Characterization of saccharide moiety in the electroplax sodium channel. Carbohydrate chains on the large peptide of the voltage-sensitive sodium channel from Electrophorus electricus electroplax have been partially characterized by the lectin-blotting technique combined with digestion using three glucosidases: neuraminidase, endo-beta-N-acetylglucosaminidase H, and peptide: N-glycosidase F. The results show that both N-linked oligosaccharides and O-linked (mucin-type) oligosaccharides are present. In N-linked oligosaccharides, the results suggest the presence of complex- and hybrid-type oligosaccharides which contain bisecting N-acetylglucosamine(s), as well as the complex-type oligosaccharides with the alpha-Fuc-GlcNAc-(Asn) residue(s). In O-linked oligosaccharides, they must carry Gal beta1----3GalNAc- moieties which contain NeuNAc residues in the terminal.


Vulvar invasive and intraepithelial neoplasia. Comparison of some epidemiological and clinical data. We have compared some of the epidemiological and clinical data of 45 patients affected by Vulvar Intraepithelial Neoplasia (VIN) and of 42 patients affected by Invasive Vulvar Neoplasia who came to our observation between 1986 and 1991. We have evaluated and compared the average age in the two groups of patients, their vulvoscopic pictures and the symptomatology referred at the time of the patients' diagnosis.


No inhibitory effects of gestrinone and medroxyprogesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins. The in vivo effects of gestrinone (R2323) and medroxyprogesterone acetate (MPA) on the estrogen production by rat ovaries were investigated. Hypophysectomized immature female rats treated with 2.5 or 5 IU of pregnant mare serum gonadotropin (PMS) were daily given vehicle only, gestrinone (0.5 mg/kg body weight) or MPA (10 mg/kg body weight), and the activities of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17, 20-lyase, 17 beta-hydroxysteroid dehydrogenase and aromatase in ovaries of these rats were measured. Gestrinone suppressed the 3 beta-hydroxysteroid dehydrogenase activity and increased activities of 17 alpha-hydroxylase, 17, 20-lyase and aromatase in ovaries stimulated by 5 IU of PMS, while MPA suppressed activities of 17 alpha-hydroxylase and aromatase in these ovaries. On the other hand, the aromatase activity in ovaries stimulated by 2.5 IU of PMS was suppressed by gestrinone and increased by MPA, and neither gestrinone nor MPA affected the production of aromatizable androgens from progesterone by these ovaries. Thus, gestrinone and MPA administrated in vivo showed divergent influences on steroidogenic enzyme activities in ovaries, but they did not affect the serum concentration of estradiol-17 beta. The present results suggest that neither gestrinone nor MPA reduced estrogen production by the rat ovary under the gonadotropin stimulation although they influenced some process of its steroidogenesis.


[Adenosarcoma of the uterus].

[Adenosarcoma of the uterus]. A case of a 67-year old woman with adenosarcoma of the uterus is reported. Adenosarcoma is a mixed mesodermal tumour with a low malignant potential. It is characterised by a benign glandular and a malignant stromal component. Adenosarcomas are usually treated by hysterectomy with bilateral salpingo-oophorectomy. Patients with myometrial invasion have an increased risk of recurrence. It may be appropriate, to consider adjuvant chemotherapy or radiation treatment for these patients.


[Meiotic drive for aberrant chromosome 1 in mice is determined by a linked distorter]. An aberrant chromosome 1 carrying an inverted fragment with two amplified DNA regions was isolated from natural populations of Mus musculus. A meiotic drive favouring the aberrant chromosome was previously demonstrated for heterozygous females. The cause for this was the preferential passage of the chromosome 1 to the oocyte. Genetic analysis made it possible to identify a two-component system conditioning the deviation from equal segregation of the homologues. The system consists of the postulated distorter and a responder. The distorter is located on the chromosome 1 distally to the responder, between the 1n and Pep 3 genes, the former acting on the responder when in the trans position. Polymorphism of the distorters was manifested as variation in their effect on the meiotic drive level in the laboratory strain and mice from natural populations.


[The role of mobile genetic elements (MGE) in microevolution]. The MGEs of Drosophila and other objects contain open reading frames (ORFs) encoding transposition enzymes, and "motifs" similar to functional sites: promoters, enhancers, heat shock regulatory sites, those of reception of different stress external signals and hormones, recombination sites, etc. In other words, MGE play a role of "movable cassettes of regulatory elements" in the genomes. The patterns of genome MGE localization are the important components of polygenic systems of character expression, the subjects of variation and evolution. The summed up density of MGE localization along the genome has probably the upper value corresponding to approx. 1 MGE copy per gene. The transpositional variability of MGE patterns could be random, non-random, self-related and inducible. The MGE patterns are important subjects of microevolution and reconstruction of trees of the pattern similarity is an effective method for its description. The patterns could be changed by selection of limited quantitative characters. The stress induction (temperature, treatment, dysgenic cross, etc.) stimulated the MGE transpositions and excisions, mass in population and multiple in individuals. The temperature induction acts probably through the system of response to heat shock treatment. The totality of MGE patterns make up the genomic system capable of quick reorganizations after stress external and genomic influences. The stress external influences are often correlated with passing of the population through the "bottle-neck" stage. The rate of transpositions has an upper limiting border, so named "boundary of regulation error catastrophe", that corresponds to approx. 1 transposition per genome, per generation. After the stress induction of transpositions this boundary could be exceeded, the state of the population norm becoming disrupted. The changes in MGE patterns are also supposed to accompany the changes of characters of isolation, i.e. to accompany the speciation.


[Participation of mobile element hobo in transposition events in the long-term instability system of Drosophila melanogaster]. The lines with an active hobo elements as well as those without any hobo fragments were hybridized with the y2sc1waG line. This resulted in the appearance of a number of mutations at the white, miniature, and some other loci. The authors analysed, in which way the hobo transposable elements take part in mutagenesis in these crosses. Most of the white mutants obtained were analysed and transpositions of hobo and Stalker elements were demonstrated. Both independent and simultaneous transpositions were found. It was shown by means of the Southern blot analysis that additional hobo or Stalker insertion into or close to the parental unknown waG insertion resulted in mutant white phenotype's shift toward both extreme and partial reversion. Possible participation in mutagenesis of other mobile elements is also under debate.


Comparative effects of mast cell degranulators on perfused systemic blood vessels of Bufo melanostictus and Rana tigrina. Three agents known to induce release of mast cell constituents, viz. polymyxin, compound 48/80 and polysorbate-80, were evaluated for effect on perfused blood vessels of R. tigrina and B. melanostictus. The mast cell degranulators caused vasoconstriction in frog and toad, except that for P-80 whose responses in toad were equivocal. Toads showed a general low responsiveness in comparison to frogs. Pharmacologic intervention with pheniramine, metergoline, hydergine, atropine and mecamylamine, respectively ruled out role of histamine, 5-HT, catecholamine or acetylcholine or even autonomic mechanisms in the above phenomena. The observations are suggestive of phylogenetic differences in biochemical profile of mast cells in amphibian species.


Immunogenicity of enhanced potency inactivated polio vaccine. Fifty two children were immunized with two doses of enhanced potency inactivated polio vaccine in order to determine its efficacy. The vaccine was very efficacious with 92.3, 92.3 and 88.3% of the children seroconverting to the three poliovirus types, respectively. The vaccine was equally efficacious whether the two doses were given at 4-week or 8-week intervals or when immunization was started at 6-7 weeks of age or later. The presence of maternal antibodies did not interfere significantly with the seroresponse to two doses of IPV-E. The study recommends that two doses of IPV-E give satisfactory seroconversion rates. Immunization can be started as early as 6 weeks age and the two doses can be given at 4 weeks interval to complete primary immunization against poliomyelitis.


Possible involvement of TGF beta 1 in the distinct tumorigenic properties of two rat colon carcinoma clones. The presence in tumors of numerous cytokines suggests that they potentially modulate tumor cell activities and host tissue remodelling. To investigate the possible involvement of transforming growth factor type beta (TGF beta) in the metastatic process of cancer development, we have studied the effect of this factor on two rat colon carcinoma cell lines. These cell clones had been previously tested and selected for their ability to develop metastases in syngenic animals or lack of it. The two cell lines were characterized for their production of TGF beta. Production of active and latent forms of TGF beta 1 in the medium conditioned by the rat colon cancer cells were quantified using a bioassay. The presence of active TGF beta 1 was demonstrated in conditioned medium from the progressive tumor (PROb) cells and significant expression of latent forms of TGF beta 1 were found in the conditioned media from both cell clones. TGF beta 1 slightly inhibited proliferation of PROb cells which had been previously described as moderately differentiated, and significantly stimulated proliferation of the regressive (REGb) cells, described as poorly differentiated. On the basis of our observations, we suggest that this endogenous factor could be involved in autocrine regulation of tumor cell activities and in paracrine regulation of stroma cell and immune responses. Active and/or latent expression of TGF beta 1 by the two rat colon carcinoma cell lines, and their variable responses to the growth factor, strongly suggest that this polypeptide is involved in the regulation of tumorigenic expression of adenocarcinoma cells.


Reduction of the metastatic potential of a RSV-transformed fibroblastic line (B77-AA6 cells) upon transplantation in essential fatty acid-deficient mice. Metastatic dissemination has been shown to be influenced by dietary lipids. In particular, diets enriched with linoleic acid have been consistently found to be effective in enhancing the metastatic potential of murine mammary tumors. This study explored whether an essential fatty acid (EFA)-deficient host can affect the capacity of a tumor to metastasize to the lung. Tumors were developed by subcutaneously injecting high metastatic B77-AA6 cells (a subclone isolated from the Balb/c 3T3 cells transformed by the B77 strain of RSV) into syngeneic mice which had been fed either a control or an EFA-deficient diet for 9 weeks. EFA deficiency did not modify the incidence, latency and growth rate of primary tumors developed from B77-AA6 cells, while it markedly reduced their capacity to reproduce lung macro- and micrometastases. These findings demonstrate that physiological levels of EFA are important for a tumor to metastasize in secondary organs.


[Nonresectable fibrolamellar hepatocellular carcinoma: outcome of 4 cases treated by intra-arterial chemotherapy]. We evaluated the role of locoregional intraarterial treatment in the management of non-resectable fibrolamellar hepatocellular carcinomas (FLHCC) in 4 women. Three patients underwent transcatheter oily chemoembolization (TOCE) (7 courses), and one received intraarterial iodized oil with chemotherapeutic drug after surgical intraarterial catheter placement (1 course). The latter procedure resulted in marked discomfort and was therefore not repeated. The courses were performed in average every 4 months. TOCE was well tolerated and resulted in a decrease in tumor size in 2 patients, which subsequently permitted a safe hepatic resection. In one patient, TOCE provided a stabilization of tumor size. We conclude that TOCE is a valuable therapeutic tool for the management of non-resectable FLHCC, in particular as it may be followed by hepatic resection.


Percutaneous drainage of a pancreatic pseudocyst. We present a patient who developed a pancreatic pseudocyst after surgery for a retroperitoneal fibrous histiocytoma invading the pancreatic tail. The diagnosis was made on the basis of CT and the tail pseudocyst resolved with percutaneous drainage only.


Effect of zinc on immune functions and host resistance against infection and tumor challenge. The effect of zinc treatment on immune function and resistance against infection and tumor challenge was studied in mice. Swiss albino mice were treated with zinc acetate (3 mg/kg body weight) in one or two intraperitoneal injections. Various immune function assays were performed in treated animals. Zinc treatment to normal animals caused potentiation of T-lymphocyte and macrophage functions. Zinc treatment was also found to increase host resistance against Candida albicans and Semliki Forest virus infections. Increased resistance against endotoxin shock and Ehrlich's ascites tumor challenge was also observed in zinc treated animals. It can be stated from this study that zinc treatment potentiates the cell mediated immunity and host resistance against infection and tumor challenge.


Hidden colonic adenomas in a patient with a family history of polyposis. We describe an asymptomatic patient with a strong family history of polyposis who was found to have flat and depressed adenomas that were not visible on colonoscopy. The diagnosis required assessment of multiple, randomly obtained biopsy specimens. Partial deflation of the colon during colonoscopy may allow hidden lesions to be seen. Biopsies should be performed in all patients with a family history of polyposis who are examined colonoscopically, even if they are asymptomatic and no lesions are visible through the colonoscope.


[Rapid diagnosis of cytomegalovirus pneumonia and Pneumocystis carinii pneumonia by using polymerase chain reaction DNA amplification]. We attempted to detect cytomegalovirus DNA (CMV-DNA) and Pneumocystis carinii DNA (carinii-DNA) in urine, blood and sputum samples of 16 leukemia patients with pneumonia, using the polymerase chain reaction (PCR). Synthetic oligonucleotide primer pair were used to amplify DNA from the major immediately genes of CMV and genes for the large subunit of mitochondrial ribosomal RNA of P. carinii. Amplified products were detected by gel electrophoresis. In two cases, CMV-DNA was detected at about the time the pneumonia occurred, and in one of the two cases, CMV-DNA was detected in the sputum sample. This patient was treated immediately with ganciclovir. After ganciclovir treatment, clinical and biochemical signs of CMV pneumonia disappeared. In three cases, carinii-DNA was detected in their sputum samples. In their blood and urine samples, carinii-DNA were not detected. This three cases were treated with sulfamethoxazole-trimethoprim and successfully treated episodes of P. carinii pneumonia. We conclude that PCR amplification may be a valuable tool for rapid diagnosing CMV pneumonia and P. carinii pneumonia.


[The relationship of clinical manifestations and age distribution in enterovirus infections--viral isolation and seroepidemiology in Aichi Prefecture]. We studied the epidemiology of enterovirus infection in Aichi Prefecture from 1985 to 1989. We examined the age distribution of aseptic meningitis patients (AM) and exanthematous disease patients (Ex) and a seroepidemiological study of echovirus type 7 (E7), E9, E18 and group A coxsackievirus type 9 (CA9), was performed. The results is as follows: 1) E7, E9, E18 and CA9 were isolated from AM and Ex but E6, E11 and group B Coxsackie viruses (CB) were isolated in fewer cases from Ex. 2) The AM was consistently increased from June to August. Whereas the Ex was seen in all seasons but a slight increase was noted between June to July, and enteroviruses (EV) isolation was increased in this season. 3) The AM occurred in 0 year olds and 4 year olds whereas the Ex was seen in 0 to 1 years. EV was mainly isolated from 0-1 year olds. 4) The relationship of clinical manifestations and age was very clear in E9 and E18, a higher proportion of children at 1 years or under were those of the Ex and most children of the latter part of 4 years were those of the AM. The Ex had the same results with E7 and CA9 but AM was increased in 0 years and 4 year olds. 5) We studied the age distributions of neutralizing antibodies against E7, E9, E18 and CA9. The positive rate of neutralizing antibody after prevalence rose between 2-5 years of age. There were few patients among the 2 to 3 year olds but the neutralizing antibody was raised in this age. I considered that reason the enteroviruses infected mainly the 2 to 6 year olds showing no clinical symptoms where as some of the 3 year olds had aseptic meningitis and some under 1 year had symptoms of exanthematous diseases.


Familial male breast cancer. A case report and review of the literature. The occurrence of breast cancer in aged male and his paternal uncle is reported. A review of previously reported cases of male breast cancer (M.B.C.) occurring in families and the association with other cancers in the family members is included. Familial or hereditary factors have not been recognized as a major contributing factor in previous reports. Seven families (63.6%) out of eleven families reported had females with breast cancer. It appears that there are some families in which males as well as females have increased risk of developing breast cancer. It is believed that this report supports the genetic predisposition of breast cancer in males. Estrogen affects the growth of breast cancer through estrogen receptor. An approach to subsequent genetic studies of breast cancer may be to focus on steroid hormone receptors.


Hepatocellular carcinoma; characteristics and possible etiologies in a group of Egyptian patients. 62 Hepatocellular carcinoma (HCC) were studied to define some possible high risk group. The males to females ratio was 3:1, and the age ranged from 24-77 years. A high percentage of history of schistosomal infection, Jaundice, blood transfusion, cirrhosis and also contraceptive pill users among the females were found. The duration of the presenting symptoms and the survival since diagnoses were analyzed.


Synergistic effect of flavones and flavonols against herpes simplex virus type 1 in cell culture. Comparison with the antiviral activity of propolis. The in vitro activity against herpes simplex virus type 1 of the major flavonoids identified in propolis was investigated. Flavonols were found to be more active than flavones, the order of importance being galangin, kaempferol, and quercetin. The efficacy against HSV-1 of binary flavone-flavonol combinations has been also investigated. The synergy demonstrated by all combinations could explain why propolis is more active than its individual compounds.


Microscopic rice bodies in rheumatoid synovial fluid sediments. To determine the clinical significance of the microscopic study of the synovial fluid (SF) sediment, 306 sediments were examined from 216 patients with the most frequently occurring acute and chronic arthropathies. The SF was obtained using a fine gauge needle. Microscopic rice bodies were seen in 53 (17.3%) of the samples studied. Forty-five (84.9%) of the samples in which rice bodies were observed were from patients with rheumatoid arthritis (RA) (p < 0.001); 34.9% of the 129 RA samples were found to contain rice bodies. The specificity of finding rice bodies in RA was 95.5%. Most rice bodies were composed of partly or totally hyalinized fibrinous material; in their interior, mononuclear cells were predominantly observed--most of them macrophagic in appearance. With less frequency the rice bodies exhibited central areas of fibrosis. Our results suggest that microscopic rice bodies are fibrinous particles derived from the entrapping of cells in the dense fibrin network present in inflammatory SF.


[A case of Fabry's disease associated with lupus nephritis]. A 36-year-old woman was hospitalized because of nephrotic syndrome. On admission, laboratory studies revealed total protein 5.9g/dl, total cholesterol 381mg/dl, urine protein 2-4g/day, C3 68mg/dl(90-185mg/dl) and the immunological tests showed that antinuclear factor, anti-DNA antibodies and the LE cell phenomenon were positive. Renal function was within normal range. After admission, renal biopsy was done. Light microscopic finding showed diffuse membranous glomerulonephritis, and vacuolization of epithelial cells. Immunofluorescent microscopic finding showed a granular specific staining for IgG, IgM, C3 and C1q along the capillary loops. Electron microscopic finding showed subepithelial and subendothelial dense deposits, and visceral epithelial cell cytoplasm containing osmiophilic multilamellar lipoid bodies. In the studies of the enzyme activities, the patient's fibroblast extract demonstrated a partial deficiency of alpha-galactosidase, and urine ceramide trihexoside was positive. But the patient's leukocyte extract did not demonstrate a deficiency of alpha-galactosidase. So Fabry's disease associated with lupus nephritis was diagnosed. It seems that the case of Fabry's disease which is an X-linked disorder caused by deficiency of the lysosomal enzyme alpha-galactosidase, associated with lupus nephritis, is extremely rare.


Analysis of a cellular model to account for the natural history of infection by the hepatitis B virus and its role in the development of primary hepatocellular carcinoma. Infection with the hepatitis B virus (HBV) can have many different outcomes. Transient infection may result in acute hepatitis or may remain subclinical. Persistent infection may also be subclinical, or may involve chronic active hepatitis, and can finally lead to the development of primary hepatocellular carcinoma. A mathematical model is given to account for the many different outcomes of HBV pathogenesis. The model is based on the assumption that the liver contains two cell populations with differing abilities to support active HBV replication and/or viral integration into the genome. The model helps account for the relationship of the different clinical courses of HBV infection to the age when the disease is acquired, together with the state of the immune system of the patient.


Mechanisms of protective effects of berbamine on ischemia/reperfusion injury in isolated rat heart. Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were significantly injured by 40 min global ischemia followed by 20 min reperfusion. Berbamine could significantly improve heart function, prevent ventricular fibrillation, reduce CK release, preserve Na,K-ATPase activity, and reduce Na+ gain and K+ loss during ischemia and Ca2+ overload during reperfusion. With the use of low temperature ESR technique, in hearts subjected to 40 min ischemia and 15 sec reperfusion, oxygen-centered free radical signals became much more intense. In the presence of berbamine, these signals decreased. Results showed that berbamine could alleviate myocardial ischemia/reperfusion injury. This effect might be due to: 1) preserved myocardial Na,K-ATPase activity and inhibition of sodium overload at the end of ischemia, which might further lead to attenuation of reperfusion-induced calcium overload, and 2) reduction of oxygen free radical generation during reperfusion.


Blood cannabinoids. II. Models for the prediction of time of marijuana exposure from plasma concentrations of delta 9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Two mathematical models are described for the prediction of time of marijuana use from the analysis of a single plasma sample for cannabinoids. The models were derived from cannabinoid data obtained from a controlled clinical study of acute marijuana smoking. Model I was based on plasma delta 9-tetrahydrocannabinol (THC) concentrations and Model II was based on the ratio of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) to THC in plasma. The two models were validated with cannabinoid data from nine published and unpublished clinical studies. The data included plasma samples obtained from infrequent and frequent marijuana smokers and after oral marijuana administration. Cannabinoid plasma concentrations had been determined by a variety of analytical methods. The accuracy of model prediction was evaluated by comparison of the predicted time of prior drug use to the actual time of exposure. Predictions of time of exposure were generally accurate but tended to overestimate time immediately after smoking and tended to underestimate later times. A second assessment of the validity of the models was made by determining if actual time of use was within the 95% confidence interval. Model I correctly predicted the time of exposure within the 95% confidence interval for 235 of 261 samples (90.0%), and Model II was correct in 232 of 260 samples (89.2%). These prediction models may be beneficial to forensic scientists in the interpretation of cannabinoid plasma levels.


Decrease in epinephrine-induced attenuation of platelet adenylate cyclase activity in depressed patients: relation with plasma electrolytes. We have measured the alpha 2-adrenoceptor-mediated inhibition of platelet membrane adenylate cyclase in depressed patients and control subjects. The results showed a decrease in the forskolin-stimulated adenylate cyclase inhibition of depressed patients compared to the healthy subjects. This suggests a subsensitivity of alpha 2-adrenoceptor in depression. However, this subsensitivity was not correlated to the severity of depression as both severely and moderately depressed patients exhibited the same percent of adenylate cyclase inhibition. The antidepressant drugs treatment induced an increase in the percent of adenylate cyclase inhibition with a trend towards the control values. However, this increase did not equal control value, and moreover both remitted and unremitted patients presented a similar change in their alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. This result raises the question about a simple and direct relation between the clinical status of depression and the power of alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. Plasma magnesium and sodium yielded correlations to this alpha 2-adrenoceptor-mediated adenylate cyclase inhibition suggesting a relation between the platelet adrenergic function and plasma electrolytes.


Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. delta 9-Tetrahydrocannabinol (THC), the primary psychoactive constituent of marijuana, is rapidly transferred from lungs to blood during smoking. Oxidative metabolism of THC yields the active metabolite, 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC), and the inactive metabolite, 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Characterization of THC's absorption phase is important because of the rapidity with which THC penetrates the central nervous system to produce psychoactive effects. This study incorporated a highly automated procedure to sample blood and to capture rapid drug level changes during and following smoking. Human subjects smoked one marijuana cigarette (placebo, 1.75%, or 3.55% THC) once a week according to a randomized, crossover, double-blind Latin square design. Samples were analyzed by GC/MS for THC, 11-OH THC, and THCCOOH. THC levels increased rapidly, peaked prior to the end of smoking, and quickly dissipated. Mean peak 11-OH-THC levels were substantially lower than THC levels and occurred immediately after the end of smoking. THCCOOH levels increased slowly and plateaued for an extended period. The mean peak time for THCCOOH was 113 min and a correspondingly longer time course of detection was observed. This study provides the first complete pharmacokinetic profile of the absorption of THC and appearance of metabolites during marijuana smoking. These findings have implications for understanding the mechanisms underlying the performance-impairing effects of marijuana, as well as for aiding forensic interpretation of cannabinoid blood levels.


Effect of L(+)-tartrate on some biochemical and enzymatic parameters in normal and glycollate treated rats. Some biochemical and enzymatic constituents were determined in the small intestinal tract tissues of normal and sodium glycollate treated adult male rats. Alterations were observed with respect to certain lipids and carbohydrate fractions in the glycollate fed rats. DNA content was also elevated in this group. The functions of the cell membrane is likely to be affected as reflected in the levels of transport ATPases and orthophospho-hydrolases. The activities of the two marker enzymes in the intestinal brush border, namely alkaline phosphatase and leucylnaphthylamidase were reduced in the glycollate administered group. Administration of L(+)-tartrate, which is a mild laxative and has a regulatory influence on oxalate metabolism, lowered the activities of Na+, K(+)- and Ca(2+)-ATPases. There was a distinct lowering in the level of acid phosphatase in the tartrate treated rats.


Analysis of forensic specimens for cannabinoids. II. Relationship between blood delta 9-tetrahydrocannabinol and blood and urine 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid concentrations. Data from five years of gas chromatographic/mass spectrometric (GC/MS) quantitation of blood, or blood and matched (i.e. concurrently collected) urine specimens, for cannabinoids have been used for two distinct evaluations. In the present study, we assessed the relationship of blood delta 9-tetrahydrocannabinol (THC) with blood and urine 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (COOH-THC) concentrations. Cannabinoid-containing (i.e. positive) forensic blood specimens (298, 135 with matched urines) were used to test for correlations and other relationships between these analytes. No correlation was found between blood THC and blood or urine COOH-THC concentrations. Significant correlations were found between the log blood and log urine COOH-THC concentration (r = 0.65). The correlations, however, were neither high nor consistent enough to suggest their use in extrapolations of urine to blood concentrations. Others have suggested that a urine COOH-THC concentration in excess of 100 ng/mL may indicate impairment. We observed this would result in 17% of individuals with blood THC less than 1 ng/mL being classified as impaired. The rate of inaccurate interpretations would increase if higher concentrations of blood THC were considered characteristic of impairment. It has been suggested that a ratio of blood COOH-THC/THC less than 4:1 is an indicator of impairment. In this study, the percentage of bloods with a ratio less than 4:1 increased as THC concentrations increased. However, THC concentrations in excess of 10 ng/mL were required before a majority (70%) of the specimens fell below this ratio, suggesting limitations to its use. Blood metabolic ratios (THC/COOH-THC) displayed a bimodal distribution.(ABSTRACT TRUNCATED AT 250 WORDS)


Amine uptake inhibition by diosmin and diosmetin in human neuronal and neuroendocrine cell lines. Human neuroblastoma cells of sympathetic origin have been used for studying the effects of diosmin and its metabolite diosmetin (vasotonic agent) on amine reuptake systems. Neuroblastoma cells take up 3H-dopamine in a specific and time-dependent manner. 3H-dopamine uptake was dose-dependently inhibited by the known antagonist desipramine. Diosmin did not affect 3H-dopamine uptake at concentrations as high as 1 mM. On the other hand the aglycone metabolite of diosmin, diosmetin, inhibited 3H-dopamine uptake in a dose-dependent manner (IC50 = 4 microM). Diosmetin inhibited 3H-dopamine uptake in control and differentiated neuroblastoma cells, as well as in small-cell lung carcinoma cells. Furthermore diosmetin also inhibited 3H-serotonin uptake in both cell types. These results demonstrate that some flavonoids act as antagonists of plasma membrane amine transporters at the molecular level and suggest that inhibition of amine reuptake at the level of peripheral sympathetic nerve terminals could be responsible for the increased vascular tone observed in vivo after treatment with these drugs.


[Prophylaxis of cytomegalovirus infections with ganciclovir in kidney transplant recipients]. In an open-labeled randomized study, prophylactic treatment with ganciclovir (day 15 to day 29) was administered to 23 cytomegalovirus seronegative patients who received a kidney from a cytomegalovirus seropositive donor. Both groups (control = 11, ganciclovir = 12) were similar in age, immunosuppressive treatments, acute rejection episodes and number of steroid pulses. A seroconversion occurred in 10 control patients (91 percent) and in 10 patients of the ganciclovir group (84 percent). A cytomegalovirus disease was observed in 10 control patients (91 percent) and in 8 patients of the ganciclovir group (66 percent). The delay between grafting and cytomegalovirus disease was significantly longer in the ganciclovir than in the control group (78.5 +/- 7.7 vs 46.5 +/- 5.5 days, P < 0.05). In conclusion, in renal transplant recipients who are at high risk of cytomegalovirus disease, prophylactic treatment with ganciclovir delays the onset of the disease and seems to decrease slightly its frequency.


Analysis of forensic specimens for cannabinoids. I. Comparison of RIA and GC/MS analysis of blood. Data from five years of radioimmunoassay (RIA) screens and gas chromatographic/mass spectrometric (GC/MS) quantitation of blood, or blood and matched (i.e. concurrently collected) urine specimens for cannabinoids have been used for two distinct evaluations. The first part, which is the subject of this study, considers comparative results from RIA and GC/MS analysis of the specimens. RIA analysis (Abuscreen urine cannabinoids kit) of methanol extracts of blood with extracted blood calibrators (122 specimens) was compared to analysis of nonextracted blood with urine calibrators (108 specimens). RIA of methanol extracts of blood was a reliable assay (limit of detection = 17 ng/mL; interassay coefficients of variation of 2-10%). RIA of nonextracted GC/MS negative blood gave significant displacement of labeled antigen, which precluded accurate quantitation using the urine-based calibrators. Comparison of RIA cannabinoid concentrations to 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (COOH-THC) concentrations measured by GC/MS yielded correlation coefficients of 0.68 and 0.23 for the methanol extract and nonextract procedures, respectively. Comparison of the qualitative accuracy of the two techniques, however, resulted in similar discrimination of GC/MS positive and negative specimens when the 20-ng/mL extracted blood calibrator was used as the cutoff for methanol-extracted blood specimens, and the 100-ng/mL urine calibrator was used as the cutoff for nonextracted blood specimens. Although qualitatively similar, the methanol extract procedure resulted in quantitatively superior analysis.


[Lymphoproliferative syndromes associated with Epstein-Barr virus in transplantation]. We report 23 cases of lymphoproliferative diseases which occurred among 2,100 patients with kidney or combined kidney+pancreas transplant. Eleven patients developed a severe diffuse disease within the first 3 months post-transplantation; immunoblastic B cells of recipient origin infiltrated the bone-marrow, transplanted organs, liver, spleen, lymph nodes, lungs, and brain; immunoglobulin abnormalities with fever, leuko-thrombocytopenia and liver dysfunction constituted the symptoms; all patients received anti-lymphocyte globulins; 9 patients were also treated with cyclosporin. Three out of 6 tumors analysed were monoclonal. Epstein-Barr virus was present in 3 lesions analysed. Treatment consisted of cessation of immunosuppressive therapy. Nine patients died with lactic acidosis. Five patients had a less severe form. Seven patients had solid tumors involving the tonsils, lungs (2), lymph nodes (2), and bladder, 8 months after transplantation. All patients received cyclosporin; 4 also received anti-lymphocyte globulins and 3 OKT3. Tumor cells were immunoblasts expressing B cells markers at a late stage of B cell differentiation; 4 tumors were monoclonal. C myc was negative. Treatment consisted of cessation of immunosuppressive therapy, antiviral agents, and monoclonal antibodies (mAb): anti-CD21 and anti-CD24 mAb therapy was followed by cure of the lymphoma in 1 patient, by transient remission in a second one and by failure in the third patient. Two patients had a recurrence of the lymphoma and received chemotherapy; 2 patients died of the lymphoma, 1 died of unrelated cause; 4 are alive, 3 of them having a good graft function.


[Viral pneumopathies after heart transplantation. Radioclinical analysis]. From a retrospective study of 80 cases of heart transplantation, the contribution of chest X-rays to the diagnosis of viral pneumonia was studied. Among 66 episodes of pneumonia, a viral cause was proved in 16 cases (CMV: 9, Herpes: 7), with 13 cases during the first 4 months. CMV pneumonia was revealed in 3 cases by a diffuse pulmonary infiltrate with a rapidity fatal outcome and in 6 cases by focal infiltrates that disappeared within 1 and 7 weeks. Herpes pneumonia was immediately revealed, in 5 cases, by a diffuse infiltrate. In 11 out of 16 cases, the viral pneumonia improved but its course was complicated by the development of another pneumonia.


[Forskolin and cyclic adenosine monophosphate inhibit the neurulation action of concanavalin A on explants of the gastrula ectoderm of amphibians]. We studied effects of forskolin, an activator of adenylate cyclase activity, and dioctanoyl-cyclic adenosine monophosphate (do-cAMP) on neutralizing (N) activity of concanavalin A (Con A). Biological testing was performed using explanted animal pole ectoderm of the Rana temporaria early gastrula. Con A treatment (200 micrograms/ml, 2 h) resulted in neutralization of 70-90% explants. If the explants were previously treated with forskolin (100 microM, 1 h), Con A effect decreased to 10%. When Con A and forskolin were applied simultaneously, no N-effect was observed. The same results were obtained with simultaneous treatment of the explants with Con A and do-cAMP (10(-5) M). Moreover, treatment with forskolin of the explants previously treated with Con A inhibited their neural differentiation. We suggest that N-effect of Con A is calcium dependent; the increase in intracellular cAMP after treatment of explants with forskolin or do-cAMP interferes with intracellular Ca2+ release and this results in the inhibited N-effect of Con A.


[Liver transplantation associated with combined adjuvant treatment in hepatocellular carcinoma. Feasibility and preliminary results]. Combined adjuvant therapy was prospectively assessed in 7 patients receiving orthotopic liver transplantation for hepatocellular carcinoma complicating cirrhosis. The protocol included hepatic arterial chemotherapy while waiting for transplant, immediate preoperative liver irradiation, and early postoperative chemotherapy. There were no postoperative deaths, and morbidity included mainly hematologic toxicity of chemotherapy. Two patients died of tumor recurrence 6 and 14 months after transplant. The remaining 5 patients are alive and free of disease with a follow-up of 7 to 26 months. These results show the feasibility of aggressive adjuvant therapy in patients transplanted for hepatocellular carcinoma and suggest a possible effect of such a protocol on the prevention of tumor recurrence.


Brachytherapy of brain tumors.

Brachytherapy of brain tumors. Temporary implants of high-activity 125iodine sources have been used in the treatment of brain tumors since December 1979 at the University of California, San Francisco. For previously untreated patients who underwent external beam radiation therapy followed by implant boost, median survival from the date of diagnosis was 88 weeks for 34 patients with glioblastoma multiforme (GM) and 157 weeks for 29 patients with nonglioblastoma gliomas (NGM). For recurrent tumors treated with brachytherapy only, median survival from the date of the implant was 54 weeks for 45 patients with GM and 81 weeks for 50 patients with NGM. Finally, in 48 patients with recurrent tumors treated with combined hyperthermia and brachytherapy, median survival from the date of the implant was 46 weeks for 25 patients with GM and 44 weeks for 7 patients with metastases; 18-month survival was 65% for 16 patients with NGM. Brachytherapy appears to be a useful technique for the treatment of selected recurrent brain tumors and selected primary glioblastomas.


Brachytherapy for malignant recurrent and untreated gliomas. Twelve consecutive patients with recurrent malignant glioma were treated with brachytherapy. Thereafter, a prospective randomized study involving 35 patients was undertaken. Although additional study is necessary, preliminary recommendation calls for treatment at diagnosis rather than at recurrence.


Molecular neurosurgery for glial and neuronal disorders. Molecular neurosurgery is the surgical use of molecules to destroy, sustain, or modulate or augment neurons, supporting cells or tumor cells within the nervous system. Molecules designed for surgical use may be engineered to be used in their molecular state or may be packaged as liposomes, viruses or genetically engineered cells. This article summarizes the current state of development of one aspect of molecular neurosurgery--the use of genetically engineered viruses to treat brain tumors. Both herpes virus and retrovirus strategies are discussed. Each virus has its own set of advantages and disadvantages that can be used in the design of an appropriate therapeutic strategy. Further application of this technology to intrinsic glial and neuronal disorders is discussed, and future perspectives are presented.


[Paraneoplastic encephalomyelitis and Lambert-Eaton syndrome]. In two men presenting with muscle weakness and disturbances of equilibrium neurophysiological examination by repeated stimulations revealed responses suggestive of Lambert-Eaton syndrome. In the first month of the disease very high levels of anti-Hu antibody were found in the serum and CSF, betraying a malignant lesion. This was confirmed by autopsy 4 months later in one patient and by bronchial biopsy 16 months later in the other patient. Both had small-cell lung carcinoma associated with paraneoplastic encephalomyelitis.


Renal transplacental carcinogenicity of 3,3-dimethyl-1-phenyltriazene in rats: relationship of renal mesenchymal tumor to congenital mesoblastic nephroma and intralobar nephrogenic rests. Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.


Hematological effects of 2',3'-dideoxycytidine in rabbits. The antiviral nucleoside analogue 2',3'-dideoxycytidine (ddC) is a DNA chain terminator and/or inhibitor of human immunodeficiency virus (HIV) reverse transcriptase. We evaluated the effects of ddC in 36 New Zealand white rabbits. Three/sex were assigned to a control group and 5 treatment groups (10-250 mg/kg/day) for 13 or 18 weeks. Blood samples were taken 1 week prior to treatment and weekly thereafter to termination with the exception of the 2 highest dose groups, where blood sample collection was terminated at week 13. Selected hematological analytes were measured weekly with the exception of prothrombin time (PT) and activated partial thromboplastin time (APTT). PT and APTT and selected biochemical analytes were measured prior to treatment, at 7 weeks, and after 13 weeks of treatment. All rabbits were necropsied. Giemsa and hematoxylin and eosin sections were prepared from methacrylate-embedded marrow. Hematological effects included decreases in red blood cell count, hemoglobin, hematocrit, and white blood cell count and increases in mean corpuscular volume and red cell distribution width. Platelets, platelet volume, PT, APTT, and mean corpuscular hemoglobin concentration values were variable or unchanged. Effects were dose-related, most were seen at 1 week, and they persisted to term. Bone marrow histopathologic changes included megalocytosis, erythroid hypoplasia, bizarre erythroid nuclear morphology, nuclear-cytoplasmic asynchrony, and increased mitotic figures. Lymphopenia caused by ddC plateaued at 2 weeks and persisted until termination. Heteropenia (neutropenia) was sporadic. Biochemical values for serum analytes were unchanged by treatment. The principal hematological effect of ddC upon the erythron was characterized as a nonregenerative macrocytic anemia with erythroid hypoplasia and megaloblastic erythropoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Quantitative and computer assisted electron microscopic and microprobe studies in dermatology. Electron microscopes are not yet routine instruments in modern dermatological pathology even though they have provided detailed data about pathological changes in the skin for more than three decades. At present, dermatopathology is still dominated by light microscopy and especially so since the introduction of immunological techniques such as the use of monoclonal antibodies. These tools applied at electron microscopic resolution, however, may provide the ultimate identification of cells and subcellular components. In addition, electron microscopes have no peers in areas of quantitative investigation at subcellular levels, e.g. morphometry. The electron microprobe provides a unique tool in elemental analysis and may be used for the analysis of conventionally prepared specimens when foreign matter, not soluble in water, is deposited in the tissue. On the other hand, with water soluble substances the technique is most effective when freeze sections are utilized. This paper gives a selected review of the present day status of quantitative skin research as analysed with electron microscopy and the related technique of electron microprobe analysis.


Why do some families become defaulters in a hospital based nutrition rehabilitation follow-up programme? Since 1989, a nutrition rehabilitation follow-up (NFU) service is being offered in the Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. Parents bring their children for treatment of diarrhoea and those with additional diagnosis of moderate to severe protein energy malnutrition (PEM) are referred to NFU. Families with severely undernourished children are encouraged to attend NFU. Some of them do not come back to NFU after the first or subsequent visits and are considered as 'defaulters'. This paper focuses on the reasons why some families become defaulters. Thirty-two defaulter families were matched with an equal number of non-defaulter families for age and gender of the child and follow-up visit number. All families were interviewed. Children from both groups had similar nutritional, socio-economic status and parental education level. The main reason stated by defaulter mothers for not coming to NFU was 'follow-up was not needed since the child was okay'. The main reason for coming to NFU stated by non-defaulter mothers was for 'the child's improvement', indicating that parental perception of the child's nutritional status differ in the two groups. A greater proportion (75%) of defaulter mothers as compared to non-defaulter mothers (41%) came to NFU accompanied by another adult. It was not possible to identify potential defaulters. Thus all families accepting NFU must be given equal attention. The poor nutritional status of the child and associated risks must be explained to the mother and other family members. The benefits of NFU to the child and family must be stressed.(ABSTRACT TRUNCATED AT 250 WORDS)


Muscarinic receptor subtypes, beta-adrenoceptors and cAMP in the tracheal smooth muscle of conventional and double-muscled calves. The total muscarinic (M1 + M2 + M3) and beta-adrenergic receptors in the tracheal smooth muscle of conventional and double-muscled calves were identified and characterized with the non-specific antagonists [3H]quinuclidinyl benzilate ([3H]QNB) and [3H]dihydroalprenolol ([3H]DHA) respectively. Although the quantity of beta-adrenoceptors in double-muscled calves was 25% lower (p < 0.05) than in conventional calves (Bmax = 327 +/- 89 fmol/mg protein), adenylate cyclase assays indicated that the basal adenylate cyclase activity and the (-)-isopropylnoradrenaline (ISO)- and sodium fluoride (NaF)-stimulated values were not significantly different between these calves. However, the density of muscarinic receptors in double-muscled calves was 40% higher (p < 0.01) than in conventional calves (Bmax = 2955 +/- 625 fmol/mg protein). Subtypes of muscarinic receptors were studied with [3H]telenzepine (M1-receptors), [3H]AF-DX 384 (M2-receptors) and [3H]4DAMP (M1 and M3-receptors). It was found that in both double-muscled and conventional calves about 40% of the receptors were of the M3-subtype, the remaining 60% being M2-receptors. From these results, it is suggested that inflammation of the respiratory tract in double-muscled calves may be complicated by an imbalance between the cholinergic bronchoconstrictor and the beta-adrenergic bronchodilator components of the autonomic nervous system.


[The architecture of the reflex arc].

[The architecture of the reflex arc]. The conceptual reflex arc in Helix is composed of identifiable local detectors, command neurons and modulatory neurons. The identification of neurons opens a perspective for identification of single synapses. The plastic changes within the reflex arc can be characterized as non-associative and associative. The non-associative plasticity (habituation and sensitization) is based on the dephosphorylation and phosphorylation of receptor and channel proteins. The associative plasticity (conditioning and extinction) is based on two levels of molecular modifications: the short-term changes underlined by the phosphorylation and dephosphorylation of receptor and channel molecules and the long-term changes referred to the expression of genes encoding structural and translocating proteins. The very selective receptor and channel modifications are due to the Hebbian plastic synapse supplemented with the principle of nonspecific (modulating) influences.


[The nervous system and the mapping of the neurons in the gastropod Helix lucorum L]. Summarized literature and experimental author's data are presented concerning the structure of the nervous system and identification of individual neurons in the snail Helix lucorum. Information about especially well-known neurons is given in a table, maps of the ganglia are presented altogether with the results of retrograde staining of different cerebral and suboesophageal nerves. Are given the references concerning morphology of the central nervous system of the snail and identifiable neurons.


Identified neuronal individuals in the buccal ganglia of Helix pomatia. The buccal ganglia of Helix pomatia are used as model nervous structures in neurophysiological and in epileptological studies. Many basic problems concerning membrane physics, functioning of the single neurons and of neuronal networks can be studied easily using these ganglia. The model character mainly comes from the relative simplicity of this nervous system and that it contains large visually identifiable neurons. As in other invertebrate nervous systems, the large neurons have proved to be individuals showing the same functional and structural properties from one animal to the next.


[Vision in the edible snail: the spectral sensitivity of the dark-adapted eye]. The spectral sensitivity of the dark-adapted eye of Helix lucorum L. was investigated using a semi-intact preparation "ball of the eye--optic nerve--cerebral ganglion". The amplitudes of responses of the electroretinogram to monochromatic stimuli of different intensities were used for a reconstruction of the spectral sensitivity. The averaged curve of the spectral sensitivity coincided well with the Dartnall's nomogram for a pigment having the maximum of spectral sensitivity near 496 nm.


[The defensive behavior of the edible snail]. Literary and experimental data are summarized on organization of defensive behaviour in Helix. Muscular and neuronal mechanisms participating in this form of behaviour are reviewed.


[The mono- and polysynaptic connections between identified neurons in the system of the passive defensive reflex in the edible snail]. A structure of synaptic connections between the identified sensory and giant command neurons of Helix lucorum was studied. It was found that EPSPs arising in the giant neuron as responses to single action potentials generation in sensory neuron consist of several monosynaptic and several polysynaptic components having different magnitude, latencies, and plasticity. The latencies of monosynaptic components are determined by different presynaptic terminals' lengths.


Processing of mechano- and chemosensory information in the lip nerve and cerebral ganglia of the snail Helix pomatia L. Neurophysiologists have long been seeking out simple model systems in which to analyse the neuronal mechanisms underlying the organisation of behaviour. The feeding behaviour of molluscs has proved to be one of the most useful simple systems for the analysis of cyclical motor patterns, the interactions of central pattern generating interneurones and the role of sensory inputs in the initiation and maintenance of the behaviour. Considerable progress has been made in one or both of the first two aspects of this research in Lymnaea, Helisoma, Limax, Planorbarius, Pleurobranchaea and Tritonia (for reviews see [3, 7, 8, 15]) and more recently, in Aplysia [39] and Planorbis [1]. The role of mechano- and chemosensory inputs in the organisation of the feeding behaviour was studied in at least twenty molluscan species (for a review see [3]). However, in only less than half of them was the analysis extended to the effect of tactile and chemical inputs on identified neurones in the buccal and cerebral ganglia which contain the feeding circuitry (Aplysia: [12, 22, 36, 41]; Pleurobranchaea: [9, 16, 17]; Tritonia: [2]; Helisona: [21]; Limax: [11, 14, 35]; Helix: [6, 19, 24-26, 32, 38]). In present chapter I would like to review our earlier findings on the processing of mechano- and chemosensory information in the lip nerves and cerebral ganglia of Helix pomatia L. These findings were published in a series of papers between 1982 and 1987 [19, 20, 24-26]. The results reviewed here prepared the way for the development of new lines of research in our laboratory on the plasticity and serotonergic modulation of feeding in this widely used experimental animal [27, 40].


[Viscero-cardiac reflexes in the edible snail]. Only two inhibitory neurons in the visceral ganglia provide the viscero-cardial and cardio-cardial reflexes of Helix pomatia. These neurons are connected in parallel and do not interact with each other. The cells have extensive receptive fields in all visceral organs which are considerably overlapped. These inhibitory neurons can provide the afferent function because of a high sensitivity to tactile stimulation of their endings. The analysis of the data showed that morphological and functional characteristics of the neurons in question corresponded completely to previously identified multifunctional interneuron V21.


[The behavioral plasticity of the edible snail and its neuronal mechanisms]. Published results concerning behavioural habituation, sensitization, long-term processes, environmental conditioning, and conditioned food aversion in terrestrial snail Helix are discussed. Neural mechanisms underlying behavioural changes are considered. Problems of participation of motivational processed and development of plasticity in ontogenesis are reviewed.


[The dynamics of the defensive and feeding conditioned reactions of the edible snail during long-term sensitization]. During the long-term sensitization in a snail there occurs an enhancement of a defensive reaction and a significant decrease of food intake. Defensive conditioning is facilitated and feeding conditioning deteriorated. The results give evidence that a formation of the state of the long-term sensitization is accompanied by a generation of a dominant defense focus.


[Conditioning and sensitization in the edible snail: the neurophysiological and metabolic characteristics]. Electrophysiological parameters and bound calcium (Ca(b)) level dynamics during sensitization development or conditioning of food aversion were studied in the command neurons of defense behaviour in the snail Helix lucorum. Responses evoked by a testing sensory stimulus were facilitated 50-60 min after the first sensitizing stimulation, while conditioned responses appeared 80-90 min after the first conditioning. It was the most essential electrophysiological difference between the long-term sensitization and conditioning. Analysis of the Ca(b)) dynamics in the neurons showed significant differences in calcium-dependent metabolism during the sensitization and conditioning, likely underlying the electrophysiological differences.


[The effect of oxytocin on the identified neurons of the brain in the edible snail Helix pomatia L]. Responses induced by a perfusion by a solution with oxytocin were examined in identified Helix pomatia L. neurons. Depolarizing, hyperpolarizing, and modulatory neuronal responses were observed. The responses under study were supposed to be associated in most of the cases with the system of cyclic nucleotides.


Estrone 3-glucuronide chemiluminescence immunoassay (LIA) and 17beta estradiol radioimmunoassay (RIA) in the monitoring of superovulation for in vitro fertilization (IVF): correlation with follicular parameters and oocyte maturity. Many works in the literature of the last years had reported that urinary approach to superovulation study is a suitable method to evaluate ovarian response to pharmacological stimulation. Before applying urinary determination of hormonal levels with a chemiluminescence immuno assay (LIA) method in early morning urine (EMU) samples, we had studied the correlation of RIA-LIA procedures with reference to follicular volumes at hCG day and to recovered oocyte maturity; in fact follicular growth and oocyte morphological features are the main parameters to evaluate a successful induced cycle. In our department the IVF cycles are daily monitored with RIA seric E2 and LIA E1-3G determination, besides ultrasound examination of follicular growth. We have studied E2 and E1-3G levels on the hCG administration day and their correlation with follicular areas and volumes; moreover, we have evaluated hormonal values on oocyte pick-up day with reference to recovered oocyte number and maturity. We have assumed as good timing for oocyte pick-up when more than 50% of recovered oocytes were of good quality (maturity score 4). We have observed that the highest pre ovulatory E1-3G value is consistent with the best timing for oocyte pick-up; it's possible to obtain a conversion coefficient follicular volumes and urinary E1-3G excretion. We have not found significant differences between plasmatic and urinary estrogenic parameters. It is important to remember the advantages connected by a not isotopic and not invasive method. The absence of discomfort for the patients may be a decisive factor to choose the monitoring method and LIA procedure may represent a valid alternative to RIA.


Induction by aerosol allergen of sustained and nonspecific IgE-mediated airway hyperreactivity in the guinea pig. Described is a guinea pig model of allergic asthma, in which animals are sensitized by intraperitoneal injections of ovalbumin complexed with aluminum hydroxide to elicit an IgE response. Aerosol exposure to ovalbumin induces acute bronchoconstriction and nonspecific airways hyperreactivity, evaluated by intravenous challenges of histamine or acetylcholine. This model mimics the hallmark features of human asthma, is induced by respired allergen and is pharmacologically modulated by prophylactic drugs (methyl prednisolone, ketotifen, theophylline) and the competitive PAF receptor antagonist SDZ 264-412.


Temporal infiltration of leukocyte subsets into mouse skin inflamed with phorbol ester. We have previously shown that multiple topical applications, over 11 days, of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a persistent inflammatory reaction characterized by edema, cell infiltration and epidermal hyperplasia. In order to characterize the cell infiltrate during the establishment of this inflammatory reaction, immunohistochemistry was performed using two monoclonal antibodies: MOMA-2, a macrophage antibody and Thy-1, a pan T-cell antibody. The level of polymorphonuclear leukocytes (PMNs) peaked by day 3 at 160-fold over nontreated controls and then subsided to a 30-fold elevation on days 7-10. By day 4, the number of macrophages increased 2.9-fold over the nontreated control and by day 10 were elevated 6.0-fold over the nontreated control. In comparison, the number of T-cells present by day 7 was significantly elevated 9.5-fold over the nontreated group and peaked at day 8 with a 19-fold elevation relative to nontreated controls. Topical treatment of animals with hydrocortisone valerate resulted in a dramatic (> 60%) reduction in the number of T-cells present in the tissue. In contrast, there was no effect of the steroid on the number of macrophages present in the tissue. The identification of specific cell types and their time course of infiltration is consistent with the development of a chronic inflammatory lesion.


Supports for enzyme immobilization.

Supports for enzyme immobilization. Macroporous silica gel, prepared from sodium silicate and hydrochloric acid, one grade of diatomaceous earth (celite 545) and nonporous glass were analyzed in terms of pore size by the mercury intrusion pressure method. The alkylamine derivatives of the above materials were examined for their suitability as supports for enzyme immobilization, using the enzyme glucose oxidase. The effectiveness of the immobilized enzyme was compared in relation to the free enzyme and particle size of the carrier. The immobilized enzyme exhibited a broader range of optimum pH and greater thermal stability, among some properties considered.


Long-term oestrogen priming on basal and oestradiol-induced release of luteinising hormone secretion in male rats. The response of prolonged oestrogen priming (by silastic implants) of the male rat hypothalamic-pituitary axis (HPA) to an oestrogen challenge test was investigated. Basal LH levels were suppressed to a maximum at two months and remained unchanged by four months. In contrast to response in human, oestrogen priming had failed to stimulate a positive feedback response to an oestrogen challenge test in the male rats. Instead, oestrogen priming might have attenuated the negative LH feedback response. Increasing the dose of oestrogen priming by increasing the duration was not effective in inducing positive feedback in the male rats. The failure of these priming regimes to stimulate positive feedback in male rats may reaffirm our earlier suggestion that oestrogen does not play an important role in activating the cyclic centre in rats. This would also contradict the suggestion that testicular secretions may have acted through conversion to oestradiol in the suppression of the cyclic system in males during the critical period of differentiation of the HPA.


Do dysplastic and adenomatous changes in large bowel hamartomas predispose to malignancy?--A report of two cases. Two patients, members of one family, with Peutz-Jeghers syndrome are described who underwent surgery for bowel obstruction. Both had multiple polyps in the gastrointestinal tract. Severe dysplasia and adenomatous change were present in two hamartomatous polyps adjacent to a stenosing colonic carcinoma in one patient and moderate dysplasia and adenomatous change were observed in two hamartomatous rectal polyps in his son. These changes support recent reports in the literature of progression towards neoplasia in these lesions.


Cytomegalovirus pneumonitis in AIDS--a case report. Respiratory infections occur commonly in patients with advanced human immunodeficiency virus (HIV) infection. Prompt accurate diagnosis is essential as many of the various available therapies have significant toxicities. We describe a patient previously diagnosed with the acquired immunodeficiency syndrome (AIDS) who was found to have cytomegalovirus (CMV) pneumonitis on bronchoscopy. His pneumonitis responded to treatment with the nucleoside analogue ganciclovir. Our patient is the first documented CMV pneumonitis in the Singapore HIV seropositive population.


Cytomegalovirus infection in renal transplant patients with hepatitis B--case report. Cytomegalovirus (CMV) infection in Hepatitis B carrier renal transplant patients who are immunosuppressed can be easily overlooked especially in those presenting with jaundice and liver failure. Recognising hepatitis due to CMV in renal transplant patients who are also hepatitis B carriers is important therapeutically as measures for the treatment and prevention of CMV infection are already available. This is especially so as Hepatitis B has a moderately high prevalence in this part of the world. We describe our clinical experience of cytomegalovirus infection in two renal transplant patients who are also asymptomatic hepatitis B carriers.


O2- scavenging activity of lignins, tannins and PSK. Iodination stimulators, such as the dehydrogenation polymer of caffeic acid (DHP-CA), a protein-bound polysaccharide (PSK), and a commercially available tannic acid, potently inhibited the luciferin-dependent chemiluminescence (LDCL) generated by opsonized zymosan-stimulated human peripheral blood polymorphonuclear cells (PMN). Continuous presence of these substances was necessary to express their inhibitory activity. The extent of inhibition paralleled their ability to scavenge the chemiluminescence generated by the xanthine-xanthine oxidase reaction. They also scavenged the chemiluminescence generated by potassium superoxide solution, but less effectively. An electron paramagnetic resonance spin-trapping technique revealed that DHP-CA significantly, but incompletely, scavenged O2-. The results suggest that O2- might be scavenged both directly by iodination stimulators, and by other oxygen radicals produced by activation of myeloperoxidase-mediated reaction.


Characterization of lactotransferrin receptor in epithelial cell lines from non-malignant human breast, benign mastopathies and breast carcinomas. The aim of this study was to investigate the presence of lactotransferrin receptor on breast non-malignant SV-40 immortalized cells (HBL100 and NB54T), benign mastopathy immortalized cells (NPM14T and NPM21T1), hst oncogene transformed HBL100 cell line (tumorigenic HH9 cells) and breast carcinoma cells (T47D, MCF7, VHB1, BT20 and MDA-MB 231). Flow cytometry analyses of the reversible binding of lactotransferrin labeled on its glycan moiety with fluorescein indicate, for the first time, that all these epithelial breast cell lines, express a specific lactotransferrin receptor. The binding parameters of [125I]-lactotransferrin to non-malignant cells, hst oncogene transformed cells and benign mastopathy cells are of the same order of magnitude as those determined for activated lymphocytes and for cancerous breast cell lines, except for MDA-MB 231 cells. MDA-MB 231 cells bind lactotransferrin with the lowest affinity and, in contrast to other analyzed breast cells, are not recognized by antibodies directed against lymphocyte lactotransferrin receptor. These results suggest that MDA-MB 231 lactotransferrin receptor is different from that characterized at the cell surface of other breast cells. In conclusion, since the lactotransferrin receptor expression was not enhanced at the surface of cancerous cell lines and was not altered by the oncogene transformation of a normal cell (HBL100) to a tumorigenic cell (HH9), the lactotransferrin receptor cannot be considered as a marker of tumor progression.


Topoisomerase II alpha and beta in human tumor cells grown in vitro and in vivo. The cellular content and the cell-cycle distribution of the 170 kD- and 180 kD-isoforms of DNA topoisomerase II were investigated in human tumor cells with specific monoclonal antibodies and by immunofluorescent detection with flow cytometry. Levels of topo II alpha were almost three-fold higher than the beta-isozyme in exponentially growing cells in vitro. In contrast, topo II alpha but not beta, was markedly reduced in plateau-phase cells. Tumor cells from surgical biopsies, mainly in G0/G1 phase, exhibited a 95% beta- versus 5% alpha-isoform expression. These results support the hypothesis that topo II alpha is mainly related to DNA synthesis, and topo II beta to DNA transcription.


Detection of single HPV copies in SiHa cells by in situ polymerase chain reaction (in situ PCR) combined with immunoperoxidase and immunogold-silver staining (IGSS) techniques. Detection of HPV by means of in situ hybridization techniques may often present problems if the number of HPV copies is too small, especially when using nonradioactive detection systems. A new way of amplifying extremely small amounts of virus DNA copies is the polymerase chain reaction (PCR), which is mostly used in vitro. In this study, we present a method for in situ PCR combined with immunogold-silver staining (IGSS) and immunoperoxidase (IMP) methods which allows the detection of single copies of HPV-DNA in SiHa cells. This method may have wide applications in routine diagnostic histopathology.


The ultrastructure of fresh and cultured cells in fifteen soft tissue and bone tumors. Cultured cells from 15 soft tissue and bone tumors and surgical specimens from 14 of these were studied by electron microscopy. The cells, cultured for one to five weeks, maintained ultrastructural features similar to those found in the fresh tumor tissue. The ultrastructural characteristics of the cultured cells were distinct enough for diagnostic purposes. Short-term cultures from all tumors were subjected to cytogenetic analysis. Clonal chromosome aberrations were found in 11 of the tumors and normal karyotypes in the remaining four. Ultrastructural analysis of cultured cells can be used for cell type identification and tumor classification.


The effect of n-6 fatty acids on normal and v-Ki ras transformed NIH-3T3 cells. The effect of exogenous gamma-linolenic acid (18:3n-6) was examined on NIH-3T3 and a subclone expressing the v-Ki-ras oncogene (DT). 18:3n-6 inhibited DT cell growth more readily than NIH-3T3 cell growth. In comparison, linoleic acid (18:2n-6) had no effect on the growth of either cell line. DT cells elongated and desaturated both 18:2n-6 and 18:3n-6 to dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) to a much greater extent than NIH-3T3 cells and had a much higher membrane fluidity. The presence of the ras gene or its product appears to increase the metabolism of polyunsaturated fatty acids and potentiate the cytostatic actions of 18:3n-6.


Influence of zearalenone on some metabolic, physiological and pathological aspects of female rabbits at two different ages. Thirty six female rabbits half of which at four months of age while the other half aged eight months. Each group of age was divided into three subgroups of an equal number and received 0.0, 0.5, and 1.0 ppm zearalenone (F-2) in the feed of young animals and 0.0, 1.0 and 4.0 ppm in the feed of the old one for 18 days. The data showed that zearalenone administration to young rabbit diets elevated body weight gain, feed intake, water consumption, digestibility and digesta contents of dry matter and ash. Haemoglobin percent, packed cell volume, and serum calcium, phosphorus and vitamin C were also increased in response to dietary F-2. Liver dry matter, ether extract and ash contents as well as bone density, ash and silica contents were considerably elevated in the young treated animals. The opposite trend however, was seen for all studied parameters of old rabbits fed on diets supplemented with F-2. On the other hand, zearalenone application caused a noticeable histopathological changes in liver, kidneys, lungs, heart, adrenal glands, spleen and uterus. Thus, and in spite of its improving the performance of young rabbits, it would not be recommended to use F-2 as anabolic agent in rabbits diet.


Effect of lignins on HIV-induced cytopathogenicity and myeloperoxidase activity in human myelogenous leukemic cell lines. We have previously reported the potent stimulation effect of lignin on the iodination of myeloperoxidase (MPO)-positive cells. We investigated here the anti-HIV (human immunodeficiency virus) activity of lignins in the MPO-positive (HL-60) and -negative (U-937) human myelogenous leukemic cell lines. Natural lignified material and dehydrogenation polymers, but not their precursors, effectively inhibited the cytopathic effect of HIV infection in both these cells as well as in MT-4 and MOLT-4 cells. HIV infection caused significant reduction of MPO activity in HL-60 cells, regardless of the presence or absence of lignins. These data suggest that MPO might not be involved in the anti-HIV activity induction by lignins.


Insertional mutagenesis in Drosophila. II. P element mediated transformation of Drosophila yakuba. Drosophila yakuba, a member of melanogaster subgroup being free of P element, acquired resistance to an antibiotic neomycin by the transformation utilizing P element. In this species, the transformation frequency was comparable to that of D. melanogaster. Further, the occurrence of 8 base pairs duplication upon the insertion of the element was confirmed. These facts suggest that the P element could be inserted into the genome in the same manner, even in D. yakuba. Any consensus for preferential insertion could not be found on the nucleotide sequence as in D. melanogaster. However, it is noticeable that a series of the short palindromic stretches was common around the insertion sites in both species. It suggests that a structural feature of DNA plays a role as a landmark for P element insertion.


Beta-adrenergic influences on doxorubicin-sensitive or -resistant P388 leukemia cells. Taking into account the possible regulatory influences of the beta-adrenergic system on lymphocyte proliferation as well as the proposed role of cyclic 3'-5'-adenosine monophosphate (cAMP) in the modulation of multidrug resistance (MDR) in tumour cells, we have tried to assess the status of the interactions between the beta-adrenergic system and a mouse lymphocytic leukemia, the P388, both as a doxorubicin-sensitive (P388) and -resistant (MDR) variant (P388/DXR). P388 showed a low total number of high affinity 125I-pindolol binding sites (340 +/- 33/cell, Kd 108 pM) when compared with normal splenocytes (1221 +/- 67 sites/cell, Kd 97 pM). The number of beta-adrenergic receptors was even lower in P388/DXR cells (230 +/- 41 sites/cell, Kd 101 pM). In addition, these receptors were subnormally expressed on the cell surface: only 26% and 52% of the total receptors were surface receptors in P388 and P388/DXR, respectively, whereas it was 87% in normal splenocytes. Isoproterenol slightly (less than 1-fold) stimulated cAMP accumulation in P388 and P388/DXR; the stimulation observed in splenocytes was 2.5-fold. In addition, the basal levels of cAMP appeared to be low (0.48 +/- 0.05 pmoles/10(6) cells in P388 and 0.71 +/- 0.08 pmoles/10(6) cells in P388/DXR; 3.47 +/- 0.28 pmoles/10(6) cells in splenocytes) in the two leukemias and they were only slightly (less than 2-fold) increased by forskolin, which otherwise stimulated about 15-fold cAMP accumulation in splenocytes; thus, P388 and P388/DXR were probably also defective in their adenylate cyclase activity. It can be concluded that, owing to multifactorial mechanisms, the lymphocytic leukemia P388, also as an MDR variant, is minimally sensitive to the direct influences of the beta-adrenergic system, probably including any effect of this system on drug-sensitivity.


Cytostatic activity of cisplatin in the presence of WR2721 and its thiol metabolite WR1065 in OVCAR-3 human ovarian cancer cells as compared to V79 fibroblasts. The effect of the modulating agent WR2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid, ethiofos) and its active thiol metabolite WR1065 on the cytostatic effect of cisplatin was investigated in a human ovarian cancer cell line OVCAR-3 and compared to that in V79 fibroblasts. WR1065 protected both OVCAR-3 and V79 cells against the cytostatic effect of cisplatin when incubated together with (co-incubation) or 15 min prior to (pre-incubation) the platinum drug. A dose-related effect up to complete protection was obtained when cells were coincubated with WR1065. Pre-incubation with WR1065 protected less and protection declined as cisplatin exposure time increased. A 60 min incubation of the cells with WR1065, starting 1 hr after a 60 min cisplatin exposure, did not protect OVCAR-3 and V79 cells from the cytostatic effect of cisplatin. The parent drug WR2721, up to a concentration of 0.01 M, did not protect OVCAR-3 and V79 cells when co-incubated with cisplatin. These results support the conclusions: a) that WR1065, and not the parent drug WR2721, is the protective species entering the cells, b) that prevention of damage is the main mechanism of protection and c) that tissues are expected to be protected by WR2721 only if WR1065 is formed and taken up by these tissues. Therefore, the preferential formation and uptake of WR1065 by non-tumour tissues is essential for a successful combination of WR2721 with platinum chemotherapy.


Replication of the pseudorabies virus in cultured pancreatic islet cells: further evidence of their paraneuronal nature. Pancreatic B cells are known to be damaged by a wide range of viruses, causing diabetes. Though these viruses belong to different taxonomic groups, their single shared characteristic is neurotropism. In the present study, pseudorabies viral infection was modelled on fetal porcine islets cultivated in vitro. It was demonstrated that the endocrine cells of the pancreas, especially B cells, were infected in vitro and so served as a medium for the replication of the virus. All stages of the morphogenesis of the virus were observed ultrastructurally within the cells. The exocrine cells located close to the endocrine ones were free from attachment and invasion of the virus. The potential of the pseudorabies virus to develop within pancreatic endocrine cells is regarded as evidence of the paraneuronal nature of these cells.


Embryonic stem cells stably transfected with mRAR beta 2-lacZ exhibit specific expression in chimeric embryos. Using the embryonic stem (ES) cell/chimera approach, we have studied the activity of the mouse retinoic acid receptor beta 2 (mRAR beta 2) promoter during ES cell differentiation and during embryonic development. Stable ES clones were isolated after introduction of a 1.8 kb mRAR beta 2-lacZ expression cassette. LacZ expression in these stable clones was specifically induced by retinoic acid (RA) in a similar fashion as the endogenous RAR beta 2 gene. Following introduction of three different ES clones into blastocysts, an integration-independent mRAR beta 2-lacZ expression pattern was obtained in chimeric embryos similar to that described by in situ hybridization and transgenic studies. Moreover, mRAR beta 2-lacZ expression was also detected at some additional sites not described before, e.g. body wall, ureter, mesonephric duct and optic stalk. Maternal RA administration at 8.5 days of pregnancy extended lacZ expression to more anterior and posterior regions. Transgenic mice were generated from germ-line transmission of the transfected ES cells; expression pattern and changes in expression upon RA induction in these transgenic embryos were identical to those in chimeric embryos. We conclude that by using the ES/chimera approach, the proximal 1.8 kb of the mRAR beta 2 promoter produces a reliable and reproducible expression pattern of the reporter gene, and that the ES cell/chimera approach is invaluable for the study of gene expression and regulation.


Elevated expression of thymidylate synthase in doxorubicin resistant human non small cell lung carcinomas. Human non-small cell lung carcinomas of previously untreated patients were analyzed for expression of thymidylate synthase (TS) using immunohistochemistry. Of the 94 tumors, 67 were positive for TS and 27 negative. A significant correlation between the expression of TS and the resistance to doxorubicin was found (p < 0.0001). Eighty-four percent of the TS-positive tumors were resistant to doxorubicin, whereas of the 27 TS-negative tumors only 44 percent were resistant. A group of patients (n = 13) were treated with combination chemotherapy including 5-fluorouracil, doxorubicin and cisplatinum. Seven of the 8 tumors which were TS-positive were clinically progressive, whereas 4 of 5 tumors which were TS-negative showed clinical remission after chemotherapy (p < 0.05; Fisher exact test). The patients whose tumors were TS negative lived significantly longer than those with TS-positive tumors. The median survival times were 185 weeks for patients with TS-negative and 41 weeks for patients with TS-positive tumors (p < 0.05; log-rank-test). Thus the expression of TS is a strong prognostic factor for resistance of tumors, clinical course and survival of patients with non-small cell lung carcinomas.


Mitochondrial DNA content and mitochondrial gene transcriptional activities in the early development of loach and goldfish. The mitochondrial DNA (mtDNA) content of the mature eggs and embryos of loach and goldfish at early developmental stages were detected by means of dot hybridization. The transcription of mitochondrial cytochrome oxidase subunit I and II (COI and COII) genes during their early development was also detected by Northern hybridization. The experimental results showed that the mtDNA content of the mature egg as well as that of the embryos during the period from fertilized egg up to hatching stage in both fishes is maintained at a constant level, giving an average value of 7.40 x 107 molecules or 1.33 ng for every embryo in loach and an average value of 1.87 x 10(8) molecules or 3.31 ng for every embryo in goldfish. In both fish embryos, the COI and COII transcripts declined gradually after fertilization until late-blastula stage and then increased in early gastrula stage. This indicated that the transcription of mitochondrial genomes of these two freshwater fishes, which belong to different families, might be activated at the beginning of gastrulation. The steady-state amounts of mitochondrial messenger transcripts existing in the embryos during the early development in both fishes seemed to be regulated by both their half-lives and the transcriptional level of the mitochondrial genomes. The results showed that the transcription of the mitochondrial genome in the early developmental process in loach and goldfish was not regulated by a gene dosage mechanism.


[The behavior of trypsin-like proteases in sulcus fluid]. The present study shows results aimed at determining whether levels of a trypsin-like protease in gingival crevicular fluid are associated with disease activity as assessed by the level of gingival inflammation and probing attachment loss. Maximum enzyme level was significantly elevated by groups with gingival inflammation and periodontal destruction. In a long-time study we find a decrease of enzyme activity with clinical therapy by scaling and root planning.


[The value of "tumor markers" in the therapy and aftercare of carcinoma of the oral mucosa]. Biochemical Markers (alpha-1-acid glycoprotein, ferritin, transferrin) and tumor associated markers (TPA, CEA, SCC-antigen) are described. Concerning the screening of oral carcinoma, the use of tumor markers is to be considered with criticism. The SCC-antigen seems to be the most useful for detection of recurrence in the follow-up. But no tumor marker can replace exact physical and ultrasound examinations.


Virus-associated demyelination in the pathogenesis of Bell's palsy. We examined the cerebrospinal fluid findings, including the activity of the myelin-associated enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), and virus serology in patients with Bell's palsy. Eighty-nine of 164 patients showed hematological and/or serological evidence of an inflammatory reaction. Examinations of the CSF disclosed an elevated total protein level and pleocytosis in 33% and 10% of the 91 patients, respectively. The activity of CNP was significantly elevated in the patient group (15.5 +/- 3.8 nmol/h/ml) as compared with the control (13.2 +/- 1.3 nmol/h/ml) (p < 0.01), suggesting the presence of intrathecal myelin breakdown. Furthermore, there was an association between antibodies against herpes simplex virus (HSV) and elevated CNP activity. The inflammatory alterations and accompanying spinal fluid abnormalities, together with the high frequency of HSV antibodies suggest that HSV-associated demyelination may play a pathogenetic role in Bell's palsy.


Aging does not alter the binding characteristics to voltage dependent calcium channels in the brain of CW1 mice. Structural age-related changes in cholinergic regions within the central nervous system of CW1 mice have been described previously. Since elevated calcium concentration has been suggested to play a role in the brain aging processes, the possible involvement of voltage dependent calcium channels in this degeneration was investigated. The binding characteristics of the calcium channel antagonist [3H](+)PN 200-110 to brains of aged CW1 mice were studied. This ligand exhibited high affinity binding (Kd values in the range of 50-70 pM) to a single type of sites with a density (Bmax) of 150-200 fmol/mg protein. No significant differences were observed between the binding parameters measured in young (3 months), mid-aged (9 and 15 months) and old (20 months) mice. Autoradiographic study confirmed these results and extended them to specific brain regions. It is concluded that age-dependent degeneration processes, observed histologically in specific brain regions of these mice, are probably not related to alterations in voltage-dependent calcium channels.


Small cell lung cancer with extensive cutaneous and gastric metastases. A case of a 60-year-old Japanese woman with small cell lung cancer involving skin and stomach is reported. She was diagnosed as primary small cell lung cancer accompanied by extensive cutaneous metastases. Three months after the last chemotherapy, she complained of nausea and vomiting. Brain CT scan showed no evidence of central nervous system involvement. Upper gastrointestinal study and upper gastrointestinal fiberscopy revealed multiple metastatic gastric tumors. Skin and stomach are uncommon metastatic sites for any malignancy. Furthermore, only a few cases with gastric metastasis could be diagnosed during their lifetime.


Regulation of the M current: transduction mechanism and role in ganglionic transmission. Slow excitatory postsynaptic potentials in sympathetic ganglia often involve suppression of a voltage-dependent potassium current termed the M current. This current is suppressed by the muscarinic action of acetylcholine, by peptides such as luteinizing hormone releasing hormone, and sometimes by alpha-adrenoceptor agonists. Activation of beta-adrenoceptors sometimes produces weak potentiation. The voltage dependence of the M current is such that its suppression increases the excitability of ganglionic neurones. Since this sometimes leads to spontaneous discharge, activation of the slow excitatory postsynaptic potential mechanism (or modulation of M current) within a sympathetic ganglion produces effects that manifest in the autonomic outflow to the target organ. In frogs, M currents are present in the neurones of both paravertebral sympathetic ganglia and cardiac parasympathetic ganglia. Since the M current is suppressed by adrenaline in the parasympathetic ganglia and these ganglia often receive adrenergic fibres from sympathetic ganglia, this might reflect an important means of interaction between the two branches of the autonomic system. At the cellular level, M-current suppression is little affected by drugs that interfere with membrane phosphorylation--dephosphorylation processes. This observation is discussed in relationship to the current understanding of the transduction mechanism for agonist-induced M-current suppression.


The integrative role of synaptic cotransmission in the bullfrog vasomotor C system: evidence for a synaptic gain hypothesis. Understanding the integrative significance of synaptic cotransmission is a central problem in autonomic physiology. What are the functional roles of slow synaptic potentials in autonomic ganglia? This paper reviews the problem and its historical roots by focusing on work in the amphibian paravertebral sympathetic system. The phenotypic properties that distinguish the sympathetic B and C cell systems are summarized. Then, a synaptic gain hypothesis is proposed for the integrative function of muscarinic and peptidergic synapses in the vasomotor C system. The model states that the peripheral output of the vasomotor system is subject to synaptic amplification by two gain stages in series. The first gain stage is postulated to arise in ganglia from interactions between two slow postsynaptic potentials; the excitatory response mediated by luteinizing hormone releasing hormone, and the inhibitory response mediated by the muscarinic action of acetylcholine. The second gain stage is postulated to arise in arteries from interactions between two postganglionic cotransmitters: epinephrine and neuropeptide Y. A circuit with these properties would enable preganglionic patterns of electrical activity to regulate the system's output over a wider dynamic range than possible without cotransmitters.


Overlapping and diverse distribution of Na-K ATPase isozymes in neurons and glia. The Na-K ATPase is the plasma membrane enzyme that catalyzes the active uptake of K+ and extrusion of Na+, thereby establishing ion concentration gradients between the inside and outside of the cell. It consumes a large fraction of the energy used in the brain. The enzyme is present in both neurons and glia. Studies of ion flux and of the properties of membrane-associated ATPase activity have suggested that there is more than one functional type of Na-K ATPase in the central nervous system. Molecular cloning has demonstrated that there are three different genes encoding catalytic (alpha) subunits and at least two genes encoding glycoprotein (beta) subunits; all are expressed in the brain. This brief review summarizes the current understanding of Na-K ATPase isozyme distribution and properties. Both neurons and glia can express different isoforms in a cell-specific manner.


Preganglionic axons from the third thoracic spinal segment fail to induce long-term potentiation in the superior cervical ganglion of the cat. A stimulus train to preganglionic axons produces long-term potentiation (LTP) of population responses of sympathetic ganglion cells evoked by the same or by other converging axons. The present study shows that preganglionic axons emerging from the spinal cord in different thoracic rami, and converging onto a common pool of ganglion cells that innervate a single target, differ in their ability to induce LTP. In anesthetized cats under partial nicotinic block with hexamethonium, the nictitating-membrane (NM) contraction evoked by stimulation of the first (T1) and third (T3) thoracic white rami (WR) was recorded. Each ramus produced a contraction of similar amplitude. In contrast, the homosynaptic potentiation produced by a 40-Hz 10-s train differed markedly. T1WR produced a potentiation of duration comparable to that produced by stimulation of the cervical sympathetic trunk, while T3WR produced either no potentiation or a potentiation of much shorter duration. The NM response evoked by T3WR, however, was potentiated by similar extent and duration as was the response evoked by T1WR when the train was applied to T1WR (heterosynaptic LTP). This suggests that the ganglionic synapses made by T3WR possess the mechanism for expressing LTP. Conversely, T3WR was ineffective at potentiating heterosynaptically the NM response evoked by T1WR. These results suggest that the ability to produce or release the LTP inducer varies markedly among sympathetic preganglionic neurons.


Cellular metabolism regulating H and M currents in bullfrog sympathetic ganglia. Much evidence has accumulated suggesting that neurons in autonomic and dorsal root ganglia possess voltage-dependent currents that link with transmitter receptors through intracellular signal transduction systems. The M current (IM), a voltage-dependent potassium current, was activated at potentials more positive than -65 mV, while the H current (IH), a voltage-dependent nonselective cationic current, was activated at potentials more negative than -50 mV. The hydrolyzable form of ATP was required to activate IM and IH. Intracellular application of calmodulin enhanced the amplitude of IM in a calcium-dependent manner. IM was reduced by W-7, a calmodulin antagonist, and by ML-9, an inhibitor of calmodulin-dependent protein kinase. IH was enhanced by intracellular loading with cyclic adenosine monophosphate (AMP) or bath application of forskolin and membrane-permeable cyclic AMP analogues. Isobutylmethylxanthine also increased the maximal conductance of IH. IH was depressed by H-8 but not by phorbol ester. It is concluded that the resting membrane conductance of these ganglion cells can be regulated by basal activities of calmodulin-dependent protein kinase and A kinase.


Separation and modulation of calcium currents in bullfrog sympathetic neurons. The calcium current of frog sympathetic neurons has relatively rapid activation kinetics (tau < 3 ms) in response to changes in voltage. Pharmacologically, the current is blocked approximately 90% of omega-conotoxin, but < 10% by dihydropyridine antagonists. This suggests that nearly all of the current is N type. However, inactivation is slow and incomplete even for depolarizations lasting > 1 s, consistent with recent evidence that N-type channels do not always inactivate rapidly. The calcium current is partially inhibited via receptors for acetylcholine, luteinizing hormone releasing hormone, substance P, ATP, and norepinephrine. These effects are mimicked by internal dialysis with GTP-gamma-S, suggesting involvement of a G protein. The transmitters affect the activation kinetics of the calcium current in a voltage-dependent manner, which can be modeled as a reversible shift of some channels to "reluctant" states in which strong depolarization is needed to produce channel opening. The effects of transmitters develop and recover with t1/2 approximately 1-2 s, so if a second messenger is involved in receptor-calcium channel coupling, it must act rapidly.