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Biomedical subjects

M Sherman

Publications and source records attributed to M Sherman.

At least 19 recordsLinked to original sources

ras transformation of simian virus 40-immortalized rat hepatocytes: an in vitro model of hepatocarcinogenesis.

Primary rat hepatocytes were transfected with simian virus 40 DNA and cultured in a chemically defined medium. Proliferating colonies developed after 2-3 weeks. Three cell lines were established by cloning albumin-secreting colonies, as identified by an immunooverlay assay. Two of the cell lines, ALB-6 and ALB-8, expressed all five liver-specific mRNAs studied, albumin, alpha-1-antitrypsin, fibrinogen, alpha-1-acid glycoprotein, and histidase. ALB-6 cells were nontumorigenic in nude mice while ALB-8 cells were weakly tumorigenic with only one of four injected nude mice developing a slowly growing tumor. Further transfection of ALB-6 and ALB-8 cells with an activated c-Ha-ras or N-ras oncogene resulted in strongly tumorigenic cells. The tumors induced by ras-transformed ALB-6 cells were moderately differentiated hepatocellular carcinomas. The tumors derived from ras-transformed ALB-8 cells were poorly differentiated, while the slowly growing tumors induced by untransfected or control DNA-transfected ALB-8 cells were well-differentiated trabecular hepatocellular carcinomas, suggesting histological dedifferentiation of cells following ras transformation. However, the synthetic capabilities of the cells were not lost in that the ras-transfected cultures and the tumors induced by ras-transformed cells retained the ability to synthesize the five liver-specific mRNAs. Thus we have developed an in vitro model of carcinogenesis in which, by sequential exposure to SV40 DNA and a ras oncogene, primary rat hepatocytes are transformed.

Animals

Post-transplant recurrent hepatitis B viral liver disease. Viral-burden, steatoviral, and fibroviral hepatitis B.

Recurrence of hepatitis is a well-documented complication of hepatitis B liver disease, post-transplantation. It is well established also that the earliest hepatocellular change is the appearance of hepatitis B viral (HBV) markers and that the disease is rapidly progressive. In this article on 17 liver transplants in 16 HBV positive patients with long-term follow-ups (100-1234 days), the distinctive pathologic features of this disease are emphasized: the extreme viral load, the steatosis, and/or fibrosis. An attempt to quantitate the magnitude of the viral burden was made and the result was a staggering figure. In one patient, an estimated 10(18) HBV core particles were present in the liver. One of two patterns of progression were noted. In four patients in addition to the massive nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B surface antigen (HBsAg) positivity, superimposed hepatitic changes led to diffuse hepatic fibrosis (fibroviral hepatitis B); and in another six patients, extraordinary hepatocellular viral marker positivity and steatosis were the hallmarks (steatoviral hepatitis B). Steatosis is not usually considered a feature of HBV liver pathology. These results suggest that more than one type of posttransfusion recurrent hepatitis B liver disease exists pathologically.

Fatty Liver

Dacryoscopy.

A miniature caliber endoscope is described for introduction into the lacrimal excretory passages. Direct observation and diagnostic inspection of the contents and lining of the lacrimal sac and naso-lacrimal duct are possible with the instrument, and complement standard examination procedures of the lacrimal outflow system.

Endoscopes

The effect of motivation on loose thinking in schizophrenics as measured by the Bannister-Fransella Grid Test.

Administered the Bannister-Fransella Grid Test of Schizophrenic Thought Disorder to 40 male schizophrenics. Half of them received a monetary reward for their performance, and half did not. The efficacy of this motivation-enhancing manipulation was verified by the fact that the group that was working for the money completed a card sorting task significantly faster than the group that received no compensation. However, the former group also exhibited more thought disorder on the grid test. The results were interpreted in terms of drive theory. It was argued that the rewarded group was more motivated and therefore more highly aroused and that this high arousal level disrupted performance on the more complex task. The findings do not support the hypothesis that lack of motivation contributes to schizophrenic cognitive deficit.

Arousal

Results of the treatment of obesity with a protein-sparing modified fast.

Thirty-six obese adults received a protein-sparing modified fast (PSMF) consisting of 1.5 g of meat protein per kilogram of ideal body weight and meeting vitamin, mineral, and fluid requirements. These studies were conducted as short-term inpatient metabolic studies followed by a program of outpatient obesity treatment. Thirty-one patients were contacted from one to 4 1/2 years from initial assessment. Significant weight loss of greater than 9 kg (20 lb) occurred in more than half the patients, and of greater than 40 lb in one-third of patients over the study period. A PSMF for weight reduction, accompanied by instruction in behaviour modification, nutrition, and exercise for maintenance of weight loss may be helpful in the management of obesity.

Adult

Gangrene in the diabetic foot: its implications and consequences.

Diabetic problems of the feet are not uncommon. Occasionally, these difficulties progress to the point where surgical intervention is required. A case was presented which involved a deep abscess of the foot that compromised the circulation to the toe. Ultimately, open toe amputation was necessary. The etiologic factors causing diabetic complications were presented and the importance of each was stressed. The preoperative considerations for surgical amputation and debridement were defined, as well as the possibility for successful healing.

Abscess

Neonatal lung defense mechanisms: a study of the alveolar macrophage system in neonatal rabbits.

Abnormal function of the alveolar macrophage system may explain the enhanced susceptibility to pulmonary infection in human neonates. This hypothesis was investigated by infecting 1- to 14-day-old rabbits with aerosols of Staphylococcus aureus and then measuring in situ rates of bacterial ingestion, inactivation, and destruction in the lapine lung. The inhaled staphylococci were killed within the lungs of 1-day-old rabbits at a significantly slower rate than that for 7- and 14-day-old rabbits (P less than 0.05). Much of this decrease was due to diminished rates of bacterial ingestion by alveolar macrophages of younger animals. Staphylococci were also killed and destroyed less rapidly within these macrophages, but these differences could not be tested for significance.

Animals

Cellular immunity in adult marasmus.

Twelve patients with recent weight loss to less than 85% of standard weight-height ratio and a serum albumin level of at least 3 gm/100 ml were considered to have the adult equivalent to marasmus. Cellular immune function was assessed by delayed hypersensitivity skin testing to Monilia and streptokinase-streptodornase, peripheral lymphocyte count, proportion of T and B cells, whole blood and isolated lymphocyte transformation to phytohemagglutinin, pokeweed mitogen, concanavalin A, Monilia, and streptokinase-streptodornase. Significant impairment of skin test reactivity while in vitro responsiveness remained intact was noted in the marasmic patients. No impairment was found in 12 individuals with recent weight loss who remained at a weight greater than the 85% weight-height ratio. In four marasmic individuals in whom weight loss was arrested by nutritional repletion, skin reactivity returned without substantial change in weight. In this type of marasmus, both depleted nutritional status and weight loss must be present for impairement of skin test responsiveness. These findings confirm relative sparing of more vital functions dependent on protein metabolism in adult marasmus compared to the kwashiorkor-like syndromes of hypoalbuminemic malnutrition seen in adults.

Adult

Effect of a protein-sparing diet and brief fast on nitrogen metabolism in mildly obese subjects.

Five young, mildly obese females consumed a formula diet providing total calories at 1.2 X basal energy expenditure and egg white protein, 1.5 gm./kg. ideal body weight (IBW), for 1 week (period 1). During period 2, lasting 3 weeks, a protein-sparing modified fast (PSMF) consisted of similar amounts of egg white without nonprotein calories followed by a 1-week total fast (period 3). In the final period (4), a PSMF with the use of meat protein, 1.5 gm./kg. IBW, alone was given for 1 week. Nitrogen balance (Nbal) measurements were made in all periods, and periods 2, 3, and 4 were compared with period 1. No significant difference existed between period 1 and period 2, although Nbal improved weekly during period 2. Nitrogen excretion in period 3 was similar to that found after 3 weeks of total fasting and was significantly negative, whereas positive balances occurred in period 4 with both periods being significantly different from period 1. Thus nitrogen equilibrium in the PSMF can be achieved with the use of protein free from fat, confirming earlier experience with meat protein. The metabolic adaption which occurs during toal fasting and results in reduced nitrogen loss develops in the course of PSMF. After a deficit in lean body mass is produced, net protein anabolism can be achieved by a PSMF despite insufficinet dietary energy.

Adult

Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast.

A protein-sparing modified fast (PSMF), which is a total fast modified by the intake of 1.2-1.4 gm. protein per kilogram ideal body weight (IBW), fluids ad libitum, and vitamin and mineral supplementation, allows effective control of carbohydrate metabolism and hunger. It reduces serum glucose and insulin concentrations in obese diabetic patients and increases free fatty acid and ketone body concentrations; ketonuria appears within 24-72 hours. When this fast was applied to seven obese adult-onset diabetics who were receiving 30-100 units of insulin per day, insulin could be discontinued after 0-19 days (mean, 6.5). In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. The PSMF was tolerated well in an outpatient setting after the initial insulin-withdrawal phase had occurred in the hospital. Significant improvements in blood pressure, lipid abnormalities, parameters of carbohydrate metabolism, and cardiorespiratory, symptoms were associated with weight loss and/or the PSMF. For diabetics with some endogenous insulin reserve, the PSMF offers significant advantages for weight reduction, including preservation of lean body mass (as reflected in nitrogen balance) and withdrawal of exogenous insulin.

Body Weight

Alpha-fetoprotein in antenatal diagnosis of congenital nephrosis.

Alpha-fetoprotein (A.F.P,) levels were found to ge significantly raised in maternal serum and amniotic-fluid samples form the 16th and 18th weeks of gestation in a woman with an apparently normal fetus but with histological evidence of congenital nephrosis of the Finnish type. Increased concentrations of A.F.P. in early pregnancy with a living fetus are therefore not specific for neural-tube defects; More likely they result from the fetal circulation. Extended investigations, including kidney morphology, should be done in cases of apparent false-positive A.F.P. tests.

Alpha-Globulins