. The first case of massive upper gastrointestinal hemorrhaging from a granular cell tumor of the stomach is reported. The clinical and pathologic characteristics of the 15 previously reported cases are reviewed and the theories of the histogenesis of this lesion are briefly discussed.


Antigenic relatedness of 17 strains of human cytomegalovirus. A 10 minute kinetic neutralization test was used to assess antigenic relatedness among 17 strains of human cytomegalovirus. Hyperimmune guinea pig sera exhibited extensive cross-reactivity. However, the data did suggest that there may be four antigenic groups represented in this collection of CMV strains. Available epidemiologic data for these strains do not provide any discernible basis for this grouping.


Hypercalcemia with suppressed parathyroid hormone in Burkitt's lymphoma. Two patients with Burkitt's lymphoma presented with severe hypercalcemia, a previously unreported complication of this tumor. Roentgenograms and radionuclide scans showed multiple osteolytic lesions in both patients. Plasma parathyroid hormone (PTH) was undetectable during the hypercalcemia phase. Chemotherapy was followed by rapid tumor lysis, hyperphosphatemia, phosphaturia and hypocalcemia. The hypocalcemic phase persisted for two weeks despite rapid normalization of serum phosphorus and renal function. Measurement of urinary cyclic AMP, an index of PTH action, indicated that parathyroid function had been suppressed by the hypercalcemia and remained suppressed for almost one week despite marked hypocalcemia.


Combined deficiency of glucose-6-phosphatase and fructose-1, 6-diphosphatase. Studies of glucagon secretion and fuel utilization. An adult woman with hypoglycemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hyperketonemia and inability to make new glucose from galactose, fructose, glycerol and alanine was found to have no hepatic glucose-6-phosphatase and deficient fructose-1,6-diphosphatase. Nonautonomous hyperglucagonemia was demonstrated and shown to contribute to the hyperlactatemia and hyperketonemia. A paradoxic hyperlactatemic response to glucose and galactose was observed. Studies of substrate utilization showed prompt adaptation to changes in dietary supply of energy which probably accounted for her never having experienced symptoms of hypoglycemia.


The swine flu immunization program: scientific venture or political folly? The author of this Article, an internationally recognized coroner perhaps best known among laymen for his incisive and tenacious criticism of the Warren Commission report on the Kennedy assassination, turns his attention to the federal government's 1976--1977 Swine Flu Immunization Program. Dr. Wecht contends that although this program may have been viewed by its key proponents as having great public health importance, or perhaps even political value, its creation and continuation nevertheless were scientifically unjustified. Furthermore, he contends, the federal government failed to inform the public adequately of important facts about the program's origins and progress, and it mismanaged the program in several important respects. Among the topics he discusses are swine flu's epidemiological history (including the 1976 Fort Dix outbreak that propelled swine flu into the national consciousness); the key elements leading to the government's decision to immunize; the government's failure to reevaluate the program seriously as problems arose; the shortcomings of the federal swine flu statute; the inadequacy of the government's investigation of the deaths of three persons in Pittsburgh within a few hours after being vaccinated (a matter that was of immediate concern to the author in his role as Coroner of Allegheny County, Pennsylvania); the long-delayed termination of the program following the emergence of a possible statistical link between the immunizations and an increase in the incidence of the Guillain-Barré Syndrome; the financial and human costs of the program; and the need for calmer, more objective decision making in future situations where immunization of the general populace is being considered.


Elevated levels of cerebrospinal fluid guanosine 3',5'-cyclic monophosphate (C-GMP) in systemic lupus erythematosus. Cerebrospinal fluid samples from patients with systemic lupus erythematosus (SLE) and neurologic involvement were evaluated for guanosine 3',5'-cyclic monophosphate (C-GMP) and cyclic adenosine monophosphate (C-GMP) content by radioimmunoassay and radioassay, respectively. Twenty-five samples from 15 patients with SLE had an average C-GMP level of 2.4 nM +/- 0.44 (average +/- SE) compared with 0.68 nM +/- 0.14 in a control group with lumbosacral pain (p less than 0.0002). No significant difference was noted in C-AMP content between patients with SLE and control subjects. C-GMP levels in cerebrospinal fluid samples from patients with SLE who had changing neurologic disease were higher than in those with stable neurologic disease. Elevated C-GMP levels in cerebrospinal fluid correlated with the leukocyte number in cerebrospinal fluid (r = 0.53 p less than 0.01), but not with the initial pressure, protein concentration or daily prednisone dosage. Experimental results suggested that leukocytes in the cerebrospinal fluid were not the source of elevated C-GMP levels. Thus, elevated C-GMP levels in cerebrospinal fluid of patients with SLE appeared to reflect neurologic involvement. C-GMP levels were alos found to be elevated in five patients with other active neurologic diseases; thus, measurement of C-GMP in cerebrospinal fluid may have more general diagnostic value.


Cure of acromegaly by operative removal of an islet cell tumor of the pancreas. We studied a 30 year old woman in whom acromegaly was cured by operative removal of a large cystic beta cell adenoma of the pancreas. We detected substantial amounts of immunoreactive human growth hormone (hGH)-like activity in a tumor tissue extract. Extracts of the tumor and a normal human pituitary gland eluted from a Sephadex G-75 column in two identical peaks. Serial dilutions of the tumor extract displaced radioactive 125I hGH parallel to a standard curve. Surprisingly, an extract of a normal human pancreas contained large amounts of hGH-like activity and gave results similar to those of the tumor extract on gel chromatography and on serial dilution displacement in the growth hormone immunoassay. Paper electrophoretic studies of 125I hGH after incubation with normal pancreatic and tumor extracts with and without enzyme inhibitors suggested that pancreatic proteolytic enzymes damaged the 125I hGH used in growth hormone radioimmunoassay and produced a false detection of hGH.


Platelet microtubules and giant granules in the Chediak-Higashi syndrome. Platelets from a child with the characteristic clinical and laboratory features of the Chediak-Higashi Syndrome (CHS) were evaluated in the electron microscope. Rare peripheral blood platelets were found to contain the giant abnormal granules observed previously in nearly all leukocytes. The discoid CHS platelets contained circumferential bundles of microtubules identical to those present in normal cells. CHS platelet microtubules responded in the same manner as those in normal cells when patient platelets were exposed to collagen, cold, or to chilling and rewarming. The findings are inconsistent with the concept that a defect in microtubule assembly is the fundamental abnormality responsible for aberrent function of CHS cells.


Effect of estrogen treatment for one year on carbohydrate and lipid metabolism in women with normal and abnormal glucose tolerance test results. Glucose, insulin, growth hormone, triglycerides, and Premarin. A prospective study of the effects of a conjugated estrogen (Premarin, 1.25 mg.) was performed in 36 women over a 1 year period. Each subject received a 3 hour oral glucose tolerance test before starting the medication and another after 1 year of use. The blood glucose levels were similar at five times during the two tests except for a significant elevation of the 1 hour value at the 1 year test. There were no changes in the plasma insulin, growth hormone, or fasting triglyceride levels. These results suggest that the cyclic administration of this estrogen does not alter lipid or carbohydrate metabolism.


Abortive and productive infections of human mononuclear phagocytes by type I herpes simplex virus. The ability of Type I herpes simplex (HSV) to replicate in normal human monouclear phagocytes was investigated. Mononuclear leukocytes were obtained from the peripheral blood of patients by Ficoll-Hypaque gradient centrifugation, and the monocytes were isolated by allowing the cells to adhere to tissue culture dishes. The monocytes (10(5.0) cells) were infected (10(7.0) PFU HSV) either immediately after isolation or were cultured in vitro for varying numbers of days and were then infected. Inoculation of freshly isolated monocytes resulted primarily in an abortive infection. HSV antigens were produced by the cells, as determined by a indirect fluorescent antibody technique, and empty herpes capsid structures were detected by electron microscopy of the inoculated monocytes; however, no increase in virus titer was noted in the cultures. Inoculation of viable cells that had been maintained for 7 days in culture resulted in a productive infection. An increase in titer was noted 24 hours after inoculation, and normal virus maturation was documented by ultrastructural study of the infected cells. The experiments show that the interaction of HSV with human mononuclear phagocytes is complex, and the data suggest that whether or not the cell replicates infectious virus may depend on the functional activity of the cell.


Simian adenoviral pneumonia.

Simian adenoviral pneumonia. In the past 6 years we have encountered 26 cases of fatal adenoviral pneumonia in six species of simian primates. O these, 22 animals were between 11 and 38 days old at the time of death, and pneumonia was the primary clinical disease. The spectrum of clinical disease varied from peracute fatal disease to inapparent disease with seroconversion. In one outbreak involving 4 infants housed together in an isolation unit, simian virus 11 was isolated from 3 of the infants and seroconversion occurred in all 4. At necropsy the lungs were voluminous, with firm gray areas of consolidation. On histopathologic examination, severe patchy necrotizing alveolitis and bronchiolitis were present. Variable edema and hyaline membrane formation, alveolar epithelial hyperplasia, and secondary bacterial pneumonia were also seen. Large basophilic intranuclear inclusions were present in bronchiolar and alveolar epithelial cells in all 26 cases. In 4 of 8 cases examined ultrastructurally typical intranuclear paracrystalline arrays of adenoviral virions were demonstrated. Intranuclear inclusion bodies were also observed occasionally in bile duct and pancreatic duct epithelium. Simian adenoviral pneumonia can be a spontaneous disease problem in laboratory-reared primates and offers excellent potential as an animal model of human adenoviral pneumonia.


Insulin binding and effects in isolated soleus muscle of lean and obese mice. To get some insight into the mechanisms of insulin resistance in obesity, insulin binding and biological effects were investigated in soleus muscles isolated from normal and obese mice. Basal and insulin-stimulated 2-deoxyglucose uptake were measured at the steady state of insulin binding. The results were consistent with the concept of spare receptors, i.e., maximal insulin effect was achieved when only about 20% of total receptors was occupied. When similar studies were applied to muscles of gold thioglucose obese or genetically obese (ob/ob) mice, and compared to lean controls: a) insulin binding was decreased; b) the insulin dose-response curve of 2-deoxyglucose uptake was shifted to the right; c) maximally insulin-stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis were markedly decreased. Insulin binding and effects returned toward normal after a 40-h fast in obese mice. These results point to two loci for the insulin resistance of skeletal muscle in obesity: 1) a decrease in the number of insulin receptors, which results in a diminished insulin sensitivity; and 2) one or more alterations beyond receptor that are responsible for the decreased responsiveness of the tissue to insulin and appear to play a major role in the insulin resistance of muscle in obesity.


Instantaneous changes of alpha-adrenoceptor affinity caused by moderate cooling in canine cutaneous veins. Experiments were performed to investigate why cooling augments the contractile responses of superficial veins, but depresses that of deep limb veins. Rings of dog's saphenous veins were mounted in an organ chamber for isometric tension recording. Cooling (from 37 to 24 degrees C) depressed the tissular uptake of [3H]norepinephrine and potentiated the contraction caused by norepinephrine and sympathetic nerve stimulation; this potentiation persisted after inhibition of the disposition mechanisms for the catecholamine and in the presence of ouabain or iproveratril. The affinity of the alpha adrenoceptors, to judge from the KA values for norepinephrine and from the pA2 values for the competitive antagonist phentolamine, was significantly greater at 24 degrees C than at 37 degrees C. Thus, an instantaneous change in the affinity of alpha adrenoceptors explains the augmented response of the cutaneous veins to adrenergic stimulation. By contrast, cooling depressed the response of femoral veins to norepinephrine and did not significantly affect the affinity of alpha adrenoceptors in this preparation, indicating that the temperature sensitivity of alpha adrenoceptors in cutaneous veins is related to chronic exposure to variations in local temperature.


Enhanced phosphorylation of myocardial sarcoplasmic reticulum in experimental hyperthyroidism. Calcium transport by cardiac sarcoplasmic reticulum (SR) was compared in hyperthyroid (HT) and euthyroid (ET) rats. Both Ca2+ uptake (97 +/- 3.1 nmol/mg per min in HT vs. 63 +/- 2.9 nmol/mg per min in ET, P less than 0.01) and CA2+ -stimulated ATPase activity (61 +/- 4.1 vs. 37 +/- 1.6 nmol Pi/mg per min, P less than 0.01) were higher in the thyroxine-treated animals. These changes were accompanied by enhanced cyclic AMP-dependent phosphorylation of cardiac SR in hyperthyroid rats (180 +/- 4.3 pmol Pi/mg per min vs. 117 +/- 4.2 pmol Pi/mg per min, P less than 0.01). SDS-polyacrylamide gel electrophoresis of cardiac SR showed that phosphorylation of a 22,000-dalton protein (phospholamban) primarily accounted for the differences between the two groups. There was no difference in the rate of SR dephosphorylation by endogenous phosphoprotein phosphatase between HT and ET rats. Differences in cyclic AMP-dependent phosphorylation between the two groups were blunted in the presence of excess exogenous cyclic AMP-dependent protein kinase. These results suggest that increased levels or activity of endogenous cyclic AMP-dependent protein kinases may partially explain enhanced calcium transport by the cardiac SR of hyperthyroid animals.


Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase. In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic adenosine 3',5'-monophosphate (cAMP), activation of cAMP-dependent protein kinase, activation of phosphorylase, and increase in contractile force. At epinephrine concentrations of 1 micron or less, acetylcholine antagonized all these beta-adrenergic effects and also increased cyclic guanosine 3',5'-monophosphate (cGMP) levels. When used alone, acetylcholine produced a rapid elevation of cGMP and markedly diminished contractile force but did not significantly lower basal cAMP levels or cAMP-dependent protein kinase activity. The data suggest that changes in cAMP-dependent protein kinase activity can explain the antagonism of epinephrine-induced activation of phosphorylase by acetylcholine, but cannot completely account for the inhibitory effect of the cholinergic agent on contractile force.


Ephaptic transmission in squid giant axons. Some characteristics of ephaptic transmission of action potentials were investigated with squid giant axons. For these studies two isolated axons were placed side by side or, on occasion, a single long axon was looped to form an "ephapse" between the axon trunk and one of its main branches. Extracellular potentials measured adjacent to axons surrounded by a very restricted volume of liquid ranged up to 80 mV in magnitude and had a shape similar to that of the membrane current. Intracellular records of the same axon regions show small voltage deflections; however, the transmembrane voltage (Vm = Vi - Vo) has the appearance of normally propagated action potentials. Ephaptic transmission of action potentials is possible when the ephaptic region is submerged in oil, as well as when the region is immersed in low-calcium solutions. When the speed of the propagated action potential is lowered by replacing the normal artifical seawater (ASW) with low-sodium ASW, some ephaptic effects are enhanced. It is concluded that in regions in which axons are confined by restricted extracellular volume, the large extracellular voltage changes arising during the passage of an action potential in one can cause ephaptic excitation in another.


Herpes virus infection alters electrical parameters of heart cell aggregates. The spontaneous beat of embryonic heart cell aggregates in culture grew gradually weaker and stopped about 18 h after inoculation with herpes simplex virus 1 (HSV-1). Before electrical activity ceased, maximal action potential upstroke velocity fell to about 20% of control values, whereas overshoot and plateau duration declined about 50%. Maximal diastolic potential was reduced by only about 10%. Eighteen hours after viral inoculation, specific membrane resistance and intercellular coupling were measured in quiescent aggregates with injected current pulses passed between two widely spaced intracellular electrodes. These parameters were unaltered as compared with control aggregates. However, pairs of infected aggregates brought into contact required 8 h to synchronize their beats; mock-inoculated aggregates coupled in less than 1 h. It is concluded that the cell surface alterations caused by HSV-1 infection specifically reduce both fast and slow inward currents and interfere with the formation of new nexal junctions.


Effect of synthetic C-terminal fragments of hGH on insulin release by isolated islets. Synthetic fragments representing the C-terminal end of the growth hormone molecule have been tested for their direct in vitro effects on insulin release by isolated rat islets of Langerhans. hGH 177-191 caused a dose-related potentiation of glucose-induced insulin release, whereas the peptide by itself caused no stimulation of insulin release from the islets. The rate curves constructed for insulin secretion as a function of extracellular glucose concentration showed that the Km for glucose is not altered in the presence of the peptide, but that the Vmax of secretion is increased. Significant potentiation of insulin release by the peptide was seen only at high extracellular concentrations of glucose. Measurement of cAMP levels in islets showed that the peptide caused no significant alteration of cAMP levels while still potentiating insulin release. It was therefore concluded that the mechanism of potentiation of insulin release by the peptide may be independent of the changes in cAMP levels in islets. hGH 172-191, too, caused potentiation of glucose-stimulated insulin release from islets, whereas hGH 179-191 was not active in this report.


Role of cyclic AMP in rat aortic microsomal phosphorylation and calcium uptake. The role of adenosine 3',5'-monophosphate (cyclic AMP)-dependent membrane phosphorylation in the regulation of microsomal calcium transport in rat aortic smooth muscle was studied. Cyclic AMP-dependent protein kinase augmented the phosphorylation of serine residues in a microsomal protein component with a molecular weight of about 44,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and the majority of 32P incorporation was in serine residue(s). The phosphorylated protein had stability characteristics of a phosphoester. The phosphorylated substrate was not extracted from the trichloroacetic acid (TCA) precipitate with organic solvents or by suspension in hot TCA; and the demonstrated hydroxylamine insensitivity suggested that the substrate was not lipid or nucleic acid. Intrinsic phosphoprotein phosphatase cleaved the labeled phosphate from the cyclic AMP-stimulated microsomes in the first 5 min of incubation. Microsomes phosphorylated in the presence of 1 micron cyclic AMP or 1 micron cyclic AMP plus 0.1 mg/ml protein kinase exhibited enhanced calcium uptake. We suggest that reversible phosphorylation of microsomal membranes may play an important role in the regulation of aortic microsomal calcium transport by cyclic AMP.


Protein kinase regulation of cardiac phosphorylase activity and contractility. The relationship between cAMP-dependent protein kinase activity and epinephrine-produced activation of phosphorylase and increase in contractility was investigated in the intact working rat heart. Epinephrine was administered as a bolus into the superior vena cava of open-chest preparations and the hearts were rapidly frozen. cAMP increased within 5 s and returned to control within 20-30 s. Protein kinase and phosphorylase kinase activity ratios increased transiently with the same time course as that for cAMP. The phosphorylase activity ratio and the rate of left ventricular pressure development increased maximally within 15 s and returned to control in 30-60 s. Continuous infusion of epinephrine caused a sustained elevation of the protein kinase. Free catalytic protein kinase activity increased proportionately with the dose of epinephrine. The beta-adrenergic blocking agent, practolol, had no effect on the basal levels of the five parameters studied, but did prevent the epinephrine-produced increases. The results suggest that the time course of cAMP-dependent protein kinase activation is appropriate if this enzyme is to play a role in the catecholamine-induced increase in both glycogenolysis and contractility in the in vivo heart.


Behavior of axenic IP-106 strain of Entamoeba histolytica in the golden hamster. Strain IP-106 of Entamoeba histolytica was isolated 12 yr ago from a case of amebic dysentery and has been maintained in axenic culture for the past 11 yr. Hamsters were inoculated intrahepatically, intraperitoneally, and intracecally with 6.5, 5.0, and 8.0 X 10(4) axenic trophozoites, respectively. With the first two routes of inoculation all the animals developed liver abscesses, and most developed amebic metastases to other sites. After intracecal inoculation only 3 out of 6 animals developed abscesses at the primary site and metastases to other sites. Most numerous metastases were obtained following intrahepatic inoculation. Intrahepatic inoculation with 1 and 2 X 10(4) axenic amebae resulted in an increase in the size of the liver abscess for a period of 2 wk and its apparent total resorption by day 17 post-inoculation, accompanied by a corresponding gain of body weight. With 4 and 6 X 10(4) amebae there was a steady increase of the size of the liver abscess and corresponding loss of body weight. High antiamebic indirect hemagglutination titers were observed only on day 17 post infection in animals inoculated with 2, 4, and 6 X 10(4) amebae. The extent of amebic metastases was roughly proportional to the size of the inoculum.


NAD nucleosidase of Agkistrodon bilineatus venom. NAD nucleosidase (NAD glycohydrolase, EC 3.2.2.5) activity in Agkistrodon bilineatus venom was observed. Using the cyanide assay method at pH 7.9, lyophilized crude venom had an activity of 0.19 units/mg. Chromatography of the crude venom on DEAE Sephadex A-50 with ammonium acetate buffer by two stage elution yielded 13 fractions. Peak NAD nucleosidase activity occurred at Fraction X. Crude venom and Fraction X NAD nucleosidase activities were thermolabile.


The treatment of operable breast cancer in the elderly female. The treatment of operable breast cancer in eighty-two patients older than seventy years was analyzed. The cancers were treated at an advanced stage and the axilla was involved as frequently as in younger women. The factors influencing survival differ because of competing mortalities from heart disease and stroke. The risks are discussed in relation to life expectancy and treatment method.


Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin and beta-bungarotoxin. Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch ("facilitation") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane.


[Basal cell adenomas of the salivary glands. Analysis of 7 cases and review of the literature. Comparative study with cylindromas]. Basal cell adenomas, of which 7 cases are reported here together with 63 others collected in the literature, are benign tumours of the salivary glands, preferentially localised in the parotid and in the upper lip. Mobile, non-ulcerated and painless, these nodules with an average diameter of 2 cm are well circumscribed, fleshy or cystic. Their morphology is characterised by the proliferation of uniform, small cells, with scarcely visible cytoplasm, arranged in layers, cords and canals, which may be ectasic or cystic. Peripheral elements, individualising these different structures, are arranged in palissades and are regularly surrounded by a basal membrane. The histological analogies between basal cell adenomas and cylindromas merely reflect their ultrastructural similarities, cellular as well as architectural. These two neoplasms may be distinguished on the basis of two essential morphological criteria:--basal cell adenomas are well circumscribed, whilst cylindromas are invasive;--the cells in adenomas are closely juxtaposed, endowing the various structures of these tumours with a dense appearance, whilst cylindroma cells are generally separated by clear spaces corresponding to extreme development of the intercellular spaces.


Cross reactions of normal bovine sera with foot-and-mouth disease virus: incidence, duration, and effect of shipping stress. Serum samples were obtained from 30 Hereford steers in an area known to be free of foot-and-mouth disease (FMD) viruses as follows: before shipment and 4 times during a 70-day period after shipment; the sera were tested for the presence of cross-reacting antibody to various viruses. Percentages of sera containing cross-reacting antibody to FMD virus detected by the plaque-reduction neutralization and the radial immunodiffusion techniques were higher for the FMD viruses Asia and SAT I5 than for the FMD viruses A5, O1, and C1. Cross-reacting antibody was usually of low titer and usually present in only 1 or 2 consecutive serum samples. The incidence of cross reactions increased after stress of shipping and thus an infective agent may be responsible. These results were compared with results from sera collected from Herefords and Holstein-Friesians in a 2nd area; results did not indicate that Herefords have an excess of cross reactions with FMD viruses.


Isolation of transmissible gastroenteritis virus from pharyngeal swabs obtained from sows at slaughter. A virologic survey was conducted to determine the frequency of transmissible gastroenteritis (TGE) virus infection in farm-raised sows. Pharyngeal swab specimens collected in an abattoir were examined for TGE virus by inoculation onto swine-testes cell culures. The virus was detected in 61 (3%) of a sample of 2,058 Iowa sows after slaughter. All TGE viral isolates, given orally to 2- or 3-day-old pigs, caused acute gastroenteritis and in some cases death. All pigs that recovered from illness had serum antibody to TGE virus.


Comparison of the lesions of Aleutian disease in mink and hypergammaglobulinemia in ferrets. Gross and microscopic lesions of Aleutian disease (AD) in mink and hypergammaglobulinemia in ferrets were compared. Both conditions were characterized by widespread proliferation of plasma cells, but proliferation was more prominent in mink infected with AD. Arteritis did not occur in hypergammaglobulinemic ferrets. Minimal or no glomerular alterations occurred in infected ferrets, but were severe in mink infected with AD. Bile duct proliferation was more prominent in diseased mink. Tissue alterations suggested that AD in Aleutian genotype mink is more rapidly progressive than is AD in ferrets, causing overt clinical disease and death. In contrast, hypergammaglobulinemia in ferrets appeared to progress more slowly, with little clinical evidence of disease. This is probably the result of a paucity of glomerular lesions in ferrets. Possible mechanisms to explain the differences in the development of lesions are discussed.


Unusual intra-abdominal metastases from carcinoma of the lung. Eleven patients with bronchogenic carcinoma underwent surgical treatment of metastatic abdominal visceral lesions. Successful surgical palliation was achieved in nine. In eight patients intraabdominal metastasis marked the first clinical sign of spread of the primary tumor outside the chest. The longest interval following diagnosis of the primary lung lesion and the appearance of the abdominal symptoms due to metastatic disease was three and one-half years.


[Multicentric reticulo-histiocytosis; review of recent literature (since 1969)]. The review of recent literature (since 1969) shows 35 cases of multicentric reticulo-histiocytosis. This entity was first described as a dermatological disease, then as a dermatoarthritis. It is in fact a systemic disease which can involve many organs but is sometimes monosymptomatic. Its fatal outcome is, sometimes, the result of a disseminated neoplasia or a lymphoma. Its clinical and microscopic features allow to distinguish it from solitary reticulo-histiocytoma, generalized eruptive histiocytoma, congenital reticulo-histiocytosis of Hashimoto and Pritzker and familial histiocytic dermato-arthritis of Zayid.


[Liver cell carcinoma associated with oral contraceptives (author's transl)]. A new case report of primary malignant hepatic tumor during a long term oral contraception is presented. A direct role of contraceptives drugs cannot be claimed because of little cases reported. Nevertheless, appearance of carcinogenic compounds in predisposed women may be evoked.


[Glucocorticoid receptors in mammary tumors in PS and C3H mouse strains (author's transl)]. Specific binding of glucocorticoids was characterized in mammary tumors and cells derived from C3H and PS mice. The binding protein satisfied all the general criteria of hormone receptors namely high affinity and binding specificity for glucocorticoids (KD congruent to 2.5 nM) for 3H Dexamethasone and limited number of binding sites (congruent to 150 femtomoles/mg Protein). The hormonal regulation of these receptors will be reported. The production of viral particles of type A and B was increased by glucocorticoids in the PS MT1 and PS MT2 cell lines derived from the PS tumors.


Effects of putative transmitters on afferent cochlear transmission. Putative transmitters and related substances were perfused through the guinea pig scala tympani while monitoring the compound action potential of the cochlear nerve (AP) and the cochlear microphonic potential. Various substances were then ranked according to their ability to reduce the AP. The more active compounds ranked: methysergide (1 mM) greater than ATP (10 mM) = tyramine (10 mM) greater than salicylate (10 mM) greater than bicuculline (10 mM) greater than asparate (10 mM) greater than glutamate (10 mM) greater than citrate (10 mM) greater than dextrose (100 mM) greater than glycine (100 mM) greater than GABA (100 mM) greater than prostaglandin E2 (1 mM) greater than serotonin (10 mM). The activity of substances at 100 mM indicates a physical, osmotic change in the cochlear structure. Activity at 10 mM and 1 mM indicated afferent transmitter-like activity for the putative transmitters and interference with the endogenous transmitter for related substances. It is concluded that several substances can be eliminated as afferent transmitter candidates, while others warrant further examination.


[Effect of estradiol-17 beta on the somatrotroph cells of the adenohypophysis in the newt (author's transl)]. The somatotroph cells of the female newt's adenohypophysis are characterized by PAS positive, acidophils, electron dense large inclusions (4-6 micrometer). The apparition of these inclusions has been studied in females during the puberty. A correlation between the ovary stages and apparition, number and ultrastructural aspects (paracrystalline arrangement) of the inclusions is established. Same inclusion genesis and aspects has been observed after treatment of young newt males by oestradiol-17 beta (5 mg/liter diluted in the aquarium water). It is concluded that endocrine activity of ovaries may be responsible of the inclusions occurence in the females.


[A case of virilizing adrenal cortical adenoma whose steroid profile evokes a partial 21-hydroxylase deficiency (author's transl)]. The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17 alpha-hydroxyprogesterone and its urinary metabolites have been identified and quantitated gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. A of the fifty-five identified steroids thirteen were compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxtlase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy.


[Virilizing tumours of the adrenal cortex with unimpaired menstruation (author's transl)]. Virilizing adenomas of the adrenal cortex entail, typically, hirsutism, amenorrhea and hypertrophy of the clitoris. We report two cases of adrenal adenoma, both revealed by hirsutism and significant biological features, but both without any alteration of the menstrual cycle. One of our 2 patients showed moderate hypertrophy of the clitoris. In the first patient, the tumour has been located thanks to dexamethasone--modifiying adrenal secretion, and in the second patient, thanks to angiography. These two cases reported are a warning never to neglect more hirsutism, even, when unobstrusive, and always to undertake minimal hormonal investigations.


Skeletal age and submaximal working capacity in boys. Skeletal age (SA) and Vo2 at a heart rate of 130 (Vo130) during work on a bicycle ergometer were measured in 237 boys 8-18 years of age. Analysis indicates that Vo130 is well correlated with SA, but also is equally well correlated with chronological age (CA), height and body weight. Age-specific correlations show that Vo130 is associated with SA from 12 through 16 years of age. Partialing out SA results in a significant decrease in the correlations of either height or weight with Vo130 only in the 12-16 year subgroup. The total common variance explained in Vo130 when regressed over CA, height and weight is affected by the presence of SA only in the 12-16 age subset. In spite of the high degree of multicollinearity among the independent variates, correlation data seem to indicate that SA and Vo130 have a slightly higher degree of relationship circumpuberally, i.e. between 12 and 16 years of age.


Osteomalacia and disorders of vitamin D metabolism. A rapidly growing understanding of the biochemical and physiological processes that underlie the metabolism of vitamin D has provided new insights into the pathogenesis of oestomalacia. Many of the vitamin D--resistant osteomalacia syndromes can now be explained on the basis of defects in the metabolic conversion of vitamin D to the biologically active dihydroxylated metabolite 1,25(OH)2D and perhaps, in some instances, to impairement of the actions of 1,25(OH)2D on target tissues. The availability of this new information has made possible the synthesis of 1-hydroxylated forms of the vitamin for therapeutic use in states of vitamin D resistance. Although many questions regarding the pathogenesis and most effective approaches in the management of osteomalacia remain unanswered, considerable progress has been made in this direction as a result of continued research on the subject.


Dialysis versus transplantation in the treatment of end-stage renal disease. Both dialysis and kidney transplantation are effective techniques for prolonging life in ESRD. Because dialysis therapy does not effect replacement of the metabolic functions of the kidney, it is less tha perfect. Successful transplantation that replaces all of the aspects of renal function is the treatment of choice. Successful transplantation is highly dependent upon the availability of a suitable donor and the appropriate tissue match, which remains a problem. Present immunosuppressive therapy required to prevent the immunoresponse causing rejection of the renal allograft is a tool too dull for the job. Since all immunoresponse is suppressed, infections are common, as are the multiple complications of cortical steroid therapy. For the dialysis patient, development of more compact effective dialysis apparatus and particularly the availability of replacement therapy hold promise. New approaches to diminishing the immune response to the graft without impairing that to microorganisms may well effect improvement in graft survival as will increasing knowledge of factors other than HLA antigens in the immunologic reaction. Development of an effective method for arresting the progress of glomerulonephritis before it reaches end-stage renal failure would obviate the necessity for dialysis or transplant therapy in appoximately two thirds of ESRD patients.


Contractile proteins in cell structure and function. 1. The cytoplasm of cells is a colloidal network of contractile proteins. Actin filaments are the major components of this network. Other contractile proteins interact with these filaments to create structural rigidity and movement. 2. The structure and function of contractile proteins is striated muscles is well characterized and thus provides a good example for extrapolitation to an analysis of contractile-protein structure and function of nonmuscle cells. However, the interaction of contractile proteins of various cells may be unique. 3. The study of contractile proteins in cells other than muscle has distinct difficulties: (a) The proteins are present in much lower concentration than in muscle, and only a few cell types are obtainable for study in quantities comparable to muscle. (b) Proteolysis and other detriments may be more severe in nonmuscle cells. (c) The organization of contractile proteins is difficult to define in nonmuscle cells. (d) The effort is diffuse; investigations examine a wide variety of different, or less commonly the same, cells. Reflecting these difficulties, a catalogue of putative nonmuscle cell fucntions related to contractile proteins reveals no one system to be definitively worked out. Nevertheless, the ubiquity of contractile proteins and the obvious importance of their intractions presages increasing relevancy for physiology and medicine.


[Interferonogenic activity of gossypol, a low-molecular substance]. The interferonogenic activity of gossipol, a low molecular substance of polyphenolic nature was shown in the cell cultures of chick embryos and organisms of mice. Pronounced prophylactic efficiency of the drug in mice with experimental infection caused by the West Nile virus was found. Definite parallelism between the intensity of interferonogenesis and the protection level from the virus affection due to the use of gossipol in mice was noted. Difference between gossipol and other known low molecular inductors of interferon, such as dyes, tyloron, propandinamine is discussed. The possibility of using gossipol as an antiviral drug is presumed.