Elevated muscle citrate does not reduce carbohydrate utilization during tetanic stimulation

The lysosomal cysteine proteinase cathepsin B is shown to be secreted by ten human colon carcinoma cell lines and to accumulate in culture media as a latent enzyme. The cell lines also secrete a physiological inhibitor of cathepsin B, cystatin C. A significant correlation was found between secretion of the latent enzyme and the inhibitor (r = 0.755, P < 0.01). The aim of the present study was to modulate the respective secretion of the two antagonists to test whether or not latency of cathepsin B was due to the concomitant secretion of the inhibitor. SW480 colon carcinoma cells were treated with the acidotropic agent ammonium chloride, phorbol 12-myristate 13-acetate, and the inflammatory cytokines TGF-beta, TNF-alpha, and IL-1 beta. Ammonium chloride significantly increased latent cathepsin B levels without affecting the constitutive secretion of cystatin C. Phorbol 12-myristate 13-acetate induced a 4- to 5-fold increase in secreted latent cathepsin B, but did not alter significantly the accumulation of cystatin C in media. The cytokines, TGF-beta, TNF-alpha, and IL-1 beta, had no major effect on the expression of these two antagonists. Latent cathepsin B released from human carcinoma cells could be efficiently activated by neutrophil elastase at neutral pH. It is concluded that latent cathepsin B is a true proenzyme rather than an enzyme-inhibitor complex. In addition, our data from neutrophil elastase activation experiments indicate that a proteolytic system for activation of the tumor cell-secreted latent enzyme may exist in vivo.     

Enrichment programs to create a pipeline to biomedical science careers

The Student Educational Enrichment Programs at the Medical College of Georgia in the School of Medicine were created to increase underrepresented minorities in the pipeline to biomedical science careers. Eight-week summer programs are conducted for high school, research apprentice, and intermediate and advanced college students. There is a prematriculation program for accepted medical, dental, and graduate students. Between 1979 and 1990, 245 high school students attended 12 summer programs. Of these, 240 (98%) entered college 1 year later. In 1986, after eight programs, 162 (68%) high school participants graduated from college with a baccalaureate degree, and 127 responded to a follow-up survey. Sixty-two (49%) of the college graduates attended health science schools, and 23 (18%) of these matriculated to medical school. Of college students, 504 participated in 13 summer programs. Four hundred (79%) of these students responded to a questionnaire, which indicated that 348 (87%) of the 400 entered health science occupations and/or professional schools; 179 (45%) of these students matriculated to medical school. Minority students participating in enrichment programs have greater success in gaining acceptance to college and professional school. These data suggest that early enrichment initiatives increase the number of underrepresented minorities in the biomedical science pipeline.     

Castor-oil induced diarrhoea in ponies: a model for acute colitis

A reproducible, reversible model of colitis induced in ponies by administering castor oil (2.5 ml/kg bodyweight [bwt] per os) was characterised by abdominal pain, fever, watery diarrhoea, dehydration, hypovolaemia, toxaemia, leucopenia, decreased serum Cl, Na and K levels and metabolic acidosis. The signs were most severe between 24 and 48 h post induction, stabilisation was frequently observed after 72 h, although diarrhoea could persist beyond 96 h. Morphological and in vitro transport studies (right ventral colon) were conducted on tissues from animals destroyed at 24, 48 and 72 h. In the caecum and colon, surface epithelial disruption and exfoliation from the basement membrane occurred between 24 and 48 h. Early signs of recovery were evident by replenishment of denuded areas with columnar epithelium at 72 h. The crypt epithelium was unaffected throughout the intestinal tract. In vitro transport studies were consistent with the morphological findings. Decreased Na-Cl absorption and normal Cl secretion indicated an impaired surface epithelium coincident with an undamaged cryptal epithelium. Increased mucosal permeability was demonstrated by high ionic conductance and large unidirectional isotopic fluxes. Tissue conductance improved during in vitro incubation suggesting epithelial repair after removal of castor oil. Changes in the population and proportion of bacteria in the faeces as diarrhoea ensued were confirmed at necropsy with a predominance of E. coli and Enterobacter/Klebsiella sp in the large bowel. The experimental induction of castor oil colitis showed many similarities to intestinal endotoxaemia and the secretory type diarrhoea encountered in naturally occurring acute colitis syndromes in horses. The model could prove applicable in studying the pathophysiological mechanisms precipitating such life-threatening disorders.     

Dependence of the peripheral blood lymphocyte reaction of schizophrenia patients to concanavalin A stimulation on the clinical parameters of the pathological process

Studies were performed on an equivalent age group of schizophrenic patients and normal donors to detect the lymphocyte reaction of the peripheral blood to concanavalin A stimulation. It was demonstrated, that in the blood of schizophrenic patients, the part of lymphocytes capable of reacting to stimulation, is 2,3 times less than in the group of normals. The studies showed that the capability of cells to react to stimulation does not depend upon the duration of the disease, the duration of the postmanifest or initial periods, but differs in patients with different forms of schizophrenia. A significant negative correlation was demonstrated between the severity of positive disorders and the lymphocyte response to stimulation.     

An in vitro model for evaluating neural stimulating electrodes

A model for in vitro evaluation of materials for use as neural stimulation electrodes is developed. Critical areas of concern in developing an in vitro test model discussed include: selection of environment, choice of material, design of stimulating equipment, and analytical procedures used to evaluate materials response. A method of providing quantitative analysis of materials response to stimulation conditions is presented. Evaluation techniques involve the use of scanning electron microscopy, x-ray spectroscopy, atomic absorption spectrometry, and potentiographic and dielectric analysis of the test electrodes. A diagnostics matrix is presented which assigns a scale factor to quantify the relative corrosion response of the candidate materials. The corrosion response of Pt electrodes is evaluated in terms of scale factors assigned through use of the diagnostics matrix.     

The clinical efficacy of the first Russian angiotensin-converting enzyme inhibitor methiopril in patients with heart failure

Changes in central hemodynamics as recorded by tetrapolar rheography were investigated in 90 coronary heart disease (CHD) patients with circulatory insufficiency (CI) receiving methiopril. Relevant clinical response was registered in 94%, hemodynamic in 83% of patients. Those with CI stage IIA and IIB benefited more. Arterial pressure went down significantly only in CHD patients with arterial hypertension. Tachycardia patients showed a reduction in pulse rate absent in bradycardia. Cardiac output increased at the expense of low afterload. Efficient doses averaged 300 mg/day.     

Quantitation of water-soluble acylcarnitines and carnitine acyltransferases in rat tissues

The water-soluble acylcarnitines isolated from rat heart, skeletal muscle, liver, and testis have been characterized. The following acyl residues derived from the acylcarnitine fraction were found: acetyl, propionyl, isobutyryl, butyryl, alpha-methylbutyryl, isovaleryl, tiglyl, caproyl, beta-methylcrotonyl and methacrylyl. The amounts of these acylcarnitines in heart, liver, testis and skeletal muscle from fed rats were determined. Acetylcarnitine was the most abundant acylcarnitine; however, appreciable quantities of propionyl-, isobutyryl-, isovaleryl-, and tiglyl-carnitine were found. The levels of carnitine octanyltransferse, carnitine acetyltransferase and carnitine palmityltransferase activities were determined in several tissues. In addition, carnitine isovaleryltransferase and isobutyryltransferase activities were measured in heart, skeletal muscle, liver, testis and kidney. In all instances the specific activity of isobutyryltransferase was similar to the specific activity of acetyltransferase. The results are consistent with the proposal that carnitine is involved in the catabolism of branched-chain amino acids.