Mutagenicity evaluation of riot control agent o-chlorobenzylidene malononitrile (CS) in the Ames Salmonella/microsome test. o-Chlorobenzylidene malononitrile (CS), a riot control agent, was evaluated for its possible mutagenic activity in the Ames Salmonella/mammalian microsome mutagenicity test. Five histidine-deficient (His-) mutant tester strains of Salmonella typhimurium--TA97a, TA98, TA100, TA102 and TA104--were used. The liquid preincubation procedure was used with metabolic activation (presence of S9 mixture) and without metabolic activation (absence of S9 mixture). For the experiments with metabolic activation, three different concentrations of S9 fraction (supernatant of Aroclor 1254-induced rat liver homogenate at 9000 g)--5%, 15% and 30% in S9 mixture--were used. Along with mutagenic activity, CS was also evaluated for cytotoxic activity in all the five tester strains of Salmonella typhimurium, both in the presence and absence of S9 mixture. The mutagenic and cytotoxic activities of CS were assessed by counting the His+ revertant colonies and by counting the microcolonies (His-, auxotrophs in the background lawn), respectively, and the respective mean values were compared with the relative negative (solvent) control. A dose range of 12.5-800 micrograms plate-1 for CS did not induce a mutagenic response either in the presence or absence of S9 mix. No change in the negative mutagenic response of CS has been observed even in the presence of an elevated level of S9 fraction in the S9 mix. A dose of 200 micrograms plate-1 for CS was found to be cytotoxic by decreasing the surviving cells as well as His+ revertant colonies; however, the effect was reduced in the presence of an elevated level of S9 fraction in the S9 mix.


Conventional and new diagnostic applications of a two-site immunochemiluminometric assay for parathyroid hormone. This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunoradiometric assay (n = 42, r = 0.67, p less than 0.001) and a widely used midmolecule radioimmunoassay (n = 21, r = 0.78; p less than 0.001). Similar good correlations were found in primary hyperparathyroidism patients (IC-MA vs immunoradiometric assay r = 0.74; p less than 0.001; ICMA vs midmolecule assay r = 0.77; p less than 0.001). As far as the hypercalcemic conditions were concerned, in 5 patients with mild primary hyperparathyroidism, ICMA PTH levels were in the upper range of those found in normal subjects, even though they were inappropriately high in respect to serum calcium values. However, serum ICMA PTH levels were clearly suppressed or undetectable in the majority of patients with cancer hypercalcemia or postsurgical hypoparathyroidism. Following calcium and EDTA infusions in patients with primary hyperparathyroidism, the behaviour of ICMA PTH levels in general parallelled that of immunoradiometric PTH assay, thus indirectly suggesting the ability of the method to measure the intact molecule.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum concentrations of osteocalcin in patients with hyperthyroidism, hypothyroidism and subacute thyroiditis. Serum concentration of osteocalcin (OC) was measured in sera from untreated patients with Graves' disease, hypothyroidism due to Hashimoto's thyroiditis, and subacute thyroiditis. Serum concentration of OC in Graves' disease and hypothyroidism were 14.1 +/- 5.6 micrograms/L and 3.8 +/- 2.7 micrograms/L, respectively which were significantly different from that of healthy subjects (Graves' disease, p less than 0.001, hypothyroidism, p less than 0.01). Serum concentration of OC in patients with subacute thyroiditis was 8.0 +/- 3.5 micrograms/L which was not statistically different from age-matched normal controls. Serial measurement of serum OC for 24 mo in 15 patients with Graves' disease after initiation of antithyroid drugs disclosed that the decline of serum OC was obtained only 24 mo after antithyroid drug therapy. On the other hand, in hypothyroid patients, increased serum OC was observed after 1-2 months treatment of L-T4. Correlation coefficients between serum concentrations of OC and T3, T4, FT3 or FT4 in all the patients with thyroid disorders were 0.66, 0.51, 0.50 and 0.54, respectively, which were statistically significant (all, p less than 0.001). These results suggest that osteoblastic activity is enhanced in hyperthyroidism and suppressed in hypothyroidism. In hyperthyroid patients, despite of normalization of FT4 concentration in relatively short period (within 3-4 mo), it took 24 mo after initiation of antithyroid drugs for OC to normalize, suggesting not only thyroid hormone per se but also some unknown factor(s) participates in serum OC secretion. In contrast to thyrotoxic patients, rapid increase in serum OC after initiation of supplemental L-T4 treatment in hypothyroidism was observed, suggesting a direct effect of thyroid hormone on the osteoblasts in patients with hypothyroidism.


Lack of correlation between sex hormone binding globulin, adrenal and peripheral androgens in precocious adrenarche. Sex hormone binding globulin (SHBG) is a specific steroid-binding plasma glycoprotein regulated by several different factors. Sex steroids are currently considered to be the main physiological regulators of this protein. Testosterone (T) in adults seems to be the main hormone active in lowering SHBG. The role of dihydrotestosterone (DHT) in such regulation, particularly in the prepubertal age, is not well understood, and no data exist about the role of 3 alpha-androstanediol (3A alpha) and its glucuronide. In adulthood, in addition to T, 5-ene steroids seems to play a role in the regulation of SHBG plasma concentration. To assess the effect of adrenal and peripheral androgens in modulating SHBG levels in the prepubertal age, we studied subjects with precocious pubarche secondary to precocious adrenarche (PA). PA represents, in fact, a good model of study as it is characterized by an increased production and action of adrenal androgen in females under 8 yr of age and in males under 9. Sixty-five subjects (55 females and 10 males; chronologic age: 3.6 - 8.2 yr (6.9 +/- 1.3, SD); bone age: 3.6 - 11 yr (7.6 +/- 1.9); BMI 17.9 +/- 3 kg/m2) were studied. Fifteen age-matched normal children (BMI 15.2 +/- 0.8 kg/m2) were studied as controls. Androstenedione (A), dehydroepiandrosterone (DHA) and its sulphate (DHA-S), T, DHT, 3Ad and its glucuronide (3AG) and SHBG were evaluated in all subjects. In PA cases serum SHBG levels (50 +/- 27 nM) were significantly lower (p less than 0.05) with respect to normal prepubertal patients.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of iodine on lipid peroxidation and ultrastructure in the thyroids of BB/Wor rats. There has been recent data suggesting that iodine potentiates lymphocytic thyroiditis (LT) by inciting oxidative stress. However, the mechanism by which iodine induces LT in genetically predisposed animals is unknown. This study was undertaken to examine LT-prone BB/Wor (LT-P) rat thyroids for signs of acute iodine toxicity and oxidative damage before the onset of spontaneous LT. Lipid peroxidation was assessed by the measurement of malonyldialdehyde (MDA) in thyroid homogenates after randomization to a treatment group receiving 0.05% iodide in the drinking water or tap water for 24 hours. Basal MDA levels were higher in LT-prone rat thyroids than Wistar rat thyroids, but iodine treatment did not influence intrathyroidal MDA levels. Electronmicroscopy demonstrated that prolonged treatment with excess iodine, increased the number of apical lysosomes. But there were no ultrastructural changes unique to LT-P rat thyroids. These data suggest that although LT-P rat thyroids may experience subclinical oxidative damage before the onset of histologically demonstrable LT, this activity is not affected by iodine.


Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients. Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child-Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non-cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension.


Magnetic resonance imaging and assessment of liver iron content in genetic hemochromatosis. Computed tomography (CT) scanning is not highly sensitive in the assessment of liver iron content and magnetic resonance imaging (MRI) appears to be more efficient. The aim of this study was to determine the effectiveness of MRI in the evaluation of liver iron content using a standard spin-echo technique. The study included 23 patients with genetic hemochromatosis and 24 non-iron-overloaded patients as controls. A comparison was made of: (a) MRI signal intensity of liver, spleen, paravertebral muscles and subcutaneous adipose tissue using two different spin-echo sequences (SE 500/28; SE 2000/28,56); (b) liver attenuation determined by a single energy CT scan; and (c) a biochemical determination of hepatic iron. There was a significant decrease in liver signal intensity in the genetic hemochromatosis group (256 +/- 201, mean +/- S.D.) compared with the control group (801 +/- 413, p less than 0.001), but there was no correlation with liver iron concentration. However, such a correlation was found and was even more highly significant than in CT when the ratio between the liver and another organ was taken into account. For a lower limit of liver/spleen ratio calculated at 0.46 (mean 2 S.D. in the control group), the specificity (0.96) of MRI was satisfactory, but the sensitivity (0.78) remained insufficient (MRI being unable to detect an iron overload of up to 125 mumol/g). Hopefully, these results might be improved in the near future by using more sensitive sequences such as gradient echo sequences.


Effects of opioid receptor blockade on luteinizing hormone (LH) pulses and interpulse LH concentrations in normal women during the early phase of the menstrual cycle. To determine the role of endogenous opioid peptides in regulating pulsatile luteinizing hormone (LH) release in the early follicular phase of the menstrual cycle of eumenorrheic women, we evaluated serum LH concentrations in blood collected every 10 min for 12 h in 27 women each studied during two menstrual cycles: (1) without pretreatment and (2) following oral administration of naltrexone, a mu opiate receptor blocking agent, at a dose of 1.0 mg/kg. Pulsatile LH release was assessed by the CLUSTER algorithm. The mean (+/- SE) integrated serum LH concentration (IU/L/min) increased following the administration of naltrexone (4715 +/- 298) in comparison to the control day (3997 +/- 381; p = 0.0008). The mean number of LH pulses (/12 h) detected on the naltrexone day (10.3 +/- 0.3) was higher than on the control day (8.9 +/- 0.4; p = 0.0068). Mean maximal LH peak height (IU/L) was greater on the naltrexone (7.8 +/- 0.5) vs control (6.7 +/- 0.5) days (p = 0.0064) as was the interpulse valley mean serum LH concentration (IU/L; 6.3 +/- 0.4 vs 5.0 +/- 0.4; p = 0.0013). No difference was noted in the mean incremental LH pulse amplitude (IU/L; 1.9 +/- 0.1 vs 2.1 +/- 0.1; p = 0.13), or peak duration (min; 40 +/- 1.8 vs 45.0 +/- 2.4; p = 0.06). Mean LH peak area (IU/L/min) was greater on the control (45.0 +/- 2.4) vs naltrexone (40 +/- 1.8) days (p = 0.0475).(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of calcitonin gene-related peptide in medullary thyroid cancer. We studied the expression of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in 18 patients with medullary thyroid cancer (MTC) in the neoplastic (primary or metastatic) tissue by immunohistochemistry and in the plasma by radioimmunoassay. CT immunoreactivity was found in 100% of the primary and metastatic MTC, CGRP was expressed in 66% of the primary tumors and in 73% of the metastases. Both the number of positive cells and the degree of staining were always higher for CT than for CGRP staining. While plasma CT concentrations were always increased in patients with metastases, 3 patients with metastases had undetectable plasma CGRP levels. A positive correlation was found between plasma CT and CGRP levels. These data indicate that CGRP is frequently expressed in MTC sections and that plasma CGRP measurement is an additional marker for MTC, although has no advantage with respect to CT measurements in monitoring the progression of the disease.


The pathogenesis of vacuoles produced in rat and mouse liver cells by a conjugate of adenine arabinoside monophosphate with lactosaminated albumin. A conjugate of adenine arabinoside monophosphate with lactosaminated albumin produced vacuoles in hepatic cells of rats and mice when given at doses 5-10 times higher than that (35 mg/kg) capable of inhibiting hepatitis B virus replication in patients with chronic hepatitis B. The vacuoles were due to the swelling of secondary lysosomes probably caused by incapacity of the lysosomal enzymes to rapidly digest large amounts of conjugate into products able to cross the lysosomal membrane. Although vacuoles progressively disappeared when conjugate administration was discontinued, the present observation suggests caution in giving the conjugate to man at daily doses higher than 35 mg/kg.


Effects of theophylline on hemodynamics and tissue oxygenation in patients with cirrhosis. Since adenosine may play a role in the hyperdynamic circulation of cirrhosis, we examined the effects of theophylline (an adenosine receptor antagonist) on systemic and splanchnic hemodynamics, tissue oxygenation and sympathoadrenal activity in patients with cirrhosis and liver failure. Theophylline (aminophylline) was administered intravenously for 30 min. Six patients received a dose of 3 mg/kg and eight others a dose of 6 mg/kg. The low dose caused plasma theophylline concentrations of 7.4 +/- 1.8 mg/ml (mean +/- S.E.), and induced a significant increase in heart rate from 84 +/- 5 to 93 +/- 8 beats/min. This dosage did not significantly change other hemodynamic values, oxygen (O2) consumption, or sympathoadrenal activity. The high dose elicited plasma theophylline concentrations of 15.8 +/- 4.0 mg/ml. This dose significantly increased heart rate from 78 +/- 5 to 87 +/- 7 beats/min and significantly decreased right atrial pressure from 2.5 +/- 1.0 to 1.4 +/- 0.8 mmHg, stroke volume from 52 +/- 3 to 47 +/- 5 ml.beat-1.m-2 and systolic arterial pressure from 140 +/- 5 to 129 +/- 6 mmHg. In contrast, O2 consumption, sympathoadrenal activity, and all other hemodynamic values (including azygos blood flow) were not significantly modified. As a result, we conclude that, in patients with cirrhosis, theophylline may cause decreased stroke volume which lowers systolic arterial pressure. In our patients theophylline also had a positive chronotropic effect but no vasoconstrictor effect on systemic and splanchnic circulation. Finally, theophylline did not improve tissue oxygenation in patients with cirrhosis.


Improvement of metastatic endocrine tumors of the pancreas by hepatic artery chemoembolization. We report the results of transcatheter intraarterial perfusion of liver with the emulsion of iodized oil and cytostatics performed as palliative treatment in three patients with hepatic metastases of pancreatic endocrine tumors. Two patients had insulinoma and one patient had glucagonoma. They were also treated by medical therapy from the time the diagnosis was made. Intraarterial perfusion of the liver was achieved by Lipiodol emulsified with streptozotocin and 5-fluorouracil. Regarding these three patients therapeutic responses were different in duration of hormone secretion decrease. Relief of hypoglycemic attacks and a significant decrease of plasma immunoreactive insulin concentration within 12 months without any additional therapy was observed in the patient with insulinoma (case no. 2). This patient had slightly increased immunoreactive glucagon concentration from the time of diagnosis. A decrease of immunoreactive insulin levels in other patient with insulinoma and an increase in plasma glucose to the euglycemic range during two months allowed a reduction of doses of somatostatin analogue and diazoxide. Due to rapid progression of the disease, intraarterial perfusion of liver was repeated three months later with the same results. Remission of symptoms was partial in the case of glucagonoma. Immunoreactive glucagon levels were not changed and there was no significant benefit of the treatment. Intraarterial perfusion of liver with iodized oil and cytostatics could be an effective, safe and repeatable method of palliating symptoms of malignant pancreatic tumors, especially in inoperable but nonterminal cases. It could allow reduction of additional medical therapy, but success of the treatment is not predictable.


Disseminated intravascular coagulation in liver cirrhosis. We measured thrombin-antithrombin III complex (TAT), soluble fibrin (SF) and D-dimer levels in 51 patients with liver cirrhosis to determine whether these tests provide new evidence for the presence of disseminated intravascular coagulation (DIC) in liver cirrhosis. TAT levels (median, range) were increased in the patient group (4.2 micrograms/l, 1.8-60.0) compared to the reference group (2.0 micrograms/l, range 1.5-7.6 micrograms/l). SF levels (0 nmol/l, range 0-80 nmol/l) were also increased in the patients as compared to the controls (0 nmol/l, 0), but there was no correlation between TAT and SF levels (r = 0.23, p less than 0.98). TAT levels did not correlate with AT-III levels (r = -0.36, p less than 0.49), but there was an inverse correlation between SF and AT-III (r = 0.60, p less than 0.001). If AT-III levels were above 0.30 U/ml, SF levels remained low, whereas SF levels were increased in patients with AT-III levels below 0.30 U/ml. These findings suggest that if sufficient AT-III is present, thrombin formation is adequately controlled, whereas at low levels of AT-III, thrombin escapes inactivation by AT-III and may act upon fibrinogen, leading to the formation of SF and a low-grade DIC. SF levels correlated well with D-dimer levels (r = 0.55, p less than 0.001), which is consistent with DIC and secondary fibrinolysis. (1) thrombin formation is increased in liver cirrhosis, as indicated by increased TAT levels in 21 of 51 patients; (2) the plasma concentration of AT-III appears to be of major importance for the development of DIC. The present study provides evidence for DIC in severe liver cirrhosis when AT-III levels are less than 0.30 U/ml.


A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results. The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss.


Sodium fluoride prevents bone loss in primary biliary cirrhosis. Low-bone-turnover osteoporosis is a common complication of primary biliary cirrhosis (PBC). Since sodium fluoride stimulates bone formation we assessed the effect of this drug on bone mass in a 2-year, prospective, double-blind trial including 22 women with PBC who were randomly assigned to receive sodium fluoride (50 mg/day) or placebo. All received calcium supplements and low doses of vitamin D. Bone mineral density of the lumbar spine was measured by dual-photon absorptiometry initially and every 6 months. Vertebral fractures were evaluated in thoracic and lumbar spine initially, and after 1 and 2 years. Seven patients in the fluoride group and eight in the placebo group completed the trial. In the fluoride group, bone mineral density did not change after 2 years (initial 1.05 +/- 0.07, final 1.07 +/- 0.06 g/cm2; p = n.s.). In the placebo group, however, bone mineral density decreased significantly (initial 1.00 +/- 0.07, final 0.93 +/- 0.06 g/cm2; p = 0.03). Moreover, in the fluoride group bone mineral density increased by 2.9 +/- 3.6%, and in the placebo group decreased by 6.6 +/- 2.6% (p = 0.04). None of the patients developed new vertebral or non-vertebral fractures. Treatment with sodium fluoride did not impair liver function or cholestasis in PBC. These results indicate that sodium fluoride prevents bone loss in PBC and therefore might be considered as a possible therapeutic agent for osteoporosis associated with this liver disease. Since a small number of patients completed the trial, further studies are required.


Echo-Doppler evaluation of acute flow changes in portal hypertensive patients: flow velocity as a reliable parameter. In order to evaluate the behavior of the portal vein cross-sectional area during changes in portal flow, two groups of subjects were analyzed in two blinded cross-over studies using echo-Doppler flowmetry. The first group (I) consisted of 21 patients with cirrhosis and 16 controls. They received a standardized meal which is known to increase portal flow. The second group (II) consisted of 31 patients with cirrhosis who received a dose of propranolol which is known to decrease portal flow. In Group I, 30 min after the meal, the portal vein blood velocity increased by 35 +/- 6% (p less than 0.01) in cirrhotic patients and by 55 +/- 5% (p less than 0.01), in normal subjects. The portal vein cross-sectional area increased significantly in normal subjects (22 +/- 2%, p less than 0.01) but not in cirrhotic patients (4 +/- 2%, n.s.). In Group II, 2 h after propranolol, there was a significant decrease in portal blood velocity (-14 +/- 2%), whereas the portal vein cross-sectional area did not show any significant changes. These data demonstrate that, in portal hypersensitive patients, the portal area measured by echo-Doppler flowmetry can be assumed to be constant and hence its calculation to estimate changes in portal blood flow can be omitted. Therefore, the use of blood velocity alone is suggested to monitor acute changes in flow in portal hypertension using Doppler flowmetry. The elimination of the portal vein cross-sectional area measurement simplifies the quantitative calculation of portal hemodynamics and increases the reliability of the technique by avoiding a source of error.


Quantitative analysis of proliferating sinusoidal cells in dimethylnitrosamine-induced cirrhosis. An immunohistochemical study. Proliferating lipocytes (fat-storing cells or perisinusoidal stellate cells of the liver) were detected by in vivo incorporation of bromodeoxyuridine (BrdU) in an experimental model of cirrhosis in the rat by dimethylnitrosamine. Lipocytes were identified by sequential double immunohistochemical staining on frozen sections using anti-desmin antibodies as a marker of cytoplasmic intermediate filaments followed by anti-BrdU antibodies to identify S-phase nuclei in animals treated for 7, 14 or 21 days. The number of desmin-positive (lipocytes) and desmin-negative (Kupffer and endothelial cells) sinusoidal cells incorporating BrdU was recorded. The labelling index of lipocytes was calculated as the percentage of BrdU-labelled desmin-positive cells with respect to total number of lipocytes. In control animals, when the total number of lipocytes was 153.9 +/- 11/mm2 (mean +/- 1 S.E.) the number of desmin-positive S-phase sinusoidal cells never exceeded 6.8 +/- 1.2/mm2 with a maximum labelling index of 4.3 +/- 0.5%. At 7 days of treatment, the values were respectively 236 +/- 26.5/mm2, 53.2 +/- 5.9/mm2 and 22.6 +/- 0.5% (p less than 0.001 vs. controls), while, at 21 days they were 272.5 +/- 21.2/mm2, 23.3 +/- 4.0/mm2 and 8.5 +/- 1.1% respectively (p less than 0.01). These results show that hyperplasia of lipocytes represents an early reaction to dimethylnitrosamine-induced liver injury. The local accumulation of lipocytes appears to occur in areas where fibrous septa develop later on.


Uridine diphosphoglucose restores lipocyte proliferation in the regenerating liver of ethanol-treated rats. The effect of continuous intraperitoneal infusion of uridine diphosphoglucose on ethanol-induced suppression of lipocyte proliferation was studied in regenerating rat livers from 1-4 days after hepatectomy. Proliferating lipocytes were positively identified using a two-sequence immunohistochemical staining for cytoplasmic desmin and bromodeoxyuridine-labelled nuclei. Hepatectomy rapidly stimulated lipocyte proliferation which peaked 2 days after hepatectomy (labelling index, 17.9 +/- 0.81%). uridine diphosphoglucose or glucose infusion did not modify the time course of lipocyte proliferation. Ethanol feeding to hepatectomized rats receiving saline or glucose infusion resulted in a 71% (p less than 0.005) and 61% (p less than 0.005) inhibition of lipocyte proliferation, respectively, 2 days after hepatectomy, thereby abolishing the characteristic proliferative peak observed in rats not treated with ethanol. In contrast, uridine diphosphoglucose infusion doubled the labelling index (13.1 +/- 2.34%) in ethanol-fed rats compared to that in corresponding rats treated with saline (5.28 +/- 1.29%; p less than 0.005) or glucose (6.51 +/- 0.64%; p less than 0.005). This resulted in the appearance of a proliferative peak, albeit smaller than normal, 2 days after hepatectomy. In sham-operated rats, lipocyte proliferation was low with a labelling index of 1.88 +/- 0.13% at the time of operation and of 1.69 +/- 0.23% 2 days thereafter. Uridine diphosphoglucose infusion to sham-operated rats for 2 days did not significantly affect lipocyte proliferation (labelling index 1.79 +/- 0.06%). The present study demonstrated that uridine diphosphoglucose does not affect lipocyte proliferation in the regenerating or sham-operated livers, but that it partially reverses the ethanol-induced suppression of lipocyte proliferation after hepatectomy.


Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis. The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis.


Evidence for the production of high amounts of interleukin-6 in the peritoneal cavity of patients with ascites. The ascites and serum concentrations of interleukin-6 (IL-6) and interleukin-1 (IL-1) were determined in 21 patients with hepatic ascites and in 9 patients with malignancy-associated ascites. There was no evidence for bacterial peritonitis in any patients. All ascites samples contained high amounts of immunoreactive IL-6 [hepatic ascites 1730 +/- 2130 pg/ml (mean +/- SD), 1160 pg/ml (median); malignant ascites 4020 +/- 1510 pg/ml (mean), 3820 pg/ml (median)] but no IL-1. The mean ascites to serum ratios of IL-6 were 96 (median 49) in patients with hepatic ascites and 587 (median 480) in patients with malignant ascites. Ascites IL-6 was biologically active as determined by the B9 cell bioassay. The results indicate that even in the absence of infection IL-6 is produced in high amounts in the peritoneal cavity of patients with hepatic or malignant ascites.


Some observations on the fine structure of the sensory cells in the neuromasts (ordinary lateral line) of the teleost Gambusia affinis. The structural and ultrastructural features of the sensory cells in the neuromasts of G. affinis were studied. These pear-shaped cels present a tuft of sensory hairs rising from the apex and a highly dense cytoplasm with multivesicular bodies, dyctiosomes, granular and smooth endoplasmic reticulum and numerous mitochondria. Large round granular dense bodies of an unknown nature can be observed inside and outside the nucleus. A great number of vesicles are present at the base of the cells, some of them associated with an afferent synapse, which also presents a presynaptic dense body. An efferent synapse with a nerve ending full of vesicles and a postsynaptic subsurface cisterna is also present at the base of these cells.


Ultrastructural localization of insulin-like immunoreactivity in the rat spinal cord. Insulin-like immunoreactive neurons were localized in the cervical, thoracic, lumbar and sacral segments of the rat spinal cord. Neurons from both the ventral and dorsal horns were labelled. The insulin-like reaction product was predominantly localized in the cell nucleus and the proximal and distal dendrites. In the labelled cell nucleus, the reaction product was scattered throughout the nucleoplasm and the inner and outer nuclear membranes but not within the nucleolus. In the labelled dendrites, the reaction product was closely associated with the parallel arrays of neurotubules. Most of the labelled distal dendrites were postsynaptic to non-labelled axon terminals. A labelled dendrite often formed the central element of a synaptic glomerulus with several non-labelled axon terminals. It is hypothesized that the insulin-like substance(s) may be modulating nuclear activities as well as neurotransmission at the synapse in the spinal cord.


Degenerative and regenerative phenomena in brain heterotopic homoplastic transplants of adult Triturus carnifex (Urodele Amphibians). The brains of adult Urodele Amphibians (Triturus carnifex Laur.) were homoplastically transplanted in conditions of complete morpho-functional isolation. Despite the heterogeneous nature of the histological aspects observed, the results point to the following general pattern for the fate of the brain transplants: 1) rooting phase (about day 5 after the operation) as indicated by degenerative patterns affecting the various encephalic districts and mainly involving the more peripheral neurons and the nerve fibers, and to a lesser extent the periventricular gray and the ependyma; 2) phase of rejection by host (from day 10 until end of experiment on day 30) as indicated by lymphocytic infiltration, the presence of macrophages and pyknoses, and the formation of a connective tissue capsule surrounding the transplant; 3) regenerative phase (from about day 10) as indicated by the onset of mitotic activity affecting elements of the ependymal epithelium and the periventricular gray, particularly in the telencephalic district. By the end of the experiment, in most of the transplants examined, degenerative processes were found to have prevailed over the regenerative phenomena. However, in some cases, and particularly in one of them, a distinctly higher degree of structural organization of neurons and nerve fibers can be observed at the telencephalic level. It may be postulated that, whenever a greater degree of compatibility exists between the host and the transplanted organ, it is possible, even in conditions of complete morpho-functional isolation, for the brain to express regenerative power through the ependyma and the matrix zones which have already been identified by some Authors in telencephalic periventricular areas or scattered through the mesencephalic gray matter.


[Neurohistological findings in the parietal cortex of children with chromosome aberrations]. In Golgi-Cox impregnated parietal cortex (regio postcentralis) of two children (20 months of age or 6 years of age) with Down's syndrome the pyramidal neurons of lamina III and V were investigated qualitatively and quantitatively. Fives types of pyramidal neurons were classified and compared statistically. As parameters for characterizing pyramidal neurons served dendritic lengths for all dendritic orders, within single dendritic fields, in apical and basal parts of the dendritic tree, and of the whole neuron. Normal values obtained in brains of the same age were not available, therefore, we compared our results with those published by other authors. To study the developmental stage of the pyramidal neurons in both our cases, we compared analogue pyramid types in both brains. The pyramidal neurons showed different qualitative abnormalities in their dendritic tree configuration. The comparison of quantitative parameters suggests the pyramidal cells of the older child show more degenerative changes, concerning especially lamina III pyramids but in lamina V pyramids as well. These changes might be structural correlates of the mental retardation: the 6 year old child was strongly retarded in clinical symptoms, too. The results are discussed and critically evaluated in view of the clinical signs of Morbus Down. Finally we should await the investigations of more cases for demonstrating the normal as well as the abnormal development of the human cerebral cortex.


The fine structure of the inferior colliculus in the cat. II. Synaptic organization. The synaptic organization of the central nucleus of the inferior colliculus (ICc) of the cat has been investigated by means of electron microscopy. On the basis of the following criteria: the size and the shape of the synaptic vesicles, the distribution and density of the vesicular population, the size and the shape of the synaptic boutons, their origin, and the characteristics of the active synaptic zones, several types of synaptic boutons in the ICc have been discriminated: LR1, LR2, SR, SSB, F1, F2, P, DCV-terminals, and "d"-profiles. The LR1, LR2, SR and SSB bouton types contain clear, round or slightly oval synaptic vesicles and form asymmetrical synapses mainly with middle sized and small dendrites and dendritic spines. LR2-terminals not rarely contact also the neuronal perikarya, whilst the SR-boutons form exclusively axodendritic and axospinous synapses. The P, F1 and F2-boutons contain a pleomorphic vesicular population (P-boutons), with an increased degree of vesicle flattening (F1 and F2-boutons) and form symmetrical axosomatic, axodendritic and axospinous contacts. Especially often the F1-boutons form axosomatic synapses, whilst the F2-terminals end mainly on dendrites. The DCV-boutons contain a mixed population of clear round synaptic vesicles and large dense core vesicles. The DCV-boutons terminate mainly on spines and small distal dendrites by means of asymmetrical synaptic specializations. The "d"-profiles originate from dendrites, and are identical to the thalamic "d"-profiles but are far more rarely observed in the ICc. The "d"-profiles are postsynaptic mainly to the LR-types, and are presynaptic to conventional dendrites, thus participating in synaptic triads. The axonal hillocks and the initial axonal segments of the larger perikarya in the ICc are substantially innervated mainly by LR and P-boutons. Glomerulus-like formations are fairly often, especially around the LR1-terminals, contacting several small postsynaptic targets. True synaptic glomeruli are only rarely observed. Branching myelinated axons are found mainly within the fibrodendritic laminae, whilst unmyelinated collaterals, emitted by myelinated axons are especially often encountered outside the laminae. Various types of myelinated axons form nodal synapses.


Developmental stages of the vomeronasal organ in the rat: a light and electron microscopic study. This paper describes the development of the rat vomeronasal organ from the stage of anlage until adulthood. Groups of four rats were sacrificed daily from prenatal day 13 (E13) until birth; at days 2, 4, 7, 10, 14 and 16 after birth; weekly from day P21 to P42 plus an additional group of adults. The vomeronasal organs were processed for light microscopy, including alcian blue-PAS and NADH-diaphorase reactions, and also for electron microscopy. For summarizing our results we propose the following developmental stages: 1. Anlage (E13). 2. Early morphogenesis (E14-16). 3. Late morphogenesis (E17 to birth). 4. Initiation of secretory activity (First postnatal week). 5. Cytoarchitectural maturity (2nd postnatal week). 6. Complete maturity (From 3rd postnatal week onwards). Our results on the maturation of the histological structure and the histochemical reactions, indicate that there may be some functional activity at birth but the development of the organ still continues during the first three postnatal weeks to acquire its full functional capability.


Systematisation of the olfactory bulb efferent projections in a lemurian primate: Microcebus murinus. In order to investigate a sensorial pathway essential in animal behavior, the efferent projections of the olfactory bulbs in Microcebus murinus were identified after transection of one olfactory peduncle and revelation of degenerating fibers by various silver staining methods. Total and partial sections have enabled the demonstration of the involvement in the olfactory projection areas of each olfactory tract: the lateral olfactory tract (LOT) and the intermediate olfactory tract (IOT), either via the medial forebrain bundle (MFB) or not. The IOT fibers innervate the cortex, the anterior olfactory nucleus, the caudate-putamen, the septum and the hippocampus on both sides. The LOT fibers reach the olfactory tubercle, the piriform cortex, the entorhinal cortex and the amygdala on both sides. Olfactory fibers could also be observed in the MFB innervating on both sides firstly the hypothalamic areas (the lateral hypothalamus, the suprachiasmatic, posterior supraoptic, mammillary nuclei and the median eminence), and then the mesencephalic structures (the locus coeruleus and the raphe nuclei). It may be concluded that the olfactory bulbs are not only connected with above-mentioned telencephalic areas, but are also directly related to the vegetative and integrative brain areas located in the hypothalamus and the brainstem and especially with the major nuclei which play an essential role in neurovegetative, neuroendocrine and behavioral regulation.


Primary projections of the lateral line nerves in larval sea lamprey, Petromyzon marinus L. An HRP study. The primary central projections of the anterior and posterior lateral line nerves were determined in the larval sea lamprey, Petromyzon marinus L. using silver staining methods and axonal transport of horseradish peroxidase (HRP). Lateral line fibers course in the dorsal portion of the octavolateral area. At the level of their entry in the medulla, all the lateral line fibers originate ascending and descending branches. The anterior lateral line nerve consists of three roots: dorsal, intermediate and ventral. Afferents of the dorsal root project to the ipsilateral dorsal nucleus. The intermediate and ventral roots project ipsilaterally to the lateral neuropil of the medial nucleus and to the cerebellar lamina, but they do not cross the midline. Contralateral projections of this nerve were not found in larvae. Primary afferents of the posterior lateral line nerve project ipsi- and contralaterally to the medial neuropil of the medial nucleus. Ascending fibers course in the ipsilateral medial nucleus, enter the cerebellar lamina, cross the midline and descend to the lateral neuropil of the contralateral medial nucleus. In the cerebellar lamina, the fibers of the anterior lateral nerve are located ventrolaterally to those of the posterior lateral nerve. Lateral line efferents were not observed in larvae.


Immunocytochemical localization of GnRH in the hypothalamus of the bat Miniopterus schreibersii schreibersii. The distribution of gonadotropin-releasing hormone (GnRH) has been examined in the hypothalamus of adult female bats, Miniopterus schreibersii schreibersii, along annual reproductive cycle by means of light-microscopic immunocytochemistry. GnRH-immunoreactive cells are localized throughout the medial basal hypothalamus, being specially numerous in the arcuate nucleus. They are generally bipolar or monopolar neurons with smooth contour, although spiny cells were also found exclusively in the arcuate nucleus from periovulatory bats. Depletion in both number and immunocytochemical labelling of GnRH perikarya is detected in pregnant and lactating bats. GnRH-immunoreactive fibers are distributed in the internal layer of the median eminence and the infundibular stalk. Pregnant and lactating animals show lower GnRH fibers content and a less intense labelling than in periovulatory and hibernating conditions. The results suggest that changes in the secretory activity of GnRH neurons may be associated with hibernation and delayed implantation that suffer these mammalian species.


Golgi study on neurons and fibers in Nucl. rotundus of the thalamus in chicks. The structural arrangement of nucleus rotundus was studied by Golgi method. Large, multiangular principal neurons, their dendrites and dendritic terminals were observed. The long dendrites and their side-branches course parallel and/or perpendicular to each-other and they are arranged about in dorso-ventral latero-medial and rostro-caudal directions. The dendrites and their side-branches develop characteristic terminal branchings. These dendritic terminals overlap each-other and the area is called dendritic terminal field. The tecto-rotundal fibers traverse the nucleus in large bundles and the final sections of fibers join to the dendrites of principal neuron and terminate in dendritic terminal fields.


[A study of risk factor in osteoporosis, femoral neck fracture and colles' fracture]. This work studied risk factors of osteoporosis, femoral neck fracture and Colles' fracture. The results were compared with those of a healthy group. Milk intake was frequent in the healthy group, but rare in the femoral neck fracture or Colles' fracture group. Most of osteoporosis and femoral neck fracture group were bed ridden, or stayed indoors for a long time before injury. They weighed less and were thin as compared to the healthy group. Decrease of activities of daily living and less body weight were risk factors of osteoporosis and femoral neck fracture, but these risk factors were more predominant in the femoral neck fracture than osteoporosis group. In this study, 74.4% of the patients with femoral neck fracture also had osteoporosis and 33.3% with Colles' fracture had osteoporosis. Colles' fracture was related to injury force and femoral neck fracture was found to be closely related to osteoporosis.


[Immunohistochemical study on the effect of high tibial osteotomy on the distribution pattern of neuropeptides in the synovium of the osteoarthritic knee]. Synovial tissue was obtained from 18 knees with medial compartmental osteoarthritis (OA) and from 20 knees on which a high tibial osteotomy had been performed. Neuropeptides were stained with a specific avidin-biotin-peroxidase method. Comparisons were made of the incidence of staining as well as the location of staining within the synovia (medial, lateral, and suprapatellar regions). The results showed that the synovium had an extensive neural network of both the somatic and autonomic nervous systems. In the medial synovium of the preoperative knees, the neuropeptides were found in abundance. An especially strong response for substance P (SP) and calcitonin gene-related peptide (CGRP) was observed at the free nerve endings. However, the postoperative incidence of SP-positive free nerve endings was reduced to 54% of the preoperative amount and the inflammation subsided in the medial region. These findings suggested that free nerve endings containing SP might be mainly involved in the inflammation and pain of OA.


[A new intramedullary nailing system for long bone fractures--biomechanical evaluation and animal study of a new intramedullary nail]. Interlocking intramedullary nails have expanded their application to the fixation of long bones especially for unstable or comminuted fractures. However, there are certain drawbacks in this method: prolongation of operative time and increased radiation hazard to the patient as well as to the surgical staff, the latter of which is especially a problem in the distal interlocking under fluoroscopic control. In order to solve the problem a new intramedullary nail (J-type) was developed and tested in vitro with Hiprox femur models as well as in vivo using canine models. The nail made of Ti-6Al-4V alloy is composed of an inner nail and an outer cylinder. The proximal portion is transversely fixed with two screws, while the distal portion is fixed into the cancellous bone with four expandable blades. The strength of fixation with this nail was compared to those with four other commercially available interlocking nails as to bending, tortional and compression stiffness as well as to the durability against repeated compression. In the present in vitro and in vivo experiments, a newly developed intramedullary nail (J-type) provides evidence for satisfactory mechanical strength. The use of J-type nail also contributes to shorter operative time and reduction of radiation hazard.


[An experimental study on repair and recovery of lacerated muscles--histological and histochemical observations]. A histological and histochemical study of the repairing process of skeletal muscle after transection and immediate suture was conducted using the gastrocnemius muscle of hamsters. The muscles were examined from one hour to twelve weeks after operation and were prepared as specimens for either transverse or longitudinal sections. During the first two days, necrotic fibers were scavenged by macrophages. Early regenerating fibers appeared at the extent of about 1-2 mm on both sides of the cut ends by the fourth day. After one week, myotubes identified as type 2C were abundant. By the fourth week regenerating fibers had grown longitudinally and bridged the injury site between the proximal and distal muscle fiber segments. After six weeks, they had almost matured histochemically. After eight weeks, there was substantial repair of the injury site with scarce fibrous tissue. This study has clearly demonstrated the histological and histochemical findings of repairing process of the skeletal muscle after transection.


Preservation of bone morphogenetic protein in heat-treated bone. In operations of bone tumors, reimplantation of resected bone after boiling or autoclaving is a simple means of obtaining both tumor necrosis and skeletal reconstruction. However, such reimplants lose their osteogenesity. We investigated whether bone inductive ability could be maintained in heat-treated bone. Bone morphogenetic protein (BMP) extracted from rabbit bone after heating for various periods at different temperatures was implanted into the muscles of mice to evaluate osteogenetic activity. The maximum new bone formation was observed in specimens treated at 70 degrees C for 10 minutes, followed by those treated at 70 degrees C for 15 minutes. We then measured the temperature in the center of a cortical bone heated in 0.15 N NaCl solution at 50 degrees, 60 degrees, 70 degrees, 80 degrees, and 90 degrees C. Cortical bone center temperature reached that of the surrounding solution within 2.5 minutes. These results indicated that heating at 70 degrees for 10 to 15 minutes was suitable for heat treated-bone to maintain bone inductive ability.


[Evaluation of school dental health activities in Hiraizumi primary school, Iwate prefecture]. The purpose of this study was to evaluate the health activities in Hiraizumi primary school, Iwate prefecture. As a result of intensive dental health activities from 1978 to 1990, which consisted of tooth brushing instruction by class, dental education for the schoolchildren and their guardians, utilization of fluoride mouth rinsing (once a week), and, by following a model school of caries prevention designated by the Ministry of Education et al., the oral health status of the Hiraizumi primary schoolchildren improved significantly compared with those of the Ohya primary schoolchildren who followed the routine school dental health activities. The results of questionnaires, taken from both primary schoolchildren in 1986 and 1989, show that the oral health behavior of the Hiraizumi primary schoolchildren also improved.


[Clinical study of maxillofacial fractures sustained during sports and games]. We performed a clinico-statistical study of the maxillofacial fracture due to sports during the period of 15 years between 1977 and 1991. Eighty-nine patients were seen with injuries resulting from 21 different sports. The incidence of the fracture was most common in rugby, followed by ski, baseball and soccer. Males were shown to be more prone to maxillofacial fracture than females (5.4:1) and the highest incidence of injuries involved the 20-29 age group followed by the 10-19 age group. The major parts of the fracture were the mandible and the alveolar process. Conservative therapy such as maxillomandibular fixation was usually performed and the clinical course was good. It was suggested that the prevention of the sports-related fracture and the time of returning to sports after the fracture will require further study.


[Studies on caries of Ishibashi rat--III. Experimental caries in Ishibashi rat]. Dental caries was experimentally induced in the Ishibashi rats (ISR) by feeding them with conventional diets or with caries-producing diets, and the pattern and severity of their induced carious lesions were compared with those of the Sprague-Dawley rats (SD). Simultaneously, serum antibody titers against Streptococcus mutans and calcium and phosphorus concentration in the sera and in the femurs were compared between the ISR and SD. The results were as follows: 1. When judged by cavities, ISR showed a higher carious incidence and average number of cavities per one rat than the SD, whichever diet the rats were fed. 2. When judged by fissure caries observed on the thin sections of the teeth, both the carious incidence and average number of fissure lesions in the ISR were not always high compared with those in the SD, and there seemed to be a great variation of caries-susceptibility in the ISR. 3. Caries in the ISR seemed to be more progressive than that in the SD. 4. There were no differences in the serum antibody titers against the S. mutans between the ISR and SD. 5. No differences in the concentration of calcium and phosphorus in the sera and femurs were observed between the ISR and SD, whichever diet they were fed.


[Alveolar bone resorption process in molar tooth region in calcium-deficient rats]. The present study was carried out to investigate the alveolar bone resorption in the molar tooth region in the rats fed a low calcium diet. Male Wistar rats (70-85g in body weight) were either fed a low calcium diet (0.05% Ca, 0.35% P) or a control diet (0.5% Ca, 0.35% P) by using a pair feeding technique. The rats were sacrificed at intervals of 3, 6, 9 and 20 days during the experimental period. Contact microradiograph of the second molar region of the mandible showed that the cancellus bone as well as the endosteal surface of the cortical bone were progressively resorbed soon after the start of low calcium feeding. At day 9, the amount of bone was reduced to about half of the control rats and 80% of the bone was diminished at day 20. In spite of the severe bone resorption, the alveolar bone proper that surrounds the molar sockets and a few cancellus bone were seen remaining and the occlusal function of the molar tooth seemed to be maintained. These results suggest that the alveolar bone quickly responded to the low calcium diet resulting in bone resorption and that the bone in the supporting tissues of the molar tooth seems to be not affected by the calcium deficiency.


Real-time respiratory monitoring workstation--software and hardware engineering aspects. We have applied advanced real-time techniques in software, that are intensively used in critical areas like space research and defence applications, to realise an Integrated Real-Time Respiratory Monitoring System at the Thorax Anesthesiology, Academic Hospital Rotterdam. The system is called the 'SERVO WINDOW'--a window to the servo ventilator. The heart of the system is a real-time kernel that uses preemptive scheduling to achieve multitasking on a IBM PC compatible hardware platform. To the clinician this means that he gets all relevant information from one source i.e. the Respiratory Workstation. The waveforms of the airway pressure, airway flow and the expired CO2 curve are displayed continuously on the screen. The Vector Loops like Pressure Volume, Flow Pressure and Flow Volume loops are also available in addition to the lung mechanics parameters like Expiratory and Inspiratory Resistances, Compliances, Peak Pressure, PEEP, etc. The Single Breath Diagram i.e. expired CO2 concentration versus volume and dead space ventilation is also calculated. The blood gas analysis data is plotted in convenient diagrams like the O2-CO2 diagram, Oxygen Chart, etc. The trend of all these parameters are available with a granularity of one minute. An industry standard laser printer is used for report generation to produce reports of the real-time waveforms, parameter values and the trends. User interface is through easy menus with the traditional keyboard, touchscreen including keyboard on screen for data entry and the mouse.


AxAudit--anaesthetic audit system.

AxAudit--anaesthetic audit system. A bar code based computerised anaesthetic audit system is described. The system consists of a data entry and validation module resident on a remote hand-held computer and a central database module resident on a desktop computer, capable of conducting extensive searches, analysis, graphing and reporting of captured data. Information is entered into the computer by 'swiping' a bar code reader across required bar codes. Information entered is constantly validated and the computer ensures a minimum data set is captured for every patient. Since data is transferred directly into a computer at the point of clinical activity, a large data set can be presented to the clinician, ensuring as complete a patient record as possible and avoiding the problems associated with traditional form-filling and the subsequent transfer of information onto a computer. The hand-held computer has data cards which can hold information on approximately 200 patients. These cards can be inserted directly into a card reader attached to a desktop computer, thus automating the process of data transfer. The AxSys Anaesthetic Audit system, AxAudit, is a bar code based, computerised audit system developed with the aim of executing effective audit in the course of normal clinical activity.


Computer assisted management of information in an intensive care unit. In order to use the capability of computers for handling large amounts of information, we developed a program for the acquisition, handling, storage and retrieval of administrative and clinical information generated in the 20 bedded multidisciplinary critical care unit of a University Hospital. At an initial phase a personal computer (PC) was used to collect information from 4362 patients, that included registration data, coded admission problems, techniques and special treatments, and final diagnosis. This information combined with free text provided a discharge report. Complementary programs allowed calculation and storage of hemodynamic and gas exchange parameters. This experience led to a second phase in which a computer with microprocessor Intel 80386 at 25 MHz, 8 MB RAM, 310 MB hard disk and a streamer for 150 MB cartridge tape back up, using UNIX operating system, permitted multiple users working simultaneously through 1 central console and 7 ASCII terminals. Data input included demographic data, previous and admission problems in coded form, present history and physical examination in free text, list of present problems in coded form, comments on evolution, record of special techniques and treatments, laboratory data, treatment, final diagnosis and facility for using all the information to elaborate the final report. Side modules provide help for drugs dosing, protocols for specific conditions and clerical routines. The system is open for connection to other areas of the Hospital. Data from more than 2000 patients have been included so far.(ABSTRACT TRUNCATED AT 250 WORDS)


A decision table and rule based interpretation system for epileptic discharges. The representation of the various features of waveforms and their correlations, in EEG recording for the diagnosis of different diseases have been carried out by many researchers due to the impact of knowledge based on expert systems development tools and techniques. The realisation of these system requires a specific hardware and software tool for its implementation, which may be a costly affair. The design and development of low cost effective system for the diagnosis of epileptic patients have been reported in this paper. Two different and linked (at certain stage) approaches (i) decision table; (ii) rule based system have been followed to model the reasoning processes of physician in the diagnosis. In the decision table the features of specific waveforms of EEG are represented in the tabular form. The features are obtained from a 8086 microprocessor based data acquisition system. The rule based system is designed with IF and THEN form of rules using Turbo-Prolog as programming language tool and is implemented on low cost PC-AT. The results obtained are at an intermediate stage of data processing by decision tables and at the final stage being carried out by rule based model. The performance of the system is evaluated by recording of EEG of some epileptic patients. The results obtained are comparable and to a certain extend appreciable in the opinion of the physician.


A portable target controlled propofol infusion system. A portable target controlled infusion system for propofol has been developed based on a Psion hand-held microcomputer and the Ohmeda 9000 syringe pump. The system uses a pharmacokinetic model which describes the distribution and elimination of propofol to achieve and maintain any selected target blood concentration. Target blood concentrations of 1 micrograms/ml, 3 micrograms/ml and 5 micrograms/ml were selected in laboratory trials and the cumulative volumes delivered by the Psion system each minute were compared with the theoretical output calculated by the pharmacokinetic model. The results obtained showed that the computer system delivered volumes which were always within 2% of the theoretical values. This system offers a convenient and simple method of maintaining anaesthesia using propofol.


The influence of "preparedness" on autoshaping, schedule performance, and choice. Two groups of experimentally naive pigeons were exposed to an autoshaping procedure in which the response key was mounted on the wall (the conventional location) or on the floor of the chamber. In two experiments, subjects readily responded to the wall key, but floor-key subjects required shaping. A subsequent experiment compared performance of wall- and floor-key groups on an ascending series of fixed-ratio schedule values, resistance to extinction, differential reinforcement of other behavior, and reversal of key assignment. Each experiment was followed by several sessions of fixed-ratio training; the performance of the wall- and floor-key groups was almost identical throughout. In the final experiment, a fixed-ratio requirement could be completed on either or both keys. Birds initially chose the key on which they had responded during the preceding (reversal of key assignment) experiment. However, within a few sessions both groups showed almost exclusive preference for the floor key. Preference for a key located on the floor may follow from the fact that pigeons are ground feeders and may thus be more "prepared" to peck the floor than to peck a wall. However, autoshaping, under the conditions prevailing here, occurred much more readily to the wall key, suggesting that pecking a vertical surface is more highly prepared. Difficulties in determining relative preparedness seem moot, however, given the lack of between-group differences in the intervening experiments. It is thus unlikely that schedule performances critically depend upon the specific operant response involved.


Selective sensitivity of schedule-induced activity to an operant suppression contingency. The sensitivity of pigeons' schedule-induced activity to operant consequences was studied in two experiments. During a 30-s interval between food presentations, a keylight stimulus brightened incrementally. Stable terminal key pecking and interim locomotor activity developed. An operant "setback" contingency was applied to activity. The contingency arranged for locomotor movements (detected by a nine-panel floorboard) to be followed by a resetting of the keylight brightness to a dimmer value and a 1-s delay of reinforcement (for individual responses). Experiment 1 showed that activity patterns were highly sensitive to their operant consequences. Accompanying key-peck rates were only transiently affected. In Experiment 2, the setback contingency was imposed during restricted portions of the trial, and differential operant control of activity was demonstrated. However, birds in this study produced higher rates of key pecking as activity rates were reduced. These results suggest that although schedule-induced activity arises in response to the temporal arrangement of stimulus events, this behavior may retain considerable sensitivity to response-consequence relations.


Choice with delayed and probabilistic reinforcers: effects of variability, time between trials, and conditioned reinforcers. In a discrete-trials procedure with pigeons, a response on a green key led to a 4-s delay (during which green houselights were lit) and then a reinforcer might or might not be delivered. A response on a red key led to a delay of adjustable duration (during which red houselights were lit) and then a certain reinforcer. The delay was adjusted so as to estimate an indifference point--a duration for which the two alternatives were equally preferred. Once the green key was chosen, a subject had to continue to respond on the green key until a reinforcer was delivered. Each response on the green key, plus the 4-s delay that followed every response, was called one "link" of the green-key schedule. Subjects showed much greater preference for the green key when the number of links before reinforcement was variable (averaging four) than when it was fixed (always exactly four). These findings are consistent with the view that probabilistic reinforcers are analogous to reinforcers delivered after variable delays. When successive links were separated by 4-s or 8-s "interlink intervals" with white houselights, preference for the probabilistic alternative decreased somewhat for 2 subjects but was unaffected for the other 2 subjects. When the interlink intervals had the same green houselights that were present during the 4-s delays, preference for the green key decreased substantially for all subjects. These results provided mixed support for the view that preference for a probabilistic reinforcer is inversely related to the duration of conditioned reinforcers that precede the delivery of food.


Intertrial-interval effects on sensitivity (A') and response bias (B") in a temporal discrimination by rats. Killeen and Fetterman's (1988) behavioral theory of animal timing predicts that decreases in the rate of reinforcement should produce decreases in the sensitivity (A') of temporal discriminations and a decrease in miss and correct rejection rates (decrease in bias toward "long" responses). Eight rats were trained on a 10- versus 0.1-s temporal discrimination with an intertrial interval of 5 s and were subsequently tested on probe days on the same discrimination with intertrial intervals of 1, 2.5, 5, 10, or 20 s. The rate of reinforcement declined for all animals as intertrial interval increased. Although sensitivity (A') decreased with increasing intertrial interval, all rats showed an increase in bias to make long responses.


Effects of response requirement and alcohol on human aggressive responding. Nine men participated in two experiments to determine the effects of increased response requirement and alcohol administration on free-operant aggressive responding. Two response buttons (A and B) were available. Pressing Button A was maintained by a fixed-ratio 100 schedule of point presentation. Subjects were instructed that completion of each fixed-ratio 10 on Button B resulted in the subtraction of a point from a fictitious second subject. Button B presses were defined as aggressive because they ostensibly resulted in the presentation of an aversive stimulus to another person. Aggressive responses were engendered by a random-time schedule of point loss and were maintained by initiation of intervals free of point loss. Instructions attributed these point losses to Button B presses of the fictitious other subject. In Experiment 1, increasing the ratio requirement on Button B decreased the number of ratios completed in 4 of 5 subjects. In Experiment 2, the effects of placebo and three alcohol doses (0.125, 0.25, and 0.375 g/kg) were determined when Button B presses were maintained at ratio values of 20, 40 and 80. Three subjects who reduced aggressive responding with increasing fixed-ratio values reduced aggressive responding further at higher alcohol doses. One subject who did not reduce aggressive responding with increasing fixed-ratio values increased aggressive responding at the highest alcohol dose. The results of this study support suggestions that alcohol alters aggressive behavior by reducing the control of competing contingencies.


Spreading activation versus compound cue accounts of priming: mediated priming revisited. Spreading activation theories and compound cue theories have both been proposed as accounts of priming phenomena. According to spreading activation theories, the amount of activation that spreads between a prime and a target should be a function of the number of mediating links between the prime and target in a semantic network and the strengths of those links. The amount of activation should determine the amount of facilitation given by a prime to a target in lexical decision. To predict the amount of facilitation, it is necessary to measure the associative links between prime and target in memory. Free-association production probability has been the variable chosen in previous research for this measurement. However, in 3 experiments, the authors show priming effects that free-association production probabilities cannot easily predict. Instead, they argue that amount of priming depends on the familiarity of the prime and target as a compound, where the compound is formed by the simultaneous presence of the prime and target in short-term memory as a test item.


How semantic is automatic semantic priming? Priming for semantically related concepts was investigated using a lexical decision task designed to reveal automatic semantic priming. Two experiments provided further evidence that priming in a single presentation lexical decision task (McNamara & Altarriba, 1988) derives from automatic processes. Mediated priming, but no inhibition or backward priming was found in this type of lexical decision task. Experiments 3 and 4 demonstrated that automatic priming was found only for associated word pairs, as determined by word association norms, and not for word pairs that are semantically related but not associated. It is argued that automatic priming in the lexical decision task occurs at a lexical level not at a semantic level.


Form-based priming in spoken word recognition: the roles of competition and bias. Phonological priming of spoken words refers to improved recognition of targets preceded by primes that share at least one of their constituent phonemes (e.g., BULL-BEER). Phonetic priming refers to reduced recognition of targets preceded by primes that share no phonemes with targets but are phonetically similar to targets (e.g., BULL-VEER). Five experiments were conducted to investigate the role of bias in phonological priming. Performance was compared across conditions of phonological and phonetic priming under a variety of procedural manipulations. Ss in phonological priming conditions systematically modified their responses on unrelated priming trials in perceptual identification, and they were slower and more errorful on unrelated trials in lexical decision than were Ss in phonetic priming conditions. Phonetic and phonological priming effects display different time courses and also different interactions with changes in proportion of related priming trials. Phonological priming involves bias; phonetic priming appears to reflect basic properties of activation and competition in spoken word recognition.


Prelexical facilitation and lexical interference in auditory word recognition. Phonological priming effects were examined in an auditory single-word shadowing task. In 6 experiments, target items were preceded by auditorily or visually presented, phonologically similar, word or nonword primes. Results revealed facilitation in response time when a target was preceded by a word or nonword prime having the same initial phoneme when the prime was auditorily presented but not when it was visually presented. Second, modality-independent interference was observed when the phonological overlap between the prime and target increased from 1 to 3 phonemes for word primes but not for nonword primes. Taken together, these studies suggest that phonological information facilitates word recognition as a result of excitation at a prelexical level and increases response time as a result of competition at a lexical level. These processes are best characterized by connectionist models of word recognition.


Direct comparison of two implicit memory tests: word fragment and word stem completion. In 3 experiments, the implicit memory tests of word fragment and word stem completion showed comparable effects over several variables: Study of words produced more priming than did study of pictures, no levels-of-processing effect occurred for words, more priming was obtained from pictures when Ss imaged the pictures' names than when they rated them for pleasantness, and forgetting rates were generally similar for the tests. A different pattern of results for the first 3 variables occurred under explicit test conditions with the same word fragments or word stems as cues. We conclude that the 2 implicit tests are measuring a similar form of perceptual memory. Furthermore, we argue that both tests are truly implicit because they meet Schacter, Bowers, & Booker's (1989) retrieval intentionality criterion: Levels of processing of words have a powerful effect on explicit versions of the tests but no effect on implicit versions.


Memory with and without awareness: performance and electrophysiological evidence of savings. Event-related potentials (ERPs) recorded on the scalp were shown to be sensitive indicators of the strength of a memory trace on both implicit and explicit tests of memory. In explicit recognition tests, the amplitude of a positive potential identified as P300 was larger for "old" than for "new" words regardless of whether the subject categorized the items correctly. This effect, however, was statistically reliable only when the recognition memory (d') was relatively high. In contrast to ERPs, the reaction times in explicit recognition were sensitive to accuracy but not to repetition. In implicit tests, lexical decisions to repeated words were faster than to newly presented words. The magnitude of the repetition effect varied neither with elapsed time since the last repetition nor with the number of previous repetitions. In contrast, the P300 elicited by the same words were sensitive to both lag and recency of repetition, suggesting that they were influenced by the episodic memory strength of the items.


Direct and indirect measures of memory for modality in young and older adults. In 2 experiments, young and older adults demonstrated modality effects of similar magnitude in perceptual identification tasks. That is, both young and older adults demonstrated more repetition priming when study and test modalities matched than when they were different, suggesting that contextual information was equally available across age. However, when asked explicitly to retrieve modality information, older adults were less accurate than young adults. These results constitute evidence for a dissociation between direct and indirect measures of memory for modality information. They call into question hypotheses that memory impairment in old age is due to deficient encoding of contextual information and challenge current accounts of modality effects in repetition priming.


Aging and memory for expected and unexpected objects in real-world settings. Adult age differences in the consistency effect were examined in 3 experiments. The consistency effect refers to items inconsistent with expectations being better remembered than items consistent with expectations. Younger and older adults walked into an office room and viewed objects that varied in their consistency with expectation. Immediate and delayed recognition tests on item information (i.e., distractors were defined by their semantic identity) revealed that both age groups recognized unexpected items better than expected items. However, when recognition of token information was requested (i.e., distractors were defined by their physical appearance), younger adults, in contrast to older adults, exhibited consistency effects. Also, under divided attention, young adults revealed the same pattern of data as did elderly adults under full attention. The results are discussed in terms of capacity-related differences in distinctive encoding.


Improving recall by recoding interfering material at the time of retrieval. Our experiments demonstrate that interference of an interpolated list of items with recall of an original list can be substantially reduced by forming Ss just before testing how to reorganize and simplify the interpolated material. In Experiments 1 and 2, Ss better recalled an initial serial list of letters when informed at testing that an interpolated list spelled a certain phrase backward. Similarly, in Experiments 3 and 4, Ss better recalled an initial list of cities when told that the interpolated cities were also names of former U.S. presidents. Control experiments rule out several simple explanations. In contrast to an editing hypothesis, the postorganizing clue helped recall even when problems of list differentiation were minimized. Current memory models appear unable to explain this benefit of a postlearning clue that enables Ss to segregate the interpolated material from the to-be-remembered material.


Intratesticular control of spermatogenesis in the frog, Rana esculenta. Adult intact and hypophysectomized (PDX) frogs, Rana esculenta, were treated with a gonadotropin releasing hormone agonist (GnRHA, HOE 766) and/or cyproterone acetate (CPA), the antiandrogen, in order to investigate the regulation of primary spermatogonial (I SPG) multiplication in vertebrates. Treatment with GnRHA (injections containing 900 ng administered for 12 days on alternate days) caused a significant increase of the mitotic index (MI) of I SPG in PDX animals and a further MI increase of SPG was observed when 0.66 mg CPA was given concomitantly with GnRHA. The treatment with 0.66 mg CPA in combination with GnRHA also increased secondary spermatocyte (II SPC) appearance. Moreover, number of nests containing spermatids (SPT) decreased as CPA, in combination with GnRHA, was administered in increasing doses (0.33 and 0.66 mg/injection). Intact animals treated with CPA (0.66 mg/injection) showed a time-dependent I SPG multiplication increase which reached highest values after 28 days. Secondary SPC also proliferated until day 28; meanwhile the number of nests containing SPT decreased. Neither testosterone nor R5020 (a progestin which is not converted to androgens) modified the basal and GnRHA-induced spermatogonial proliferation. These results confirm that in the frog, Rana esculenta, spermatid formation is impaired by CPA treatment and that I SPG multiplication is enhanced by a direct effect of GnRHA; moreover, we suggest that the absence of spermatids constitutes a signal promoting spermatogonial proliferation.


Analysis of puberty-accelerating pheromones. Two experiments were performed to test putative puberty-accelerating pheromones. In the first experiment, 37 weanling female house mice of the ICR strain were exposed to 1 of the following 3 treatments: an airborne mixture of 0.05 M isoamylamine and 0.05 M isobutylamine, fresh male mouse urine, or distilled water, as the control. Neither the amine mixture nor the male urine accelerated first estrus in the mice following airborne exposure to these compounds. In the second experiment, 37 weanling female mice of the same strain were exposed to the same chemicals as in the first experiment by direct contact to the oro-nasal groove. The mixture of isoamylamine and isobutylamine did not accelerate puberty, but direct contact with the male urine accelerated puberty as evidenced by uterine weights.


Changes in brain gonadotropin-releasing hormone, plasma estradiol 17-beta, and progesterone during the final reproductive cycle of the female sea lamprey, Petromyzon marinus. Changes in ovarian morphology, brain gonadotropin-releasing hormone (GnRH), plasma estradiol, and progesterone were examined during the 1988 and 1989 spawning migrations of the adult female sea lamprey, Petromyzon marinus. There were significant increases through time in brain GnRH (1989) and plasma estradiol (1988 and 1989), with progesterone levels fluctuating (1988 and 1989) during the freshwater phase of the spawning migrations. In 1989, brain GnRH and plasma estradiol levels gradually increased through time until just prior to spawning when levels decreased. During 1988, there were no significant changes in GnRH, which may reflect lower temperatures in that year. These data provide new information on brain GnRH during the final maturational processes in the female sea lamprey.


Effects of an augmented nerve supply on forelimb regeneration in the adult mud frog, Rana rugosa. Forelimbs of the adult mud frog Rana rugosa, when amputated midway through the zeugopodium, regenerate heteromorphically. The resulting regenerative outgrowths were mostly rod shaped and consisted of a cartilaginous core, in which the base was ossified, and muscle elongated distally along the cartilage, the whole being covered by connective tissue and skin. The tip of the regenerating muscle reached a point distally about one third of the length of the regenerative outgrowths. When the innervation of forelimb stumps was augmented by surgical diversion of the ipsilateral sciatic nerve, the amputated limbs regenerated mostly as spatula-shaped outgrowths, which were longer than those of normally innervated forelimbs. Such hyperinnervated regenerates exhibited less ossification of cartilage, or sometimes none at all. However, the regeneration of muscle was more extensive. That is, it reached more than half way along the regenerative outgrowth. Furthermore, denervation resulted in the absence of regeneration in all cases examined. These results clearly indicate that limb regeneration in Rana rugosa is dependent upon the degree of innervation, not only for the early stages of regeneration, but also for the growth and differentiation of the regenerative outgrowth.


Sustained attention and the Type A behavior pattern: the effect of daydreaming on performance. The present study examined the ability of Type A and Type B subjects to sustain attention during a 40-min visual vigilance task. It was predicted that Type A subjects would perform better than Type B subjects and that the performance of both groups would be related to the frequency of daydreams during the vigil. Type A subjects outperformed Type B subjects with regard to perceptual sensitivity (A') and number of signal detections. Although both groups reported an increase in the number of their daydreams as the vigil progressed, Type A subjects reported fewer daydreams during each period of watch than did Type B subjects. In addition, an inverse relationship was found between the number of signal detections and the frequency of daydreams.


Effects of spatial disruptions on reading speed for fast and slow readers. Forty-five subjects read three paragraphs at their normal reading speed and were timed. The first paragraph was presented normally, and the others were shown either with spaces that had been filled in or with spaces that were randomized in size. The subjects' initial reading speed declined with both alterations, but to a greater extent with the filled text. Moreover, the reduction in reading speed was greater for the 10 fastest readers than for the 10 slowest readers. This pattern of performance may reflect a floor effect with slower readers in the filled condition, but the authors interpreted the results as providing further support for Hochberg's peripheral search guidance (PSG; 1970) stage of reading.


Effects of same-modality interference on immediate serial recall of auditory and visual information. Two studies investigated the effects of same-modality interference on the immediate serial recall of auditorily and visually presented stimuli. Typically, research in which this task is used has been conducted in quiet rooms, excluding auditory information that is extraneous to the auditorily presented stimuli. However, visual information such as background items clearly within the subject's view have not been excluded during visual presentation. Therefore, in both the present studies, the authors used procedures that eliminated extra-list visual interference and introduced extra-list auditory interference. When same-modality interference was eliminated, weak visual recency effects were found, but they were smaller than those that were generated by auditorily presented items. Further, mid-list and end-of-list recall of visually presented stimuli was unaffected by the amount of interfering visual information. On the other hand, the introduction of auditory interference increased mid-list recall of auditory stimuli. The results of Experiment 2 showed that the mid-list effect occurred with a moderate, but not with a minimal or maximal, level of auditory interference, indicating that moderate amounts of auditory interference had an alerting effect that is not present in typical visual interference.


Induced arousal and orienting tasks as determinants of intentional recall. In this study, the author examined the effects of intention to learn, noise, and different types of orienting tasks on short-term and long-term recall for 15 Hindi paired-associates. Intention to learn improved recall, as did encoding of semantic features, and noise impaired both short-term and long-term recall. The analysis of short-term recall scores indicated that there were no significant interactions between these factors, but the analysis of long-term recall scores indicated that there were significant interactions between noise and orienting tasks and between intentionality and orienting tasks.


Pictures as a means of conveying information. These two experiments, which were conducted at a large midwestern American university, demonstrated that naive art observers can recognize tangible objects that are represented realistically in a picture. However, naive art observers cannot perceive the abstract themes that are portrayed in a picture unless they are informed about the relationships between the pictorial symbols and the concepts they represent.


Hypermnesia using auditory input.

Hypermnesia using auditory input. The author investigated whether hypermnesia would occur with auditory input. In addition, the author examined the effects of subjects' knowledge that they would later be asked to recall the stimuli. Two groups of 26 subjects each were given three successive recall trials after they listened to an audiotape of 59 high-imagery nouns. The subjects in the uninformed group were not told that they would later be asked to remember the words; those in the informed group were. Hypermnesia was evident, but only in the uninformed group.


Null effect of mood as a semantic prime. Semantic tasks, such as lexical decision making and word recognition, have not produced a mood priming effect. Earlier studies have been criticized because they included (a) mood induction techniques that required instruction to feel the mood, and (b) the use of overlearned tasks that did not require controlled processing. In this pair of experiments, the authors attempted to address these criticisms. However, the results of this study did not demonstrate a mood priming effect for happy and sad subjects who appraised sentence content as being happy or sad. The results of this study supported the dissociation of semantic and episodic memory.


NMR investigations of Mn(II)-leucine-enkephalin complexes in [2H6]-DMSO solution. Structural and kinetic features of the Mn(II)-Leu-enkephalin binding equilibria were delineated by measuring 13C and 1H NMR spin-lattice relaxation rates. The temperature dependence of such rates showed that some carbons were experiencing slow exchange regimes such that kinetic parameters at room temperature could be calculated (k(off) = 1400 sec-1, delta H* = 12.0 kcal/mol, delta S* = -9.9 e.u.). The paramagnetic rates of fast exchanging carbons were interpreted by the Solomon-Bloembergen-Morgan theory to provide structural parameters. The terminal carboxyl and amino groups were shown to be the binding sites. The motional correlation time (tau c = 0.6 nsec at 298 K) was calculated by measuring selective and double-selective 1H spin-lattice relaxation rates for the free peptide. The number of coordinated ligands was evaluated by considering the distance of the Leu CO in the complex at 2.54 A, as shown by molecular models. Finally, carbon-Mn(II) distances were calculated and the molecular model of the 1:1 complex was built.


Siderophore-mediated iron (III) transport in the mycelia of the cultivated fungus, Agaricus bisporus. Three structurally diverse iron (III) sequestering compounds (siderophores) were isolated from the supernatants of early stationary phase iron-deficient cultures of vegetative mycelia of the cultivated mushroom, Agaricus bisporus (ATCC 36416). The compounds were purified as their ferric chelates to homogeneity by gel permeation, cation exchange, and low-pressure reversed phase C18 chromatographies, and characterized as trihydroxamic acids. The chelates were identified as ferrichrome, ferric fusarinine C, and an unusual compound, des (diserylglycyl) ferrirhodin (DDF) by HPTLC cochromatography and electrophoresis against authentic samples, hydrolysis and amino acid analysis, and FAB-MS and 1H NMR spectroscopy. The iron transport activities of the three compounds (and of some structurally similar exogenous compounds) in young mycelial cells were determined by time- and concentration-dependent kinetic assays and inhibition experiments (CN-, N3-) using 55Fe(3+)-labeled chelates. 55Iron (III) uptake mediated by all three compounds was found to be via high affinity, energy-dependent processes; transport effectiveness was in the order: ferrichrome > DDF >> ferric fusarinine C. The relative uptake of iron by lambda-cis ferrichromes was: ferrichrome > ferrirhodin >> ferrichrome A; transport activity by the delta-cis fusarinines was: ferric fusarinine C > tris cis-(and trans-) fusarinine iron (III) >> ferric N1-triacetylfusarinine C.


Inactivation of yeast phosphoglycerate kinase by Cr-ATP complexes and its implications on the conformation of the enzyme active site. Exchange-inert beta, gamma-bidentate Cr(H2O)x(NH3)y ATP complexes inactivate yeast phosphoglycerate kinase (PGK) by forming a coordination complex at the enzyme active site. The observed inactivation rates ranged from 0.019 min-1 to 0.118 min-1 for Cr(NH3)4ATP and Cr(H2O)4ATP, respectively. Incorporation of one mol of Cr-ATP to the enzyme was sufficient for complete inactivation of the enzyme. The presence of Mg-ATP protected the enzyme against inactivation by Cr-ATP. The other substrate 3-phosphoglycerate (3-PGA), when present, reduced the observed inactivation rates. The reduction of the k(obs) by 3-PGA was proportional to the number of NH3 ligands present in the coordination sphere of Cr3+ in the Cr-ATP complex, suggesting that in the ternary enzyme-Cr-ATP-3-PGA complex 3-PGA may be coordinated to the metal ion. When the effector sulfate ion was present, the presence of 3-PGA did not cause any further effects on the observed inactivation rates. This suggests that bound substrates are in a different arrangement at the active site when sulfate is present and therefore 3-PGA may not need to displace a ligand from Cr3+. Additionally, PGK exhibited a stereoselectivity for the binding of Cr(H2O)4ATP. delta diastereomer of Cr(H2O)4ATP yielded an order of magnitude smaller Ki value compared to the value observed with the lambda isomer. The recovery of enzyme activity was observed over a period of a few hours upon removal of excess Cr-ATP. The presence of substrates and/or effector ion sulfate did not alter the observed reactivation rate. There was no difference in the reactivation rates of the enzyme which was inactivated with Cr(H2O)4ATP or Cr(NH3)4ATP with and without 3-PGA. Increasing the ligand exchange rates of Cr3+ of Cr-ATP by increasing the pH value of the recovery medium from 5.9 to 6.8 increased the rate of recovery by a factor of 8. The pH dependence of the reactivation indicated that one hydroxyl group is involved in the recovery of the enzyme activity in enzyme CrATP and enzyme.CrATP.3-PGA complexes.


Synthesis and characterization of N-methyliminodiacetato trans-R,R-, trans-S,S-, and cis-1,2-diaminocyclohexane platinum (IV) complexes: crystal structure of chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato) platinum(IV) chloride. The compounds, chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato)platinum(IV) chloride, chloro(trans-S,S-1,2-diaminocyclohexane)(N-methyliminodiacetato) platinum(IV) chloride, and chloro(cis-1,2-diaminocyclohexane)(N-methyliminodiacetato)platinum (IV) chloride, were prepared and characterized by elemental analysis, IR, and 195Pt NMR. The crystal structure of one of these three compounds, chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato) platinum(IV) chloride, was determined by x-ray single crystal diffraction. This compound is particularly interesting because the 1,2-diaminocyclohexane (DACH) ring is in a twist-boat configuration rather than the chair configuration previously reported for other DACH platinum compounds. The crystal structure consists of two independent cations and anions, with all atoms between these two independent molecules (except those in the chiral DACH) related by a pseudo-inversion center. Both platinum atoms have slightly distorted octahedral coordination, with angles ranging from 81.8 to 100.8 degrees. Crystallographic details: space group P2(1) (monoclinic); a = 19.864(5) A, b = 7.026(2) A, c = 12.446(3) A, beta = 106.64(2) degrees; Z = 4; R = 0.036 for 2333 reflections.


Hallervorden-Spatz disease: clinical and MRI study of 11 cases diagnosed in life. The diagnosis of Hallervorden-Spatz disease (HSD) has usually been made post mortem, although the recent description of characteristic abnormalities in the globus pallidus has suggested the possibility of an in vivo diagnosis. We present the clinical histories, neurological features and MRI findings of 11 patients, diagnosed as having HSD. Generalized dystonia with predominance of oromandibular involvement, behavioural changes followed by dementia and retinal degeneration were present in all the patients. MRI pallidal abnormalities consisted of decreased signal intensity in T2-weighted images, compatible with iron deposits, and of a small area of hyperintensity in its internal segment ("eye of the tiger" sign). We propose that the combination of these neurological signs with these MRI findings could be considered as highly suggestive of a diagnosis of HSD in living patients.


Abnormalities of cerebral blood flow in the acute phase of bacterial meningitis in adults. The frequency, course and clinical significance of changes in regional cerebral blood flow (rCBF) during bacterial meningitis were investigated in 14 adult patients. The results of 99mTc-hexamethylpropylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) were compared with the clinical signs and findings using cerebral angiography and conventional CT. HMPAO SPECT was performed 2-15 days (median 4.5 days) after the onset of neurological disease. Decreased HMPAO accumulation was detected in 13 patients. SPECT studies revealed focal hypoperfusion corresponding to the clinical symptoms in 6 patients suffering from hemiparesis or hemiataxia. Conventional cranial CT disclosed brain infarction in only 1 patient. Focal hypoperfusion was also found in 7 of 8 patients without clinical evidence of focal neurological deficits. In 6 patients, HMPAO SPECT findings were abnormal although cerebral angiography was normal. At follow-up examinations 3-45 weeks after the acute disease, abnormalities revealed by HMPAO SPECT had improved or had even disappeared in all patients studied. Our results indicate that reduced rCBF is a frequent finding in bacterial meningitis in the adult. In most patients it probably represents a functional and reversible disorder without structural lesion detectable on CT.