Tetralogy of Fallot with anomalous origin of left pulmonary artery. Between 1971 and 1990, 7 patients of tetralogy of Fallot with anomalous origin of left pulmonary artery underwent intracardiac repairs at Tohoku University Hospital. They were 2 males and 5 females with ages ranging from 4 to 26 years old. The right pulmonary artery connected to right ventricle in all cases, whereas no communications between right ventricle and the left pulmonary artery were found. The left pulmonary artery directly originated from the ascending aorta in 2 patients (group I) and connected to the ductus arteriosus in 5 patients (group II and III). In 2 patients (group II), the left pulmonary artery was separated from the pulmonary arterial trunk by the intraluminal membrane, receiving blood supply through the ductus. In the remaining 3 patients (group III), there were no continuations between both pulmonary arteries. At the correction, communication between the left pulmonary artery and the pulmonary arterial trunk could be reconstructed in groups I and II. However, it was not possible in group III, because the ductus arteriosus and the left pulmonary artery had already been occluded before the intracardiac repair. In group III, ventricular septal defect was closed using a one-way valved patch or a perforated patch to decrease supersystemic right ventricular pressure. Postoperative right ventricular aortic pressure ratio was between 0.5 and 0.8 in groups I and II, and between 0.8 and 1.0 in group III. Three patients (one in each group) died after the operation. Severe pulmonary vascular obstructive disease was found in the left lung of group I.(ABSTRACT TRUNCATED AT 250 WORDS)


Radioresponse and prognosis of malignant glioma. Radioresponse and prognosis of 91 malignant gliomas were studied to examine the efficacy of radiotherapy. There was no case of complete response. No statistically significant difference was observed among the prognoses of patients with various radiation methods. General survival rate was significantly higher than relapse-free survival rate both in astrocytoma grade III and in glioblastoma. This means that the retreatment after relapse is exceedingly important in any malignant glioma. In comparison with reported resection alone data, the efficiency of radiotherapy was evident in astrocytoma grade III and a part of glioblastoma; cases with minimal or no contrast enhanced area (CEA) in CT scans prior to irradiation. Poor radioresponders of glioblastoma with CEA should be reoperated.


Effect of chronic consumption of methylparathion on rat brain regional acetylcholinesterase activity and on levels of biogenic amines. Wistar rat pups (female) were exposed to methylparathion (MPTH) by gastric intubation in single doses, or in a chronic regimen of different durations. A single dose of 1 mg MPTH/kg body weight in 15-day-old pups caused a significant decrease of acetylcholinesterase (AChE) activity in cerebellum (CE), motor cortex (MC) and brain stem (BS). The effect began to appear in about 20 min after administration, the peak effect was attained in 120 min and later on this waned off completely by 24 h. The effect was similar in young (15 days) and in adult (70 days) rats. A single dose of 0.2 mg MPTH/kg in 15 day old pups caused a reduction of AChE activity only in the BS, while a 0.1 mg MPTH/kg single dose given to 15-day-old pups caused no effect even in seven regions of the brain examined. Effect of low dose chronic administration of MPTH on AChE activity was also studied in CE, MC, BS, hippocampus (HI), striatum-accumbens (SA), spinal cord (SC) and also in the hypothalamus (HY). Administration of 0.1 mg MPTH/kg from second day to 15 days of age caused significant reduction of AChE activity in only 2 of the 7 brain regions studied. Administration of double the dose (0.2 mg MPTH/kg) and for a longer duration (2nd day to 150 days of age), caused a depression in all the brain regions studied. In all these regions, the levels of NA, DA and 5HT did practically not change. The results suggest that chronic consumption of MPTH leads to a moderate decrease of AChE activity in several brain regions.


Absence of interactions on hepatic retention and 7-ethoxyresorufin-O-deethylation activity after co-administration of 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 2,4,5,2',4',5'-hexachlorobiphenyl. Interactions between 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PnCDD) and 2,4,5,2',4',5'-hexachlorobiphenyl (HxCB) on hepatic retention of PnCDD and on cytochrome P450 related enzyme activities were studied in male C57BL/6J mice. Animals received 8 nmol PnCDD/kg orally, alone or in combination with 1-416 mumol HxCB/kg. Co-administration of HxCB did not alter the hepatic retention of PnCDD or the 7-ethoxyresorufin-O-deethylation (EROD) activity induced by PnCDD as observed after 1 week. A small antagonistic effect on total cytochrome P450 content and 7-pentoxyresorufin-O-depentylation (PROD) activity was observed at a dose of 8 nmol PnCDD/kg and 1 mumol HxCB/kg. Furthermore, a significant induction of PROD activity by PnCDD was found. This was not expected, since PROD activity is considered to be a specific marker for CYP2b related enzyme activity and this type of cytochrome P450 is not induced by polychlorinated dibenzo-p-dioxins such as PnCDD. It is concluded that, under these short-term experimental conditions, no toxicokinetic basis was found to explain the antagonistic effects on hepatic cytochrome P450 related activities observed in the present study or in other studies.


Effects of 2,5-hexanedione on the ovary and fertility. An experimental study in mice. Sixty-day-old virgin female Swiss CD1 mice were treated with 1.5% 2,5-hexanedione in their drinking water; control mice received tap water; duration of treatment was either 4 or 6 weeks. Under these conditions the treated mice did not show any clinical symptoms although electromyography revealed some signs of polyneuropathy. Protein and DNA content per mg of ovarian tissue in treated mice were not significantly different from controls. Histological examination of ovarian sections at the light microscope level showed no significant alterations after exposure. A morphometric study revealed a statistically significant reduction in the number of growing oocytes after 6 weeks of treatment. For fertility studies three groups of 15 female mice each were treated for 0, 4 or 6 weeks as above and then permanently housed with untreated proven breeder male mice (one male per female); cages were checked daily for newly born mice. All litters appeared normal by gross examination. During the first 14 weeks of continuous mating the mean litter size (number of newborns per litter) remained about 11.4 in all groups; this number subsequently began to decrease. Control and 4-week treatment regression curves did not differ statistically, while the slope of the 6-week line was significantly steeper, indicating a faster decrease in litter size over time and a shortening of fertile life in the latter group of treated females.


Cadmium-induced hepatic endothelial cell injury in inbred strains of mice. Susceptibility to cadmium (Cd) hepatotoxicity differs among inbred strains of mice. For example, C3H/HeJ mice are sensitive to Cd-induced hepatotoxicity, whereas DBA/2J mice are resistant. The mechanism of genetic predisposition to Cd hepatotoxicity is unknown. A contemporary theory for acute target organ intoxication maintains that Cd initially damages vascular endothelium and parenchymal cell injury is a secondary event that results from localized ischemia. In the present study, the hypothesis that hepatic endothelial cells (EC) of C3H mice are more susceptible to Cd toxicity than those of DBA mice was tested. Hepatic parenchymal and endothelial cells were grown separately on monolayer cultures for 22 h and subsequently treated with various concentrations of Cd. Hepatocellular toxicity was assessed by lactate dehydrogenase leakage and intracellular K+ loss, whereas endothelial cell injury was assessed by trypan blue exclusion and the inhibition of protein synthesis. The susceptibility of hepatocytes to the cytotoxic effects of Cd was identical between strains. In contrast, the vulnerability of EC to Cd intoxication was strain-dependent. When exposed to 2.5-10.0 microM Cd, EC of Cd-sensitive mice were more susceptible to the cytotoxic effects of Cd than those of Cd-resistant mice. Basal metallothionein (MT) levels as well as Cd uptake into EC were similar in the two strains. Following Cd exposure, EC of Cd-sensitive mice accumulated similar amounts of MT as EC of Cd-resistant mice. These observations suggest that the microvasculature in livers of inbred mice is the target tissue responsible for strain-dependent susceptibility to Cd-induced liver injury. The mechanisms that account for this genetic variation in endothelial cell response to Cd are unknown, but do not appear to be related to the cellular disposition of Cd nor to a defect in the metabolism of MT.


Liver delta-aminolevulinate dehydratase activity in amitriptyline- or chlorpromazine-treated rats. Amitriptyline (AMT) and chlorpromazine (CPZ) (0.5 mg per animal, i.p.) were injected into rats separately for 30 days and their effects on heme metabolism in liver were examined. Significant decreases in the delta-aminolevulinate dehydratase activity were observed following the administration of both drugs (mean value of AMT-group: 6.58 U/g tissue; and CPZ-group: 7.04 U/g tissue) in comparison to that of controls (11.71 U/g tissue); however total liver heme content was not altered. When 24-h urinary excretions of delta-aminolevulinate (ALA) and porphobilinogen (PBG) were measured on the last day of the experiment, a slight (AMT-group: 38.40 micrograms/day) to distinct (CPZ-group: 59.11 micrograms/day) increase of urinary ALA was observed, while PBG excretion tended to decline only moderately under CPZ (3.52 micrograms/day), but significantly in presence of AMT (2.16 micrograms/day). Mean values obtained from control group were 32.12 micrograms/day for ALA and 4.25 micrograms/day for PBG.


The relative effects of hypoxic hypoxia and carbon monoxide on brain function in rabbits. New Zealand white rabbits were exposed to control conditions (n = 11), or to either a progressive hypoxic hypoxia produced by dilution of oxygen (O2) with nitrogen (n = 10) or a 1% carbon monoxide (CO) admixture for 15 min (n = 11). Both exposures caused a significant increase in cerebral blood flow (CBF) of up to 300% such that O2 delivery to the brain was unchanged. In the hypoxia group, a cortical somatosensory evoked response (CSER) was unaffected until the arterial O2 tension was below 20 mmHg. At this time, the rabbits became hypotensive, O2 delivery to the brain decreased dramatically and the CSER could not be elicited. In contrast, despite the maintenance of O2 delivery to the brain during and after the CO exposure, the CSER voltages were halved during the exposure and only recovered to about 80% of baseline subsequently. We conclude that the primary toxicity of CO to the brain in rabbits is not due to a reduction in O2 delivery.


Endrin-induced urinary excretion of formaldehyde, acetaldehyde, malondialdehyde and acetone in rats. Previous studies have shown that endrin induces an oxidative stress in rats as demonstrated by an increase in hepatic lipid peroxidation, a decrease in glutathione content and a decrease in the activity in selenium-dependent glutathione peroxidase. We have therefore examined the effects of orally administering 1.5, 3.0, 4.5 and 6.0 mg endrin/kg on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. The simultaneous determination of these four lipid metabolites may be a useful biomarker for assessing exposure to xenobiotics which induce an oxidative stress and enhanced lipid peroxidation. Urine samples were collected up to 72 h post-treatment. The identities of the lipid metabolites were confirmed by gas chromatography-mass spectroscopy, while the 2,4-dinitrophenylhydrazine derivatives of these metabolic products were quantitated by high pressure liquid chromatography. Maximum increases in the excretion of the four lipid metabolites occurred at approx. 24 h post-treatment at all doses with no significant increases in excretion occurring thereafter. The maximum increases in excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approx. 160%, 93%, 121% and 162%, respectively, relative to control values. Seventy-two hours after endrin administration, the liver weight/body weight and spleen weight/body weight ratios significantly increased while the thymus weight/body weight ratio markedly decreased. The results demonstrate that endrin induces dose- and time-dependent alterations in lipid metabolism with the enhanced excretion of specific metabolic products in the urine.


Effect of endosulfan (thiodan) on vitellogenesis and its modulation by different hormones in the vitellogenic catfish Clarias batrachus. This programme was planned in order to study the reproductive dysfunction caused by endosulfan in the fish Clarias batrachus with special reference to vitellogenesis. Vitellogenin was measured by radioimmunoassay. Endosulfan caused a drastic reduction in the plasma vitellogenin which was partially reversed by estradiol-17 beta (E2) in intact and ovariectomized fish. Hormones in combination were more effective than any single hormone in overcoming the impact of endosulfan. Triiodothyronine (T3), ovine luteinizing hormone releasing hormone (oLHRH) were effective in minimizing the effect of endosulfan whereas cortisol (F) and ovine somatotropic hormone (oStH) did not reduce the effect of endosulfan. Amongst the combined hormone treatments, E2 + oLHRH and E2 + T3 were the most potent in overcoming the effect of endosulfan on vitellogenesis.


A subpopulation of 12-O-tetradecanoylphorbol-13-acetate-induced papillomas is not inhibited by retinoic acid. The inhibitory effect of retinoic acid (RA) on 12-O-tetradecanoylphorbol-13-acetate- (TPA) induced mouse skin tumors was studied. Two subpopulations of tumors, small (< 2 mm) and large (> or = 2 mm) appeared after 12 weeks of cutaneous promotion by TPA (10 nmol), following initiation by application of 2 x 100 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) to the skin. RA in the doses of 17 and 34 nmol, prior to each TPA treatment inhibited (P < 0.05) the formation of small tumors at 12 weeks of promotion. However, RA in either dose did not inhibit the formation of large (> or = 2 mm) tumors. Ten weeks following withdrawal of all treatments, the number of large tumors persisted in a significantly (P < 0.05) higher number as compared to small tumors in all groups. Our results provide evidence for the existence of tumor subpopulations with a differential response to RA. In addition, elevated levels of metallothionein (MT) expression were demonstrated in papillomas induced by TPA, 72 h after the last TPA treatment. Comparing papillomas treated with RA prior to each TPA treatment and papillomas treated with TPA only, demonstrated that the elevated MT expression in papillomas was unaffected by RA. This indicated that RA did not affect the expression of a protein that showed elevated level in TPA-induced papillomas.


Characterization of the toxicity of distamycin derivatives on cancer cell lines and rat heart. The cytotoxicity and cardiotoxicity of benzoyl mustard (FCE 24517) and epoxamido (FCE 24561) synthetic derivatives of distamycin A were reported in the present study. The 50% inhibiting concentration (IC50) of colony formation of FCE 24517 on human SNB-19 glioblastoma, A2780 ovarian cancer and DU 145 prostate cancer was at least three times lower than that of FCE 24561; on the same cell lines the IC50 of DXR was up to 14 and 240 times higher than that of FCE 24561 and FCE 24517, respectively. Isolated rat hearts perfused with concentrations of both derivatives equivalent to their respective IC50 values did not show any significant change in ECG parameters, contractility and coronary flow. Compared to control hearts, FCE 24517 10(-6) M induced a significant increase in PR interval, reduction in + dF/dtmax, heart rate and coronary flow, while FCE 24561 10(-6) M produced a modest but significant increase in S alpha T segment and decrease in + dF/dtmax. Rats treated with FCE 24561 3, 6 or 12 mg/kg, intravenously (i.v.), once weekly for 3 weeks had a modest increase in S alpha T segment and QRS complex duration, while a slight alteration of S alpha T segment and QRS complex duration were observed in rats given FCE 24517 1 or 2 mg/kg i.v. once weekly for 3 weeks. No cardiac histologic alterations were found in hearts from rats receiving FCE 24517 or FCE 24561. For comparison, the cardiotoxicity of doxorubicin (DXR) was evaluated in the same experimental models; perfusion of hearts with DXR 10(-6) M induced severe alterations in all parameters of the isolated hearts; the administration of DXR 3 mg/kg i.v. once a week for 3 weeks was associated with a widening of the S alpha T segment and QRS complex and cardiac histologic picture was markedly altered. In conclusion, distamycin A derivatives display elevated cytotoxicity while no substantial cardiotoxicity was observed.


Individual serum bile acids as early indicators of carbon tetrachloride- and chloroform-induced liver injury. Individual serum bile acids (SBA) are emerging as potentially useful early indicators of liver injury. This study was undertaken to compare the usefulness of individual SBA with the routinely used assays for detecting the effects of the hepatotoxicants carbon tetrachloride (CCl4) and chloroform (CHCl3). Serum samples were assayed for liver injury by determination of alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP), bilirubin and total bile acid (by enzymatic kit). These results were compared with levels of individual SBA measured by high performance liquid chromatography (HPLC). Liver samples from CCl4-treated rats were taken for light and electron microscopic examination. The highest dose for each chemical caused increases in serum ALT and AST but not ALP. Chloroform at the highest dose increased bilirubin. Total SBA levels as assayed by the kit were elevated in response to CCl4 and CHCl3 at doses below which serum enzymes and bilirubin were increased. Some individual SBA were increased at a still lower dose for each of these two chlorinated solvents. At the lowest dose of CCl4 tested no consistent light microscopic or ultrastructural changes were found. At all the higher doses periacinar cells displayed typical accumulation of lipid droplets and degranulation and dilation of rough endoplasmic reticulum. The extent of the ultrastructural changes were dose-dependent. Thus individual SBA assayed by HPLC may be considered as a very sensitive indicator of liver injury induced by the classical hepatotoxicants carbon tetrachloride and chloroform.


Assessment of the immunotoxic potential of the fungicide dinocap in mice. The immunotoxic potential of dinocap was evaluated in female C57BL/6J mice following in vivo and in vitro exposure to this fungicide. In in vivo studies, groups of mice were dosed by gavage with technical grade dinocap at dosages ranging from 12.5 to 50 mg/kg per day for 7 or 12 days and selected immune functions examined. Mice dosed at 50 mg/kg per day dinocap died after 4 days of dosing. Twelve days of dosing with dinocap at 25 mg/kg per day resulted in decreased thymus weights and cellularity, and increased spleen weights. No changes were observed in body weight, absolute differential peripheral leukocyte counts, the lymphoproliferative responses to B- or T-cell mitogens, the mixed lymphocyte reaction, or natural killer (NK) cell activity of spleen cells from mice exposed to dinocap. Lymphoproliferative responses to concanavalin A (Con A) and phytohemagglutinin (PHA), however, were reduced in thymocytes from mice dosed at 25 mg/kg per day dinocap. The cytotoxic T lymphocyte (CTL) response to P815 mastocytoma cells was enhanced in mice exposed for 7 days to 25 mg/kg per day dinocap. Exposure of mice for 7 days to 25 mg/kg per day dinocap also caused a significant reduction in the IgM and IgG plaque-forming cell (PFC) response to sheep red blood cells (SRBC). A time-course study indicated that dinocap-induced suppression of the IgM PFC response was due to a delay in the peak PFC response to SRBC. In vitro studies using murine thymocytes cultured with dinocap (10 micrograms/ml for 72 h) resulted in suppression of the proliferative response to Con A and PHA. Exposure of thymocytes to dinocap in vitro for as little as 30 min resulted in suppression of the mitogen-stimulated response in the absence of any apparent direct cytotoxic effect. These results suggest that dinocap alters the immune system of the mouse, however, these effects are relatively modest in terms of adverse immune function and are only seen at relatively high exposure levels.


Murine strain differences in metabolism and bladder toxicity of cyclophosphamide. Cyclophosphamide (CP) undergoes metabolic activation, generating phosphoramide mustard and acrolein which are believed to be responsible for the cytostatic and toxic effects, respectively. In this study, CP-induced bladder toxicity (hemorrhagic cystitis) was found to be significantly greater in the ICR than the C57BL/6N (C-57) strain of mice. Strain differences exist in the distribution of CP metabolites to the bladder, as evidenced by consistently higher levels of acrolein equivalents measured in the urine of the sensitive ICR strain. These differences may arise from strain variation in the oxidative metabolism of CP by the mixed-function oxidase system. However, intrinsic factors within the bladder may also be involved in the resistance exhibited by C-57 mice. Support for this hypothesis is provided by the significant increase in hemorrhagic response and permeability of ICR compared to C-57 bladders exposed to equivalent levels of acrolein by intravesicle instillation. Basal protein thiol levels were higher in C-57 than in the ICR strain. However, the effects of acrolein on protein thiol content did not correlate with toxicity suggesting that these groups are not the critical targets for CP-induced bladder injury.


Silicone implants and systemic immunological disease: review of the literature and preliminary results. Silicone has been utilized as an implant in reconstructive surgery. For years, silicone has been considered to be biologically inert and essentially harmless. Several studies and case reports show that female patients treated with silicone implants developed a systemic disease associated with immunological abnormalities. Removal of the silicone implants was associated with recovery and resolution of the immune abnormalities. Recently, specific antibodies to silicone have been isolated in children with silicone implants. Additionally, immunological abnormalities and high incidence of systemic progressive sclerosis in patients with silicone implants or injections further support the notion that silicone is not biologically inert, and can cause a syndrome of a systemic disease and immunological abnormalities. The specific mechanisms and duration of the latency period is not yet fully understood.


Immune alteration associated with exposure to toxic chemicals. Immunological abnormalities including lymphocyte subset, lymphocyte immune functional assays, chemical antibodies, and different markers for autoimmune response were examined in individuals exposed to a variety of chemicals in computer manufacturing plants. A comparison of 289 individuals exposed to chemicals to 120 controls revealed that exposed individuals had a significantly higher percentage with either increased or decreased T helper/T suppressor ratios. In addition, the individuals with abnormal T4/T8 ratios demonstrated significant elevation in chemical-hapten antibodies. Therefore, 87 exposed subjects with abnormal T4/T8 ratios were selected for further evaluation by lymphocyte phenotypic expression and T cell, B cell, NK activity, and autoimmune markers, and were compared to 60 controls. The comparison of exposed individuals with controls indicated elevation of T cell (CD3), B cell (CD19), and activated T cell (CD10, CD15, CD26, CD38), suppressed T cell and B cell function decreased or increased NK cell cytotoxic activity. Autoimmunity due to chemical exposure was evidenced by elevation of TA1 phenotype frequencies and presence of rheumatoid factor, immune complexes, ANA, and anti myelin basic protein antibodies. We conclude that chemical exposure may induce immune abnormalities including immune suppression and autoimmunity.


Effects of tetrachloroethylene on hepatic and splenic lymphocytotoxic activities in rodents. The industrial solvent tetrachloroethylene (TCE) is a liver carcinogen in experimental animals but is without significant genotoxicity. Presumably some nongenotoxic mechanism accounts for its cancer-causing effects. We have therefore investigated the effects of TCE on splenic and hepatic lymphocytotoxic activities in Sprague-Dawley rats and B6C3F1 mice, following in vivo and in vitro exposure to TCE. Natural killer (NK), natural cytotoxic, and "natural P815 killer" activities were measured in liver- and spleen-derived immune cells. Humoral and T-cell mitogenesis were assayed in lipopolysaccharide and Con-A-stimulated splenic cells, respectively. TCE administration in vivo did not significantly alter the various immunological parameters assessed, while in vitro exposure to TCE inhibited natural cytotoxic activity from liver and spleen in mice and rats. NK and "natural P815 killer" activity in rat cells exposed in vitro to TCE were also inhibited. Thus, TCE is capable of directly inhibiting natural lymphocytotoxic activity, which is indicated by these in vitro effects. While an inhibitory effect was not observed when immune cells were isolated from in vivo treated animals, the in vitro data do support the possibility that a direct inhibition of natural immune function may play some role in the carcinogenic effects of TCE in experimental mice.


A study of the carcinogenicity of glycidol in Syrian hamsters. The industrial chemical glycidol is a directly acting mutagen and a broadly acting carcinogen in rats. It was administered to Syrian golden hamsters (20 male and 20 female) by gavage of 12 mg twice a week for 60 weeks. The total dose per animal was 1.45 g or 20 mmol. Survival was not different from control hamsters treated with corn oil/ethyl acetate. Of the treated males, 9 had tumors and 13 of the treated females had tumors, some of which were adrenal cortex tumors seen in controls. More tumors were seen in the glycidol-treated hamsters than in controls, but the spleen was the only notable target organ and the number of animals with spleen hemangiosarcomas was small. Glycidol appeared to be less carcinogenic in hamsters than in rats or mice.


Isolated cells in the study of the molecular mechanisms of reperfusion injury. Isolated cells make it possible to study mechanisms of cell and tissue injury under well-defined conditions, including the interaction of different cells in coculture experiments. Isolated cells, either in suspension or in monolayer cultures, have also been used to study the mechanism of reperfusion injury--in this case better termed as reoxygenation injury in view of the experimental approach taken. In hepatocytes, Kupffer, and endothelial cells, reoxygenation injury resulted in necrosis primarily mediated by reactive oxygen species released by various sources such as mitochondria (hepatocytes) and NADPH oxidase (Kupffer cells). In contrast, contracture was a characteristic feature of reoxygenation injury occurring in cardiomyocytes without loss of cytosolic enzymes. Beside reactive oxygen species, Kupffer cells were activated to release prostanoids and a decrease in endothelial cell-mediated fibrinolysis occurred upon reoxygenation. Reoxygenation injury in endothelial cells was significantly increased when neutrophils were added at the time of reoxygenation, presumably due to additional generation of reactive oxygen species and the release of proteases. As exemplified for the liver, these experiments suggest a mechanism of reperfusion injury in which the various cell types of a given tissue differ significantly in their response to hypoxia-reoxygenation but in which they interact with each other in a complex pathobiochemical network via various mediators such as cytokines, and tissue damaging effector molecules such as reactive oxygen species. Future experiments with isolated cells will allow detailed analysis of the underlying molecular mechanisms.


Does nitrogen dioxide exposure increase airways responsiveness? A number of reports have suggested that exposure to nitrogen dioxide (NO2) may cause increased airways responsiveness (AR). Twenty studies of asthmatics and five studies of healthy subjects exposed to NO2 were used to test this hypothesis using a simple method of meta-analysis. Individual data were obtained for the above studies and the direction of change in AR was determined for each subject. Only studies with available individual data were used. Subjects from these studies whose directional change in AR could not be determined were excluded. The fraction of positive responses (i.e. increased AR) was determined for all subjects within a group and tested for significance using a sign test. Data were also grouped according to NO2 concentration and by whether the exposure included exercise. There was an overall trend among asthmatics for AR to increase (60%) but this was primarily due to increased AR seen in resting exposures (70%). Among healthy subjects AR also increased with NO2 exposure but only at concentrations above 1.0 ppm. This analysis suggests that NO2 exposure causes increased airway responsiveness in healthy and asthmatic subjects but that exercise during exposure may modify this response in asthmatics.


Comparison of open and blind histopathologic evaluation of hepatic lesions. This paper explores the controversy among scientists on whether microscopic evaluation of tissue slides should be done in an open or blind fashion. Definitions are given and discussed that provide a better focus to the problem. An experiment was conducted in which hepatocellular degeneration and necrosis in rats were assessed both openly and blindly. The results indicate that 'simple bias' is present when the slides are read openly. Valid comparisons among treatment groups are possible in the presence of simple bias, provided appropriate control groups have been incorporated into the experimental design.


The effect of duration of exposure on sulfuric acid-induced pulmonary function changes in asthmatic adolescent subjects: a dose-response study. To evaluate the pulmonary effects of varying doses of sulfuric acid, adolescent subjects with asthma were exposed to 35 or 70 micrograms/m3 sulfuric acid for 45 or 90 min. Exposure was carried out during intermittent moderate exercise. The pulmonary functions measured before and after exposure were FEV1, FVC, and total respiratory resistance. The 45 min exposures were associated with larger decreases in FEV1 (-6% or -3%) than the 90 min exposures (-1% or +2%). Analysis of variance of the change in FEV1 among the exposures revealed that the 45 min exposure to 35 micrograms/m3 was significant (p = 0.03). The p value for 45 min exposure to 70 micrograms/m3 was not significant (p = 0.08). Using analysis of variance, neither of the 90 min exposures was associated with a significant decrease in FEV1 compared to air exposure. Also, none of the changes in FVC or RT was significant. When baseline to post-exposure changes were compared for each of the five test atmospheres using paired t tests, both of the 45 min exposures were associated with statistical significance (p < 0.001 for 35 micrograms/m3 and p < 0.005 for 70 micrograms/m3). This baseline to post exposure change was not statistically significant for the 90 min exposures. The reason for the lesser effect on pulmonary function at increased exposure duration is not known; it may be due to changes in either varying deposition patterns or changes in buffering capacity of the cells lining the airways. With respect to individual sensitivities to H2SO4, the data showed a significant consistency across test atmospheres.


Zinc and copper in tissues of rats with blood hypertension induced by long-term lead exposure. Male Sprague-Dawley rats received for 14 months 0, 15, 30 and 60 micrograms/ml of lead in drinking water. Both blood pressure and tissue lead were augmented with a dose-response effect, while cardiac inotropism was increased only in the rats treated with 60 ppm of lead. In the exposed animals, zinc and copper were unchanged in kidneys and testicles and augmented in the brain, while copper, but not zinc, was reduced in the heart. These data suggest a possible relation between the modifications of copper and zinc metabolism and the effects of lead on cardiovascular homeostasis.


Human exposure assessment. I: Understanding the uncertainties. Exposure estimates produced using predictive exposure assessment methods are associated with a number of uncertainties that relate to the inherent variability of the values for a given input parameter (e.g., body weight, ingestion rate, inhalation rate) and to unknowns concerning the representativeness of the assumptions and methods used. Despite recent or ongoing consensus-building efforts that have made significant strides forward in promoting consistency in methodologies and parameter default values, the potential variability in the output exposure estimates has not been adequately addressed from a quantitative aspect. This is exemplified by remaining tendencies within federal and state agencies to use worst-case approaches for exposure assessment. In this study, range-sensitivity and Monte Carlo analyses were performed on several different exposure scenarios in order to illustrate the impact of the variability in input parameters on the total variability of the exposure output. The results of this study indicate that the variability associated with the example scenarios range up to more than four orders of magnitude when just some of the parameters are allowed to vary. Comparison of exposure estimates obtained using Monte Carlo simulations (in which selected parameters were allowed to vary over their observed ranges) to exposure estimates obtained using standard parameter default assumptions demonstrate that a default value approach can produce an exposure estimate that exceeds the 95th percentile exposure in an exposed population.


Human exposure assessment. II: Quantifying and reducing the uncertainties. Alternative methods of human exposure assessment that reduce and/or allow quantification of the uncertainties associated with exposure estimates are surveyed and illustrated. These alternative approaches include (1) use of more appropriate exposure parameter default values rather than values that result in extreme exposure estimates; (2) incorporation of time-activity data to better define appropriate exposure duration values; (3) the use of reasonable exposure scenarios rather than the traditional Maximally Exposed Individual (MEI) approach; (4) the use of stochastic approaches such as Monte Carlo-based and information analysis-based methods; (5) use of bivariate analysis to identify the extent to which interdependencies between different exposure parameters affect the distribution of exposure estimates; (6) use of less-than-lifetime exposure and risk assessment; and (7) incorporation of physiological considerations relevant to absorbed dose estimation, including route-specific impacts, use of improved absorption factors, and application of pharmacokinetic models. Other ways to improve the exposure assessment process, including assuring statistical equivalency in comparing different exposure estimates and incorporation of sensitive subpopulation considerations are also discussed, as are key research needs.


Teratological assessment of glutaraldehyde in rats by gastric intubation. Pregnant rats were given glutaraldehyde (GA) by gastric intubation at a dose of 0, 25, 50 or 100 mg/kg on days 6-15 of pregnancy. Maternal toxicity occurred in the 100 mg/kg group as evidenced by a significant increase in maternal death and a significant decrease in maternal body weight gain and food consumption. A significantly lowered fetal weight was also found in the 100 mg/kg group. No significant change induced by GA was detected in the incidence of postimplantation loss. Morphologic examinations of fetuses revealed no evidence of teratogenicity of GA. It could be concluded that GA has no teratogenic effects on rat offspring even at a dose which induced severe maternal toxicity.


Protection of B cells against the effect of alloxan. Alloxan induces diabetes in laboratory animals through the destruction of the endocrine pancreatic B cells. The mechanism of alloxan toxicity is still obscure. This study was conducted to investigate the effects of superoxide dismutase (SOD) or reduced nicotinamide adenine dinucleotide (NADPH) treatment on the B cells in isolated rat islets prior to alloxan treatment. Islets were treated with SOD (1000 U) or 0.1 mM NADPH for 10 min followed by alloxan treatment (0.18 mg) for 5 min. Insulin secretion was studied in samples incubated for 60 min in media supplemented with glucose (1.8 mg/ml). Morphological examinations were conducted on fixed samples after the alloxan treatment. SOD significantly protected the islets from the cytotoxic effect of alloxan. Although alloxan decreased insulin secretion to 35% of the control, SOD increased this level to 73% of the control values. NADPH did not provide any protection to the islets. Insulin secretion from islets treated with NADPH and alloxan was not different from that after alloxan treatment alone. Morphological changes were observed in the islets treated with alloxan alone or alloxan in the presence of NADPH. Islets exhibited multiple cellular necrosis, marked degranulation and extensive vesiculation of the endoplasmic reticulum and Golgi complex. Mitochondrial enlargement with disrupted cristae and mitochondrial ruptures were prominent. However, islets treated with SOD and alloxan were similar to the control except for the enlarged mitochondria. The increased insulin secretion from islets treated with SOD and alloxan reinforces the free radical hypothesis of alloxan toxicity. The markedly enlarged mitochondria was one of the targets through which alloxan destroyed the B cells.


Ganglioside GM1 counteracts the enhancing effects of subacute toluene exposure on apomorphine-induced locomotor activity. Previous studies indicate that subacute toluene exposure enhances the effects of postsynaptic doses of apomorphine on locomotor activity in the rat. We have now studied the effects of the ganglioside GM1 on toluene-affected apomorphine-induced (1 mg/kg, s.c.) locomotion, motility, and rearing. Treatment with GM1 (10 mg/kg, i.p., 1 h before exposure) was found to counteract or even reverse the enhancing effect of toluene on apomorphine-induced locomotion and rearing, but had similarly to toluene no significant effects on apomorphine-induced motility or on spontaneous locomotor activity. The antagonistic effects of GM1 may be due to its ability to block toluene-induced changes in D2 receptor binding.


In vitro cytotoxicity of methylated phenylenediamines. The acute cytotoxicities of methylated phenylenediamines (PDs) were evaluated with the neutral red assay, using BALB/c 3T3 mouse fibroblasts as the bioindicators. When the test agents were grouped according to their degree of methylation, good correlations were noted between their in vitro cytotoxicity and their in vivo myotoxicity to experimental animals, as well as to their in vitro autoxidation rates. For test agents of comparable methylation, the sequence of potency was ring-methylated p-PD > N-methylated p-PD >> N-methylated o-PD > N-methylated m-PD.


Liver thymidine kinase activity after cadmium-induced hepatotoxicity in rats. Intraperitoneal (i.p.) administration of a cadmium (Cd) salt at concentrations of 1.0, 2.5 and 4.0 mg CdCl2/kg body wt. caused severe liver injury in rats 24 h after administration. The toxic effects were most evident in the intermediate dose of 2.5 mg. Thymidine kinase (TK), the key enzyme of the salvage pathway of DNA biosynthesis, was affected in all Cd-treated groups. TK activity presented lower values at the highest Cd-induced hepatotoxicity.


In vivo-in vitro replicative DNA synthesis (RDS) test using perfused rat livers as an early prediction assay for nongenotoxic hepatocarcinogens: I. Establishment of a standard protocol. To establish a standard protocol for an in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test using male F344 rats for screening nongenotoxic (the Ames-negative) hepatocarcinogens, experimental conditions were examined. After treatment with three model hepatocarcinogens, isolated hepatocytes showed highest RDS incidences when plated at a density of 5 x 10(4) cells/ml. Spontaneous RDS incidences in hepatocytes from rats aged 9 weeks or older showed a constant value. The use of hepatocytes from 9-week-old rats at the 5 x 10(4) cells/ml plating density was therefore determined as the standard. Based on the distribution of mean spontaneous RDS incidences over 105 additional experiments (0.4 +/- 0.18%, with SEM), an RDS incidence of over 1% was adopted as the criterion for a positive response in our rat liver RDS test.


In vivo-in vitro replicative DNA synthesis (RDS) test using perfused rat livers as an early prediction assay for nongenotoxic hepatocarcinogens: II. Assessment of judgement criteria. To better establish in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test using male F344 rats as a screening assay for nongenotoxic (the Ames-negative) hepatocarcinogens, judgement criteria were assessed after single-gavage treatment with seven model compounds. The profiles of RDS induction by the compounds were analysed in terms of both time-course and dose-dependence. Our data reveal that a value of 2% or more for RDS incidence should be judged as positive and that of less than 1% RDS incidence as negative using maximum tolerance dose (MTD) concentrations in time-course experiments at 15, 24, 39, 48 and 63 h. In the case of an incidence value between 1 and 2%, the finding of a clear dose-dependence was considered to justify the conclusion of a positive effect for 1/4 MTD, 1/2 MTD, MTD and 2 x MTD at a fixed time. The established judgement criteria are planned for introduction in detection of nongenotoxic hepatocarcinogens (the Ames-negative carcinogens) using the RDS test.


DNA damaging activity of cadmium in Leydig cells, a target cell population for cadmium carcinogenesis in the rat testis. To clarify the mechanism by which Cd initiates rat testicular cancer, the ability of Cd or H2O2 to induce DNA single strand breakage was evaluated in testicular Leydig cells using a simple and rapid DNA precipitation method. Effects of Cd, Fe, Zn and Ca on the oxidant-induced DNA damage and effects of reduced glutathione (GSH) on the genotoxicity caused by the peroxide and/or Fe were also assessed. H2O2 induced strong DNA single strand breakage. Cd alone did not exhibit such a genotoxicity nor did it enhance the peroxide-induced DNA damage. Ca and Fe(II) potentiated the oxidant-induced DNA single strand breakage, while Zn partially protected cells from the oxidative damage of DNA caused by the peroxide. GSH attenuated single strand breaks of DNA brought about by H2O2 and/or Fe. These results suggest that the initiation of carcinogenesis in the rat testis by Cd is triggered by active oxygen species such as H2O2, which is generated by the metal exposure, rather than by a direct genotoxicity of Cd. The oxidant-mediated initiation is clearly a complicated event accomplished by multiple factors.


Aromatase and testosterone fatty acid esters: the search for a cryptic biosynthetic pathway to estradiol esters. The estradiol fatty acid esters (lipoidal derivatives, LE2) are extremely potent estrogens that accumulate in fat, including fat of menopausal women. These steroidal esters are protected from metabolism and are converted to the free, biologically active steroid through the action of esterases. Previous studies have shown that biosynthetic pathways in the adrenal gland exist in which steroid fatty acid esters are substrates. This led us to determine whether a cryptic aromatase pathway exists in which testosterone esters could be converted directly into LE2. We tested a representative fatty acid ester, testosterone stearate, both as an inhibitor and as a substrate for the aromatase enzyme from human placental microsomes. This ester had neither activity. In addition, we tested [1 beta-3H]testosterone acetate as a substrate for this enzyme complex, measuring the production of 3H2O as evidence of aromatization. Although the rate of reaction was considerably slower than that of testosterone, 3H2O was produced. However, when [2, 4, 6, 7-3H]testosterone acetate was incubated and the steroidal products isolated, we found that hydrolysis of the substrate had occurred. Both [3H]-labeled testosterone and estradiol were found, and very little if any [3H]estradiol acetate was formed. Thus, we conclude that an aromatase pathway involving testosterone esters does not exist and that the sole source of LE2 is through direct esterification of estradiol.


Chromatographic and mass spectrometric characteristics of 20-dihydroaldosterone. The 20 alpha-reduced derivative of aldosterone, 20 alpha-dihydroaldosterone, was needed as reference compound in order to continue the studies on 18-hydroxylation in the Y-1 adrenal cell line. It was obtained by reduction of aldosterone with sodium borohydride. Analysis of the products of the reaction as methoxime trimethylsilyl (MO-TMS) derivatives by gas chromatography (GC) and GC-mass spectrometry (GC-MS) showed three possible forms of the compound. Their identification was confirmed by comparison with the products obtained by stereospecific reduction of aldosterone using 3 alpha,20 beta-hydroxysteroid dehydrogenase. Chromatographic behavior and mass spectra are given for the three forms of 20 alpha-dihydroaldosterone as the MO-TMS derivatives; that is, the 18-aldehyde, the 18,11 beta-hemiacetal, and the 11 beta:18,18:20 alpha-acetal. The possible origin of these different forms is discussed as a function of these results and of the results obtained by complementary analysis on high-performance liquid chromatography.


Production and specificity of antisera raised against 25-hydroxyvitamin D3-[C-3]-bovine serum albumin conjugates. In order to obtain specific antisera for use in the enzyme immunoassay of 25-hydroxyvitamin D3, three hapten-carrier conjugates having different lengths of bridges at the C-3 position were prepared from 25-hydroxyvitamin D3 by coupling with bovine serum albumin using the active ester method. The specificity of anti-25-hydroxyvitamin D3 antisera elicited in rabbits was tested by a cross-reaction study with closely related secosterols and by measuring the plasma levels of 25-hydroxyvitamin D3 by means of radioimmunoassay using tritium-labeled antigen. The results indicated that the specificity of the antisera obtained is higher than that of vitamin D-binding protein, and that some of these antisera are suitable for enzyme immunoassay.


Effects of carbenoxolone administered acutely to adrenalectomized rats (in vivo) on renal and hepatic handling of corticosterone by 11 beta-hydroxysteroid dehydrogenase. The in vivo effect(s) of carbenoxolone (CS) on renal 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), hepatic 11 beta-OHSD, and 5 beta-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11 beta-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11 beta-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11 beta-OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11 beta-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 microM and 50 microM corticosterone, as was 5 beta-reductase (P < 0.05) using 4 microM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11 beta-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11 beta-OHSD and 5 beta-reductase with no inhibition of renal 11 beta-OHSD.(ABSTRACT TRUNCATED AT 250 WORDS)


X-ray structure analysis of 3,11,17-trioxoandrostane-5 alpha-carbonitrile and of 17 alpha-ethoxycarbonyloxy-3-oxoandrost-4-ene-17-carbonitrile. The crystal and molecular structures of the title compounds were determined by x-ray diffractometric analysis. Torsion angles and puckering parameters are reported for both compounds. In 1 the 5 alpha-cyano group influences the A-ring conformation. The carbonate ester 3 crystallizes in the monoclinic P2(1) space group with two molecules (I and II) in the asymmetric unit. The D-ring conformation is to some extent different between I and II.


Estrogen metabolism, not biosynthesis, in rabbit articular cartilage and isolated chondrocytes: a preliminary study. Because serum estrogen levels are associated with the presence of osteoarthritis, and cartilage tissue is known to contain estrogen receptors, it is of interest to determine the extent to which estrogen is biosynthesized and/or metabolized in cartilage tissue or isolated chondrocytes. In this preliminary study, using a sensitive assay method, estrogen synthetase (aromatase) was undetectable in articular cartilage or isolated chondrocytes in culture from immature female rabbits. However, estrogen metabolism, specifically estrogen 17 beta-hydroxysteroid dehydrogenase activity, was detected in homogenized cartilage tissue, and at substantially higher specific activities in freshly isolated chondrocytes. These fresh chondrocytes, assayed in culture without any exogenous cofactor, demonstrated a significantly higher activity for converting the weak estrogen, estrone, to the more potent estrogen, estradiol. Chondrocytes grown to confluence in culture had very low estrogen 17 beta-hydroxysteroid dehydrogenase specific activity. Homogenized cartilage tissue, tested only with added NADPH as cofactor, also showed a preference for estradiol as the principal product, but this may have been primarily due to the use of reduced cofactor. If subsequent experiments confirm the presence of estrogen 17 beta-hydroxysteroid dehydrogenase activity, and its preference for converting estrone into estradiol, in human cartilage tissue and chondrocytes, this could have substantial implications in the estrogen dependency of osteoarthritis.


Convenient synthesis of 18-hydroxylated cortisol and prednisolone. 18,20-Epoxy-11 beta,17 alpha,20 beta,21-tetrahydroxypregn-4-en-3-one was synthesized by the application of hypoiodite reaction to the cortisol acetonide. The intermediary 18-iodo derivative was converted to the 11-oxo steroid by chromic acid prior to silver ion-assisted solvolysis. Removal of the protective group with hydrochloric acid was finally carried out to give the desired 11 beta,17 alpha,18,21-tetrahydroxypregn-4-ene-3,20-dione as the hemiacetal form. 18,20-Epoxy-11 beta-17 alpha,20 beta,21- tetrahydroxypregna-1,4-dien-3-one was also prepared from prednisolone through a similar reaction sequence.


Administration of pregnenolone and dehydroepiandrosterone to guinea pigs and rats causes the accumulation of fatty acid esters of pregnenolone and dehydroepiandrosterone in plasma lipoproteins. Steroids were administered continuously to guinea pigs and rats using subcutaneously applied silastic tubing implants, and the effects on circulating steroid and steroid conjugate levels were monitored. Using implants filled with pregnenolone, we observed that pregnenolone had a marked effect on increasing the levels of its fatty acid-esterified derivative, while dehydroepiandrosterone-releasing implants produced a rise in circulating nonconjugated dehydroepiandrosterone, androst-5-ene-3 beta,17 beta-diol, androstenedione, testosterone, and lipoidal derivatives of both dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol. Implants filled with androstenedione produced a 20-fold increase in plasma androstenedione levels relative to untreated controls and a corresponding five-fold increase over control testosterone levels. No fatty acid-esterified derivative of testosterone could be detected within the plasma. Lipoproteins were isolated from both rats and guinea pigs treated with implants filled with pregnenolone or dehydroepiandrosterone. The steroid and steroid fatty acid esters present in each fraction were analyzed, revealing that approximately 75% of all the fatty acid esters of pregnenolone recovered in the lipoproteins was localized within the high-density lipoprotein (HDL) fraction of both guinea pig and rat plasma. Similarly, lipoidal dehydroepiandrosterone was found associated predominantly with the low-density lipoprotein and HDL fractions in the guinea pig, while in the rat this steroid conjugate was exclusively within the HDL fraction. High-density lipoprotein-incorporated tritiated pregnenolone fatty acid esters and dehydroepiandrosterone fatty acid esters were injected into castrated male guinea pigs to study the fate of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS)


Studies on anabolic steroids. 10. Synthesis and identification of acidic urinary metabolites of oxymetholone in a human. Two major unconjugated acidic metabolites of oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one, 1), namely, 17 beta-hydroxy-17 alpha-methyl-2,3-seco-5 alpha-androstane-2,3-dioic acid (2) and 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 beta-carboxylic acid (6a), were detected by gas chromatography/mass spectrometry in urine samples collected after oral administration of 1 to a human volunteer. Reference steroid 2 was synthesized and identified. The identification of urinary metabolite 6a was based on the synthesis of its stereoisomers and the isomerization of the methyl ester 6b to its 2-epimer, 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 alpha-carboxylic acid methyl ester (9b). The mechanisms accounting for the formation of these acidic metabolites are discussed.


Antihormonal properties of some new A-homo-B, 19-dinor steroids of the androstane series. On solvolysis of Westphalen-type steroids with a leaving group in the position 6 beta (e.g., 2), products of elimination (followed by rearrangement and fragmentation of the steroid skeleton) were prepared (e.g., 4 and 5). These products were subsequently converted to suitable analogs of the compound, which has been reported to promote hair growth (1). Compounds 11 to 13 exhibited strong antiandrogenic activity in vivo; however, this activity could not be interpreted either in terms of inhibition of 5 alpha-reductase or by strong binding to an androgen receptor.


[The significance of developmental anomalies of the thyroid cartilage for the practice of forensic medical expertise]. The authors discuss developmental abnormalities of the thyroid cartilage and its injuries in blunt injuries of the neck. Basing on two cases, they describe developmental abnormalities (no joining between the superior horn and the lamina or complete absence of one of the superior horns) that during autopsies were considered, to be resultant from injuries.


[A schematic representation of the thoracic skeleton for the analysis of multiple fractures]. A scheme of the thoracic skeleton (a superior projection) is suggested for practical forensic medical evaluation. The scheme presents concentrically arranged costal arches connected to the image of the breast bone and the thoracic portion of the spine, with the ordinal numbers of the ribs, vertebrae, and anatomic lines. Special marks indicate rib fractures and other associated signs (repeated injuries, bleedings, whether the injury was inflicted in life or was postmortem, etc.). After the scheme is filled in, one may analyze a three-dimensional image of the injuries to determine the site and direction of an external exposure and its order.


[The forensic medical determination of the time of occurrence of subdural hemorrhages in the acute period of fatal craniocerebral trauma]. Presents the results of spectrophotometric and histologic examinations of subdural bleedings, meninges and brain matter in the acute period of a lethal craniocerebral injury. Discusses the possible use of a complex of histologic and biochemical studies in determination of the period elapsed since the injury.


[The diagnosis of pulmonary tuberculosis in the forensic medical study of cadavers]. Presents analysis of cases when pulmonary tuberculosis was diagnosed during autopsy by forensic medical experts. Before death the patients were not registered at tuberculosis control centres and were administered no treatment for tuberculosis.


[The chemical action of gun powder gases on biological tissues in a point-blank shot]. Chemical effect of gun powder gas on the biologic tissues manifests by red-brown staining of the tissues, mainly at the expense of methemoglobin and sulfhemoglobin. Scarlet staining of the tissues at the edges of gun-shot wounds is not a specific marker of a shot made from a short distance; it may emerge several hours after wounding at the expense of hydroxy-hemoglobin and is not at all related to the chemical effect of gun powder gas. The conditions conducive to scarlet staining are an open wound permitting free oxygenation by air oxygen and hemoglobin transfer from the injured red cells into blood plasma and adjacent tissues.


[The supplementary signs of strangulation asphyxia]. Analyzes the results of forensic medical examinations of the corpses after hanging. The findings were as follows: two strangulation grooves are seen on the corpse's neck after hanging, that are similar to the grooves seen after strangulation with a loop and subsequent hanging of a corpse; the presence of bruises on the neck, along with the strangulation grooves, is indicative of a strangulation made by the hands, whereas half-moon shaped bruises may be self-inflicted during hanging.


[The use of high-pressure liquid chromatography for identifying barbiturates in cadaveric material]. A method for chemical toxic analysis of barbiturates has been developed, making use of acetone as an extracting agent and high-pressure liquid chromatography for the identification of the isolated substances. Analysis with the use of this method is preceded by extraction and chromatographic purification. The co-extractive substances do not interfere with the identification of barbiturates.


[A clinico-morphological analysis of the traumatic substrates to cerebral injuries in different inertial loads on the brain]. The relationships between the inert tension of the head and the morphologic substrates of brain injuries were under study. A comparative clinical and morphologic analysis of lethal contusion and axonal injuries underlie this investigation. Differences in the neurologic semeiotics and CT data in such injuries are presented. The authors discuss the mechanisms of the physical processes in the skull, resulting in focal and diffuse injuries of the brain. Quantitative assessment of the traumatic cerebral substrates is given and relations of these parameters to the conditions of the head trauma (the direction of the external injurious factor action) and the clinical picture are shown. The results of this study may be useful in establishing some circumstances of craniocerebral injuries.


[The extraction of deoxypeganin from aqueous solutions with organic solvents]. Studies of deoxypeganin extraction with various organic solvents have shown that up to 88% of the agent can be easily extracted by chloroform if the medium pH values are 11-12. The presence of electrolytes in deoxypeganin aqueous solutions does not influence the degree of the agent extraction with organic solvents.


[Mandibular sandwich technique build up with lyophilized cartilage]. High resorption rates of onlay bone grafts for augmentation of the atrophic mandible led to the invention of the sandwich technique. In Zurich the first sandwich augmentation procedure with homologous lyophilized cartilage was performed in 1982. 50% of our examined patients were operated on 5 to 8 years ago. We describe the longterm results concerning resorption (23.8% after 4.65 years) and the even integration of the lyophilized cartilage with radiologic evidence of calcification and bony incorporation, even in patients with preoperative severely compromised tissues, as in cases after osteomyelitis or radiotherapy.


[Pathological changes in face and skull in acromegaly]. 31 patients (mean age 52.7 years) suffering from persistent symptoms of a growth hormone producing pituitary adenoma underwent both clinical and roentgenological examinations. The results of standardized x-ray analysis of the viscero- and neurocranium were compared with those of a group of 25 healthy subjects (mean age 42.1 years): Although several remarkable changes were observed, statistically significant changes of the facial skeleton could be found only in the lower jaw. The main contribution to its elongation was given by the chin prominence and the condyle. The findings in the neurocranium could be divided in symptoms of first and symptoms of second choice. With the help of these parameters, a score was established to facilitate interpretation of early signs of acromegaly in lateral skull radiographs. Two clinical symptoms found in our patient sample have not been mentioned before in literature about acromegaly: the so-called "hanging columella" and marked changes in diameter of the canalis mandibularis.


[Phase-contrast and polarization microscopic studies of the myocardium in forensic medical practice]. Describes the major acute pathologic changes in the myocardiocytes detectable by phase-contrast and polarization microscopy. Demonstrates the significance of these changes for a correct diagnosis of sudden coronary death, death from ethanol poisoning or closed injuries of the heart after blunt trauma of the chest.


[Vestibuloplasty with Kirschner wire fixation]. We present a new method of fixation for creation of the vestibular sulcus in cases of open or closed submucous vestibuloplasty. Kirschner-wires (diameter 0.5 mm) are drilled through the mucous membrane into the bone. The wires keep the hand cut oval elastic sheets in place to adapt the mucous membrane to the periosteum at the deepest point of the vestibule respectively. Advantages of the method in comparison to other fixation techniques are discussed.


[Psychology and recurrence tendency in relation to age at operation for prognathism]. Within this study patients with mandibular prognathism were studied as to their psychological situation pre- and postoperatively with the help of the Freiburg Personality Evaluation Sheet. Since it was our special interest, whether psychologically it makes a big difference whether the patients were operated during the time of adolescence or after the age of twenty, the postoperative investigation was carried out with special reference to this point. Without any doubt, the correction of prognathism improved the psychological situation of the patients. It was obvious that for those patients in between fourteen and seventeen the improvement was more helpful than for those patients after the age of twenty. On the other hand the rate of recurrence was much higher within the group of those patients operated in between fourteen and seventeen (29.8%) than for those patients which were operated later than at age twenty (8%). The ideal age for the correction of mandibular prognathism must be found individually. While the operation at an early time is more helpful for the psychological situation of the patients, it must on the other hand be seen that for this age-group the danger of recurrence is higher.


Barriers to perioperative patient teaching in Kuwait. 1. Although nurses agree that perioperative instruction is an integral aspect of surgical nursing, in many hospitals, there is little evidence to show that active and planned patient teaching is being conducted. 2. Arab and non-Arab nurses differed in their perceptions about obstacles to patient teaching. Lack of time and language barriers emerged as the two outstanding barriers; lack of encouragement and support from co-nurses and patients' anxiety were considered weak barriers. 3. Failing to address these barriers and disregarding the short- and long-term benefits of structured patient teaching could lead to a new health worker, the health educator. This would further fragment patient care and weaken nurses' credibility.


Death with dignity: significance of religious beliefs and practices in Hinduism, Buddhism, and Islam. 1. Nurses can help individuals more readily deal with death and dying by examining cultural variations in death reactions and rituals. This helps to humanize care. 2. Caring for a dying client is a complex and challenging responsibility and requires physical, emotional, and spiritual support to ensure a peaceful and dignified death. 3. Clients turn to religion for peace and comfort during times of crisis, such as serious illness and impending death. It is necessary to understand the impact of religious beliefs and practices to provide quality holistic care.


The element of care in the operating room. 1. Perioperative nurses are experts in attending to imminent physiological needs of patients. However, when these needs seem paramount, focus on a patient's feelings often become a lower priority. 2. Being cared for is a basic human need. Just as perceptions of needs vary among individuals, so do caring needs. It is essential that nurses value the components of caring and demonstrate caring from a holistic perspective. 3. OR nurses can communicate caring by identifying staff to patients, providing reassuring information, monitoring self-talk, touching the patient, and responding to the patient as an individual.


Laser disc decompression.

Laser disc decompression. 1. The incidence of low back pain is a growing force in today's economy. 2. Laser disc decompression (LDD) is an effective alternative for lumbar laminectomy in those patients meeting the approved criteria. 3. LDD can be done on a same day surgery basis without the ill effects of a general anesthetic.


Write now: a guide to publishing.

Write now: a guide to publishing. 1. With the elimination of time constraints, fear of rejection, and lack of understanding of the publication process, effective communication and sharing of experiences and expertise among nurses can be enhanced through writing for publication. 2. Important author responsibilities, such as being aware of the number of manuscript copies to be sent with the original, typing and reference format of the journal, letters of transmittal, and acknowledgements, can be found in the journal's guidelines. 3. Understanding the publication process and learning how to use the components can lead to positive results for prospective authors.


Triggering signaling cascades by receptor tyrosine kinases. Growth factor receptors that are tyrosine kinases (RTKs) regulate growth and differentiation of cells in many organisms, including flies, worms, frogs, mice and humans. There has been recent progress in understanding the mechanism by which these receptors transduce signals. Worm and insect studies on RTKs have relied primarily on genetics, while the mammalian studies have employed a combination of molecular genetics and biochemistry. While many RTKs seem to have unique features, there are also many general signal transduction principles that emerge from these studies. In this review, we will focus on common signaling molecules, using RTKs from both vertebrates and invertebrates as examples.


Common subunits of cytokine receptors and the functional redundancy of cytokines. Several distinct cytokines often exhibit similar biological activities. The findings that high-affinity receptors for a group of cytokines with similar function share a common subunit with a critical role in signal transduction have provided a molecular basis for the functional redundancy of cytokines. Since the common subunit, together with distinct cytokine-specific receptor subunits, form high-affinity receptors, binding of one cytokine to its high-affinity receptor can be competed for by other cytokines in the same group.


G proteins.

G proteins. The family of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) serves an essential role in transducing receptor-generated signals across the plasma membrane. Recent findings reveal unexpected functional roles for individual G protein subunits. Thus, GTP-binding alpha-subunits and the beta gamma-subunit complex can influence the activity of effector molecules independently or simultaneously, either synergistically or in opposition, to elicit a complex constellation of cellular events.


Signal transduction crosstalk in the endocrine system: pancreatic beta-cells and the glucose competence concept. Crosstalk between intracellular signalling systems is recognized as the principal means by which a cell orchestrates coordinate responses to stimulation by neurotransmitters, hormones or growth factors. The functional consequences of crosstalk are evident at multiple levels within a given signalling cascade, including the regulation of receptor-ligand interactions, guanine nucleotide-binding proteins, enzyme activities, ion channel function and gene expression. Here we focus on the pancreatic beta-cells of the islets of Langerhans to illustrate the important role crosstalk plays in the regulation of glucose-induced insulin secretion. Recent studies indicating a synergistic interaction in beta-cells between the glucose-regulated ATP-dependent signalling system and the hormonally regulated cAMP-dependent signalling system are emphasized. This interaction gives beta-cells the ability to match the ambient concentration of glucose to an appropriate insulin secretory response, a process we refer to as the induction of glucose competence. The glucose competence concept may provide new insights into the etiology and treatment of non-insulin-dependent diabetes mellitus (Type II diabetes).


Crosstalk among multiple signal-activated phospholipases. Transduction of extracellular signals across the plasma membrane often involves activation of several phospholipases that generate multiple, sometimes interconvertible, lipid-derived messengers. Coordination and integration of these signal-activated phospholipases may require crosstalk between both the messengers and target protein constituents of these pathways.


Protein kinase C, calcium and phospholipid degradation. In most cells, calcium signals are transient, while the resulting physiological responses often persist longer. The sustained activation of protein kinase C has been postulated to be essential for maintaining such cellular responses. It is becoming clear that an elaborate network involving protein kinase C, calcium and degradation of membrane phospholipids may generate several molecules that are necessary for sustaining the activation of protein kinase C itself. Multiple members of the protein kinase C family show distinct responses to calcium and the phospholipid degradation products, suggesting their unique functions in cell signalling.


Control of transcription factors by signal transduction pathways: the beginning of the end. Signal transduction pathways regulate gene expression by modulating the activity of nuclear transcription factors. The mechanisms that control the activity of two groups of sequence-specific transcription factors, the AP-1 and CREB/ATF proteins, are described. These factors serve as a paradigm explaining the transfer of regulatory information from the cell surface to the nucleus.


The serum response element.

The serum response element. The promoters of many genes whose transcription is rapidly and transiently induced following growth factor or mitogen stimulation of susceptible cells contain a common regulatory element, the serum response element (SRE). As the transcription factors that bind the SRE and the signalling molecules that affect its activity are characterized in more detail, the major challenge is to elucidate the signalling pathways that link cell-surface receptors to the SRE, and to determine the mechanism by which signalling events modulate transcription factor activity.


Signal transduction through the T-cell antigen receptor. The mechanism by which ligand binding to the T-cell antigen receptor triggers the T-cell activation program has long been one of the most fascinating questions in lymphocyte biology. Here, we review recent insights into the transmembrane signaling functions of this multisubunit receptor complex.


Signal transduction and the actin cytoskeleton: the roles of MARCKS and profilin. MARCKS and profilin, two actin-binding proteins, are discussed to illustrate the mechanism by which extracellular signals are coupled to changes in the structure of the actin cytoskeleton. MARCKS is a filamentous actin-crosslinking protein that appears to function as an integrator of protein kinase C and calcium (Ca2+)/calmodulin signals in the regulation of actin-membrane interactions. New data suggest that profilin is activated by the coordinated action of receptor tyrosine kinases and phospholipase C-gamma 1 to stimulate the stabilization of actin filaments.


Protein sorting in mitochondria.

Protein sorting in mitochondria. Most polypeptides that are imported into the mitochondrial matrix use a common translocation machinery. By contrast, proteins of the other mitochondrial compartments are imported by a variety of different mechanisms. Some of these proteins completely bypass the common translocation machinery, others use only the outer membrane components of this machinery, and still others use components of this machinery from both the outer and inner membranes. Import to the intermembrane space compartment provides examples of all three possibilities.


Does hydrophobic hydration destabilize protein native structures? Water in the immediate vicinity of a non-polar solute has characteristically low entropy and high heat capacity at 25 degrees C. Common opinion has been that the insolubility of such species is caused by thermodynamic changes associated with the formation of these layers of abnormal water, 'hydrophobic hydration'. Recently, however, it has been proposed instead that hydrophobic hydration favors solution of hydrocarbons, or hydrocarbon sidechains, in water and therefore promotes protein unfolding. It is argued here that available data do not convincingly support this hypothesis.


The ATP-dependent glutathione S-conjugate export pump. The ATP-dependent glutathione S-conjugate export pump (GS-X pump) plays a physiologically important role as a member of the 'phase III' system in xenobiotic metabolism as well as in the release of biologically active endogenous substances from cells. In addition, this export pump is potentially involved in the modulation of the antiproliferative action of certain antitumor agents.


How to make a glycoinositol phospholipid anchor. Essentially all eukaryotic cells express proteins on their surface that are anchored by a glycoinositol phospholipid. This anchor moiety may endow such proteins with unusual properties. The definition of the biosynthetic path that constructs these anchors is now in its final stages. Mutations that interrupt this path are, remarkably, compatible with survival of cells in culture, but are associated with at least one human disease.


Signal peptidases in prokaryotes and eukaryotes--a new protease family. Signal peptidases remove targeting peptides from pre-proteins and play central roles in the secretory pathway, as well as in the delivery of proteins to the mitochondrial intermembrane space and to the lumen of thylakoids. The catalytic mechanism of pre-protein cleavage has long been an enigma, but recent data from site-directed mutagenesis and sequence alignment studies suggest that signal peptidases may constitute a new type of serine protease, mechanistically related to the beta-lactamases.


Interaction of malarial infection and glucose-6-phosphate dehydrogenase deficiency in Muria gonds of district Bastar, central India. Muria gond tribals (n = 473) from district Bastar, central India, an area known to be hyperendemic for malaria, were investigated for malarial infection and glucose-6-phosphate dehydrogenase deficiency. The frequency of G-6-PD deficiency was 21.3% among male subjects and 3.7% among females. Assay of malarial antibodies showed that seropositivity as well as the level of antibodies was significantly higher in male subjects with normal enzyme levels as compared with males G-6-PD deficiency. Females with normal G-6-PD enzyme levels too had higher seropositivity as well as level of antibodies against malaria as compared with females having G-6-PD deficiency. This suggests that G-6-PD deficiency correlates with a higher degree of resistance.


Antimalarial drug sensitivity patterns in the western province of Zambia. Implications for the management of primary health care (PHC). The management of acute malaria consists of chemotherapy aimed at restoring the normal function of all organs. Appropriate treatment is dependent upon extensive knowledge of the drug sensitivity patterns of the malaria parasites in the area. This is also important for chemoprophylaxis. Drug sensitivity patterns and recrudescence rates for Mongu (Western Province in Zambia) are suggestive of a likely increase in resistance to both chloroquine and sulfadoxine-pyrimethamine (Fansidar). We found RI (19.4%), RII (1.5%) and RIII (4.4%) resistance to chloroquine and RII (4.3%) resistance to Fansidar. This calls for careful consideration of treatment schedules, legislation pertaining to the distribution of drugs in the general public and alternative antimalarial control strategies.


A comparative study of four serological methods for diagnosis of acute and chronic Chagas' disease in Brazilian patients. Complement fixation (CF), indirect immunofluorescence (IFAT), latex agglutination (LA) and the enzyme-linked immunosorbent assay (ELISA) were applied to assess the diagnostic value of antibody determination in Brazilian patients with acute or chronic Chagas' disease. Patients with various forms of leishmaniasis and healthy individuals from the endemic region were used as specificity controls. Whereas LA, IFAT and ELISA identified 81% of acutely ill patients, CF had no diagnostic potential in this phase of the disease. In later stages CF showed a sensitivity of 69% as compared to 100% for LA, IFAT and ELISA, irrespective whether patients presented clinically as chronic asymptomatic or chronic symptomatic cases. Cross-reactivity with anti-leishmania antibodies was observed in 23%, 38% and 77% of serum samples in LA, ELISA and IFAT, respectively, but not in CF.


Bacteriological and serological study of pertussis in Abeokuta, Nigeria. Charcoal horse blood agar is the medium of choice for isolation of Bordetella pertussis from patients with early whooping cough. Since sterile animal blood often is not available in developing countries, a field study in Nigeria was undertaken to evaluate donated human blood as supplement to charcoal agar. Out of 209 children with suspected early pertussis, 33 were culture-positive (isolation rate 16%). Out of 188 children studied serologically by enzyme immunoassay, 36 (19%) were seropositive. The satisfactory isolation rate of 16% shows that culturing for B. pertussis on charcoal human blood agar can be tried in countries, where there is no regular supply of bacteriological media with animal blood.


Congenital syphilis. Diagnosis in places with limited facilities. The cases of 4 newborns with congenital syphilis (CS) seen in a rural hospital in Tanzania are reported. Clinical signs may be caused by other diseases than CS and are not conclusive. Therefore, uniformity in diagnostic criteria based on clinical symptoms and serology is essential for comparative clinical and epidemiological studies in places with limited facilities. The surveillance case definition for congenital syphilis introduced by the Centers for Disease Control (CDC) in 1988 and revised in 1989 [1] offers the opportunity to report congenital syphilis not only in places with sophisticated equipment but also in places with limited facilities.


Prevalence of bacterial agents of diarrhoeal disease at the National University Hospital, Singapore and their resistance to antimicrobial agents. Over a 50-month period, 4,508 stool specimens from patients with diarrhoea were bacteriologically examined at the National University Hospital, Singapore. Salmonella serotypes other than the typhoid and paratyphoid bacilli were the most common finding, being isolated in 10.8% of cases. Campylobacter jejuni was unexpectedly infrequent (1.9%); Aeromonas hydrophila was found in 1.8%. No other aerobic pathogen occurred in more than 1% of cases. Clostridium difficile was sought only when requested, and was isolated from 9.6% of cases tested. Testing for enteropathogenic Escherichia coli was limited to children under 1 year old. Gentamicin was active against the greatest number of aerobic isolates, followed by chloramphenicol and cotrimoxazole. The C. difficile isolates were all sensitive to metronidazole.


Febrile convulsions: factors and recurrence rate. One hundred and forty-seven children admitted consecutively with their first febrile convulsion were studied to assess the influence of certain factors on the recurrence rate of seizures. The younger the age at first occurrence the more likely the recurrence rate. Those with moderate degree of pyrexia (39-39.9 degrees C) were found to be ten times more likely to have subsequent recurring convulsions compared to those with high degree of pyrexia (40 degrees C and above) or those with mild degree of pyrexia (38-38.9 degrees C). Furthermore, the recurrence rate was five times higher in first-born compared to siblings second-borne or more. The overall recurrence rate was 29.3% with the frequency varying between 1 to 2 times. A male preponderance was observed. These factors might be of prognostic value in terms of risk for recurrence.


Prevalence of human immunodeficiency virus-infection among pregnant women attending ante-natal clinic in Maiduguri, north-eastern Nigeria. A seroepidemiological survey conducted among 1,059 pregnant women in Maiduguri, North-eastern Nigeria from September, 1988 to April, 1990 showed that 5 women or 0.47% were positive for HIV antibodies. Three of the women (0.28%) were positive for HIV-1 while 2 others (0.19%) were positive for HIV-2; this is consistent with the known fact that both viruses are active in West Africa, a sub-region of which Nigeria is part. Detailed information available on 4 of the 5 seropositive women and their husbands did not reveal any known risk factor favouring HIV-infection. In addition to the 5 confirmed seropositive women, 10 others (0.94%) gave Western blot patterns that were neither HIV-1 nor HIV-2. The significance of this observation, if any, needs to be clarified.


Mouth-to-anus transit-time predicts the severity of fecal water loss in acute dehydrating diarrhea. The mouth-to-anus transit time was estimated in 24 young children admitted to an outpatient rehydration unit with acute dehydrating diarrheal disease by adding an oral fecal marker (brilliant blue) to the first draught of oral rehydration solution. Transit times ranged from 30 to 242 min. There was a highly significant (logarithmic) relationship between rate of fecal output and transit time (r = 0.74; p < 0.001). Three of 24 subjects could not be rehydrated orally, were declared treatment failures, and were hospitalized for intravenous therapy. All of them had had an initial transit time of less than 50 min, and constituted three of the four subjects with this rapid rate of transit. Thus, a rapid mouth-to-anus transit time had a 100% sensitivity to predict treatment failures and a 75% predictive accuracy for a "positive" test. Although our series is small, the findings suggest that fecal markers may be useful in remote areas to assist in the early detection of diarrheal episodes that cannot be managed by oral rehydration therapy.


Reproduction and maternal nutrition in Madura, Indonesia. The prevalence and severity of chronic energy deficiency (CED) among women of reproductive age as well as its consequences on the newborn and the mother were assessed in a longitudinal study. More than 40% of the mothers had a Body Mass Index (BMI) less than 18.5 before pregnancy, a level below which CED is considered to exist. Weight gain during pregnancy was low, on average 6.6 kg. Taking the difference between 4 week postpartum weight and pre-pregnant weight as net weight gain during pregnancy, mothers with a BMI less than 18.5 before pregnancy gained weight while those with a higher BMI lost weight. This observation suggests that the partitioning of energy to the fetus and the mother depends on the energy reserves of the mother before pregnancy. The functional significance of BMI as an indicator of CED is illustrated by its relation with birth weight. Similarly, 4 week postpartum, weight and BMI were predictive for the weight changes in the mother in the first 12 months after delivery. The groups with the lowest values gained weight, while the heaviest mothers lost weight. In view of the negative effects of CED among women of reproductive age on the infant and the mother, maternal undernutrition should receive the same attention as malnutrition among preschool children.


Milk macronutrient levels during the first month of term and preterm Nigerian mothers. The lactose levels of the transition milk of term mothers were significantly higher compared with preterm mothers (5.87 versus 5.32 g/100 ml). The same trends were found in colostrum and mature milk. These differences were not significant. The protein contents of the colostrum in term mothers were significantly lower than in their preterm counterparts (1.80 versus 2.20 g/100 ml). Again the same trend (not significant) was showed in transition and mature milk. A significantly lower level of fat in milk of term mothers than of preterm mothers was found in all 3 types of milk (1.84 versus 2.26; 2.16 versus 2.95; 2.72 versus 3.32 in colostrum, transition milk and mature milk respectively). This study showed differences in the macronutrients measured in the different types of milk, hence term babies in Baby care units should be fed term milk and preterm babies with preterm milk.


Antinutrients content of some locally available legumes and cereals in Nigeria. Plant protein is the cheapest source of protein available to mankind but unfortunately the protein is accompanied by antinutrients. The quantity of oxalate and tannin in acha, bambara groundnut, guinea corn, millet, sesame seed, soybean and tiger nut were chemically analyzed. The white variety of sesame seed and soybean have the highest oxalate and tannin contents of 8.25 mg/g and 0.15 mg/g respectively. Among the cereals the black and brown varieties of millet have the highest oxalate and tannin contents of 4.65 mg/g and 0.07 mg/g respectively. The presence of these antinutrients makes plant (especially legumes) protein partially available and of poor quality.


Angioid streaks in Uganda.

Angioid streaks in Uganda. A study on the ophthalmoscopic appearance of angioid streaks and their suspected association with local and systemic diseases among ugandan Africans is presented. In all 40 eyes of 20 patients were studied and the results indicate an interesting association with certain diseases.


Painless peripheral lymphadenopathy in Nigerian children. We conducted a diagnostic biopsy during a period of 8 years (January 1981 - December 1988) on 74 consecutive children (aged under 16 years) who attended the University of Calabar Teaching Hospital, Calabar, for chronic enlarged painless lymphadenopathy, with a view to determining the diseases that commonly present with this symptom in our environment. Histological diagnoses returned were predominantly tuberculosis, neoplasms and nonspecific reactive changes. Each of these conditions was evenly distributed among the entire age group. Neoplasms were mainly Hodgkins and non-Hodgkins lymphoma, with Burkitt's tumour the commonest childhood tumour in Nigeria not contributing significantly to the neoplastic lymphadenopathy. Regional enlargement rather than generalised lymphadenopathy seems to be dominant, the commonest sites of involvement being the cervical followed by the inguinal regions. Chronic lymph node enlargement appears to be rare in our environment and only a few disease conditions manifest with peripheral nodes despite the large number of infections and other inflammatory diseases in Nigerian children.


Trichinosis from wild boar meat in Gojjam, north-west Ethiopia. An outbreak of trichinosis associated with ingestion of meat from a wild boar in Gojjam administrative region, Ethiopia, is reported. Of the 30 soldiers, 20 who ate the meat raw, became ill and 5 of them were admitted to the Armed Forces General Hospital (AFGH). Even though they presented with a typical history and clinical features the disease was not even suspected at the peripheral hospital. The diagnosis was confirmed, at the AFGH, by deltoid muscle biopsy in all the 5 cases. Trichinosis being increasingly recognized as a public health problem in Ethiopia, warrants public education and more awareness by health workers.


Hernia in northern Jordan. Some epidemiological considerations. This retrospective study covers the authors' experience over five years of 1,722 primary hernia repairs in 1,722 patients of all ages. An analysis of some epidemiological features is presented and discussed. Inguinal hernia was by far the commonest variety accounting for more than 84% of the total series. Regardless of sex and type of hernia, 60% of all hernias were right-sided while not more than 5% were bilateral. The male to female ratio for the entire series was 4.3:1 and 8.2:1 for the inguinal hernia group. The main findings of this retrospective study are in direct accord with other series reported in the literature. Furthermore, we suspect our results are typical of those to be found in large and comparable general community hospitals in Jordan.


[The effect of cadmium on the survivability of colony-forming hematopoietic cells in mice exposed to x-ray irradiation]. It has been reported elsewhere that in addition to enhancing the expression of metallothionein genes, the previous injection of cadmium salts into sublethally X-irradiated mice increases by 10 times the number of endogenous spleen colonies. To understand the mechanism of the strong radioprotective cadmium effect donors and recipients were treated separately. It is shown that the survival of exogenous bone marrow colony-forming cells in lethally irradiated recipient remains at the control level independently of the donor cadmium treatment, whereas the injection of cadmium nitrate to recipient mice leads to the stimulation of colony formation by 1.7-1.8 times. The data allow to conclude that the cadmium effect on the survival of colony-forming hemopoietic murine cells after X-irradiation is not mediated by the enhanced expression of metallothionein genes.


[Eukaryotes devoid of the most important cellular organelles (flagella, Golgi apparatus, mitochondria) and the main task of organellology]. Comparative evidence on the lack of three important organelles (flagella, Golgi-complex, mitochondria) in cells and organisms at the cellular level of organization has been summarized for all the four eukaryotic kingdoms--Protista, Fungi, Plantae and Animalia (Metazoa). It is established that in the course of evolution these organelles may undergo the total reduction. There is no cellular organelle to be regarded as universal, indispensable. There are only three main obligatory cell components--the plasmalemma, nucleus and cytoplasm (with applied cytoskeleton, cytomembranes and ribosomes). The reduction of flagella (cilia) is occurring in different taxa independent of the transition of protists from the flagellate type of locomotion to the amoeboid, gliding of metabolizing ones, and in the number of metazoan cells. The members of Protista and Fungi, which line in microaerobic or anaerobic conditions, nearly inevitably lose their mitochondria. The tendency to lose Golgi-complex is demonstrated in protists with parasitic mode of life, especially in combination with anaerobiosis. There is so far no satisfied morphological criterium that could say with certainty whether the lacking of flagella, Golgi complex or mitochondria in the low eukaryotes may be primary or secondary (as the result of reduction). Data on the composition, structure and RNA nucleotide sequences cannot be either the straight evidence. A comparative analysis of these data shows that the ribosomes of the primary eukaryotes were, presumably, of a prokaryotic type. Their eukaryotization was carried out for a long time during the evolution of the low eukaryotes (Protista and Fungi), probably, independently in different phylogenetic lines. It is unknown at what steps and in what main phylogenetic lines the three above mentioned organelles may have appeared. It is proposed to single out a special division of cytology--organellology (organoidology)--as an individual science whose main purpose may be investigation of the origination, evolution and disappearance of organelles.


[The capacity for reactive DNA synthesis of the myocytes in the heart conduction system in experimental and clinical myocardial pathology]. The DNA synthesis has been studied in the conductive system (CS) myocytes, compared to that in atrial and ventricular myocytes: 1) in the left ventricular myocardial infarction induced in two- and three-week-old and adult rats, 2) after isoproterenol injections to adult rats and mice, and 3) in the hypertrophied human heart. The extent of DNA synthesis reactivation was evaluated by the cumulative labeling indices in experiments with multiple 3HTdR injections to rats and mice. In the human cardiac myocyte nuclei, the DNA content was determined by the Feulgen-cytophotometry. The difference between the control and experimental mean values of the labeling indices for CS myocyte nuclei was statistically significant only for atrioventricular part of the CS in the infarcted hearts of adult rats. In the human heart CS the ability of myocytes to polyploidization varies from one cell type to another, the lowest being in nodal cells.


[The structure of the reticulum of Mauthner's neurons in tadpoles of the clawed toad grown under increased gravitational force]. The ultrastructure of the Mauthner cells (M-cells) and the behaviour of Xenopus laevis tadpoles, reared from eggs under increased gravity (2.9 g) which changes the activity of an afferent vestibular input, were investigated. Besides, a study was made of tadpoles after the hindbrain ablation at earlier embryonal stages which significantly altered the microenvironment of M-cells. It is shown that experimental treatments enhance the proliferation of endoplasmic reticulum and its derivatives, so called subsurface cisterns, in the subsynaptic areas. Some structural changes of the synaptic active zones and the cytoskeleton of M-cells were also noticed. It is assumed that the development of the endoplasmic reticulum promotes an intense removal of calcium ions from subsynaptic areas. The plasticity of the endoplasmic reticulum together with other ultrastructural changes apparently stipulate the adaptation of neurons to changed conditions of functioning.


[A stereoscopic analysis of centrosome structure in the cells of a tissue culture under the action of energy metabolism inhibitors. I. 2,4-Dinitrophenol, deoxyglucose, sodium azide and the calcium ionophore A23187]. A 30-min action of energy transfer inhibitors (2,4-dinitrophenol, deoxyglucose, azide and calcium ionophore A23187) on tissue culture cells results in a significant increase in the quantity of microtubules around the centrosome. After the action of all the inhibitors, mostly increases the number of long microtubules with free proximal end oriented towards the centrosome. It is suggested that energy transfer inhibitors may stimulate foundation of microtubules on the centrosome and stabilize free microtubules, while they exert no effect on the frequency of detachment of microtubules from the centrosome.


[The production of "pure" cultures of neurons from the brain of human embryos]. A method has been developed for preparing essentially pure primary cultures of neurons from 10-12 week old fetal human brain. This method is based on the 1) capacity of neurons to form multicellular aggregates, 2) cultivation in chemically defined medium, and 3) treatment with cytosine arabinoside as antimitotic agent. This procedure allowed the preparation of highly purified (95 per cent and more) neuronal aggregate cultures. Ultrastructural analysis of these cultures following one and 8 days has revealed their partial differentiation during cultivation.