Trolox C, a lipid-soluble membrane protective agent, attenuates myocardial injury from ischemia and reperfusion.

The lipophilic antioxidant Trolox C, a vitamin E analog, was administered to isolated, buffer-perfused rabbit hearts subjected to 25 min of global stop-flow ischemia and 30 min of reperfusion. In six hearts, Trolox C (200 microM) was infused for 15 min immediately prior to ischemia and for the first 15 min of reperfusion. Six control hearts received only vehicle. Gas chromatography analysis confirmed that effective myocardial levels of Trolox were attained. At 30 min reperfusion, the recovery of left ventricular developed pressure was 56 +/- 3% of baseline in control hearts versus 70 +/- 4% in Trolox-treated hearts (p < .01). There was also significant improvement in recovery of Trolox-treated hearts in diastolic pressure and both maximum and minimum values of the first derivative of left ventricular pressure (dP/dt). Creatine phosphokinase release into the coronary effluent at 30 min of reperfusion was 16.5 +/- 8.4 IU/min in untreated and 6.3 +/- 1.0 IU/min (p < .05) in Trolox-treated hearts. Thus Trolox C, a lipophilic antioxidant, attenuated myocardial injury during stop-flow ischemia and reperfusion.


Effect of oxidant stress on calcium signaling in vascular endothelial cells.

The endothelial cell is recognized as a critical modulator of blood vessel tone and reactivity. This regulatory function of endothelial cells occurs via synthesis and release of diffusible paracrine substances which induce contraction or relaxation of adjacent vascular smooth muscle. In response to stimulation by blood-borne agonists such as bradykinin or histamine, the endothelial cell utilizes cytosolic ionic Ca2+ as a trigger in the transduction of the stimulatory signal into a paracrine response. Considerable evidence has accumulated to indicate that various forms of biologically important oxidant stress alter vascular function in an endothelium-dependent manner. Further, oxidant stress is known to alter the mechanisms which govern Ca2+ homeostasis in the endothelial cell. Recently, we have described a model in which the oxidant tert-butylhydroperoxide is utilized to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. In this model, three temporal phases are evident and consist of (1) inhibition of the agonist-stimulated Ca2+ influx pathway, (2) inhibition of receptor-activated release of Ca2+ from internal stores and elevation of resting cytosolic free Ca2+ concentration, and (3) progressive increase in resting cytosolic Ca2+ concentration and loss of responsiveness to agonist stimulation. In this review, the mechanisms which characterize agonist-stimulated Ca2+ signaling in vascular endothelial cells, and the effects of oxidant stress on signal transduction will be described. The mechanisms potentially responsible for oxidant-induced inhibition of Ca2+ signaling will be considered.


Reactive oxygen intermediates and human immunodeficiency virus (HIV) infection.

HIV infection affects various parts of the immune system, including the CD4+ lymphocytes and mononuclear phagocytes, and causes a progressive immunodeficiency. This renders the patient susceptible to various opportunistic infections and neoplasms. Reactive oxygen intermediates (ROI) are important for the intracellular killing of microorganisms by mononuclear phagocytes and neutrophils. Although data are discrepant, several studies suggest that the generation of ROI is impaired in mononuclear phagocytes, and possibly also in neutrophils, from HIV-infected individuals. This may lead to deficient killing of intracellular microorganisms predisposing the HIV-infected patient to certain opportunistic infections. Recently, in vitro studies have shown that ROI activate the intracellular transcription factor nuclear factor kappa B (NF-kappa B) which stimulates HIV replication. Intracellular antioxidant systems, such as the glutathione system, seem to be of importance for the regulation of ROI levels and thus probably for HIV replication in vitro. However, the role of ROI in regulation of HIV replication in vivo is unknown at present. The role of ROI in HIV infection is thus difficult to assess, both at the cellular and clinical level. Reduced intracellular concentrations of ROI may lead to impaired phagocyte microbicidal functions, thus predisposing HIV-infected patients to various opportunistic infections. On the other hand, increased ROI levels may be associated with a stimulation of HIV replication leading to clinical deterioration.


Effects of catecholamines on eicosanoid synthesis with special reference to prostanoid/leukotriene ratio.

Catecholamines (adrenaline, dopamine, and noradrenaline) stimulate prostanoid synthesis by acting as "cosubstrates." On the other hand, many inhibitors of leukotriene synthesis, such as nordihydroguaiaretic acid and caffeic acid, have a catecholic structure. Catecholamines have opposite effects on prostanoid and leukotriene synthesis in human polymorphonuclear leukocytes and whole blood. Basic phenols (catechol, hydroquinone, and phenol) also increase the prostanoid/leukotriene ratio in polymorphonuclear leukocytes. These actions correlate to their antioxidant capacities and oxidation potentials, and they are not mediated via adrenergic receptors. There is only limited knowledge about the effects of natural catecholamines on the prostanoid/leukotriene ratio in vitro and in vivo. Indirect data suggest that catecholamines could increase prostanoid production in physiological or pathological situations, such as heavy physical exercise, myocardial infarction, and surgical stress. This interaction may also be of clinical importance in asthma, gastric ulcer, and psoriasis, where decreased prostanoid/leukotriene ratios have been reported.


Protein A of quinolinate synthetase is the site of oxygen poisoning of pyridine nucleotide coenzyme synthesis in Escherichia coli.

De novo biosynthesis of pyridine nucleotide coenzymes in Escherichia coli is initiated by an enzyme complex (quinolinate synthetase) containing protein B which converts L-aspartate into iminoaspartate and protein A, which then generates quinolinate on the pathway to the coenzymes. This complex has been shown to be poisoned by hyperbaric oxygen. We performed assays made dependent on both proteins B and A versus only protein A, using cell-free extracts of hyperbaric-oxygen poisoned and aerobically grown cells. The specific activities were reduced by similar amounts of 68% and 60%, respectively, when measured in assays made dependent on enzymes B and A virus only protein A that was derived from oxygen-poisoned extract. Thus, protein A is the oxygen-sensitive component.


Isolation of a malondialdehyde-deoxyguanosine adduct from rat liver DNA.

In previous studies, an adduct of malondialdehyde (MDA) with guanine was identified in rat and human urine. Subsequent detection of an adduct with deoxyguanosine (dG) in urine prompted an investigation of its possible occurrence in DNA. Rat liver DNA was hydrolyzed using nuclease P1 and alkaline P-ase and subjected to deoxyribonucleoside analysis using reverse phase high-pressure liquid chromatography (HPLC) with fluorescence detection. A compound was isolated that could not be separated from a synthetic pyrimidinopurine adduct of MDA and dG (dG-MDA). Partial hydrolysis released guanine (Gua), Gua-MDA, and dG in amounts that, in aggregate, were the molar equivalent of the starting material calculated by fluorescence analysis as dG-MDA. Complete acid hydrolysis of the isolate yielded an equimolar amount of MDA. Analysis of liver DNA isolated from growing rats yielded a value for dG-MDA content of 9.0 +/- 1.6 pmol/100 micrograms DNA (mean +/- SEM, N = 5). This value is approximately 7 times those reported for the 8-hydroxy deoxyguanosine content of rat liver nuclear DNA. This study demonstrates that DNA is modified in vivo by reactions of its guanylate moiety with MDA, and indicates that, at least in the case of rat liver DNA, the prevalence of such modifications is greater than those caused by reactions with hydroxyl radicals.


Modification in amino acids of Dead Sea Scroll Parchments.

Fragments of Dead Sea Scroll Parchments were extracted for collagen and subjected to amino acid analysis. In modern parchment samples, 90% or more of the protein could be extracted in hot aqueous solution as collagen. In the ancient specimens, 70% or less was extractable. The hot-solution insoluble material was analyzed for collagen. In the soluble extract, the quantity of tyrosine, histidine, and methionine was reduced. Dityrosine was detected. The need to extend such studies is discussed.


A chelator is required for microsomal lipid peroxidation following reductive ferritin-iron mobilisation.

In the past, antioxidant and chelator studies have implicated a role for iron-dependent oxidative damage in tissues subjected to ischaemia followed by reperfusion. As ferritin is a major source of iron in non-muscular organs and therefore a potential source of the iron required for oxygen radical chemistry, we have determined conditions under which ferritin iron reduction leads to the formation of a pool of iron which is capable of catalysing lipid peroxidation. Under anaerobic conditions and in the presence of rat liver microsomes, flavin mononucleotide (FMN) catalysed the reduction of ferritin iron as shown by both continuous spectrophotometric measurements of tris ferrozine-Fe(II) complex formation and post-reaction Fe(II) determination. The presence of either ferrozine or citrate was not found to alter the time course or extent of ferritin reduction. In contrast, the addition of air to the reactants after a 20 min period of anaerobic reduction resulted in peroxidation of the microsome suspension (as determined with the 2-thiobarbituric acid test) only in the presence of a chelator such as citrate, ADP or nitrilotriacetic acid. These results support the concept that reduced ferritin iron can mediate oxidative damage during reperfusion of previously ischaemic tissues, provided that chelating agents such as citrate or ADP are present.


Circadian variations in antioxidant defences and lipid peroxidation in the rat heart.

Circadian variations in antioxidant defences and lipid peroxidation were investigated in 12 rat hearts perfused during light (i.e., at 08.00, n = 6) and dark cycle (i.e., at 19.00, n = 6). Higher levels of non proteic thiol compounds (P < 0.01), glutathione transferase activity (P < 0.05) and lipid peroxidation (P < 0.01) were detected in evening-excised hearts, associated with a lower (P < 0.05) selenium-dependent glutathione peroxidase activity; superoxide dismutase and glutathione reductase activities, as well as vitamin E content, were similar in the two groups. Moreover, a greater release of thiobarbituric acid reactive substances (P < 0.01) and proteins (P < 0.05) was detected in the myocardial effluent of another group of 5 evening-excised hearts perfused with Krebs-Henseleit buffer containing 30 microM cumene hydroperoxide, as compared to 5 light-cycle hearts. In conclusion, a higher oxidative stress seems to be operative in the rat heart during early stages of the dark phase, in spite of the increase level of non proteic thiol compounds (namely, glutathione). An imbalance of antioxidant defences, and/or higher radical generation and unsaturation degree of biomembranes lipids, may be hypothesized to favour myocardial oxidative stress at the beginning of the motor activity phase in rats.


Lipoate prevents glucose-induced protein modifications.

Nonenzymatic glycation has been found to increase in a variety of proteins in diabetic patients. The present study examined a possibility of preventing glycation and subsequent structural modifications of proteins by alpha-lipoic acid (thioctic acid) as lipoate, a substance which has gained attention as a potential therapeutic agent for diabetes-induced complications. Incubation of bovine serum albumin (BSA) at 2 mg/ml with glucose (500 mM) in a sterile condition at 37 degrees C for seven days caused glycation and structural modifications of BSA observed by SDS-PAGE, near UV absorption, tryptophan and nontryptophan fluorescence, and fluorescence of an extrinsic probe, TNS (6-(p-toluidinyl)naphthalene-2-sulfonate). When BSA and glucose were incubated in the presence of lipoate (20 mM), glycation and structural modifications of BSA were significantly prevented. Glycation and inactivation of lysozyme were also prevented by lipoate. These results suggest a potential for the therapeutic use of lipoic acid against diabetes-induced complications.


["Saddam syndrome:" acute psychotic reactions during the Gulf War--renewal of concept of brief reactive psychosis].

6 patients came to our psychiatric emergency room during the first 2 weeks of the Gulf War presenting the clinical picture of acute delusional paranoid psychosis (4 women and 2 men between the ages of 30-77). 4 were without previously known psychopathology, while the other 2 were known to have had some nonpsychotic cognitive impairment. The first 4 recovered completely within a short time while the other 2 continued to have psychopathological symptoms. We discuss psychogenic or reactive psychosis, and the concept of reactivation when cumulative trauma exceed the individual's personal threshold, as may occur during a war. Different phenomenological syndromes may follow.


[Living with celiac disease].

Celiac disease (CD) is caused by ingestion of gluten-containing foods by gluten-sensitive individuals. The gluten causes malabsorption by damaging their intestinal mucosa. Adherence to a gluten-free diet is not simple, because the composition of foods stocked on store shelves is often not known, Patients with CD, particularly when adolescent, often refuse to comply with the diet; and parents are occasionally unable, or unwilling, to prepare gluten-free food. Furthermore, school teachers are usually ignorant of the specific dietary requirements of these patients. We examined physical, scholastic, and social aspects of CD patients in comparison with their siblings in the same age groups (10-18 years) to determine whether CD and the need to keep a diet influence these parameters. 25 CD patients and 14 of their siblings were interviewed at home where they filled a questionnaire. The mean adherence to a gluten-free diet was 96.6%; the heights of the patients were comparable to those of their siblings. We did not find significant differences in scholastic achievement and social adjustment between patients and siblings. It appears that children and adolescents with CD can live with their disease and keep a gluten-free diet while performing satisfactorily in school. However, some complained of difficulties, such as feeling uneasy at social gatherings, wanting to discuss their disability with friends, and feeling unhappy. Some were angry at society for pitying them and considering them as having a disease, while the patients considered themselves as having a food sensitivity.


[Cytokines in anorexia nervosa--nutritional or neuroimmunal changes?].

Natural cell-mediated cytotoxicity (CMC), spontaneous release of tumor necrosis factor (TNF-alpha) by mononuclear cells in vitro, and PHA-induced interferon (IFN-gamma) production were examined by standard methods in 14 females with anorexia nervosa (AN) and marked weight loss and in 16 normal matched controls. The results were confirmed by neutralization with monoclonal antibodies. In the anorectic patients there was a significant increase in TNF production (16 +/- 5 vs 4 +/- 3 mu/ml), and depressed CMC (4 +/- 2 vs 10 +/- 3 lytic units per 50/10(6) cells) and IFN-gamma production (172.5 +/- 25 vs 367 +/- 34 mu/ml). Following successful refeeding and nutritional rehabilitation, all values returned to normal. Thus there are changes in cytokines and defective natural cytotoxicity in AN, apparently related to undernutrition and not to neuroimmunomodulation. The increased TNF-release may further suppress food intake and enhance tissue catabolism, suggesting that nutritional rehabilitation should be the earliest therapeutic goal in anorexia nervosa.


[The day-care unit as a framework for successful community rehabilitation].

Due to rapid advances in psychiatric treatment, increased sophistication of welfare services, and increasing life expectancy, the number of psychiatric patients is increasing rapidly. Many of them do not have the necessary adaptive capacity to deal satisfactorily with their daily functions, such as housework, financial arrangements, and medical treatment. These patients could be assisted in day-care treatment units. We present the ideology and the different models of psychiatric day-care units which are becoming widely used in treatment, especially for rehabilitation of chronic mental patients.


[Lithium augmentation for mianserin-resistant depression in the elderly].

Depression in the elderly is characterized by a prolonged course and resistance to pharmacological treatment. Moreover, in old age sensitivity to the anticholinergic and cardiac side-effects of tricyclic antidepressants (TCA) increases. Recently new antidepressants with fewer side-effects have been developed. Of these, trazodone and mianserin have been particularly recommended for the treatment of depression in older patients. However, the effects of these new compounds on depression are similar to those of the older TCA's, leaving a substantial number of elderly patients with resistant depression. While there are many publications on the potentiation of the effect of TCA's by lithium carbonate, there is little data on the potentiation of the effects of trazodone and of mianserin by lithium, and no reports of their combined use in elderly patients. Birkhimer et al. reported a case of successful treatment of refractory depression with trazodone and lithium in a 45-year-old man. Heninger et al. successfully treated 2 treatment-refractory patients (aged 52 and 58 years, respectively) with a combination of mianserin and lithium. Price et al. reported that 85% of 12 drug-resistant patients improved when treated with lithium and mianserin, but only 22% of 9 patients treated with lithium and trazodone. We report a 73-year-old man with resistant depression whose physical condition contraindicated tricyclic antidepressants, in whom the combination of mianserin and lithium was both safe and effective.


[Combined tricyclic antidepressants and ritalin in elderly depressives].

Psychostimulants, including ritalin (methylphenidate), were used as antidepressives in the '50s but were then replaced by tricyclics and MAO inhibitors. Treatment of depression with psychostimulants is still controversial. Several anecdotal reports in the past decade approved the use of tricyclic antidepressants (TCA) together with methylphenidate in apathetic and withdrawal states in medically ill and in elderly patients. Ritalin elevates mood by releasing catecholamines and blocking their re-uptake, and also increases serum TCA levels. 5 men and 5 women between the ages of 65 and 79 were diagnosed as suffering from major depressive disorders, either single or recurrent, based on the Revised Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). They had been treated with TCA for up to several months with no response. Following addition of methylphenidate, 5-15 mg/d for 2 weeks, 4 men and 3 women improved rapidly, 2 of them within 24 hours.


[Withdrawal reactions after clomipramine].

Abrupt or gradual discontinuation of tricyclic antidepressants may precipitate withdrawal symptoms. The most common of these are general somatic or gastrointestinal distress, anxiety and agitation, sleep disturbance, akathisia, parkinsonism, paradoxical behavioral activation and mania. There are very few reports of withdrawal reactions following discontinuation of clomipramine since it has not been in use in the US until recently. 2 patients with withdrawal symptoms following discontinuation of clomipramine are presented. A 45-year-old man had general somatic symptoms, including headache, myalgia, weakness, fatigue (flu-like syndrome) and nervousness and insomnia after clomipramine, 75 mg/d, had been discontinued abruptly. All symptoms disappeared without treatment after 3 days. A 47-year-old woman presented mainly with severe insomnia, anxiety, agitation, jitteriness and tension after discontinuing a low dose of 25 mg/d of clomipramine. Symptoms disappeared after she started self-treatment with 50 mg/d of the drug. It is important to differentiate withdrawal symptoms from relapse of the primary psychiatric disorder.


[Subclinical renal involvement in rheumatoid arthritis].

No evidence of renal involvement was found in 104 patients with rheumatoid arthritis in routine laboratory tests, including serum creatinine, urea, uric acid, sodium, potassium, calcium, phosphorus, and urinalysis. In view of recent publications (1-9) which report renal involvement in rheumatoid arthritis, we studied 16 patients of our group (nonrandomized, 3 men and 16 women, average age 55.4 years, average duration of disease 11.9 years). We examined creatinine clearance, urinary excretion of alpha-2 microalbumin, beta-2 microglobulin, cystine, and urine concentration and acidity after a 10-hour fast. 10 patients had disturbances in 1 or more of the functions examined, in 9 of whom tubular functions were involved. In 6 there was no evidence of renal involvement. There was no correlation between renal involvement and past or present therapy, but there were direct correlations between renal involvement, duration of disease and age. Thus we found evidence for subclinical renal damage not revealed by routine laboratory tests in patients with rheumatoid arthritis. This damage should be taken into consideration when operation, examination with contrast material, or treatment with other nephrotoxic agents are being considered in these patients.


[Poststreptococcal reactive arthritis].

Reactive arthritis is defined as arthritis of 1 or more joints, in association with infection at a distant site, but without the infective agent being found in the synovial fluid. Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever, have been classified as having poststreptococcal reactive arthritis. We describe 6 patients seen during the winter of 1991 who had various clinical presentations of poststreptococcal reactive arthritis. This condition is considered by some as a distinct disease, but by others as part of the spectrum of acute rheumatic fever.


[Brucella infection of the testis mimicking malignancy].

A testicular mass is a diagnostic challenge, as it may include both benign and malignant processes. Due to the difficulty in diagnosis and the need to prevent complications, it is sometimes necessary to perform orchiectomy. We present an unusual case of brucellosis in which the presenting features were persistent cough for 6 months and a right testicular mass. The clinical picture and ultrasound findings suggested malignancy. Orchiectomy and medical treatment resulted in rapid resolution of symptoms.


[Sweet's syndrome in a young woman].

Sweet's syndrome is an uncommon and dramatic skin disease associated with systemic symptoms such as fever, headache and arthralgia. Since it is also accompanied by an increased erythrocyte sedimentation rate and leukocytosis, it may be confused with severe systemic infections and other systemic illnesses. We describe a 30-year-old woman who presented with typical features of the disease. They included high fever, headache, sore throat, increased sedimentation rate, and a painful violaceous, nodular and papular rash on her limbs and upper trunk. Histologic features included dense neutrophilic infiltration and edema of the dermis, with foci of leukocytoclasia, but without leukocytoclastic vasculitis. There was a dramatic repose to treatment with prednisone.


Mitochondrial dysfunction in the non-obstructed lobe of rat liver after selective biliary obstruction.

In order to elucidate the function of non-obstructed hepatic lobe during partial cholestasis, we have examined the effects of selective biliary obstruction on the mitochondrial energy transducing system in rat liver. The non-ligated lobe became hypertrophic after ligation of the bile ducts that drained 90% of the liver, and there was no increase in the level of serum bilirubin, alkaline phosphatase activity, or bile acids. However, mitochondrial oxidative phosphorylation function, specific enzymic activities of the oxidative phosphorylation complexes, and the subunit contents of these complexes were markedly decreased in the non-obstructed lobe at 4 weeks after the 90% biliary obstruction. There was no increase in the specific content of mitochondrial DNA. The mitochondrial energy transducing system in the non-obstructed lobes is not enhanced, but is significantly impaired during prolonged selective biliary obstruction, despite normal serum biochemical data and hypertrophy of the non-ligated lobe. These results imply early release of obstruction of cholestatic lobe, e.g. by biliary drainage, would be beneficial for maintaining the mitochondrial function in the non-cholestatic lobe.


Octylonium bromide in the treatment of the irritable bowel syndrome: a clinical-functional study.

We investigated the effect of octylonium bromide on a number of symptoms and functional aspects of the irritable bowel syndrome. Seventy-two patients complaining mainly of abdominal pain were studied in a double-blind trial (octylonium bromide 40 mg tid for 4 weeks or placebo). Clinical parameters were: abdominal pain, bloating and bowel frequency. Sigmoid manometry with simultaneous recording of the thresholds for distension and/or pain upon graded inflation of an endoluminal balloon was performed before and at the end of treatment. In contrast to placebo, octylonium bromide significantly reduced pain and bloating, and significantly increased (p < 0.02) the pain threshold throughout the treatment period. However, comparison with the placebo group failed to show any relevant differences. Neither treatment influenced the frequency of bowel movement. Sigmoid motility during distension was significantly reduced after octylonium bromide (p < 0.05), but it did not change after placebo. In conclusion, octylonium bromide is capable of reducing symptoms and motor reactivity of the sigmoid in patients with irritable bowel syndrome.


Predictors of relapse in peptic ulcer.

Four hundred and two patients with peptic ulcer were selected for acute therapy with either pirenzepine (100 mg/day) or cimetidine (800 mg/day) using the envelope method. Those who achieved healing within 3 months (251 patients) were randomized in a double-blind fashion to maintenance therapy with either pirenzepine (75 mg/day) or placebo. In a preliminary study of 163 patients in which a multiple regression life-table method was employed, 4 out of 15 possible predictors were found to have a significant influence on relapse. These were site of ulcer lesions, psychological stress, endoscopic findings at the time of healing of the original ulcers, and acute therapy. Stratified analysis of the evolution of relapse by the Cutler-Ederer life-table method indicated that several other factors also influenced relapse in certain patient subgroups. Most relapses (93.8%) occurred at the same site as, or close to the site of, the original ulcers, indicating that ulcer scars also play a role in relapse.


Early cancer of the gastric remnant--with special emphasis on the importance of follow-up of gastrectomized patients.

Seven patients with early cancer of the gastric remnant (group 1) and nine with gastric remnant cancer which developed after surgery for early gastric cancer (group 2), were studied clinicopathologically. The findings can be summarized as follows: In group 1, the majority of cases were classified as type I by gross type. Most lesions were in the posterior wall of the remnant stomach. All lesions were differentiated carcinomas. In group 2, of the nine early gastric tumors resected at the initial surgery, six were present at site A and three at site M. The gross type of the tumor was varied. Six patients underwent a Billroth II, and two a Billroth I, resection. The findings at the second operation (for gastric remnant cancer) showed that five lesions were located in the gastric stump or anastomosed region and four in the posterior or anterior wall of the remnant stomach. Histologically, the lesions included four undifferentiated and five differentiated carcinomas. Of the nine lesions involving the gastric remnant, only two were at an early stage, the remaining seven being at an advanced stage. The outcome was extremely poor in this group. Many of the patients died of carcinomatous peritonitis. In summary, a large percentage of the patients of group 1 had a type I lesion in the remnant stomach. In group 2, more than half of the lesions were located in the gastric stump or at the site of the anastomosis, and the majority of the lesions were at an advanced stage.(ABSTRACT TRUNCATED AT 250 WORDS)


Results of orthotopic liver transplantation: a personal experience.

The authors report on their experience of 158 liver transplants performed on 135 patients. Nineteen underwent re-transplantation and four of these required a second re-transplantation; total number of re-transplantations: 23 (14.6%). Hepatic cirrhosis was the most common indication (50.6%), of which alcoholic cirrhosis was the most common type (32.5%). The authors briefly report on their operative techniques and the results of their procedures. The operative mortality (30 days) was 13.3% (18 out of 135 patients). Complications included nine cases of hepatic artery thrombosis (5.7%), four of arterial stenosis (2.5%), one case of portal venous stenosis (0.63%), four cases of post-operative portal venous thrombosis (2.5%), seven of biliary fistula (4.4%; five following choledochocholedochostomy and two following choledochojejunostomy), and two cases of common bile duct stenosis (1.3%). The actuarial survival rate at 48 months is 80%.


TRH-immunoreactivity in chronic pancreatitis.

Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release.


Surgical management of biliary cystadenocarcinoma.

Four patients, one woman and three men, with biliary cystadenocarcinoma were surgically treated during a 7-year period. The mean age was 58 years. Symptoms prior to admission were mild, and blood tests including liver function tests, CEA and AFP were for the most part within the normal range. Surgery followed diagnostic work-up including US, ERCP, CT, angiography and MRI. Radical surgery was accomplished in three patients by extended left lobectomy in two and extended right lobectomy in one patient, respectively, in this latter patient preceded by therapeutic embolization of the right portal branch prior to resection, while the fourth patient had a palliative resection. Histological examination revealed papillary adenocarcinoma with mucin production within the cyst. The size of the cyst (maximum diameter) varied between 4.5 and 24 (mean 12) cm. The postoperative course was uneventful in all patients. Two patients are alive with no sign of recurrence 5 and 53 months after surgery, while two patients died after 26 and 75 months, respectively. Thus, radical resection of this rare kind of malignant hepatic tumor seems to offer a chance of long-time survival.


Morbidity and mortality after abdominal operations for cancer.

A review of 316 consecutive patients operated on for intra-abdominal cancer was undertaken to analyze the incidence of postoperative morbidity and mortality and identify contributory factors. The overall postoperative morbidity and mortality after operations performed for primary cancer were, respectively, 26% (75/288) and 7% (20/288), and those seen after operations for recurrent cancer 43% (12/28) and 29% (8/28). Factors that were statistically associated with a fatal outcome were recurrent cancer (p = 0.0005), palliative resection (p = 0.005), a serum albumin level under 35 G/L (p = 0.011) and a weight loss of more than 5 kilograms (p = 0.046); those associated with a significantly greater complication rate were a serum albumin level under 35 G/L (p = 0.000004), a weight loss of more than 5 kilograms (p = 0.00007), intra-abdominal carcinosis (p = 0.0057), and an emergency procedure (p = 0.048). Infective complications were more common among the patients who underwent resective surgery than among those operated on non-resectively. It is concluded that preoperative malnutrition is predictive of both postoperative complications and increased mortality, and that recurrent disease and palliative surgery are associated with high postoperative mortality.


Prophylactic effect of albendazole in experimental peritoneal hydatidosis.

To determine the effectiveness of prophylactic short-term administration of albendazole in experimental peritoneal hydatidosis this substance was given at a dose of 15 mg/kg for 96 hours prior to scolex implantation. In contrast to the 81.8% of the controls, only 11.1% of the experimental animals developed intraperitoneal hydatidosis over a period of 18 weeks (p < 0.001). The newly defined cyst index was also decreased from 2.09 to 0.22 by the administration of albendazole (p < 0.005). It is concluded that albendazole, when given for 96 hours prior to any suspected intraperitoneal spillage of viable hydatid cyst contents could significantly reduce secondary peritoneal hydatidosis.


Portal vein thrombosis following sclerotherapy.

We present the case of a woman with idiopathic portal hypertension who underwent sclerotherapy for bleeding esophageal varices. She had a rebleed 27 months after complete eradication of esophageal varices. Endoscopy showed bleeding gastric varices. Ultrasonography, and later splenoportography, revealed a large thrombus in the right branch of the portal vein causing gross dilation of the portal and splenic vein. A proximal splenorenal shunt was done to decompress the portal system and hence gastric varices. Repeat endoscopy 4 weeks after surgery revealed complete disappearance of the gastric varices, while ultrasonography at 38 weeks showed marked decompression of the portal system with complete disappearance of the thrombus from the right branch of the portal vein. No new thrombus formation was seen.


Treatment of locoregional recurrence after intentional curative resection of pancreatic cancer.

In order to analyze the results of treatment of patients with locoregional recurrence after intentional curative resection of pancreatic cancer, a retrospective study was performed. During the period 1978-1988, 108 patients underwent an intentional curative resection fo the pancreas. In 34 patients locoregional recurrence occurred, all within a period of three years (cumulative recurrence rate 56%). Sixty-eight percent of the patients presented with upper abdominal pain, and 62% with weight loss. Survival was significantly better (p = 0.02) in the group of 18 patients without distant metastases (1-year survival 22%) than in the 16 patients with distant metastases (1-year survival 0%). Five patients without proven distant metastases were treated by resection or chemotherapy. The mean survival was 33 months (range 6-74) in the treated group, and 4 months (0.4-7 months) in the untreated group, p = 0.002. In this retrospective study the longest survival was seen after radical resection of locoregional tumor recurrence. We therefore recommend that patients with locoregional recurrence without distant metastases after intentional curative resection of pancreatic cancer be treated.


Review of operative indication and prognosis in gastric cancer with hepatic cirrhosis.

Prognosis following surgery for gastric cancer has markedly improved as a result of early diagnosis, advances in operative techniques, and perioperative management. However, gastrointestinal surgery in patients with hepatic cirrhosis has continued to be associated with a high operative morbidity and mortality. On the basis of a detailed classification of the preoperative hepatic conditions into three risk groups, we have established a preoperative means of assessing surgical indication. Depending on the preoperative assessment, 40 gastric cancer patients with hepatic cirrhosis underwent surgical exploration. Thirty-seven patients (92.5%) received gastric resection, while 3 patients (7.5%) were non-resectable. Postoperative complications occurred in only 8 patients (20%), and no anastomotic leakage occurred; the overall operative mortality was zero. The five-year-survival rate following a curative resection, as calculated by Kaplan-Meier statistical analysis, was 51.4% (n = 30).


The risk of cholecystectomy for acute cholecystitis in diabetic patients.

In order to evaluate the risk of acute cholecystitis in diabetic patients, we analyzed 2,700 consecutive cholecystectomies, 566 of which were performed in the presence of acute cholecystitis. Of these patients 123 had diabetes mellitus (DM) and 433 had no diabetes (ND). The aim of this study was to establish the comparative risks in the two groups. We found that diabetics are more likely to be operated on in the acute stage of their disease (22% vs. 12%). The DM group had a higher rate of septic bile, gangrenous changes and perforations of the gallbladder wall. The morbidity rate was higher in the DM group (21% vs. 9%), and mortality was slightly higher in the DM group. The degree of additional operative risk does not in our view justify recommending cholecystectomy in diabetic patients with asymptomatic gallstones. Early surgery however, is highly recommended in diabetics with symptomatic gallstones and acute cholecystitis.


Results of transhiatal esophagectomy in cancer of the esophagus and other diseases.

We present the results we obtained during the last 12 years with transhiatal esophagectomy. Two hundred and eighty-three patients were operated on using this procedure; 171 of them underwent the operation for cancer of the esophagus, 73 for cancer of the cardia, and 11 for cancer of the hypopharynx. The tumor stage, the operative technique, and the type of esophageal replacement (stomach: 62.9%; colon: 37.1%) are described. Overall operative mortality was 5.6%, mainly as a result of respiratory insufficiency. Long-term survival was 11.9% at five years for cancer of the esophagus, much lower than the 48.3% for cancer of the cardia.


Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels.

The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.


Management of pancreatic injuries.

With the aim of aiding the accurate diagnosis and treatment of patients with pancreatic injuries, we reviewed the medical records of all those patients, treated for traumatic pancreatic lesions at our hospital in the period between 1971 and 1987. For all twenty-four male patients the mechanism of the injury, the diagnostic methods employed, associated injuries, location of the pancreatic injury, the presence of pancreatic duct lesion, treatment, the final outcome, and complications are described. In our view, the high mortality rate of patients with pancreatic trauma is due not to the pancreatic injury per se, but to the severe concomitant injuries resulting from a high-energy trauma. On the basis of the literature and our own experience we designed a flow chart for the management of pancreatic injuries. If the history and physical examination indicate that intra-abdominal injury might be present, radiographic and ultrasound investigation are the diagnostic methods of choice. Patients without pancreatic duct injury can be treated with debridement and external suction drainage. If pancreatic duct lesion is presented and is located to the right of the superior mesenteric vessels, treatment should consist of partial pancreatic resection and pancreatico-jejunostomy or a Whipple procedure. If the pancreatic duct lesion is located to the left of the superior mesenteric vessels, distal pancreatectomy and splenectomy with pancreatico-jejunostomy, should be performed.


Influence of beta blockade on branched chain amino acid concentrations in cirrhosis.

Cirrhosis of the liver is typically accompanied by low plasma levels of the three branched chain amino acids (BCAA). These patients also demonstrate increased concentrations of several hormones such as insulin, glucagon and catecholamines. Catecholamines have been shown to influence the plasma levels of amino acids in healthy subjects and diabetics. In the present study, amino acid concentrations were investigated before and up to 3 hours after beta blockade (Inderal, 40-80 mg, n = 10) or fasting (n = 8) in cirrhotic patients. In the basal state the patients had low levels of all three BCAA, as compared with healthy subjects. Norepinephrine was more than 3 times as high in the patients (3.65 +/- 0.6 vs. 0.84 +/- 0.08 nmol/l, p < 0.01) while epinephrine was only slightly raised (0.43 +/- 0.1 vs. 0.25 +/- 0.06 nmol/l, NS). Significant correlations were observed between the concentrations of norepinephrine and individual as well as the sum of the three BCAA (r = 0.43-0.62, p < 0.05-0.001), while no correlation was observed between the BCAAs and epinephrine or insulin. Three hours after beta blockade the concentrations of leucine (basal: 74 +/- 6, 180 min: 89 +/- 6 mumol/l, p < 0.05) and valine (basal: 110 +/- 10, 180 min: 132 +/- 11 mumol/l, p < 0.01) had increased significantly. A similar tendency was observed for isoleucine. No changes were observed after prolonged fasting. The results suggest that catecholamines, primarily norepinephrine, might contribute to the low levels of BCAA in cirrhotics.


Differential diagnosis of space-occupying lesions of the liver with MR imaging.

In a retrospective study of 84 patients who underwent MRI examination of the liver the qualitative parameters margin, shape, internal structure, signal intensity and the presence of a capsule were evaluated in 152 lesions comprising 48 hemangiomas, 54 secondary deposits, 23 hepatomas, 8 simple cysts, 17 hydatid cysts, 1 abscess and 1 focal fatty infiltration. Our main objective was to differentiate hemangiomas from secondary deposits and hepatomas. In hemangiomas the combination of smooth margin (98%) round or oval shape (90%) homogeneity (96%) very high signal intensity on T2-weighted sequence (94%), and the complete absence of capsule helped to distinguish them from secondary deposits and hepatomas in the majority of cases. It is concluded that with MR imaging we can establish the diagnosis of focal lesions of the liver in about 95% of cases.


Relationship of cholecystectomy and detachment of the common bile duct to chronic bile duct dilation.

A combination of a cholecystectomy and detachment of the supportive tissue surrounding the extrahepatic bile duct results in chronic bile duct dilation. To clarify whether this cholangiectasis is due to the detachment of the surrounding tissue or to the cholecystectomy, we have studied 4 groups of adult mongrel dogs, i.e., a control group given a sham operation (n = 20), a group given cholecystectomy (n = 20), a group that had the surrounding tissue detached from the bile duct (n = 20), and a group given both a cholecystectomy and detachment of the surrounding tissue (n = 29). On examination by cholangiography at 1, 2, 3, and 4 weeks after the initial laparotomy, no significant cholangiectasis was found in dogs subjected to either cholecystectomy alone or to detachment of the surrounding tissue alone. In contrast, in dogs subjected to a cholecystectomy combined with detachment of the bile duct, the bile duct gradually dilated, resulting in significant cholangiectasis at 4 weeks. However, the intrabiliary pressure, the residual pressure, and the actual resistance value, which are indices of a passage disturbance in the sphincter of Oddi, were normal in all 4 groups. It is therefore concluded that both the extirpation of the gallbladder, and the lack of supportive tissue surrounding the bile duct were responsible for the resulting cholangiectasis.


Extended excision of the ampulla of Vater--a new operative technique for elderly patients.

This report describes a 72-year-old female patient treated by extended excision of recurrent ampullary carcinoma. The procedure comprised pylorus-preserving resection of the descending segment of the duodenum, and excision of a large portion of the pancreatic head using an ultrasonic surgical dissector. Restoration of food transit, pancreatico-jejunal and choledocho-jejunal anastomosis by a Roux-en-Y reconstruction was readily accomplished. The operation, which has the advantage of being more radical and accurate than the standard excision of the ampulla of Vater, and less time-consuming and mutilating than the Whipple procedure, may be indicated in elderly patients with ampullary carcinoma.


Ectopic ACTH-producing adenocarcinoma of the stomach.

A 73-year-old female was admitted to our hospital because of weight loss and pretibial edema. Plasma levels of adenocorticotropic hormone (ACTH) and cortisol were elevated, and neither hormone showed circadian rhythm. Dexamethasone (2 mg for 2 days) failed to reduce the urinary excretion of 17-hydroxycorticosteroids and the plasma cortisol level. The stomach biopsy specimens showed a moderately-differentiated papillo-tubular adenocarcinoma. Computed tomography of the abdomen showed multiple metastases to the liver. Immunohistochemical staining of the autopsy specimens showed immunoreactive ACTH in the primary tumor cells of the stomach as well as the metastatic tumor cells of the liver. On the basis of the clinical, histological and immunohistochemical findings, we diagnosed this patient as having ectopic ACTH syndrome caused by adenocarcinoma of the stomach.


Chronic dyspnea and suicide in elderly men.

In a structured psychological autopsy study of suicide in older adults, 14 cases in which the subjects experienced chronic dyspnea in the months or weeks before death were examined. Thirteen of the subjects were white men. Most had a diagnosable psychiatric disorder, although none had previous contact with a mental health professional. Other common characteristics were chronic or terminal heart or lung disease, very recent contact with a primary physician, prior experience of self or a significant other suffering a debilitating disease, and a fiercely independent and inflexible personality type. The cases illustrate the intricacy of risk factors associated with suicide and alert other investigators and health care professionals to a possible link between chronic dyspnea and suicide risk.


Religious affiliation and major depression.

Data from the Duke Epidemiologic Catchment Area survey were used to examine the relationship between religious affiliation and major depression among 2,850 adults in the community. Religious affiliations were categorized into six groups: mainline Protestant (27 percent), conservative Protestant (59 percent), Pentecostal (4.2 percent), Catholic (2.4 percent), other religions (2.6 percent), and no affiliation (4.4 percent). The six-month prevalence of major depression among Pentecostals was 5.4 percent, compared with 1.7 percent for the entire sample. Even after psychosocial factors such as gender, age, race, socioeconomic status, negative life events, and social support were controlled for, the likelihood of major depression among Pentecostals was three times greater than among persons with other affiliations. Carefully designed studies are needed to understand the complex interactions of religion and mental health.


Perspectives on effective advocacy for homeless mentally ill persons.

To make appropriate treatment and public policy recommendations to address the problems of homeless mentally ill persons, it is important to differentiate the homeless mentally ill population from the homeless population in general. Effective advocacy for homeless mentally ill persons should have realistic goals that address the specific needs of that population rather than attempt to change the basic problems of society. The effective advocacy that has secured services for developmentally disabled persons can serve as a model. Mental health professionals' limited response to the problems of homeless mentally ill persons has further stigmatized mentally ill persons in general; one of the most powerful actions mental health professionals could take to fight stigma would be to help provide treatment and residential alternatives for homeless mentally ill persons. The recommendations of both the first and the second American Psychiatric Association task forces on the homeless mentally ill are discussed.


Ethical issues for academic participants in state-university collaboration programs.

State-university collaboration programs often create ethical dilemmas for participants because of their conflicting values, goals, and expectations. Treatment and administrative staff in state agencies often seek to create an atmosphere of managed stability rather than fostering patients' autonomy. Academic participants in collaboration programs often feel impelled to change the system, even though the goal of collaboration requires them to find common ground with state agency staff. Academic participants must decide whether collaboration programs will contribute to needed reforms without overly compromising professional and academic standards. If they cannot endorse the values and quality of care provided in state systems, they must consider whether their participation should be conditioned on an agreement to work toward change. However, even in situations that are improving, clinicians must not let temporary compromises become permanent.


Patterns of utilization of outpatient mental health services by children and adolescents.

Although as many as one-fifth of children and adolescents may meet DSM-III criteria for at least one psychiatric diagnosis, data from the Minnesota Department of Human Services for 1988 show that only 20 to 38 percent of children and adolescents in the state who are eligible for medical assistance and who are potentially in need of psychiatric care are referred for or seek treatment. A study of publicly funded mental health care for youths under 18 found that in 1988 the average cost for state-supported psychiatric services per outpatient case was $520, compared with $8,556 per inpatient case. However, overall cost of state-supported mental health services for youths under 18 increased by 28 percent between 1987 and 1988, primarily due to increases in payments for inpatient care of patients with dual diagnoses of mental illness and chemical dependency.


Indicators of adverse somatic outcome in three Veterans Affairs nursing homes.

Frequencies of undernutrition, bedsores, and deterioration in activities of daily living were compared in three Veterans Affairs nursing homes serving both chronic psychiatric patients and medical or neurological patients. The three facilities varied in the proportions of patients with adverse outcomes, with one home having noticeably higher rates for both subgroups of patients. In each home, the two subgroups were equally likely to show evidence of adverse outcome, suggesting that differences in the frequency of adverse outcomes among the facilities were accounted for by extrinsic factors related to quality of care rather than intrinsic factors related to patient characteristics.


The economic burden of mental illness.

Mental illness imposes a substantial burden on individuals and society. Using data from national surveys and a newly developed methodology for calculating costs, the authors estimate that in 1985 the total economic costs of mental illness were $103.7 billion. Of this total, direct treatment and support costs were $42.5 billion, or 11.5 percent of total personal health care spending for all illnesses. Morbidity costs--the value of reduced or lost productivity--amounted to $47.4 billion. Mortality costs--the lost value of productivity due to premature death resulting from mental illness--were estimated to be $9.3 billion, or 5.1 percent of total productivity losses for all deaths. Other related costs, including the cost of caregiver services, amounted to $4.5 billion.


Health care reform issues call for plain talk.

Getting the health care reform message out to your community is vital, writes the author, but learning how to communicate that message is equally critical. To do that, he says, you must know your audience, establish common ground with as many people as possible, and say what you have to say in language they can understand. The media filter, he says, poses a persistent challenge to communicating the issue.


Choosing specifiers: an evaluation of the basic tasks model of graphical perception.

Effect sizes obtained from 39 experiments were used to evaluate the predictions of the basic tasks model of graphical efficacy. This model predicts that performance will be attenuated with graphical displays as a function of the particular specifier, or visual dimension, used to code data values. In this review the basic tasks model predicted performance more accurately than did Tufte's data-ink principle. In addition, variability in effect sizes across studies revealed that the model was more successful at predicting performance in local (focusing) tasks than in global information synthesis tasks. Furthermore, the model was better at predicting performance in tasks requiring the use of physically present rather than remembered graphs. Further differences in effect sizes resulted from variability in the exact specifiers used in experimental graphs. Minimal differences were obtained among graphs that used position, length, or angle as specifiers. However, graphs that used area or volume to represent quantitative values were associated with consistently worse performance than found with other formats.


Graphical displays: implications for divided attention, focused attention, and problem solving.

When completing tasks in complex, dynamic domains observers must consider the relationships among many variables (e.g., integrated tasks) as well as the values of individual variables (e.g., focused tasks). A critical issue in display design is whether or not a single display format can achieve the dual design goals of supporting performance at both types of tasks. We consider this issue from a variety of perspectives. One relevant perspective is the basic research on attention and object perception, which concentrates on the interaction between visual features and processing capabilities. The principles of configurality are discussed, with the conclusion that they support the possibility of achieving the dual design goals. These considerations are necessary but not sufficient for effective display design. Graphic displays map information from a domain into visual features; the tasks to be completed are defined in terms of the domain, not in terms of the visual features alone. The implications of this subtle but extremely important difference are discussed. The laboratory research investigating alternative display formats is reviewed. Much like the attention literature, the results do not rule out the possibility that the dual design goals can be achieved.


Distance and organization in multifunction displays.

One approach to organizing information in a multifunction display (MFD) is to place related screens of information closer to each other. This study identified three metrics that could be used to operationalize the concept of distance in an MFD. The proposed distance metrics-navigational (the number of choice points lying between two screens), organizational (the hierarchical structure of the data base), and the cognitive (the user's perception of relationships among screens)-were empirically examined by using a simulated, hierarchically arranged, menu-driven MFD in an aviation context. Subjects engaged in two tasks that required them to access different target screens from various starting screens in a 290-screen MFD. The tasks differed in the navigational mechanisms subjects were allowed to use to navigate around the MFD and the relationships between the starting and target screens. The results suggest that the three distance metrics are meaningful within the context of a multifunction display.


Using stereokinetic effect to convey depth: computationally efficient depth-from-motion displays.

Recent developments in microelectronics have encouraged the use of 3D data bases to create compelling volumetric renderings of graphical objects. However, even with the computational capabilities of current-generation graphical systems, real-time displays of such objects are difficult, particularly when dynamic spatial transformations are involved. In this paper we discuss a type of visual stimulus (the stereokinetic effect display) that is computationally far less complex than a true three-dimensional transformation but yields an equally compelling depth impression, often perceptually indiscriminable from the true spatial transformation. Several possible applications for this technique are discussed (e.g., animating contour maps and air traffic control displays so as to evoke accurate depth percepts).


Spatial judgments with monoscopic and stereoscopic presentation of perspective displays.

Spatial judgments with monoscopic and stereoscopic presentation of perspective displays were investigated in the present study. The stimulus configuration emulated a visual scene consisting of a volume of airspace above a ground reference plane. Two target symbols were situated at various positions in the space, and observers were instructed to identify the relative depth or altitude of the two symbols. Three viewing orientations (15, 45, or 90 deg elevation angle) were implemented in the perspective projection. In the monoscopic view, depth cues in size, brightness, occlusion, and linear perspective were provided in the format. In the stereoscopic view, binocular disparity was added along the line of sight from the center of projection to reinforce the relative depth in the visual scene. Results revealed that spatial judgments were affected by manipulation of the relative spatial positions of the two target symbols and by the interaction between relative position and viewing orientation. The addition of binocular disparity improved judgments of three-dimensional spatial relationships, and the enhancement was greater when monocular depth cues were less effective and/or ambiguous in recovering the three-dimensional spatial characteristics.


Chromaticity and luminance as coding dimensions in visual search.

Visual search times were measured as a function of chromaticity and luminance differences between a target and distractor stimuli. Results showed that mean search time increased linearly with the number of distractors if the luminance difference between target and distractors was small but was roughly constant if the luminance difference was large. Similar results were previously found for chromaticity differences. With the number of distractor stimuli held constant, the mean search time decreased with increases in the difference between target and distractors, up to some critical difference. Further increases in target-distractor difference had little effect. Results were similar for targets defined by luminance and chromaticity. There was some advantage to combining luminance differences with chromaticity differences when the target was dimmer than the distractors. Generally there was no advantage for combining a chromaticity difference with a luminance difference when the target was brighter than the distractors.


Visibility of transmissive liquid crystal displays under dynamic lighting conditions.

Liquid crystal displays maintain superior contrast under bright sunlight conditions compared with cathode-ray tube displays. This attribute, along with reduced weight, volume, and power requirements, make liquid crystal displays especially desirable for use in vehicular applications. The present experiment was designed to determine the luminance requirements for transmissive liquid crystal displays viewed under a wide range of lighting conditions typical of many vehicular environments. Both the ambient illumination incident on the display surface and the forward-field-of-view adaptation luminance were parametrically manipulated. The visual task involved speeded spatial discrimination responses for detection of the gap in a modified Landolt-C acuity target. The results indicate that under the worst lighting conditions tested, a display luminance of approximately 180 cd/m2 yielded asymptotic spatial discrimination performance. The results have been incorporated into a predictive visual performance model for spatial discrimination tasks, which describes the present data well and represents a first step toward a device-independent model of display visibility.


Characterization of a 28-kD polymorphic polypeptide detected by two-dimensional electrophoresis of human platelets.

A genetic polymorphism of a human platelet polypeptide with a molecular weight of 28 kD detected by two-dimensional electrophoresis was investigated in family and population studies, and cell distribution. The 28-kD polypeptide showed autosomal codominant inheritance of two alleles. The gene frequencies of the two alleles were 0.925 and 0.075, respectively. The 28-kD polypeptide was observed in lymphocytes, neutrophils, eosinophils and monocytes, in addition to platelets. This polypeptide showed good reproducibility in electrophoresis, and appears to be useful as a genetic marker of the human genome in gene mapping and pedigree analysis.


Effective population size of a rural village on a large plain (Veggiano, Padua, Italy).

A small municipality of about 2,000 inhabitants on a large plain (that of the river Po, which flows across the whole of Northern Italy) was chosen as a model to study the level of genetic isolation of a population which is not delimited by clear geographical barriers. Wright's treatment of isolation by distance was considered to be applicable to this case. Estimates of the non-random component of inbreeding and of the immigration rate in the past showed that, despite the deeply rural environment, the population turnover in the area was extremely rapid. Although the parameter estimates were computed on the basis of little direct empirical evidence, it was concluded that the effective population size was at least one order of magnitude larger than might appear when considering the total population size of the municipality.


Deletional types of alpha-thalassaemia in central Java.

The frequency of deletional alpha-thalassaemia in a Javanese population sample (n = 103) was investigated at three restriction sites of the alpha-globin gene (BamHI, BglII and RsaI). The overall gene frequency of alpha+ deletional thalassaemia was found to be very low (0.03). Leftward (-alpha 4.2) and rightward (-alpha 3.7) deletions and triplicated genes were present in equal frequency (0.015 and 0.005, respectively).


Type II hereditary angio-oedema associated with two mutations in one allele of the C1-inhibitor gene around the reactive-site coding region.

The polymerase chain reaction and nucleotide sequence analysis have been used to characterise two point mutations in the eighth exon of one allele of the C1-inhibitor gene in a kindred with type II hereditary angio-oedema (HAE). The mutations comprise a G to A substitution at C1-inhibitor gene nucleotide 16789 and an upstream C to T substitution at nucleotide position 16765. This represents the first report of these two mutations in the same C1-inhibitor allele in type II HAE. The molecular genetic pathogenesis of HAE is discussed in the light of these findings.


Serological identification of HLA-B13 subtypes.

A serological approach is used to confirm subtypes of HLA-B13 originally observed by one-dimensional isoelectric focusing (1D-IEF). Sixty anti-B13 alloantibody sera were screened against Chinese panel cells. Two clusters of sera showing distinct reactive patterns were identified. One is a shorter reactive pattern than the other. Using these serological reaction patterns, the B13 antigen can be divided into two subtypes, B13.1 and B13.2, in the Chinese population. These serological subtypes appear to correlate well with the 1D-IEF patterns of B13 subtypes. The serological subtyping is also in agreement with the differences in nucleotide sequence previously determined to exist in B13 antigen subtypes. Family studies show that both B13.1 and B13.2 segregate as HLA-B locus alleles. Gene frequencies for B13.1 and B13.2 were 0.0676 and 0.0612, respectively, in our study population of 337 southern Han Chinese.


Distribution of ORM1, C6, C7 and APO C-II allele frequencies in populations from mainland Italy and Sardinia.

The genetic variation of the human plasma proteins ORM1, C6, C7 and APO C-II was investigated by isoelectric focusing followed by immunoblotting in populations from mainland Italy and Sardinia. The frequencies of ORM1*1 were 0.621 and 0.564, while those of C6*A were 0.657 and 0.706 on mainland Italy and in Sardinia, respectively. In the Roman sample, 8 heterozygotes with C6 variant alleles were encountered, while none were observed in Sardinians. For C7 and APO C-II a number of heterozygotes with the rare alleles C7*2 and APO C-II*2 were found, but their frequency did not reach polymorphic levels in either population. The two populations showed a significant difference in the gene frequencies distribution for ORM1.


PI and TF subtypes in Chuetas (Majorcan Jews).

PI and TF subtypes were studied in a sample of 137 individuals of the Chueta population. In addition to the PI*M alleles, PI*S, PI*Z, and PI*F were observed in the PI system. In the TF system no TF*B or TF*D alleles were found. PI results were compared with those of some Jewish and non-Jewish populations. The relatively high frequency of PI*S is indicative of a substantial Spanish influence. There are no previous data available on TF*C subtypes in Jews. The very low TF*C3 frequency in Chuetas (lower than in Spain) indicates that this allele may be extremely rare or absent in other Jewish populations.


Blood groups in relation to carcinoma of cervix uteri.

Data are presented on AB0 and RhD blood groups in 186 patients suffering from carcinoma of cervix uteri and 274 controls from Delhi, India. A strong association is observed between carcinoma patients and blood group A, and a slightly weaker association with blood group B. There is no significant association with RhD blood group. The available data in other populations confirm the association with AB0 blood group.


Glucose-6-phosphate dehydrogenase variants in Hawaii.

Sequence analysis has been performed on the DNA of 13 glucose-6-phosphate dehydrogenase (G6PD) deficient males from Hawaii, 6 of Filipino, 6 of Laotian, and 1 of Chinese extraction. Four different mutations were found: A-->T at cDNA nt 835, G-->A at nt 871, C-->T at nt 1360, and G-->A at nt 1388. The mutations at nt 835 and nt 1360 have not been described previously, and the latter, in particular, appears to be relatively common. The nt 1360 mutation changes the same codon as is altered in a previously described mutation, G6PD Andalus.


The inverted Y-chromosome polymorphism in the Gujarati Muslim Indian population of South Africa has a single origin.

Y-specific polymorphisms were studied in Gujarati Muslim Indians possessing a Y-chromosome pericentric inversion [inv(Y)] in an attempt to prove a common genetic origin for the inversion. The p49a/TaqI and p49a/PvuII haplotypes were determined for 9 normal and 8 inv(Y) Gujarati Muslim men. Men with the inversion possessed identical TaqI and PvuII profiles, as opposed to 7 different TaqI and 8 different PvuII haplotypes observed in the 9 normal men. These results provide conclusive evidence for a common genetic origin of the inverted Y chromosome observed in this Gujarati Muslim community.


Biochemical characterization of Trop-2, a cell surface molecule expressed by human carcinomas: formal proof that the monoclonal antibodies T16 and MOv-16 recognize Trop-2.

Trop-2 is a cell surface structure recognized by the 162-46.2 mAb and expressed by most human carcinomas. Since the 162-46.2 mAb works poorly in immunoprecipitation, to characterize the structure of Trop-2 we searched for other mAbs directed against this molecule. Selection of candidates was performed by analyzing the characteristics of mAbs directed against epithelial cells and by comparing the staining pattern of each mAb with the one of the 162-46.2 on frozen sections of human epidermis. Two mAbs, T16 and MOv-16, were selected for further analysis. Formal proof that candidate mAbs reacted with Trop-2 was obtained by comparing their binding patterns to mouse L cells transfected with the Trop-2 gene by genomic DNA transfection and selected by FACS using the FITC-162-46.2 mAb. In immunofluorescence FACS analysis the FITC-T16 and FITC-MOv-16 mAbs specifically stained Trop-2 transfectants. The specificity of binding was confirmed by selective blocking of the staining by the respective unconjugated mAb. Interestingly, cross-blocking studies indicated that the 162-46.2, T16 and MOv-16 mAbs recognize the same epitope or closely spaced ones on the Trop-2 molecule. T16 and MOv-16 efficiently immunoprecipitate Trop-2 from Trop-2 transfectants and from the human cell line OVCA-432, indicating that it is a cell surface glycoprotein, with an apparent molecular weight of 57 kD in non-reducing conditions. A weaker band of 38 kD is often co-precipitated with the 57 kD form in an apparently specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)


A monoclonal antibody produced against a rat esophageal carcinoma cell line reacts with an integrin-like molecule expressed by rat epithelial cells.

A monoclonal antibody, designated MAb-5A IIgG1), was generated against a tumorigenic rat esophageal epithelial cell line, B-2T. MAb-5A reacted with a series of non-tumorigenic and tumorigenic epithelial cell lines derived from F-344 rat esophagi or tracheas. However, the highest level of antigen expression was detected on tumorigenic rat epithelial cell lines. A trace amount of antigen was detected in primary cultures of normal rat epithelial cells derived from either esophagi or tracheas. MAb-5A did not react with rat fibroblasts. MAb-5A reacted with B-2T derived tumor tissues propagated in vivo but showed only slight reactivity with normal rat esophageal epithelial tissues. Cell surface radioiodination, extraction and immunoprecipitation experiments were conducted to characterize the antigen molecule. Analysis of the immunoprecipitates by SDS-PAGE and autoradiography revealed two protein bands with mobilities corresponding to approximately 140 and 120 kDa, respectively. Under reducing conditions the 140 kDa band shifted to approximately 120 kDa whereas the 120 kDa band shifted upward to approximately 130 kDa. The non-reduced/reduced mobilities of these bands suggest that they may be members of the integrin family of matrix receptors. A polyclonal antibody to the beta 1 subunit immunoprecipitated two similar bands detected by MAb-5A, further suggesting that the antigen complex may be related to members of the integrin superfamily.


Production of a monoclonal antibody that defines the alpha-subunit of the feline IL-2 receptor.

A mAb, termed 9F23, to feline Con A-stimulated PBMC was prepared to characterize feline IL-2R. 9F23 was identified by FACS studies, which showed that the antigen was expressed at a high density on Con A-induced feline T cell blasts while 9F23 binding was not detected on nonactivated PBMC or the Crandell feline kidney cell line CRFK. Chemical crosslinking of 125I-IL-2 to membrane IL-2Rs on Con A-stimulated feline PBMC under the low-affinity condition resulted in detection of a major 65-kDa band. 9F23 specifically immunoprecipitated the IL-2.IL-2R alpha complex in a cell extract; in contrast, neither anti-human IL-2R alpha H48 nor anti-mouse IL-2R alpha 7D4 reacted with the complex. Moreover, immunoprecipitation with 9F23 of the extract from surface-iodinated Con A-stimulated PBMC showed a major 50-55 kDa band. Furthermore, 9F23 had no effect on either IL-2-driven proliferation of the Con A-stimulated PBMC or IL-2 binding. Finally, the expression of feline IL-2R alpha on Con A-stimulated PBMC was up-regulated by addition of exogenous IL-2. Thus, 9F23 defines an epitope different from the IL-2 binding site on the alpha-subunit of feline IL-2R.


Detection and neutralization of bovine tumor necrosis factor by a monoclonal antibody.

Monoclonal antibodies (MAbs) have been produced which are specific for bovine tumor necrosis factor (TNF). MAb BC9 detects bovine TNF in a radioimmunoassay with a detection limit of 24 pg/ml. BC9 also neutralizes the in vitro biological function of bovine recombinant TNF. The activity of 250 ng TNF/ml was entirely neutralized by 1% ascitic fluid. When ascites was added at a saturating concentration (10% ascitic fluid), up to 25 micrograms TNF per ml was neutralized. The neutralizing effect of BC9 was seen in cytotoxic assays using L929 cells and WEHI 164 clone 13 cells. The cytotoxic activity of supernatants from in vitro activated bovine monocytes was entirely blocked by BC9.


Lack of effect of recombinant human interferon-alpha 2b on expression of 17-1A antigen on human colon cancer cells.

The effects of recombinant human interferon alpha (rHuIFN-alpha 2b) on cell growth, expression of antigenic receptor sites (r) and the affinity constant (Ka) of monoclonal antibody CO 17-1A IgG were studied on two human colorectal cancer cell lines, CX-1 and SW 1116. Cells were incubated with varying concentrations of rHuIFN-alpha 2b prior to exposure to 125I-labeled 17-1A IgG at 37 degrees C following which r and Ka were determined by means of Scatchard plots. Varying concentrations of rHuIFN-alpha 2b had significant growth inhibitory effects on CX-1 and SW 1116 cells, which were time and concentration dependent, but no effects on expression of r and Ka compared to controls. Our data indicate that rHuIFN-alpha 2b does not invariably increase the expression of tumor-associated antigens and that this effect may be independent of its antiproliferative activity. The in vitro response or lack thereof of neoplastic cells to rHuIFN-alpha 2b may be useful to identify those patients who potentially might gain from a clinical course of rHuIFN-alpha 2b for either therapeutic or diagnostic purposes.


Negative effect of multiple antigen injections on the yield of murine monoclonal antibodies obtained by hybridoma technology.

One of the critical steps in the preparation of monoclonal antibodies is the obtainment, by in vivo immunization and boost, of the maximal number of antigen-activated B lymphocytes. In hybridoma laboratories, the common procedure is to immunize a group of mice with several antigen injections and use the mouse showing the highest serum antibody titre for the fusion experiment. The observation that the use of mice hyperimmunized with human red blood cells failed to yield a high number of monoclonal antibodies, led us to study the effect of multiple antigen injection prior to the fusion experiment. The results obtained showed that the maximal yields of monoclonal antibodies were obtained using mice that had received only one or two antigen injections while the mice immunized with three antigen injections consistently yielded at least a three-fold reduction in the number of monoclonal antibodies. The negative effect could not be reversed by prolonged resting of the animals and suggests the induction of a tolerance/suppression state which can prevent the final activation step. These results point out to the importance of avoiding the hyperimmunization of mice for the preparation of a high number of monoclonal antibodies by standard hybridoma technology.


Cloning hybridomas in a reversible three-dimensional alginate matrix.

Alginate is a transparent polymer of guluronic and mannuronic acids that provide a favorable microenvironment for cell growth. Alginate gelation is calcium dependent and temperature independent. To facilitate the isolation of stable and productive antibody-producing hybridomas, we have developed a technique of cloning hybridomas in the three-dimensional alginate matrix. To provide cavities for hybridoma growth, we encorporated 10-15% (v/v) gelatin into the alginate prior to gelation. We have cloned more than 90 monoclonal antibody-producing hybridomas using the alginate matrix. The alginate matrix is readily reversible with the addition of a calcium chelator. The alginate matrix permits efficient cloning in limited incubator space, without the use of a feeder layer, and with minimal amount of medium. The transparent matrix also permits easy screening for clonality and growth.


Instability of a hybridoma cell line in a homogeneous continuous perfusion culture system.

In this study several analytical techniques were applied to obtain information about the stability of expression, the yield, and the integrity of a monoclonal antibody (Mab) produced by hybridoma cell line RIV6 in a homogeneous continuous perfusion culture system. The total antibody as well as the isotype-specific antibody contents decreased continuously during the course of cultivation, while the viable cell concentration remained constant. The origin of the discrepancy between the Mab contents observed by two enzyme-linked immuno sorbent assay (ELISA) systems during the steady state was due to fragmentation of the IgG molecule, either cytoplasmic or in the culture fluid, as determined by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The IgG-secreting cells as well as the fraction of cells containing a high cytoplasmic IgG content decreased continuously during cultivation. The isoelectric focusing (IEF) pattern showed the appearance of two additional bands after five days of cultivation. This work indicates that cell line RIV6 is unstable in the culture system used, with respect to cell properties and product formation.


Cloning and reexpression of a functional human IgM anti-lipid A antibody.

The human hybridoma cell line HR78 secretes a human antibody of the IgM isotype directed against bacterial endotoxin. The cell line produces low levels of antibody and, more importantly, the antibody product is likely to be impure since two and perhaps more species of heavy chain are being synthesized as judged by cloning and expression studies. To address these issues, the cell line was used as a source of mRNA for the construction of cDNA libraries and the subsequent isolation of the sequences encoding heavy and light chains. Expression of these chains in a non-immunoglobulin producing murine hybridoma cell line resulted in a monoclonal antibody that bound antigen in a manner essentially identical to that observed for the parental antibody. Moreover, the level of expression of human IgM in selected clones was increased approximately 50-fold over the parental cell line and was comparable to or better than antibody expression by a typical murine hybridoma.


Intraspecific sexual isolation in Drosophila.

Intraspecific sexual isolation was examined among wild strains of Drosophila malerkotliana, D. parabipectinata and D. pseudoananassae by multiple-choice method in Elens-Wattiaux mating chamber. In D. pseudoananassae, mating between two strains tested was random and isolation estimate was close to one. In one out of 6 crosses, involving geographic strains of D. malerkotliana, there was significant deviation from randomness and isolation estimate remained low which shows non-random (preferential or positive assortative) mating. In D. parabipectinata, the deviation from randomness was statistically significant due to higher number of homogamic matings in three crosses involving wild strains derived from geographically distant places and isolation estimate remained low in these crosses. The results provide evidence for incipient sexual isolation within D. malerkotliana and D. parabipectinata as a result of genetic divergence.


Gonado-modulatory effects of high humidity is pineal dependent in Indian palm squirrel Funambulus pennanti (Wroughton).

F. pennanti presented a clear biphasic pineal mediated seasonal sexual cycle. This sexual cycle was essentially characterised by a very short period of sexual quiescence with an arrest of spermatogenesis during October-November. A small but clear decrease in sexual activity was also observed during March-April. This decrease in sexual activity, however, had no quantifiable effect on spermatogenesis. Sexual recrudescence was observed from December-January. The testes remained sexually active from January till September. Almost an inverse relationship was observed between pineal and testicular weight. Pinealectomy, however, prevented naturally induced gonadal regression during both the periods, i.e. September-November and February-April. Exposure of animals to high RH (80 +/- 4%) during sexually active phase induced a steep regression in testicular weight of sham-operated animals even in the presence of gonad stimulatory long photoperiod (16L:8D) and high temperature (40 degrees +/- 5 degrees C) while exposure of animals to moderate RH (65 +/- 5%) during sexual regression phase partially prevented testicular regression even in presence of inhibitory short photoperiod (11L:13D) and normal environmental temperature (30 degrees +/- 5 degrees C). Pinealectomized animals, neither exhibited testicular regression in February-March nor had involuted testes in September-October, thus, suggesting that the effect of humidity is mediated via the pineal gland.


Localization and detection of ovarian follicular fluid protein in follicles of human ovaries.

Human ovarian follicular fluid protein has been partially purified and the active fraction designated as hGF2. Using specific polyclonal antiserum to hGF2, it was observed to be localized immunohistochemically in the granulosa cells of medium but not large follicles of human ovary. The hGF2 levels were estimated by ELISA in serum and follicular fluid of 10 gonadotropin-stimulated women recruited for IVF-ET programme. The results revealed a 3-fold increase in the concentration of hGF2 in follicular fluid compared to that in serum of these patients. These data indicate that the protein is secreted by granulosa cells and plays an important role in the regulation of follicular maturation and ovulation.


Age related modulation of circadian time structure of blood, plasma and tissue variables in male domestic fowls.

To study modulation of circadian time structure of 11 blood, plasma and tissue variables in male domestic fowls, as a function of age, three experiments were made in one-day-old fowls (72) standardized by 12L:12D. In the first experiment, at 6 week age, 24 birds were killed by decapitation, four each at six different circadian stages (2, 6, 10, 14, 18 and 22 hr after light onset, HALO). Equal number of birds were killed at similar circadian stages at the age of 12 and 18 week in the second and the third experiments, respectively. Age affected both, the circadian patterns and the mesors (24 hr mean values). The circadian pattern included amplitude (half of the total extent of variation) and acrophase (estimated time of peak) for each variable. The results clearly suggest that the pattern of circadian rhythm may vary as a function of age of the bird.


Electrokinetic behaviour of subpopulations of T lymphocytes in allografted mice.

In AKR(H-2k) mice transplanted with DBA/2(H-2d) skin grafts, the mean electrophoretic mobilities (EPM) of total lymph node cells (LNC) and T cells were significantly reduced. Subpopulations of T lymphocytes, viz. CD4- (CD8- (CD4+) T cells were obtained by depletion treatment of T cells with monoclonal antibodies specific for these surface antigens and complement. Determination of EPM of these two subpopulations revealed that the electrokinetic change following immunostimulation equally afflicted these two subpopulations. These data thus confirmed that CD4+ as well as CD8+ T cells were activated in MHC unmatched allograft rejection.


Effect of chemically different calcium antagonists on lipid profile in rats fed on a high fat diet.

Different classes of calcium antagonists, viz. verapamil (diphenylalkylamine), diltiazem (benzothiazepine), nifedipine, felodipine and nimodipine (dihydropyridines), were examined for their effects on lipid profile in rats. Clofibrate was the reference standard. Clofibrate significantly prevented the rise of serum triglycerides and total cholesterol produced by high fat diet and raised antiatherogenic index to 1.6 times than that of high fat diet controls. Of the calcium antagonists studied, felodipine was most effective in preventing the rise of serum triglycerides and total cholesterol in high fat diet fed rats. Felodipine's antiatherogenic index was very high (886%)--much more than that of clofibrate (303%). Diltiazem and nimodipine which also significantly prevented the rise in triglycerides and total cholesterol produced by high fat diet had a moderately beneficial antiatherogenic index similar to that of clofibrate. Though verapamil and nifedipine slightly increased the triglyceride levels, total cholesterol levels were reduced only by verapamil and not by nifedipine. Despite this both these drugs moderately raised antiatherogenic index similar to clofibrate.


Effect of variations in temperature of injected saline on early development of chick embryo.

Development of chick embryo is sensitive to the incubation temperature and increase or decrease in incubation temperature produces defect in development but the effect of drug solution injected at variable temperatures on developing chick embryo has not been established so far. Fresh embryonated eggs were incubated and saline was administered at various temperatures after 17 hr of incubation. Embryos were harvested to see the effect of temperature variations of injected saline on neural tube formation. Normal neural tube development was seen only at 37 degrees C, hot or cold saline produced maldevelopment of neural tube. Thus it is concluded that any solution or drug which needs to be injected should ideally be used at 37 degrees C, as temperature lower or higher than that may vitiate the results.


Respiratory responses and blood sugar level of the crab, Barytelphusa cunicularis (Westwood), exposed to mercury, copper and zinc.

Barytelphusa cunicularis (Westwood), a freshwater crab was exposed to mercuric chloride, copper sulphate and zinc sulphate from 0 to 12 hr and the oxygen consumption of the animal was measured in order to study the stress caused by these heavy metals. Normal oxygen consumption was affected by the three heavy metals. Similarly, crabs exposed to sublethal concentrations of the same pollutants for 24, 48, 72 and 96 hr showed an elevation in the blood sugar level with a maximum increase at 48 hr. The results indicate a switch towards glycolysis in order to overcome the anaerobic stress caused by the heavy metals.


Distillery effluent treatment using Artemia.

Artemia functions as living filter for the secondary treatment of distillery effluent, which reduces up to 69% of the total solids and 33.34% of BOD in the saline medium of 60 ppt. Chemical analysis of diluted effluent after treatment with Artemia showed a significant (P less than 0.001) decrease in the electrical conductivity, calcium and potassium values. However, an increase in sodium concentration and pH values, was recorded during experiment.


Potentiation of hypoglycemic response of glibenclamide by piroxicam in rats and humans.

Influence of piroxicam (PX) on glibenclamide (GL) induced hypoglycemia has been studied in rats, healthy human volunteers and diabetics. GL per se has significantly reduced blood sugar levels in rats and in humans. PX per se has significantly reduced BSLs, in diabetics, while having no significant influence on blood sugar level in rats and healthy human volunteers. Prior administration of PX has potentiated the hypoglycemic effect of GL in rats, healthy human volunteers and diabetics. GL, PX + GL administration have also significantly influenced the glucose tolerance test (GTT) in healthy human volunteers.


Alterations in metabolic activity of Cysticercus fasciolaris on some anthelmintic treatments.

Effect of candidate compounds 81-470 i.e. methyl [5[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazole-2-yl]- carbamate and 86-162 i.e. methyl-5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate along with reference drugs mebendazole and praziquantel on energy metabolism of C. fasciolaris recovered from rats treated with single dose of 500 mg/kg, ip was investigated. All the drugs significantly lowered the rate of uptake of glucose and alanine by the parasite. Suppression in the formation of lactate, the major end-product, was also noticed. Nonetheless the ratio of lactate produced versus the substrates consumed was not substantially affected. The recovered cysticerci also possessed less glycogen and ATP compared to the normal parasites. Although the effects exerted by the drugs were of the identical nature, they significantly differed in the magnitude of their action. Mebendazole followed by praziquantel maximally affected all the above metabolic activities while 86-162 proved to be the weakest in action. The results suggest that the examined drugs exert their chemotherapeutic activity by interfering with uptake of glucose and alanine but do not significantly alter their catabolism.


Mechanisms of Bacillus cereus enteropathy.

Three strains of Bacillus cereus isolated from sausages (Salami and Trekker, RANBAC, Ranchi) produced enterotoxin which caused vascular permeability in skin and haemorrhage in the ligated ileal loops of rabbits. Histopathological studies revealed haemorrhage and congestion in submucosa, mononuclear cell infiltration in lamina propria and submucosa and villous atrophy. Histochemical studies ruled out the effect on mitochondrial enzymes of intestinal epithelial cells. Purified enterotoxin given intradermally to rabbits caused severe necrotic reaction at the site of injection and death within 4 hr. Histopathological changes observed in liver included congestion of portal veins and sinusoids, vacuolar degeneration of hepatocytes, and hyperplasia of bile ducts. These suggested that B. cereus enterotoxin affected the capillaries of blood vessels locally and also systemically resulting into release of proteinaceous exudates and red blood cells.


Correlative studies on mating speed and metric traits in Drosophila malerkotliana.

Relationship between mating speed, an important component of fitness, and morphological characters such as lengths of wing, femur, tibia and first tarsus have been analysed in D. malerkotliana. Flies mating first have longer wings and forelegs and mating flies have lower coefficient of variability in wing length than nonmating ones. Age seems to have no detectable effect on the relationship between these metric traits and mating speed.


Antimutagenic activity of Terminalia chebula (myroblan) in Salmonella typhimurium.

Antimutagenicity of water and chloroform extracts of dried myroblan Terminalia chebula was determined against two direct acting mutagens, sodium azide and 4-nitro-o-phenylenediamine (NPD) in strains TA100 and TA1535, and TA97a and TA98 of Salmonella typhimurium respectively and S9-dependent mutagen 2-aminofluorene (2-AF) in TA97a, TA98 and TA100 strains. Water extract reduced NPD as well as 2-AF induced his+ revertants significantly but did not have any perceptible effect against sodium azide included his+ revertants in TA100 and TA1535 strains of S. typhimurium. The pre-incubation studies, where the extract was incubated at 37 degrees C for 30 min with the said mutagen prior to plating, enhanced the inhibitory effect. Autoclaving the water extract reduced the inhibitory effect but the reduction in the effect was not significant. No inhibitory effect was observed in any of the strains and against any of the test mutagens with chloroform extract.


Effect of RMI 12,936, an antiprogestational steroid on decidual cell reaction and embryos in rat.

Subcutaneous administration of RMI 12,936 at a dose level of 2 mg/rat on day 5 of unilaterally pregnant rat having trauma-induced decidual cell reaction (DCR) in the contralateral uterine horn, suppresses DCR, induces resorption of implanted embryos and leads to decrease in the plasma level of progesterone. Progesterone replacement (D 5-8) in this situation reverses DCR suppressive effect of RMI 12,936 but fails to prevent resorption of implanted embryos. It is concluded that possibly the drug simultaneously exerts embryotoxic as well as luteolytic effects, but these effects are independent.


Evaluation of Biken test for detection of Salmonella enterotoxin.

Biken test by using antiserum to purified Salmonella enterotoxin (SE) was standardized and carried out to screen salmonellae for their enterotoxigenicity. As many as 101 strains of Salmonella belonging to 15 different serotypes isolated from foods of animal origin were subjected to Biken test. Of these, 68 (67.32%) were found seropositive. The test correlated with the rabbit ligated ileal loop (RLIL) test completely for the detection of enterotoxin producing salmonellae with 24 test strains. However, 5 of the 13 strains which were negative in the RLIL test, yielded positive results with the Biken test.


Effect of graded doses of naloxone on renal function in canine hemorrhagic shock.

All the parameters of renal function (inulin clearance, para amino hippuric acid clearance and urine flow) which were depressed during experimentally induced hemorrhagic shock in dogs improved significantly in addition to improvement in mean arterial pressure (MAP) after bolus administration (iv) of 1 or 2 mg/kg naloxone. A smaller dose (0.5 mg/kg) of naloxone, however, did not improve the renal function. Even renal arterial injection of the same dose of naloxone showed no improvement in the renal function. In both these cases the improvement in the MAP was significantly less as compared to other groups of animals which received 1 or 2 mg/kg naloxone. It may be concluded that (a) naloxone at doses of 1 or 2 mg/kg improved the renal function by improving MAP and (b) naloxone has no direct action on renal vasculature.


Neurophysiological alterations following fluvalinate administration in mice.

Median lethal dose (LD50) of fluvalinate (Marvik 25EC) was 105 (94.6-116.5 mg/kg, ip) in albino mice. Gross observable signs were dose dependent and indicative of central and peripheral nervous system stimulation. Fluvalinate, at 10.5 and 21.0 mg/kg, ip doses in mice, facilitated maximal electroshock seizures, reduced reaction time in analgesic test and enhanced duration of ether anaesthesia. Acute and subacute (7 days) treatment at lower and higher doses enhanced pentobarbitone sleeping time. Acute and subacute treatment (7 days) with phenobarbitone (50 mg/kg, ip) prior to fluvalinate enhanced toxicity of fluvalinate.


Effect of malathion on antioxidant defence system in human fetus--an in vitro study.

Malathion under in vitro condition even at lower concentration (250 ppm) altered the level of enzymes associated with glutathione cycle and antioxidant defence system in human fetal brain and liver. Such changes involved alterations in glutathione status and extent of lipid peroxidation. The inhibitory effect of malathion was dose dependent in case of human fetal brain and was more vulnerable than fetal liver. This alteration (inhibition or activation) was maximum in case of tissues from fetuses of early period of development, suggesting greater susceptibility of human fetus towards this organophosphorus insecticide.


Effect of antioxidants on adenosine triphosphatase activity of brain and heart in male mice during ageing.

The present study deals with the effect of butylated hydroxy anisole, propyl gallate and alpha-tocopherol on ATPase activity of brain and heart in ageing male mice. The activity of both the tissues significantly increased during pre-reproductive and reproductive phases. However, during the post-reproductive phase, ATPase activity of heart increased while that of the brain remained unaltered. The enhanced activity could be attributed to interference by the antioxidants in cellular metabolism and/or their free radical scavenging effect.