Nucleotide sequence studies of polyoma DNA. The Hpa II 3/5 junction to the Hpa II 4/Hae III 18 junction, encoding the origin of DNA replication and the 5' end of the early region. The nucleotide sequence of polyoma DNA, from near the Hpa II 3/5 unction to the Hpa II 4/ae III 18 junction has been determined by the chemical method of Maxam and Gilbert (Maxam, A., and Gilbert, W. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560--564). The sequence contains 878 base paris, including the origin of DNA replication and the region known to encode the hr-t function. The region corresponding to the origin of DNA replication contains several short-repeated sequences and palindromes. There is a 30-base-pair region with striking similarity to the corresponding region of SV40, and, as in SV40, a portion of that sequence is capable of forming a stable hairpin loop. In the region encoding the hr-t function, there is apparently a single open reading frame extending from position 188 to theHpa III 4/Hae III 18 junction. The potential translation product of this open frame begins with an initiation codon starting at position 188, and the first five amino acids of this product are Met-Asp-Arg-Val-Leu. This sequence is similar to the NH2-terminal five amino acids of SV40 small t-antigen known from nucleotide and amino acid sequencing to be Met-Asp-Lys-Val-Leu.


Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content. The fact that colchicines inhibits hepatic secretion of very low density lipoprotein (VLDL) particles has been interpreted to mean that microtubules are involved in hepatic VLDL secretion. To further define this relationship, we have attempted to see if changes in hepatic VLDL secretion are associated with changes in hepatocyte microtubule or tubulin content. Accordingly, hepatic secretion of VLDL was increased in rats, and the hepatocyte content of both microtubules (using quantitative morphometric methods) and tubulin (using a time-decay colchicine binding assay) was determined. In acute experiments, VLDL secretion was increased by perfusion of isolated rat livers for 2 h with varying concentrations of free fatty acids (FFA). Results indicate that hepatic VLDL triglyceride (TG) secretion at perfusate FFA levels of 0.7 muEq/ml is threefold greater (P < 0.01) than when livers are perfused without added FFA. However, no differences are observed in the content of microtubules in these livers: specifically, microtubules occupy 0.029 percent of hepatocyte cytoplasm in livers perfused without FFA and 0.030 percent of cytoplasm in livers perfused with FFA. In chronic experiments, rats were fed for 1 wk with either standard rat chow or a hyperlipidemic (sucrose/lard) diet. With the experimental diet, plasma triglyceride levels increase threefold over controls, and liver VLDL-TG production, as determined by [(3)H]glycerol turnover studies, is 55 percent greater (P < 0.01) than controls. However, microtubules occupy 0.027 percent of the cytoplasm of hepatocyte cytoplasm whether rats are on standard or hyperlipidemic diets. Furthermore, the tubulin content of isolated hepatocytes does change, and represents 1 percent of hepatocyte soluble protein, irrespective of diet. These results suggest that increases in hepatic VLDL secretion can occur without any demonstrable change in hepatocyte assembled microtubule or tubulin content, and raise questions as to the role played by microtubules in hepatic VLDL secretion.


Microtubules and cyclic AMP in human leukocytes: on the order of things. We have shown previously that the beta-adrenergic agonist isoproterenol (2muM) and the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) produce a much greater increase in cyclic AMP in human leukocytes that have been pretreated with colchicine (or with other agents that affect microtubule assembly) than in control leukocytes. The effects of colchicines were both time- and dose-dependant. These and other data suggested that the generation of cyclic AMP is normally restricted by an intact system of cytoplasmic microtubules. If so, then the same time and dose dependencies might apply to other colchicines-induced changes in leukocyte function. We have now assayed the distribution of concanavalin A (Con A)-receptor complexes on the leukocyte membrane, taking into account that leukocytes competent to assemble microtubules show a uniform distribution of surface- bound Con A whereas microtubule-deficient cells accumulate Con A in surface caps. We have found that the effect of colchicine on capping is also both time- and dose dependent, and that the dose-response relationships conform to those required to increase cyclic AMP levels. These findings provide further evidence that both colchicine-induced Con-A capping and colchicine- induced cyclic AMP generation depend upon the relaxation of constraints normally imposed by cytoplasmic microtubules upon the plasma membrane, which limit, respectively, lateral mobility of the lectin-receptor complexes, and expression of hormone-sensitive adenylate cyclase. Moreover, colchicine-induced Con-A cap formation is not affected even by very large changes in leukocyte cyclic AMP levels. Thus, elevated cyclic AMP levels do not appear to promote the dissolution of microtubules; rather, the dissolution of microtubules permits the generation of increased amounts of cyclic AMP.


Sex differences among clients of an emergency care unit for alcoholism. Compared male and female clients of an emergency care unit for the treatment of alcohol-related crises on a number of basic characteristics and procedural variables. Female clients were found to be significantly younger and more likely to be employed than males. The two groups did not differ reliably with respect to educational level or marital status. Females were found to be referred to the center by Alcoholics Anonymous and family members more often than were male clients, and male clients were referred more often by police than were female clients. The two groups also differed with respect to disposition at time of discharge, with more females judged as not needing additional treatment and more males viewed as needing additional treatment, but family or patient was not ready at the time.


A smoking satiation procedure with reduced medical risk. Tested the efficacy of a smoking satiation procedure with reduced medical risk. As predicted, experimental taste satiation (holding smoke in the mouth with occasional inhalations) suppressed habitual smoking as effectively as rapid smoking satiation. In view of the extensive relapse problems that follow the singular application of aversive conditioning procedures, follow-up hypnosis and counseling treatments were applied in order to assist Ss in maintaining smoking cessation. At the time of the 6-month follow-up contact, confirmed abstinence reports for 66% of all Ss who received treatment were obtained.


Internal organization of membranes at end bulbs of Held in the anteroventral cochlear nucleus. The end of bulb of Held in the rostral ventral cochlear nucleus of the chinchilla and guinea pig was studied with the freeze-fracture technique. The end bulb has multiple, small active zones which are uniformly distributed within the calyceal portion of this terminal. Single or small groups of active zones are surrounded by enlarged channels of extracellular space often containing processes of astrocytes. Small plasmalemmal deformations occur at these active zones. The number of these deformations is thought to be indicative of exocytotic transmitter release because they are more frequent in animals fixed in a noisy environment compared to animals fixed in a quiet environment. Thus, our study provides a basis for the quantitative study of changes in transmitter secretion at a central nervous system synapse driven by a controllable natural stimulus. The postsynaptic active zone at end bulbs resembles other excitatory synapses in the central nervous system in having an aggregate of large particles on the external membrane leaflet. This junctional aggregate of particles is coextensive with the presynaptic active zone and with the postsynaptic density seen in thin sections. Several perisynaptic aggregates of particles are deployed around each active zone on the external membrane leaflet. These irregularly-shaped aggregates occur preferentially opposite the channels of enlarged extracellular space and along the edge of the end bulb and are not components of intercellular junctions or plasmalemmal contacts with cytoplasmic organelles. Although the function of the different particle aggregates on the postsynaptic membrane is not clear, our findings provide a basis for studying the factors controlling and maintaining their structure as well as more evidence that a consistent relationship exists between types of synaptic action and structure of the postsynaptic membrane.


Melanoacanthoma. Ultrastructural and immunological studies. Electronmicroscopic studies confirmed that melanoacanthoma is a non-nevoid elevated epithelial tumor composed of keratinocytes of both basaloid and spinous differentiation and of large dentritic melanocytes. The block in transfer of pigment from melanocytes to keratinocytes was found not to be complete. Langerhans cells, present in the malpighian layers were normal in morphology. Immunofluorescent studies and an immunoprecipitin assay also showed our patient's melanoacanthoma not to be related to malignant melanoma.


An ultrastructural study of the formation of "dark" and "light" cytoplasmic inclusions by murine cytomegalovirus in mouse submandibular gland. Electron micrographs of acinar cells of the submandibular glands of CFW mice infected with murine cytomegalovirus, Smith strain, were studied. The resulting viral intracytoplasmic inclusion bodies were classified into two groups termed "light" (relatively electron-lucent) and "dark" (relatively electron-dense). It appeared that the "dark" type was the late stage of inclusion body maturation.


Enhanced collagenase activity in diabetic rat gingiva: in vitro and in vivo evidence. Gingiva from alloxan and streptozotocin-diabetic rats exhibited markedly enhanced collagenolytic activity in tissue culture. This effect was eliminated by puromycin or by repeated freeze-thawing of the tissue prior to incubation. Soluble extracts of the diabetic gingiva in situ were found to contain breakdown products of collagen similar in size to the reaction products generated by tissue collagenase. These fragments were not detected in the control tissue. This study indicates that experimental diabetes stimulates the synthesis of gingival collagenase in culture and that a similar effect occurs in vivo.


Microleakage of several class V anterior restorative materials: a laboratory study. The study was designed to evaluate the marginal leakage of abraded gingival areas in extracted teeth using five anterior composite resin acid-etch restorative materials and a glass ionomer cement, ASPA. In using three of the composite resin restorative materials, Simulate, Cervident, and Concise, there was a layer of unfilled resin between the etched tooth surface and the composite resin. Restodent and Enamelite were placed directly on the etched tooth surface. The results of the study indicate that there is a significantly greater degree of marginal leakage at the gingival margin than there is at the occlusal or incisal margin of composite restorations. In addition, greater marginal leakage was observed in those restorations where no layer of unfilled resin was placed between the etched tooth surface and the composite resin. The glass ionomer cement showed no marginal leakage at intervals of one day, three months, and six months; however, a small amount of leakage was observed at the incisal or occlusal and gingival margins at a year on half of the autoradiographs. A study has been initiated to determine leakage patterns around composite resin restorations placed in teeth with naturally occurring cervical erosion or abrasion.


Target antigens for H-2-restricted vesicular stomatitis virus-specific cytotoxic T cells. Cytotoxic thymus-derived lymphocytes from mice infected with vesicular stomatitis virus (VSV) are H-2 restricted and virus specific for the Indiana and New Jersey strains of VSV. VSV-Indiana-immune T cells can lyse target cells infected with the temperature sensitive (ts) mutant ts 045 about 30 times better when target cell infection occurs at the permissive rather than the non-permissive temperature. Since this mutant fails to express the glycoprotein at the cell surface when grown at the nonpermissive temperature, our results support the view that the viral glycoprotein is involved in defining the major target antigen for VSV-specific T cells. However, the tl 17 mutant that expresses a mutant glycoprotein at the cell surface was lysed, suggesting that the expressed mutated glycoprotein can cross-react with Indiana wild-type glycoprotein. Targets infected at the nonpermissive temperature with VSV ts G31 (mutant in the matrix protein) are still susceptible to T cell-mediated lysis but at a lower level of sensitivity. These results are compatible with the interpretation that for VSV-specific T cell lysis of infected target cells, the viral glycoprotein is a major target antigen and must be expressed, and that the matrix protein plays a lesser role, probably by indirectly influencing glycoprotein configuration at the cell surface.


Polymorphonuclear leukocytes as secretory organs of inflammation. Polymorphonuclear (PMN) leukocytes mediate that phase of inflammation at which vascular responses become translated into tissue injury. After phagocytosis, the PMN leukocyte generates derivatives of molecular oxygen (O2-.,OH., and H2O2) that stimulate a metabolic burst and assist in the killing of microorganisms. They also release oxidation products of membrane fatty acids (e.g., arachidonate), which are detected as thromboxanes and protaglandins. After interaction of phagocytic ligands (immune complexes and C3b-opsonized particles), the PMN leukocyte secretes lysosomal enzymes from open phagocytic vacuoles, and, especially when phagocytosis is blocked by cytochalasin B, secretes them directly into the cell's surrounding fluids. Secretion is enhanced by agents that elevate intracellular levels of cyclic GMP, and inhibited by agents that raise cyclic AMP. These reciprocal changes are associated with assembly and disassembly (respectively) of cytoplasmic microtubules. These cytoskeletal structures, together with contractile elements, regulate in part the secretory events of inflammation in which lysosomal constituents (e.g., elastase, collagenase, and cathepsin G) are diverted from their intracellular depots to an inappropriate assault on the tissues of the host.


Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic epidermis in vitro. The comparative inhibitory potency of papaverine and Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) on cyclic AMP-phosphodiesterase (cAMP-PDE) and cyclic GMP-phosphodiesterase (cGMP-PDE) activities and their effect on the levels of cAMP and cGMP were examined in psoriatic epidermis. At concentrations of 5 X 10(-4) M, papaverine inhibited the hydrolysis of both cAMP and cGMP by either the low or high Km psoriatic epidermal PDE nearly 100% (p less than .0001) while Ro 20-1724 selectively inhibited the hydrolysis of cAMP 94% (p less than .0001) but had no significant effect on cGMP hydrolysis. When keratomed psoriatic epidermal slices were incubated in 5 X 10(-4) M papaverine or Ro 20-1724 the tissue levels of cAMP were increased 343% or 1395% respectively (p less than .001) with no concomitant change in the levels of cGMP. Selective inhibition of cAMP hydrolysis by Ro 20-1724 and its greater effectiveness in elevating cAMP levels in slices of psoriatic epidermis is one explanation for its clinical superiority in treating psoriatic lesions.


Comparison of five regimens for treatment of experimental clindamycin-associated colitis. The hamster model of clindamycin-induced enterocolitis was studied to determine the natural course of the disease and the response to five therapeutic regimens. Tissue culture assays of stools from untreated animals showed that colitis toxin is present at low titers within 24--36 hr after challenge with clindamycin; titers of toxin in subsequent specimens of stool increased progressively until the animals died on days 2--4 after challenge. Therapeutic regimens tested in this model were initiated 24 hr after clindamycin challenge when the majority of the animals had evidence of colitis toxin. Methylprednisilone, an anion exchange resin, and gas gangrene polyvalent antitoxin had a minimal effect on toxin titers in stool and failed to delay substantially death due to enterocolitis. Vancomycin and tetracycline eliminated toxin in stools and delayed death. However, the salutary effects of these antibiotics were noted only during the course of their administration since all animals died of enterocolitis and had high titers of toxin when treatment was discontinued.


Inactivation of cytomegalovirus and Semliki Forest virus by butylated hydroxytoluene. Butylated hydroxytoluene (BHT) is an antioxidant that is widely used in foods because it prevents spoilage by delaying degradation of lipid components. This hydrophobic compound inactivated human and murine cytomegalovirus (CMV) and Semliki Forest virus (SFV). Both human and murine CMV were inactivated more than 90% by 40 microgram of BHT/ml after incubation for 1 hr at 37 C. Under the same conditions, SVF was inactivated about 75%, whereas poliovirus, which does not contain lipid membrane as a part of its structure, was not inactivated at all. Vaccinia virus was less sensitive to BHT than was CMV or SFV.


Cytomegalovirus infection in guinea pigs. I. Viremia during acute primary and chronic persistent infection. Studies on the pathogenesis of cytomegalovirus (CMV) infection in guinea pigs have revealed two distinct phases of infection, without any signs of clinical disease. During acute primary infection, viremia was easily demonstrated and infectious virus was recovered from various tissues, including lung, spleen, and kidney, of the infected animal two to 10 days after inoculation. Chronic persistent infection was readily established thereafter. In animals with chronic persistent infection with high levels of circulating antibody, infectious virus was consistently isolated from the salivary gland and pancreas. Evidence of CMV in the blood of the persistently infected animals was detected only occasionally and only when a highly sensitive method and/or a large inoculum was used. However, the anticoagulant heparin was found to inactivate CMV significantly during collection of blood. These data suggest that CMV was indeed circulating in the blood of apparently health but persistently infected animals for prolonged periods. Such infected blood could conceivably be the source of CMV infection when large quantities of blood are given to susceptible recipients.


Cytomegalovirus infection in guinea pigs. II. Transplacental and horizontal transmission. Transplacental transmission of cytomegalovirus (CMV) was demonstrated in guinea pigs, but transmission only occurred during acute primary maternal infection. Infectious CMV was isolated from 27 of 44 placental tissues and nine of 37 fetal tissues (including brain, lung, and kidney) tested five to 24 days after maternal infection. Fetal infection occurred at different stages of gestation ranging from 28 to 60 days. No virus was detected in the tissues of 43 fetuses examined that were taken from pregnant guinea pigs that had been infected for greater than 30 days. The maternal animals had significant levels of circulating neutralizing antibody concurrent with infectious CMV in the salivary glands at the time of sacrifice. Contact infection was accomplished when infected and uninfected animals of either the same sex or oppsite sexes were paired and housed together for one to three months. Among the seven male contact guinea pigs housed with infected females, five showed virus in their salivary glands, and all seven showed rises in titer of antibody; five of the females became pregnant. In contrast, when infected and uninfected animals of the same sex were paired and housed together, only one of 13 contact animals had virus in the salivary gland, and four of 13 had rises in titer of antibody. Thus sexual contact appeared to be more efficient than environmental contact in the spread of CMV infection.


Effects of gentamicin on trypsin, chymotrypsin, and collagenase. The effects of gentamicin on three proteolytic enzymes were studied. Gentamicin was tested at concentrations of 0.5-500 microgram/ml. Trypsin was tested at 0.5 microgram/ml using p-tosyl-L-arginine methyl ester and at 0.1 and 0.5 microgram/ml using azocoll as the substrate. Chymotrypsin was tested at 0.1 and 0.5 microgram/ml with azocoll. A soluble [14C]collagen assay was used to measure activity of collagenase derived from Clostridium histolyticum. The profiles of proteolytic activity vs. gentamicin concentration were similar for all three enzymes. At lower concentrations of gentamicin (less than 70 microgram/ml), there were two peaks of enhanced protease activity generally followed by inhibition. These unusual multiphasic effects of gentamicin on three different proteases are not presently understood, but they imply a previously unreported mode of action for this antibiotic.


Nasopharyngeal angiofibroma.

Nasopharyngeal angiofibroma. Three cases of nasopharyngeal angiofibroma have been described along with the histopathological findings, treatment and a brief review of the literature on the subject. It is of interest that one of these cases, histologically proven, was a female and this in spite of some rigidly held views about the strict sex linkage of the lesion. The tumour is uncommon but it is possible that unfamiliarity with the histopathology, as well as the likelihood of cessation of activity at any stage, may in part be responsible for its low recorded prevalence. The progress of each patient after four, two and one year respectively gives cause for some optimism, but the long-term prognosis must remain guarded.


Solubilization and partial characterization of human and porcine thyrotrophin receptors. Thyrotrophin (TSH) receptors have been extracted from human and porcine thyroid membranes by treatment with Triton X-100. 125I-Labelled bovine TSH was used to monitor receptor activity. Analysis by gel filtration and electrophoresis on acrylamide gels containing sodium dodecyl sulphate suggested that Triton extracts of human thyroid membranes contained TSH receptors with a molecular weight in the region of 50 000 closely associated with Triton micelles of approximate molecular weight 300 000. Isoelectric focusing studies indicated that the Triton-solubilized TSH binding activity had an isoelectric point of pH 4--4.5. The soluble TSH receptors were heat-labile, showed optimum TSH binding at pH 7.4 and reduced hormone binding at high ionic strength. The TSH binding characteristics of membrane-bound and solubilized human TSH receptors were similar and both preparations gave curved Scatchard plots. Solublized porcine TSH receptors appeared to have a similar molecular weight to the human receptors and were also closely associated with Triton micelles of approximate molecular weight 300 000. Scatchard analysis of TSH binding to membrane-bound or solubilized porcine TSH receptors gave approximately linear plots with association constants of 2.8 +/- 0.95 (S.E.M.) X 10(9) and 1.7 +/- 0.27 x 10(9) l/mol respectively. Comparison of the binding capacities of the solubilized and membrane-bound porcine receptors indicated that the 0.5% Triton extracts contained 40% of the original TSH binding activity and that this was present at a concentration of 25 ng/ml.


Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines. Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis.


Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions. The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased by 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased by 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1--1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contrast, secretion of lysozyme was not affected by glucocorticoids or other steroids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Effects were detected within 1--6 h after addition of the glucocorticoids, became maximum by 24 h, and were reversed during a similar time period after removal of the hormones. The extent of inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1--10 nM) similar to those that half-saturated the specific glucocorticoid receptors in these cells. At high concentrations of dexamethasone (100--1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (greater than 95%) than the secretion of elastase (60--80%). Progesterone alone had no effect on secretion, but it blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1--100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone. These data support the regulatory role of glucocorticoids on macrophage functions at physiological concentrations.


The generation and regulation of lymphocyte populations: evidence from differentiative induction systems in vitro. Results with a dual assay, for the induction of Thy-1+ T cells and of CR+ B cells from marker-negative precursors, confirm that thymopoietin is at present the only known selective inducer of prothymocytes. In contrast, various inducers, including ubiquitin, are active in both assays. Pharmacological evidence indicates that there are different cellular receptors for ubiquitin and thymopoietin. Prothymocytes and pro-CR+ B cells compose two distinct populations in bone marrow and spleen; their distribution in density gradients is different, and elimination of either population enriches the other proportionately. There are no noteworthy differences between induction of these two populations in regard to (a) kinetics, (b) dependence on temperature and protein synthesis, (c) activation by cAMP, and (d) inhibition by cGMP. The opposite inductive effects of cAMP and cGMP were corroborated by the use of pharmacological agents that raise or lower the levels of intracellular cyclic nucleotides. In contrast, a third induction assay, which monitors acquisition of the PC+ surface phenotype, indicates that this differentiative step, the last known for B cells, is initiated by cGMP and inhibited by cAMP. Induction of PC is also inhibited by thymopoietin, signifying that the inductive selectivity of thymopoietin is not due to restriction of its receptors to the T lineage cells. Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program. This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes. Present data conform to a general scheme in which the cyclic nucleotides cAMP and cGMP, and agents that affect intracellular levels of these mediators, influence reciprocally the early and late (functional) phases of lymphocyte differentiation as a whole, while thymopoietin influences reciprocally the differentiation of the B and T classes of lymphocyte.


Tampon culture for quantitation of cervicovaginal herpes simplex virus. From 10(1) to 10(6) TCID50 (mean tissue culture infective doses) per ml HSV I and II can be quantitatively recorded from vaginal tampons. Tampons and sterile cotton swabs are equally sensitive in recovering HSV I and II. Direct cotton swab cultures of the cervix and cervicovaginal tampon cultures from the same patients recovered similar quantities of HSV, ranging from 1.5 to 6.5 log10 TCID50/ml in 5 patients.


Rotavirus infections in adults in association with acute gastroenteritis. During an epidemic of acute gastroenteritis in Helsinki, in March--May 1976, 18 out of 40 adult patients showed electron microscopic and/or serologic evidence for rotavirus infection. Rotavirus was most frequently seen in the fecal suspensions from 2 to 6 days after the onset of the symptoms but persisted in one patient for as long as 10 days. An increase in the complement-fixing (CF) serum antibody titers against the related Nebraska calf diarrhea virus (NCDV), or an initially high titer and subsequent significant decrease, was seen in all but one patient with rotavirus-positive feces, and in 6 additional patients. This suggests that using electron microscopy as the only diagnostic procedure a considerable number of rotavirus infections in adults remain undetected. Immune response against autologous or homologous rotavirus was also documented by immunoelectron microscopy. Complement-fixing antibody titers against NCDV decreased significantly from the convalescence values over a half-year observation period, but still remained clearly above the titers of a gastroenteritis-negative control population.


A nonlytic transforming mutant of herpes simplex virus type 2. A small-plaque mutant (NO.69) of herpes simplex virus type 2 (HSV-2) strain 333 has been previously isolated and characterized in this laboratory. This mutant was shown to produce a high ratio of noninfectious to infectious particles when grown at the nonpermissive temperature in hamster embryo fibroblasts [Westmoreland D. and Rapp F. (1976). Journal of Virology [8:92--102]. In this study, we have demonstrated that it is possible to obtain noninfectious stocks of this virus which retain transforming ability in a biochemical transformation assay specific for detection of the HSV gene for thymidine kinase. This mutant contains a DNA genome that has a density identical to the DNA of wild-type virus. Virus and cell DNA synthesis after infection with the mutant at both the permissive and nonpermissive temperature are similar to that observed in cultures infected with the parental virus. Clones of mouse cells biochemically transformed by this virus contain HSV antigens and are presently being examined for oncogenicity.


Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen. Complement-fixing (CF) antigen, prepared from cytomegalovirus (CMV)-infected cells and solubilized by urea and Tween-20, was fractionated on agarose gel columns. Its molecular weight was 1.5--5 X 10(7) daltons, and it contained 5 major peptides with molecular weights from 60,000--90,000 daltons. The peptide with a molecular weight of 70,000 daltons which was present in the solubilized CF antigen was absent in a soluble fraction from infected cells without CF activity and may be, therefore, important in this respect. The antigens present in the CF antigen did not elicit neutralizing antibody.


Experimental respiratory syncytial virus pneumonia in cebus monkeys. Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 10(8) plaque-forming units (pfu) of wild-type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 10(8) pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus.


Brain reaggregate cultures: biochemical evidence for myelin membrane synthesis. Myelin membrane synthesis was studied using mechanically dissociated fetal rodent CNS which formed spherical reaggregates while being maintained in rotating culture flasks. These reaggregate cultures exhibited myelinogenesis in vitro after precisely the same period of time needed for myelin synthesis to commence in vivo. The myelin membrane related enzymes, 2', 3' cyclic nucleotide phosphohydrolase (CNP) and cerebroside sulfotransferase (CST), appear similar in their specific activities and follow the same developmental patterns that these enzymes exhibit in vivo. In addition, phosphorylation of myelin basic protein occurs by the third week in vitro which agrees with previously published in vivo studies. These experiments indicate that this nerve-cell culture system may be a appropriate model for studying the biological regulation of myelinogenesis as well as a variety of other nervous-system functions.


Intracranial space-occupying masses in mental hospital patients: necropsy study. During a three year period 1970--1973 necropsies were performed on 200 patients who died in a mental hospital in the Transvaal, South Africa. There was no selection of cases other than availability of consent for postmortem examination. The necropsy rate for this period was 56%. The patients belonged to three racial groups, Black, White, and Coloured, the latter being defined as those of mixed blood. Among these 200 cases, 27 were found at necropsy to have an intracranial space-occupying mass. Mention is made of the literature dealing with the incidence and diagnosis of intracranial space-occupying masses in mental hospital patients, and the incidence of intracranial space-occupying masses in the different racial groups in South Africa.


Myasthenia gravis: further electrophysiological and ultrastructural analysis of transmission failure in the mouse passive transfer model. Using the mouse passive transfer model the mean amplitude of miniature endplate potentials and endplate potentials of mice treated with myasthenic immunoglobulins was markedly decreased. Miniature endplate potential frequency and quantum content of endplate potentials were normal, arguing against a major presynaptic disarrangement. Under electron-microscopy no gross structural alterations of endplates were demonstrated. It is concluded that the mouse passive transfer model closely resembles human myasthenia gravis of recent onset.


Synaptic transmission without action potentials: input-output properties of a nonspiking presynaptic neuron. 1. Input-output properties of the inhibitory synaptic connection between non-spiking neurons (EX1) and gastric mill (GM) neurons were examined in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Current was injected into and the voltage was recorded during current injection, two independent microelectrodes were used. 2. The EX1-GM synaptic connection is a conductance-increase inhibitory type, with an input-output curve that resembles the curve for the squid giant synapse. There is a threshold level of depolarization for transmitter release from the presynaptic cell. Beyond that threshold, increasing presynaptic depolarization causes increasing postsynaptic hyperpolarization (and inhibition). 3. A long presynaptic current step always causes a postsynaptic response with an initial peak of hyperpolarization followed by a decay to a less hyperpolarized plateau level. The plateau level is maintained, in most cells, for the duration of the presynaptic depolarization even over long periods (30 s). 4. The peak, but not the plateau, part of the postsynaptic response is sensitive to the past history of the synaptic connection. If a large conditioning pulse is applied to the presynaptic cell causing a large postsynaptic hyperpolarization, then the postsynaptic response to a later presynaptic test depolarization will have a reduced peak, leaving the plateau component unchanged.


Skeletal uptake of pyrophosphate labeled with technetium-95m and technetium-96, as evaluated by autoradiography. For animal experimentation, the 95m and 96 technetium isotopes offer many advantages over technetium-99m. Their long physical half-lives and the emission of extranuclear electrons of low penetrating power make it possible to obtain autoradiograms of a great precision. The uptake of technetium stannous pyrophosphate by the epiphyseal plate was studied using liquid-emulsion microautoradiography, 3 hr after i.v. injection into 10-week-old rabbits. Microautoradiograms showed a well-defined and rather specific pattern of localization with intense uptake beneath the epiphyseal disk on the extremities of the vascular buds and a lack of accumulation in the cartilage, whether calcified or uncalcified. In the metaphysis, the label was located where new bone was being laid down and also over the cytoplasm of osteoclasts. We deduce from these results that in normal bone the general distribution of this tracer reflects mainly the arrangement of the blood supply, but the specific sites of accumulation are the bone-forming surfaces and the active resorbing osteoclasts.


Cystosarcoma phylloides in the adolescent female. Two cases of cystosarcoma phylloides in the adolescent female are presented and the literature reviewed. This lesion is usually benign. Even when malignant, simple excision has been curative in 2 or 3 cases. Therapy recommended is local excision with a small margin of normal tissue.


Calcific thrombi of the inferior vena cava in infants and children. Calcified caval thrombus should be considered in any infant or child where calcifications are noted in the high right retroperitoneal area on plain x-rays of the abdomen. Although typically bullet-shaped in configuration, the calcium distribution in the neonate may be atypical or incompletely developed, suggesting neuroblastoma. Definitive diagnosis can be made by inferior vena cavagram. As no deaths or complications have been attributed to the lesion in the cases thus far reported, no specific treatment is recommended.


REM motivation induced by brief REM deprivation: the influence of cognition, gender, and personality. Prominence of the brain's right-hemisphere information processing and intensity of dream experience are two theoretically related constructs that have been proposed as important psychological aspects of REM sleep. Either view is consistent with the prediction that the effect of REM deprivation will depend in part on the nature of cognitive activity that is initiated at the onset of each REM period and that "substitutes" for the interrupted REM process. In the present study, the effect of REM deprivation was more striking for female subjects given a digits task than for female subjects given a fantasy-reporting task during awakening used to induce REM deprivation for the first 6 hours of the night. High neuroticism appeared to exaggerate the effect. No corresponding pattern was observed for the male subjects. These preliminary finding may be exaggerated by cognitive activity that is functionally incongruent with those processes. The results also raise interesting questions about individual differences.


The mechanism of chlorothiazide-induced carbohydrate intolerance. In order to establish the mechanism(s) of chlorothiazide-induced hyperglycemia, measurements of blood glucose, plasma insulin, liver glycogen and hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels, and liver phosphodiesterase activity were made in rats administered 10, 25, 50 or 100 mg/kg of the drug. Comparison of data obtained on these animals with those from controls revealed significant and dose-dependent increases in blood glucose, decreases in liver glycogen, increases in hepatic cyclic AMP and inhibition of phosphodiesterase. Although basal insulin levels were significantly increased at the two higher doses of chlorothiazide, ratios of blood glucose/plasma insulin levels showed suppression of insulin secretion at all four doses. However, this suppression was not dose-related. All effects of the drug were maximal at 2 hours after subcutaneous administration. The results of this investigation indicate that the primary mechanism of chlorothiazide-induced carbohydrate intolerance is cyclic AMP-mediated stimulation of glycogenolysis and inhibition of glycogenesis. Suppression of insulin secretion is secondary but probably contributes to the hyperglycemia.


Neuraminidase production by clostridia.

Neuraminidase production by clostridia. The production of neuraminidase (EC 3.2.1.18) by a range of clostridial species was investigated with techniques previously developed to distinguish neuraminidase-negative and neuraminidase-positive strains of Clostridium perfringens (welchii). Large amounts of extracellular neuraminidase were produced by representative strains of C. perfringens and C. septicum in the test media. Under similar conditions, two strains each of C. chauvoei and C. tertium were found to produce small amounts of the enzyme. All of 12 strains of C. sordellii were clearly shown to produce neuraminidase, often in large amounts, but none of five strains of the closely related but non-pathogenic C. bifermentans had demonstrable neuraminidase activity. No neuraminidase was produced by C. novyi (oedematiens) types A-D (10 strains), C. tetani (6), C. botulinum types A, B, C or E (4), C. sporogenes (4), C. histolyticum (4) or by single strains of five other clostridial species. Clostridial neuraminidase was predominantly extracellular and was not calcium-dependent. The investigation took account of variations in growth and enzyme production in different media. It was necessary to prolong the neuraminidase-assay reaction time to 24 h and to monitor for the presence of NAN-aldolase (EC 4.1.3.3) to define true negatives. It is suggested that neuraminidase production may be of value in taxonomic studies and that its production by several pathogenic species of clostridia may be of interest in studies of pathogenicity and virulence.


The use of an immunoperoxidase technique to investigate by light and electron microscopy the sites of binding of Clostridium welchii type-D epsilon toxin in mice. Mice were given an intravenous dose of formalinised C. welchii type-D epsilon prototoxin and an immunoperoxidase technique was used to demonstrate this antigen in the tissues. The antigen was found to bind to the luminal surface of the endothelial lining of certain blood vessels, to the luminal surface of the cells lining the loops of Henlé and distal convoluted tubules in the kidney, and to the hepatic sinusoids. As it has been shown previously that formalinised epsilon prototoxin and epsilon toxin can compete for the same receptor sites it is postulated that the binding sites demonstrated represent the location of the receptors for C. welchii type-D epsilon toxin.


In-vitro effects of Clostridium welchii type-D epsilon toxin on guinea-pig, mouse, rabbit and sheep cells. Epsilon toxin, at relatively low concentrations, killed guinea-pig peritoneal macrophages in vitro. The cells became swollen, the nuclear and cytoplasmic membranes "blistered" and discontinuous, and the cytoplasm appeared structureless. Formalinised epsilon prototoxin was shown to bind closely to the outer surface of the cells and it is concluded that this site represents the location of the receptors for epsilon toxin. In addition the toxin at higher concentrations killed rabbit peritoneal macrophages after increased periods of incubation, but had no demonstrable effect on other cells from guinea-pigs, rabbits, mice and sheep.


Serial studies of virus multiplication and intestinal damage in gnotobiotic piglets infected with rotavirus. A serial study of rotavirus infection in gnotobiotic piglets is described. They were infected when 7 days old and the course of infection was followed for 21 days, by immunofluorescence and histological examinations of the intestinal epithelium and by titration of the virus content of the gut lumen. There appeared to be two stages of recovery of the intestinal wall, the earlier stage involving non-immune mechanisms and the later invloving antibody.


Rapid microwave fixation of rat brain.

Rapid microwave fixation of rat brain. A new microwave device which inactivates brain enzymes rapidly and uniformly is described. From the results obtained with microwave irradiation at two power levels (0.8 kW and 4.5 kW), it has been demonstrated that the high power microwave irradiation has several advantages over the low power irradiation. In its application to neurochemical studies, significant increase in the DOPAC level was found in the irradiated brain, while there were no statistical differences in the levels of NE, DA, 5-HT and 5-HIAA between microwave irradiation and decapitation. Significant increase in the Ach level and marked reduction of the choline level were observed after microwave irradiation. There were no significant differences in the level of cyclic GMP in the brain between the two methods of sacrifice, while significant reduction of the cyclic AMP level was observed in the irradiated brain.


Multifocal nephroblastic neoplasia.

Multifocal nephroblastic neoplasia. Among 23 patients with multifocal metanephric neoplasia were 14 patients with 43 grossly visible subcapsular tumorlets, 0.3-3.5 cm in diameter, that were apparently derived from nodular renal blastema. Tumorlets are defined as circumscribed lesions that are visible on the exterior surface of the kidney, produce either a raised nodule or, in a few instances, a shallow depression, and are independent of the main tumor(s). Most tumorlets displayed homogeneous epithelial maturation. A substantial minority of tumorlets retained a blastemic character and a few were histologically malignant. Tumorlets tended to be multiple and bilateral but were absent in 9 patients with multifocal disease, including 4 of 10 with bilateral tumors. About half the lesions that achieved tumorlet status, including those that gave rise to clinical tumors, underwent malignant transformation. Contralateral tumorlets should not be mistaken for metastasis and do not adversely affect prognosis. The incidence of neoplasia among young, close relatives of patients with multifocal disease appeared to be excessive, but no clear excess of major anomalies, hemihypertrophy, or minor genitourinary tract anomalies was revealed by a retrospective survey of hospital charts.


Superoxide dismutase activity of normal murine liver, regenerating liver, and H6 hepatoma. By means of both direct assay and gel electrophoresis, normal A/J mouse liver was shown to possess both Cu-Zn and Mn superoxide dismutase (SD) activity. H6 hepatoma cells contained Cu-Zn SD activity, but no Mn SD activity was detectable. Isolated mitochondria from normal liver contained both forms of the enzyme, but isolated mitochondria from H6 hepatoma cells contained no SD activity. To ascertain whether this loss of Mn SD activity was characteristic of these tumor cells or was simply a property of rapidly dividing cells, SD activity was measured in regenerating liver. Mn SD activity was present in the regenerating liver at all times after surgery. Hence loss of the Mn SD activity seemed to be a characteristic of some tumor cells but not of corresponding rapidly dividing normal cells.


Suppressed murine mammary tumor virus (MuMTV) expression in RIII female mice treated neonatally with goat antiserum to MuMTV. Passive immunization of newborn inbred RIII (R3) mice with the globulin fraction of goat antiserum to murine mammary tumor virus (MuMTV) successfully suppressed MuMTV expression in the milk of some of the treated mice throughout nine successive lactations. No mammary tumors developed in the MuMTV-suppressed mice during the first 9 months, whereas all untreated R3 female breeders expressed MuMTV in the milk of the third lactation, and all developed tumors before 9 months of age (mode and median: 189 days).


Differential effects of beta-naphthoflavone and pregnenolone-16alpha-carbonitrile on dimethylnitrosamine-induced hepatocarcinogenesis. The effect of administration of beta-naphthoflavone (beta-NF) or pregnenolone-16alpha-carbonitrile (PCN) on the hepatocarcinogenicity of dimethylnitrosamine (DMN) in male SD rats was explored. Both beta-NF and PCN are potent repressors of the low Michaelis constant enzymatic form of DMN-demethylase, a mixed-function oxidase that catalyzes DMN demethylation. DMN-induced hepatocarcinogenesis was inhibited by PCN and was enhanced by beta-NF. Seven liver tumors were found in 45 rats fed DMN plus PCN compared to 14 liver tumors in 43 rats fed DMN alone; 32 liver tumors were found in 43 rats fed DMN plus beta-NF. No liver tumors were detected in rats that received only PCN, beta-NF, or the administration vehicles. Of the 53 liver tumors observed, 53% were angiosarcomas; this type of tumor was found in all 3 groups of rats that received DMN.


Prevalence of murine mammary tumor virus antibody and antigens in normal and tumor-bearing feral mice. Approximately 20% of normal male and female feral mice (Mus musculus) from areas with populations having either high [Lake Casitas (LC) and La Puente] or low (Bouquet Canyon) spontaneous lymphoma incidence expressed murine mammary tumor virus (MuMTV) gp52 in specific tissues. Sera from a low percentage (6%) of mice from the same trapping areas contained precipitating antibody specific for MuMTV. Although moderate to high levels of MuMTV gp52 were expressed in mammary tumor tissues of 3 of 7 LC mice and 3 of 3 (C57BL/10ScSn X LC)F1 mice, the same animals showed no detectable MuMTV-precipitating antibody. Neither MuMTV antibody nor tumor-associated MuMTV gp52 was defected in 10 LC mice bearing lymphomas or in 5 LC mice bearing hepatomas. Low levels of MuMTV gp52 expression and MuMTV antibody were also detected in subspecies of M. musculus and in the more distantly related species M. cervicolar. Compared with normal and tumor-bearing inbred mice of high (C3H/HeN) and low (C3H/HeN foster-nursed on NIH Swiss) mammary tumor strains, normal and tumor-bearing feral mice express MuMTV gp52 and MuMTV-precipitating antibodies at low frequency.


Chromosome banding patterns and breakpoints of three transplantable hepatomas induced in rats by aromatic amines. The chromosome constitution of transplantable hepatomas H-35tc1, 7316A, and 8994 induced in ACI male, BUF female, and BUF male rats, respectively, by monocyclic or polycyclic aromatic amines was studied by Giemsa banding techniques. Hepatoma H-35tc1 was hyperdiploid, with a dominant stemline of 46 chromosomes. The stemline of the heterogeneous 7316A was in the hypotetraploid region (75-8,). Hepatoma 8994 had a near-triploid complement; most metaphase cells and chromosome numbers from 62 to 68. Thirty marker chromosomes were detected. Nineteen rearanged chromosomes were in hepatoma 8994, whereas only 8-10 markers could be found in the 80 +/- 3 chromosome complement of hepatoma 7316A. Two constant common markers were noted: mar2, a chromosome No. 11 with translocation short arm in H-35tc1 and 8994, and mar10 (mar10a), a chromosome No. 1 with a duplicated segment at breakpoint q54 in hepatomas 7316A and 8994. An analysis of the distribution of 232 breakpoints in the rat karyotype, 26 identified in the hepatomas and 206 collected from the literature, revealed a statistically significant excess of breaks in chromosomes No. 1, 2, 3, and 10 (P less than 0.001). The X- and Y-chromosomes showed a considerably lower number of breaks than anticipated (P less than 0.01). Even after a history of continuous transplantation for 10 years, these 3 hepatomas retained intact sex chromosomes that corresponded to the phenotype of the primary host. Preservation of the sex chromosomes in the hepatomas may be attributed to a lower susceptibility of the sex chromosomes than of the autosomes to breakage.


Control of melanogenesis in mouse melanoma cells of varying metastatic potential. The control of melanin production, tyrosinase activity, and cell replication by melanocyte-stimulating hormone (MSH) and cyclic AMP (cAMP) was examined in differentially metastasizing B16 mouse melanoma variants. In B16-F1 cells (low metastatic potential), MSH or cAMP greatly elevated tyrosinase activity and melanin content while inhibiting cell replication. The same parameters in B16-F5 cells (intermediate metastatic potential) were altered to a much lesser degree, whereas B16-F10 cells (high metastatic potential) were not significantly affected by MSH or cAMP. Therefore, a correlation exists between loss of hormonal regulation and increased metastatic potential.


Suppression and immunotherapy of the guinea pig line-10 hepatocarcinoma mediated by nonviable Staphylococcus aureus. Suppression of growth of the line-10 guinea pig hepatocarcinoma was achieved after the simultaneous injection of line-10 cells and heat-killed Staphylococcus aureus. Growth of tumor was also suppressed when line-10 cells were injected alone, contralaterally, at the same time as the vaccine mixture. Immunity developed to subsequent line-10 cell challenges but not to other syngeneic tumors. Similar results were obtained with the use of protein A-rich or -deficient strains of S. aureus. Multiple intratumor injections of heat-killed S. aureus were therapeutically effective against 6-day tumors. The antitumor effects of nonviable S. aureus were similar in many ways to those of living BCG or bacterial products suspended in oil droplets.


The respiratory epithelium. V. Histogenesis of lung carcinomas in the human. One hundred human primary lung carcinomas were studied by light and electron microscopy and by light microscopic histochemistry to demonstrate mucosubstances. The tumors were classified histogenetically and were grouped into three major categories depending on their cell of origin: 1) tumors from basal and/or mucous cells; 2) tumors from neurosecretory cells; and 3) tumors from Clara cells. Most carcinomas (88%) arose from basal and/or mucous cells. These were subdivided into epidermoid carcinomas (21%), combined epidermoid and adenocarcinomas (46%), and adenocarcinomas (21%). The criteria for epidermoid differentiation included the presence of tonofilament bundles, poorly developed endoplasmic reticulum and Golgi apparatus, and well-developed desmosomes. The criteria for adeno differentiation included well-developed endoplasmic reticulum and Golgi apparatus, poorly developed desmosomes, the presence of extracellular and/or intracellular alveoli, and/or other evidence of cellular secretion such as secretory granules. In adenocarcinomas with extracellular alveoli, typical junctional complexes were also present at the luminal aspect where the cell apexes bordered the alveolus. With these criteria, combined epidermoid and adenocarcinomas were the most common type of lung carcinoma. We anticipate that the new data will clarify categories such as small cell anaplastic carcinoma and large cell carcinoma of the World Health Organization classification. In addition, the histogenetic classification of lung tumors may be of value in the future in studies of risk factors, prognosis, prevention, and treatment of lung cancer.


Spermatic cord sarcoma in adults.

Spermatic cord sarcoma in adults. The clinical courses are presented for 6 patients with sarcoma of the spermatic cord seen between 1967 and 1976. There were 3 fibrosarcomas, 2 liposarcomas and 1 malignant fibrous histiocytoma, making the total reported cases of spermatic cord sarcoma 212. Management of spermatic cord sarcoma is discussed.


Nephroblastoma occurring in a multilocular cystic kidney. A case of a nephroblastoma in a multilocular cystic kidney in a 5-year-old child is reported and the related literature is reviewed. Because of the unreliability of preoperative and intraoperative diagnostic modalities in identifying a coincidental nephroblastoma nephrectomy is recommended for multilocular cystic disease of the kidney in children.


Toward less hazardous cigarettes. Current advances. Critical levels of selected cigarette smoke constituents have been expressed in terms of maximum numbers of pre-1960 cigarettes that a smoker may consume daily without increasing his mortality risk substantially above that of a nonsmoker. This could still imply an important risk, although it may be difficult to detect. We relate these levels to the yields of 27 current low tar and nicotine commercial cigarettes, as measured at the Oak Ridge National Laboratory. In addition, the yields of these selected constituents concomitant with the yield of 1 mg of nicotine are provided as a guide for the smoker who titrates or adjusts his smoking pattern to accommodate a fixed daily intake of nicotine.


Pituitary pigmentary hormones. Relationship of melanocyte-stimulating hormone to lipotropic hormone. Pituitary control of pigmentation has known for more than 60 years. Since 1969, beta-melanocyte-stimulating hormone (beta-MSH) has been accepted as the main pituitary pigmentary hormone in man. Its "constant companionship" with adrenocorticotrophic hormone (ACTH) has also been repeatedly demonstrated. Current investigations challenge both of these concepts. Human beta-MSH immunoreactivity has been shown to be actually due to beta-lipotropic hormone (beta-LPH), a larger molecule that within itself contains the entire amino acid sequence of beta-MSH. Human beta-MSH does not exist in vivo; it is merely an extraction artifact formed by enzymatic degradation of beta-LPH. It would appear likely that beta-LPH, not beta-MSH, is the constant companion of ACTH.


Transfusion-related short-incubation hepatitis in hemophilic patients. Nine episodes of a unique short-incubation form of hepatitis were observed during five years in six hemophilic children after infusion with commercial factor VIII concentrate prepared by two different manufacturers. Five patients with a single episode had no previous infusion for 14 months to 14 years. One patient with several episodes had no previous infusion for at least seven months preceding each episode. The illness was mild and self-limited. No seroconversions to cytomegalovirus, Epstein-Barr virus, toxoplasmosis, or hepatitis A virus occurred. Acute hepatitis B virus infection was also excluded. The findings suggest the presence of one or more non-A, non-B hepatitis agents associated with factor VIII concentrates.


Congenital mesoblastic nephroma and polyhydramnios. Polyhydramnios and premature delivery complicated the pregnancies of three women whose infants were born with renal tumors. In each case the tumor was a mesoblastic nephroma. The liquid of polyhydramnios enhances detection of masses in the fetal abdomen by ultrasound. In the future, mesoblastic nephroma may, therefore, be diagnosed antenatally. Tumors in these infants, which have proved in most cases to be benign, are usually cured by surgical removal. Occasionally, local infiltration and adhesions prevent removal. The fate of the infant with residual tumor is not known.


Primary mucinous adenocarcinoma of the appendix with bilateral Krukenberg ovarian tumors. After experiencing intermittent episodes of abdominal pain for two years, a 28-year-old woman developed partial small bowel obstruction. Barium enema and colonoscopy revealed the source of obstruction to be an apparent cecal carcinoma. At exploratory laparotomy a primary adenocarcinoma of the appendix with bilateral Krukenberg ovarian metastases was found. This is a rare occurrence and, to our knowledge, the first well-documented case in the English literature. These case also demonstrates difficulties in the preoperative diagnosis of adenocarcinoma of the appendix.


[Evaluation of renal cyclic adenosine monophosphate, serum parathyroid hormone and phosphate reabsorption in recurrent calcium urolithiasis, healthy controls and hyperparathyroidism (author's transl)]. In three groups (n = 12 each) of male controls (22--43 years), patients with recurring calcium urolithiasis (21--36 years) and hyperparathyroidism (HPT; 17--71 years) proven by surgery renal cyclic adenosine monophosphate (RcAMP), fractional tubular phosphate reabsorption and serum parathyroid hormone (PTH) were measured during endogenous creatinine clearance. RcAMP (muMol/g creatinine) was: controls 1.48 +/- SEM 0.27; stone formers 2.037 +/- 0.343 (not significantly different); HPT 6.234 +/- 0.454 (p less than 0.001). There is no overlap between HPT and controls. Phosphate reabsorption is least in HPT (0.84 +/- 0.015), higher in controls (0.924 +/- 0.004) and stone formers (0.941 +/- 0.007). All differences are statistically significant. Under the conditions selected (moderate hydration of individuals) Serum PHT (pg-equiv/ml) is lowest in stome formers (less than 100--339), higher in controls (less than 100--933) and HPT (400--1150). there is no overlap in PHT between the former and the latter group but a marked one between controls and HPT. For clinical purposes the resulting diagnostic uncertainty in a given patient can be overcome by additional determinations of RcAMP and ionised serum calcium: when referring to serum PTH HPT patients fall outside, RCU patients within 2 standard deviations of either parameter in control subjects. This procedure presently appears superior to those proposed in the past (urinary cAMP etc.) but requires confirmation in larger patient populations. Moreover, since HPT prevails in middle and upper age decades, their RcAMP values and those of RCU patients should be related to a range seen in closely age- and sex-matched controls.


Isolation of mouse hepatitis virus from infant mice with fatal diarrhea. An epizootic of fatal diarrhea occurred in mice which were approximately 10 days of age. The enteric lesions were similar to those reported in lethal intestinal virus of infant mice, but many diseased mice also had necrotic hepatitis. Mouse hepatitis virus antigen was demonstrated in the affected intestine and liver, and a virus that produced syncitium formation in mouse brain tumor cell culture was isolated from the intestines, livers, and brains. The virus was capable of producing intestinal and hepatic lesions similar to the naturally occurring disease after inoculation into suckling mice. Electron microscopy revealed viral particles within affected intestinal epithelial cells of the inoculated mice.


Further observations on spontaneous neoplasms in the Mongolian gerbil, Meriones unguiculatus. One hundred sixty Mongolian gerbils, Meriones unguiculatus, were examined for the presence of naturally occurring lesions. The first recognized cases of cecal adenocarcinoma, testicular teratoma, and sebaceous gland pad carcinoma were found. Neoplasms previously reported from the gerbil and also seen in the present study included ovarian theca lutein and granulosa lutein cell tumors, sebaceous gland pad adenoma, cutaneous squamous cell carcinoma, malignant melanoma, and renal and splenic hemangiomas. Calcinosis cutis was also observed in two male gerbils.


Cardiac paraganglioma (chemodectoma): a case report and review of the literature. A rare case of paraganglioma (chemodectoma) of the heart is reported. This is the fifth case reported in the world literature and only the second case discovered in a living person. A review of the historical background, embryology, anatomy, and pathology of the paraganglia is provided. The previously reported four cases are also discussed.


Bronchoplastic procedures in the treatment of carcinoid tumors of the tracheobronchial tree. Sixteen patients, aged 10 to 70 years, had carcinoid tumors of the lower respiratory tract treated by various resective tracheobronchoplastic procedures. These represent 8.8 percent of 181 patients with carcinoid lesions treated during a recent 20 year period. All 16 patients had respiratory symptoms, and one patient also had the carcinoid syndrome. Roentgenographic changes ranged from a mass or atelectasis (or both) through unilateral lung hyperinflation to clear lungs with subtle filling defects in major airways. All tumors were visualized endoscopically, and 13 patients had biopsies. Histopathologically, all tumors were "typical" carcinoids . Before operation, the patients had minimal or no respiratory insufficiency, although flow-volume and ventilation-perfusion abnormalities were noted when major airways were affected. Surgical management at thoracotomy was as follows: (1) simple wedge tracheobronchotomy without lung resection (five patients); (2) bronchial sleeve resection without lung resection (three patients); and (3) bronchial sleeve with upper lobe resection (eight patients). These 16 operations were performed with eight technical anatomic variations. No early or late deaths occurred. One patient had early transient atelectasis, and three patients required late endoscopic removal of suture granulation tissue. All patients were alive without recurrence of tumor or carcinoid syndrome or other respiratory complications 6 months to 19 years postoperatively. Pulmonary resection should be avoided unless there is histologic evidence of tumor extension into lung parenchyma or irreversible pulmonary suppuration distal to the obstructive tumor.


Combined therapy for small cell undifferentiated carcinoma of the lung. Fifty-eight patients with small cell lung cancer were treated from September, 1974, to March, 1976, with combined chemotherapy and radiotherapy. Surgical resection of the lung lesion was performed in three patients, and a number of surgical diagnostic methods were carried out in the remaining patients with unresectable of disseminated lesions. Nineteen patients were from the Veterans Administration Hospital and 39 from Indiana University Medical Center. The median Karnofsky performance status was 60. Thirty-nine patients had extensive disease, and 19 had disease limited to the chest and supraclavicular area. All patients received chest radiotherapy and prophylactic whole brain radiation. Adriamycin, cyclophosphamide, and vincristine were given on day 1 and continued every 3 weeks. There were 27 (48 percent) partial remissions of a median duration of 26 weeks. There were 25 patients (43 percent) with complete remission. The median survival for the entire group was 51 weeks. Six of 58 patients (10 percent) are alive and disease free from 24 to 38 months after treatment. Six of 19 patients with limited disease (32 percent) are presently alive and disease free. This includes one patient in whom surgical resection was performed. Combined therapy influences favorably the prognosis of small cell cancer of the ling, expecially in those patients with limited disease and favorable performance status.


Adenoid cystic carcinoma (cylindroma) and mucoepidermoid carcinoma of the bronchus. Factors affecting survival. A review was made of the presentation, treatment, and follow-up of 20 patients with adenoid cystic carcinoma and 12 patients with mucoepidermoid carcinoma of the bronchus who were seen at the Mayo Clinic during the 50 year period 1927 through 1977. Three forms of therapy were employed: complete surgical resection, radiation therapy alone, and radiation therapy after endoscopic removal of tumor tissue. Superior results were obtained in the group with adenoid cystic carcinoma, when complete resection was possible. Significant survival and palliation of sepsis was achieved with subtotal resection. The mucoepidermoid carcinomas in this series were classified on the basis of histologic differentiation. Mucoepidermoid carcinoma of Grade 1 was managed by conservative pulmonary resection. Mucoepidermoid carcinoma of Grades 2 and 3 showed a greater propensity for malignancy. Widespread dissemination caused death with unresectable high-grade mucoepidermoid carcinomas of Grades 2 and 3.


Lack of effect of halothane on E, EA, and EAC rosette formation and cyclic AMP level of human lymphocytes. The effect of halothane on rosette formation and cyclic adenosine monophosphate (cyclic AMP) level of human lymphocytes was investigated. A 4- or 24-hour incubation with 2% halothane had no significant effect on "early" or "late" E, EA and EAC rosette formation or intracellular cyclic AMP levels of human lymphocytes whereas cytochalasin B, which affects microfilament action, reversibly inhibited both E and EA but not EAC rosette formation. It is suggested that halothane in clinical concentrations neither disturbs the function of microfilaments, essential for E and EA rosette formation, nor affects the metabolism of cyclic AMP in unstimulated human lymphocytes.


Current principles of dietary therapy of diabetes mellitus. "Diet therapy" is a term with multiple implications. Current concepts, and the principles upon which they are based, are examined, and an attempt is made to elaborate diet therapy in the context of the pathogenesis of diabetes.


[Morphology of nasopharyngeal fibroma (author's transl)]. Light and electron microscopic investigations of four cases with juvenile nasopharyngeal fibroma revealed the characteristic structures like a fibrous stroma, and inclination to hyalinisation and formation of scar like tissue, a lacunar thin walled vascular component, a high amount of mast cells, and of fibroblasts with different nuclear bodies and particles. The well known electron dense nuclear inclusions were subdivided into three groups of size. The tumor cell nuclei also contained five different types of more or less complex bodies with spherical shape. In addition to the earlier described ultrastructural properties of the tumor the nuclei of the tumorous fibroblasts were found to contain virus like particles measuring 40 to 55 nm in diameter. These particles were aggregated to groups; they were different from chromatin condensations and from perichromatin granules. The structure and size of  the smaller particles was not comparable to that of the electron dense nuclear inclusions regarded as pathognomonic in the nasopharynegal fibroma.


[Intravascular coagulation fibrinolysis syndrome (ICF) in patients with epipharyngeal juvenile angiofibroma (author's transl)]. In two patients with epipharyngeal juvenile angiofibroma we could find coagulation disorders in the sense of the disseminated intravascular coagulation fibrinolysis syndrome (IFC), which was clinically latent before, but became manifest during or after surgery. The author tries to explain the mechanism of its development.


[Biochemical-immunological comparison of the lymphoid cells of tonsils and adenoids (author's transl)]. We compared human lymphoid cells isolated from faucial and palatine tonsils by means of 9 different biochemical-immunological parameters. The cell populations were identical in all values. Evidence as to the biological equivalence of the tissues is disclosed.


[Rare causes for epistaxis (author's transl)]. Rare causes for nosebleeding are different benigne and malignant tumors of the nose and aneurism of the internal carotid artery. Two cases of rupture of an aneurism of the internal carotid artery are reported. One case with a hemangioma of the nasolacrimal duct and the problematic therapy of epistaxis are discussed in cases with Osler's disease.


Rehabilitation of schizophrenics in a developing country (five years of Fountain House, Lahore, Pakistan). Facilities for psychiatric treatment in Pakistan are extremely limited. While efforts are in the offing for the extension of Mental Health Services by the Government, a voluntary organization has been running a rehabilitation centre for the mentally ill in Lahore, called Fountain House, since 1971. An important aspect of this pioneer venture is the collaborative links with Fountain House, New York. The results of follow-up studies conducted over a period of 4 years show that programmes and ideas developed in one country can be profitably utilized in another country.


An effect of corticosteroids and 100% oxygen on aryl hydrocarbon hydroxylase, cytochrome-c reductase, and free radical formation by rat lung microsomes. Activity of aryl hydrocarbon hydroxylase (AHH), cytochrome c-reductase, and NADPH oxidase, and epinephrine oxidation to adrenochrome were determined in lung microsomes from intact, adrenalectomized, and adrenalectomized cortisol-treated female rats under ambient and hyperoxic conditions. Microsomal adrenochrome formation, which is initiated by superoxide anion or other free radicals, was increased by adrenalectomy and decreased by cortisol treatment. Exposure of animals to 100% oxygen caused a further increase in adrenochrome formation. NADPH-cytochrome c-reductase and AHH activities were increased in incubations of microsomes from animals which had received cortisol in vivo while adrenalectomy led to decreases activity. NADPH oxidase activity was increased by cortisol in lung microsomes in the presence of either epinephrine or cytochrome c. Epinephrine conversion to adrenochrome in the presence of lung microsomes was blocked by SOD, but NADPH-cytrochrome c-reductase and AHH activity were unaffected.


Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects. The effect of obesity on the relationship between very low density lipoprotein (VLDL)-triglyceride (TG) production rate and concentration was studied in 80 subjects whose TG concentrations ranged from 41-1315 mg/100 ml and whose relative weight varied from 0.74-1.46. There was a positive correlation between VLDL-TG production rate and plasma TG concentration in all 80 patients (r = 0.78), which was highly statistically significant (p less than 0.001). Both male and female subjects were subdivided into quartiles on the basis of relative weight; the relationship between VLDL-TG production rate and plasma TG concentration was found to be comparable in all subgroups. These observations suggest that moderate degrees of obesity do not affect VLDL-TG kinetics in patients whose plasma TG levels vary over an extremely wide range.


Impaired very low density lipoprotein and triglyceride removal in broad beta disease: comparison with endogenous hypertriglyceridemia. The removal rate of apoprotein-B (apo B) in very low density lipoprotein (VLDL) was decreased in individuals with broad beta disease when compared with endogenous hypertriglyceridemia. Following the injection of 125I-VLDL isolated from individuals with endogenous hypertriglyceridemia, both VLDL apo B fractional catabolic rate (0.058 +/- 0.029 hr-1) and VLDL apo-B turnover rate (0.300 +/- 0.070 mg/kg/hr) were lower in broad beta disease than in endogenous hypertriglyceridemia (fractional catabolic rate 0.112 +/- 0.046, p less than .05; turnover rate 0.640 +/- 0.199, p less than .005) despite equivalent plasma concentrations of VLDL-apo-B. Furthermore, conversion of VLDL apo-B to LDL was impaired in broad beta disease relative to endogenous hypertriglyceridemia. Differences in the kinetics of lipoprotein lipase-related triglyceride removal during a maximal heparin infusion were also demonstrated between these two disorders. These differences suggest an abnormality in the interaction of lipoprotein lipase with the lipoproteins of unusual composition in broad beta disease. This is further supported by the normalization of lipoprotein composition in broad beta disease by estrogen therapy, with a simultaneous change in the kinetics of lipoprotein lipase-related triglyceride removal towards those seen in endogenous hypertriglyceridemia.


Pathophysiology of lipoprotein transport. A system for classification of genetic and acquired forms of hyperlipidemia in humans based on lipoprotein physiology is described. Most hyperlipidemia can be accounted for by defects in one of four sites of physiologic regulation: (1) triglyceride-rich lipoprotein production, (2) lipoprotein lipase-mediated triglyceride catabolism, (3) remnant lipoprotein catabolism, and (4) extrahepatic cholesterol-rich lipoprotein catabolism.


Insulinoma: poor recognition of clinical features is the major problem in diagnosis. Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from "insulinoma" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders.


[Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)]. 100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases.


"Twitch box": a new device to monitor neuromuscular blockade. It is proposed that this "twitch box" be used whenever monitoring of neuromuscular transmission is indicated, since it is simple to use under clinical conditions, does not require critical placement or adjustment of the hand, produces quantitative information comparable to the force transducer, and is safe.


Electron paramagnetic resonance investigation of high-spin iron (III) in cancer. The concentration of iron (III)-transferrin (IT) in whole blood and serum, along with another high-spin (five unpaired electrons) iron complex (probably IT) accumulated by tumor tissue, was investigated by electron paramagnetic resonance (EPR) spectroscopy during the development of Murphy-Sturm rat lymphosarcoma. The observed changes in concentration (microgram/ml) of IT in sera/blood were generally complementary to those from tissue and the character of the modifications suggested the existence of three distinct phases of systemic response to the implantation: (1) an initial response, evidenced by a sharp reduction in serum IT and somewhat high tissue-IT concentration (microgram/g); (2) a period in which the tumor is (2) a period in which the tumor is becoming established, indicated by relatively constant tissue IT levels and near normal serum IT; and (3) the onset of rapid cell multiplication, characterized by increased total tissue-IT accumulation that rises to above 200% of normal available serum iron, increasing tissue-IT concentration, and rapidly declining serum-IT concentration. The results suggest that, in the face of an implanted tumor there are two detectable abnormal serum-IT responses: (1) an initial change, probably due to systemic blockage of iron reutilization; and (2) extraction of IT from serum by multiplying tumor cells, which is probably a major contributor to reduced serum-IT levels and ultimately anemia.


Location of the cleavage sites on the SV 40 DNA map produced by the restriction endonucleases Pst 1 and Bam 1. Restriction endonucleases from Providencia stuartii (Pst 1) and Bacillus amyloliquefaciens H (Bam 1) cleave SV 40 DNA at two and one specific sites, respectively. Using EcoRI and Hind III endonuclease restriction sites as reference, the two Pst I sites were mapped at 0.050; 0.265 and the Bam I site was mapped at 0.170 of the genome length, clockwise, from the single EcoRI cleavage site.


[Clofibrate in type IIa hyperlipoproteinemia. Reduction of apolipoprotein B (author's transl)]. After changing over from the usual eating habits to a "reasonable" restricted diet rich in polyene saturated fats and saturated fatty acids, additional treatment with 1 g clofibrate twice daily produces a significant reduction of concentration of total cholesterol and Apo B by about 24% in the serum of patients with Type IIa hyperlipoproteinemia after 2 weeks. In contrast to this the serum concentration of triglycerides and phospholipids shows an insignificant tendency to fall during the whole duration of the trial. The results suggest that the additional cholesterol reducing action of clofibrate in patients with hyperlipoproteinemia Type IIa who have already been treated by diet is mainly achieved by the reduction of LDL-cholesterol, the atherogenic properties of which are well known.


[Cardinal symptom: uterine hemorrhage (author's transl)]. Uterine hemorrhages are dependent on the vascular architecture of the endometrium: the endometrial spiral arteries supply sectors strictly separated from each other at intervals of about 1.4 mm. Their function is so closely coupled with the endocrine regulation of the cycle that the presence of hormonal receptors in the vessel wall must be assumed. Menstrual bleeding is an instructive example of morphologically detectable endocrine controlled processes. Endometrial hemorrhage in adenocarcinoma appears early, but it is not an early symptom because the surface epithelium remains intact at first. The diagnosis of precancerous changes in the endometrium (adenomatous hyperplasia--carcinoma in situ) is based on the condition of the surface epithelial cells. Extrauterine pregnancies, miscarriages and trophoblastic diseases are usually diagnosed from the uterine hemorrhage. The quality of the hemorrhage in early pregnancy has less diagnostic importance than, for example, in dyshormonal hemorrhagic disorders.


Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet alpha-adrenergic receptors. Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their alpha-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an alpha-adrenergic antagonist. These platelets contained an average (mean +/- S.E.) of 210 +/- 18 and 227 +/- 27 3H-DHE binding sites per platelet--less than half that found on control platelets, 464 +/- 37 (P less than 0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of alpha-adrenergic receptors may account for diminished functional responsiveness of platelets to epinephrine in some patients with essential thrombocythemia.


Tangier disease: one explanation of lipid storage. Normal high-density lipoproteins are absent from plasma in Tangier disease, and the disorder is characterized by accumulation of cholesteryl esters in several tissues, particularly those of the reticuloendothelial system. Electron microscopy of the abnormal high-density lipoproteins in the plasma of three patients with Tangier diseases revealed large (68-nm), flattened, translucent particles in all cases. These particles were most abundant in the plasma of the splenectomized patient. Restriction of dietary fat eliminated or drastically reduced the numbers of these particles among the Tangier high-density lipoproteins. Thus abnormal products of chylomicron metabolism that appear to occur in plasma in this disorder may be targets for phagocytosis and may be at least one source of the cholesteryl esters that accumulate in reticuloendothelial tissues in Tangier disease.


Antibiotic irrigation and catheter-associated urinary-tract infections. To investigate the efficacy of antibiotic irrigation in preventing catheter-associated urinarytract infection, we carried out a randomized controlled trial of a neomycin-polymyxin irrigant administered through closed urinary catheters. Eighteen of 98 (18 per cent) of the patients not given irrigation became infected, as compared with 14 of 89 (16 per cent) of those given irrigation, yielding a mean daily incidence of 5 per cent in each group. The distribution of organisms and their antibiotic sensitivities differed in the two groups, the organisms from the patients with irrigation being more resistant. Disconnections of the catheter junctions were associated with high rates of infection. The rate of disconnections of the junctions in the group given irrigation was almost twice that of the control group because of the presence of the extra junction on overall infection rate represents the result of two opposing phenomena: the increased entry of organisms and the suppression of a portion of them.


Response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia in human subjects. We determined the response of 1alpha,25-dihydroxyvitamin D3 after mithramycin-induced hypocalcemia in eight subjects with polyostotic Paget's disease of bone. Thirty-six hours after infusion of mithramycin (25 microgram per kilogram), the average calcium declined from 9.9 +/- 0.14 (S.E.M.) to 8.0 +/- 0.19 mg per deciliter (P less than 0.005). Serum parathyroid hormone increased from 122 +/- 6 to 226 +/- 36 microliter eq per milliliter (P less than 0.05), serum phosphate decreased from 3.8 +/- 0.11 to 2.9 +/- 0.14 mg per deciliter (P less than 0.005), and urinary cyclic 3,5'-adenosine monophosphate increased from 4.6 +/- 0.35 to 7.5 +/- 0.80 mumol per gram of creatinine (P less than 0.005). Serum 1alpha25-dihydroxyvitamin D3 rose from 98 +/- 12 to 332 +/- 61 pM (P less than 0.05), the increase following the changes in parathyroid hormone and phosphate by 12 to 24 hours. When this lag period was taken into account, there was a significant relation (P less than 0.01) between the increase in 1alpha,25-dihydroxyvitamin D3 and changes in parathyroid hormone (correlation coefficient, r = +0.91) and phosphate (r = -0.96). The relatively rapid response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia occurs with a time course consistent with regulation by parathyroid hormone and phosphate.


High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus. Cattle in upland areas of Scotland and northern England are substantially more prone to alimentary cancer than those of the immediately neighbouring lowlands, and epidemiological evidence implicates a combination of papilloma virus and bracken in the aetiology of the disease. Here Professor Jarrett outlines the circumstantial case against these agents and discusses its implications.


Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study. Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.


Transformation by concanavalin A of the response of molluscan neurones to L-glutamate. Concanavalin A causes in all Aplysia and Helix neurones a depolarising response to L-glutamate. The Con A-induced glutamate response is pharmacologically distinct from the three cell-specific glutamate responses (two inhibitory, one excitatory) that can be elicited from untreated molluscan neurones. The transformation in glutamate sensitivity brought about by Con A does not seem to be related to the lectin's capacity to produce redistribution of receptor sites in cell membranes.


High affinity of carozolol for beta-adrenoceptors coupled to the adenylyl cyclase in ventricular myocardium of kitten and Xenopus laevis. Catecholamine-induced stimulation of adenylyl cyclase in ventricular membranes of kitten and Xenopus laevis was antagonized competitively by carazolol. Apparent equilibrium constants ranging between 100-170 pM were estimated for the beta-adrenoceptor-carazolol complex.


The lack of active bile acid transport in AS-30 D ascites hepatoma cells. The uptake of cholic acid as well as taurocholic acid into AS-30 D ascites hepatoma cells showed linearity with respect to incubation concentrations. It has been suggested that these processes can be described as simple diffusion. In further experiments it could be shown that ascites hepatoma cells were unable to conjugate cholic acid. These results may have significance in the phalloidin action on hepatocytes.


[Convergence of reticulo-, vestibulo- and rubrospinal influences on motor neurons of the cervical region of the cat spinal cord]. Intracellular recording of synaptic potentials of 93 cervical motoneurons was performed in cats under stimulation of medial longitudinal fasciculus, Deiters vestibular nucleus and red nucleus. Under stimulation of medial longitudinal fasciculus and Deiters nucleus in motoneurons of the forelimb muscles distal groups excitatory reactions were predominant and in motoneurons of proximal extensors inhibitory reactions prevailed. When stimulating the red nucleus excitatory and inhibitory reactions were recorded almost in equal number of cells independently of functional significance of corresponding muscles. Monosynaptic EPSPs were recorded in 1/5 of motoneurons under stimulation of the medial longitudinal fasciculus and only in several cases during stimulation of vestibular and red nuclei. In the other cases stimulation of the structures investigated caused polysynaptic reactions in motoneurons which arose after a series of 2-3 stimuli. In 62% of motoneurons when stimulating different structures under study the reactions were of the same direction. The mutual facilitation of reactions was revealed under stimulation of different inputs. The data obtained show that interaction of influences of the studied structures occurs to a considerable extent at the level of spinal interneurons.


Effect of parathyroid hormone and insulin on extracellular cyclic adenosine-3',5'-monophosphate in patients with benign and malignant breast tumors. Basal excretion of cyclic adenosine monophosphate (cAMP) and its basal level in blood plasma in breast cancer (BC) patients and those with fibroadenomatosis did not differ essentially. However, intravenous injection of parathyroid hormone (100 U) and insulin (0.08 U/kg body weight) was followed by a much less rise in urine-cAMP excretion and blood-cAMP levels in BC patients than in benign process in mammary gland. A substantial correlation between changes in plasma cAMP level and the degree of insulin-induced hypoglycemia was not observed. There was a negative correlation between reponse to parathyroid hormone and insulin and body overweight in BC patients. It was suggested that body fat content may influence the peculiarities of metabolism of extracellular cAMP in cancer patients considerably.


Effect of irradiation on enzyme activities of cyclic AMP system in the neuro- and adenohypophyses. The enzyme activities of cyclic AMP system in the neuro- and adenohypophyses were studied, immediately after an irradiation by a single whole body exposure of 1600 R, in an attempt to find whether this intervention causes the changes in the responsiveness of the cyclic AMP regulatory system. In the irradiated rats the neurohypophyses revealed a reduced activity of adenylate cyclase, moderately increased activity of phosphodiesterase and slightly decreased activity of protein kinase, including the value stimulated by cyclic AMP. In the adenohypophyses the irradiation did not cause any significant changes in the enzyme activities of the cyclic AMP system, except of slightly decreased adenylate cyclase activity. The possible relationship of the plasma level of antidiuretic hormone immediately after irradiation and the enzyme activities of cyclic AMP system is discussed.


Dissociation of tubular sites of action of saline, PTH and DbCAMP on renal phosphate reabsorption. The effects of saline expansion, parathyroid hormone (PTH) administration and dibutyryl cyclic 3'5'-adenosine monophosphate (DbCAMP) infusion on renal phosphate reabsorption were examined in acutely thyroparathyroidectomized (TPTX), phosphate infused dogs by the recollection micropuncture technique. Saline expansion reduced whole kidney phosphate reabsorption from a mean of 66.1 to 50.4% of filtered load. This response was entirely accounted for by an inhibition of proximal tubular phosphate reabsorption which fell from a mean of 35 to 21% of the filtered phosphate load. Both PTH and DbCAMP produced a fall in whole kidney phosphate reabsorption comparable to saline. However, this effect was the sum of inhibition of both proximal tubular and distal nephron phosphate reabsorption. These studies demonstrate the important role of the distal nephron in modulating urinary phosphate excretion.


Characterization of protein kinases from adrenal medulla. A study of cytosol and nuclear enzymes. Since phosphorylation of chromosomal proteins by cyclic AMP-dependent protein kinases (EC 2.7.1.37) enhances template activity of adrenal medulla chromatin (9), we have studied the properties and regulation of protein kinases isolated from chromaffin cell cytosol and nuclei. DEAE-cellulose chromatography revealed three peaks of kinase activity in the nucleus (nPKI, nPKII, nPKIII) and two in the cytosol (cPKI, cPKII). The three nuclear enzymes, as well as cPKII, did not require cyclic AMP to express their catalytic activity. nPKI and nPKIII preferred acidic substrates as PO3-4 acceptors, while nPKII and the cytosol enzymes preferred basic PO3-4 acceptors. Enzyme recombination experiments using protein kinase regulatory subunits from cytosol suggested that cPKII was the catalytic subunit of cPKI. In contrast, the nuclear enzymes were not catalytic subunits of the cyclic AMP-dependent protein kinase in the cytosol (cPKI). Only the cytosol protein kinases could be inhibited by endogenous heat-stable protein kinase inhibitors. The nuclear and cytosol cyclic AMP-independent protein kinases were distinguishable on the basis of their sedimentation constants as well as Mc2+ and Mn2+ requirements.


[Value of isotope scintigraphy and angiography in the diagnosis of brain neoplasms]. The results of cerebral angiography and isotope scintigraphy were compared in 50 patients with brain tumours. The usefulness of each method for detection, localization and determination of the size of the tumour was evaluated. The overall detection rate of brain tumours was 92% in the case of angiography and 90% for scintigraphy, the possiblity of localization was 86% and 90% and size determination was 50% and 74% respectively. Scintigraphy often failed in the diagnosis of astrocytomas and tumours situated near the base of the brain, but this method was more reliable in evaluating the site and size of tumours than angiography.