Biomedical subjects
Publications and source records attributed to M Lesser.
Dexamethasone suppression tests were given to 10 patients with panic disorder and 22 depressed patients. All patients with panic disorder were normal suppressors, and nine depressed patients were nonsuppressors. The mean cortisol levels of the two groups differed significantly.
Cathepsin B and prolyl endopeptidase activity was determined in purified rat pulmonary and peritoneal macrophages and cathepsin B was determined in blood monocytes. The activity of cathepsin B in pulmonary macrophages was more than two times higher than in resident peritoneal macrophages and about eight times higher than in circulating monocytes. The simple process of peritoneal lavage with PBS induced an increase in cathepsin B activity in peritoneal macrophages that by 96 and 144 hr reached those levels observed in pulmonary macrophages. Both pulmonary and peritoneal macrophages contain prolyl endopeptidase activity. Repeated peritoneal lavage induced a significant increase in the activity of the enzyme, but not of the magnitude observed for cathepsin B. The data suggest that the transformation of monocytes into macrophages is associated with a significant increase in cathepsin B activity and that this increase is much greater in pulmonary than in peritoneal macrophages.
N, N1-bis (dichloroacetyl) diamine 1, 8-octomethylenediamine (WIN 18,446) is an experimental drug which was first investigated as a male contraceptive. It is soluble in lipid solvents but not in water. The administration of 1,200 to 1,600 mg/kg to pregnant rats on the tenth day of gestation produced multiorgan fetal malformations. Smaller doses, 400 to 800 mg/kg, especially if divided over 2 or 3 days, caused perinatal death. Thus, 60 to 100% of offspring of rats given WIN 18,446 on the tenth and 11th days of gestation died at birth or within 4 days (Taleporos et al., 78). The present study investigated such deaths. At doses of 200 mg/kg on day 10 or 50 mg/kg on days 10 and 11, 67% of offspring had defective or absent diaphragms, 48% had tracheobronchiomegaly with cystic lungs, and 67% had pleural hemorrhage. At doses of 100 mg/kg given on 1 day or 25 mg/kg each day for 2 days, 50% had tracheobronchiomegaly with cystic lungs and rudimentary acini. At lower doses (18.8 mg/kg X 2 or 12.4 mg/kg X 3), a majority of fetal lungs had rudimentary acini, thick septa, few capillaries, and wide cuffs of perivascular connective tissue. Thus, a chemical given during organogenesis produced dysgenesis of the respiratory apparatus. Varying the dose produced malformed lungs with persistently deficient acini which model such human lung faults as tracheobronchiomegaly (Mournier-Kuhn Syndrome; Mounier-Kuhn, '32), bronchiolar dysplasia (Wilson-Mikity Syndrome), and perinatal death with acinar failure resembling neonatal hyaline membrane disease.
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Sixty-four adult patients with soft-tissue sarcomas received adjuvant chemotherapy with a six-drug combination regimen after surgery. Seventy percent remain free of disease with a median follow-up of 50 months. Only seven patients have died of their disease, all within the first 24 months after surgery. Most patients experienced severe nausea and vomiting secondary to the actinomycin D and dacarbazine parts of the protocol, and three patients experienced frank Adriamycin cardiomyopathy. Toxicity from this combination was otherwise mild. The 58% recurrence rate of 12 patients who discontinued therapy early because of nausea was significantly greater than the 23% rate for those who completed or relapsed on therapy (P = 0.01). Adjuvant chemotherapy should be considered after surgery for patients with soft-part sarcomas, especially those with high-grade tumors that have a considerable risk of recurrence.
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Two proteolytic enzymes, a cathepsin B-like activity and prolyl endopeptidase activity, were demonstrated in cellular elements and fluids obtained from human bronchopulmonary washings and in fragments of human lung tissue. Model synthetic substrates were used for the determination of enzyme activities. Cathepsin B-like activity was determined with N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-arginyl-2-naphthylamide. The rate of reaction with this substrate was 300 times greater than the rate with alpha-N-benzoyl-DL-arginyl-2-naphthylamide, a substrate commonly used for the determination of cathepsin B activity. Prolyl endopeptidase was determined with N-benzyloxycarbonyl-glycyl-L-prolyl-sulfamethoxazole as the substrate. The two model substrates make possible the determination of enzyme activities in as little as 10 to 50 microliters of lavage fluid. High cathepsin B-like activity and prolyl endopeptidase were generally associated with high macrophage counts in lavage fluids. This observation and the findings that cathepsin B activity is more than 4.5 times higher in normal monocytes than in neutrophils and that prolyl endopeptidase activity could not be detected in normal neutrophils suggest that the enzymes in lavage fluids are mainly derived from macrophages. Large differences in cathepsin B-like activity in certain lavage fluids containing similar macrophage counts suggest the possibility of enzyme induction in these cells. High cathepsin B-like activity and prolyl endopeptidase were also found in lavage fluids after removal of cells by centrifugation. The possibility that these enzymes affect collagen turnover and lung remodeling needs to be explored.
Serum zinc levels (SZL), serum copper levels (SCL), and the Cu/Zn ratio were evaluated in 50 patients with epidermoid cancer of the head and neck to treatment with respect to site and stage of disease. There was no significant difference in these parameters compared to healthy normal controls. We could not appreciate any diagnostic or prognostic value in these parameters in patients with head and neck cancer. There was, however, a sex-related difference for SZL in men with oral cavity and women with laryngeal lesions, and a trend toward decreasing SZL and increasing SCL and the Cu/Zn ratio with advanced stage of disease.
The nude mouse human tumor-bearing system is a useful model for studying the efficacy of new drugs against human tumors. A panel of six selected human tumor heterotransplants was used to assess the activity of m-AMSA. No effect was seen against malignant schwannoma, malignant lymphoma, liposarcoma, neuroblastoma, or malignant melanoma. A testicular carcinoma appeared to respond to m-AMSA: however, statistical evaluation demonstrated that this was not significant. No evidence was found to support the use of m-AMSA as a sensitizing agent for radiation.
A modification of the leukocyte adherence inhibition method is described which utilizes 51Cr-labeled blood mononuclear cells placed in microwells. The test is reproducible, objective, employs approximately 2,000 cells per well, and allows multiple replicates of several antigens. With the two antigens tested, SK-SD and PPD, both increases and decreases of leukocyte adherence are observed. Serum proteins are important in the medium and inactivated AB serum gave the best results. A good correlation was observed between this leukocyte adherence test and positivity of skin testing,
The efficacy of desacetyl vinblastine amide (DVA) was tested against five human sarcomas heterotransplanted into nude mice. Marked antitumor effect was found against a lipoblastic liposarcoma, including complete regressions of tumor in some animals. A lesser, though statistically significant, antitumor effect was observed with a malignant schwannoma. No antitumor activity was seen against a leiomyosarcoma, epithelioid sarcoma, or Ewing's sarcoma. We conclude that DVA deserves study in the treatment of human patients with malignant sarcomas.
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Nine patients with disabling pneumoconiosis were selected over a three-year period for study because of a work history of kaolin exposure. All had worked in the Missouri firebrick industry. Chest roentgenograms from all nine and lung tissue from two were consistent with silicosis. Worksite analysis of airborne dust at several Missouri firebrick factories revealed that some current workers are exposed to both free silica (up to 4.5%) and cristobalite (up to 8.9%) at levels exceeding the threshold limit value (TLV). Analysis of airborne dust from several kaolin processing plants in South Carolina and Georgia revealed that a few workers are exposed to about 1% free silica at levels occasionally exceeding the TVL. We conclude that silicosis is a serious risk for Missouri kaolin workers and a potential risk for workers in South Carolina and Georgia. A prevalence survey is needed in Missouri to assess the problem.
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UNLABELLED: To assess the validity of fetal breast size measurement as a sonographic marker in fetuses with Down syndrome. METHODS: Fetal breasts were studied in 26 fetuses with trisomy 21 and 78 fetuses with normal chromosomes. Breasts were identified and measured in a cross-sectional plane of the fetal chest at the level of the four-chamber view of the heart. Normal fetuses had a mean breast size of 3.8 mm +/- 1.1 mm. Fetuses with Down syndrome had a mean breast size of 1.9 mm +/- 0.7 mm (p < or = 0.0001). Diminished breast size measured by ultrasound in the second trimester may be helpful in identifying fetuses with Down syndrome.
Through understanding predictors of needle sharing, it may be possible to design AIDS prevention interventions more effectively. Data were collected from a sample of 416 patients in two New York City methadone programs in 1990. Questions were asked about needle sharing and about a battery of predictors covering 11 psychosocial domains. Based on factor analysis, these were reduced to seven factors: criminal history, antisocial characteristics, social integration, severity of psychiatric problems, current drug involvement, physical health, and personality disorders. Bivariate analyses showed that criminal involvement, antisocial characteristics, social integration, and age were significantly related to needle sharing. With the seven factors, as well as age, gender, and ethnicity simultaneously examined by means of regression analysis, it was found that criminal involvement, severity of psychiatric problems, and age were all positively associated with needle sharing. Implications for treatment are discussed.
The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in 28 cats with naturally occurring renal failure, 39 cats with hyperthyroidism, and 33 clinically normal cats. The mean systolic and diastolic blood pressures in the normal cats were 118.4 +/- 10.6 mm Hg and 83.8 +/- 12.2 mm Hg, respectively. In the cats with chronic renal failure, both the systolic (146.6 +/- 25.4 mm Hg) and diastolic (96.6 +/- 15.2 mm Hg) blood pressures were significantly higher (P less than 0.0001 and P less than 0.01, respectively) than in the normal cats. Elevations in systolic and/or diastolic blood pressure were recorded in 17 (61%) of the 28 cats with chronic renal failure. In the 39 untreated hyperthyroid cats, both the mean systolic (167.9 +/- 28.9 mm Hg) and diastolic (111.6 +/- 21.5 mm Hg) pressures also were significantly higher (P less than 0.0001) than normal. Increased systolic and/or diastolic blood pressure was recorded in 34 (87%) of the 39 hyperthyroid cats. In seven cats with hyperthyroidism that were reevaluated two to four months after successful treatment of the hyperthyroid state, there was a significant fall in mean systolic pressure (P less than 0.05) from a pretreatment value of 159.5 +/- 15.4 mm Hg to a posttreatment value of 132.0 +/- 1.62 mm Hg. Overall, the results of this study indicate that mild to moderate hypertension is common in cats with chronic renal failure and in cats with untreated hyperthyroidism. In addition, the hypertension appears to be reversible following successful treatment of the hyperthyroid state.
Endopeptidase 24.11 (EP 24.11; also called neutral endopeptidase, enkephalinase, CALLA, or CD10) and endopeptidase 24.15 (EP 24.15) are widely distributed neutral metalloendopeptidases that degrade a number of bioactive peptides including substance P, bradykinin, neurotensin, and chemotactic peptides. In this study we used sensitive substrates and specific inhibitors to quantitate the levels of these enzymes in purified peripheral human blood leukocytes obtained from healthy blood donors. We found that neutrophils did not contain detectable amounts of EP 24.15. In contrast, T lymphocytes, B lymphocytes, and monocytes contained significant amounts of the enzyme (446 +/- 248,314 +/- 183, and 484 +/- 212 nmol/mg protein/h, respectively). Neutrophils contained significant amounts of EP 24.11 (266 +/- 130 nmol/mg protein/h). Significantly lower levels of the enzyme were found in T lymphocytes, B lymphocytes, and monocytes (94 +/- 31, 87 +/- 38, and 20 +/- 13 nmol/mg protein/h, respectively). These findings suggest that the effects of some bioactive peptides on peripheral blood leukocyte function may be modulated by these enzymes.