Biomedical subjects

M Lesser

Publications and source records attributed to M Lesser.

At least 19 recordsLinked to original sources

PubMed1992

Phenotypic analysis of 1-B-D-arabinofuranosylcytosine deamination in patients treated with high doses and correlation with response.

Two phenotypes for 1-B-D-arabinofuranosylcytosine (ara-C) deamination corresponding to a ratio of distribution for "slow" (ratio, less than or equal to 14) vs "fast" (ratio, greater than 14) deaminators of 70%:30%, have been determined on the basis of studies on plasma ratios of 1-B-D-arabinofuranosyluracil/ara-C (ara-U/ara-C) in 56 subjects treated with high-dose ara-C (3 g/m2 infused i.v. over 3 h). A positive correlation of age with the concentration of ara-U was observed. In a subgroup of 36 patients with leukemia, the ara-U/ara-C pattern was similar to that observed for all 56 subjects. In these leukemic patients, who were treated with combinations of ara-C plus other conventional agents, a tendency toward a positive response (complete response + partial response) was found for those showing low ara-U/ara-C ratios (slow deaminators). The phenotypic effect of deamination in acute leukemia needs to be evaluated prospectively.

Adolescent↗

PubMed1992

Lipopolysaccharide-induced stimulation of alveolar macrophage opsonin-independent phagocytosis.

Alveolar macrophage (AM) opsonin-independent phagocytosis may be an important process by which bacteria are cleared from the airspaces. Although it has been shown that clearance of bacteria from the lung is altered in association with endotoxemia, the effect of endotoxemia on opsonin-independent phagocytosis is unknown. Because alterations in AM opsonin-independent phagocytosis could potentially influence bacterial clearance in the lung, we studied the effects of the intravenous injection of Escherichia coli lipopolysaccharide (LPS) into rats on AM opsonin-independent phagocytosis of latex particles. AM obtained by bronchoalveolar lavage (BAL) 2 or 4 hr after injection of LPS demonstrated phagocytosis comparable to AM from control animals. In contrast, AM obtained 12 hr after injection of LPS demonstrated a nearly threefold increase in phagocytosis. Depletion of serum complement with Naja naja cobra venom factor (CVF) did not alter LPS-induced augmentation of phagocytosis. Furthermore, phagocytosis of AM obtained by BAL 2 or 12 hr after activation of complement by injection of CVF was not significantly different from that of AM from control animals, indicating that complement activation alone was not sufficient to stimulate opsonin-independent phagocytosis. These observations suggest that opsonin-independent phagocytosis may represent an important route of bacterial uptake by AM following endotoxemia, and that LPS-induced stimulation of AM opsonin-independent phagocytosis may occur independently of activation of complement by LPS.

Animals↗

PubMed1992

Use of the Dementia Rating Scale as a test for neuropsychological dysfunction in HIV-positive i.v. drug abusers.

Intravenous drug abusers (IVDAs) represent an increasing proportion of the HIV epidemic. Forty-three IVDA's (22 HIV-negative, 21 HIV-positive) were studied using the Mattis Dementia Rating Scale (DRS). All subjects had used intravenous heroin, but reported that they were drug-free at the time of testing. HIV-positive subjects were predominantly symptomatic and were dichotomized into AIDS and non-AIDS groups. All subjects with abnormal DRS scores were HIV-positive (57% of all HIV-positives). All HIV-negative subjects had normal DRS scores while 43% of the positive group obtained such scores. The DRS reliably identifies neuropsychological impairment, and may be a useful screening tool in this population.

AIDS Dementia Complex↗

PubMed1992

Substance use in a school-based clinic population: use of the randomized response technique to estimate prevalence.

Students attending school-based clinics acknowledge only minimal involvement with drug or alcohol use. In order to explain this unanticipated finding, we used a statistical method called randomized response to study adolescents in one school-based clinic. The sample consisted of 133 students (57% female; 75% black, 20% Hispanic, 5% other; and 58% grades 9-10, 42% grades 11-12). Using both lifetime and 30-day prevalence rates, these students revealed more cigarette smoking and alcohol use on randomized response than they had on questionnaires completed earlier the same academic year, minimal involvement with either marijuana or cocaine use by either method, and a similar amount of sexual activity by both methods. This study demonstrates that randomized response can be a useful method to generate more truthful group responses from adolescents.

Adolescent↗

PubMed1992

Induction of emphysema in hamsters by intratracheal instillation of cathepsin B.

Current theories of pathogenesis suggest that pulmonary emphysema develops in humans because of progressive loss or derangement of lung elastin through a process mediated by elastolytic enzymes released by inflammatory cells. Neutrophils are considered primary etiologic factors because these cells produce and release two potent serine proteinases that cause emphysema when instilled into the lungs of animals. It has been suggested that alveolar macrophages also contribute to the development of emphysema through production of several enzymes with elastolytic activity, including the lysosomal cysteine proteinases cathepsin B and cathepsin L, but this has not been verified experimentally. In the current study, we instilled 115 micrograms of active cathepsin B into the lungs of hamsters three times at 48-h intervals. After 6 wk microscopic evaluation revealed that lung sections of five of seven animals given cathepsin B contained focal areas of enlarged and distorted alveoli, in the absence of fibrosis, which were similar to changes seen in the lungs of animals given papain intratracheally. Morphometrically, mean linear intercept (micron) values were significantly higher (p less than 0.025) in animals given cathepsin B (204.4 +/- 20.8) as compared with control animals (173.2 +/- 7.8), and internal surface area (sqcm) values were significantly lower (935 +/- 120 versus 1,083 +/- 56 in control animals), thereby confirming that airspace enlargement had developed after instillation of the enzyme. Lung volumes (ml) and compliance (ml/cm H2O) were not significantly higher in animals given cathepsin B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Goblet cell hyperplasia in large intrapulmonary airways after intratracheal injection of cathepsin B into hamsters.

Goblet cell hyperplasia (GCH) is a frequent histologic finding in the airways of smokers. Experimental observations suggest that the process may be caused by increased proteinase activity in the airways. To investigate the possible role of cathepsin B in the development of GCH, male Syrian golden hamsters were given three intratracheal injections of bovine spleen cathepsin B or buffer (pH 5.5) at 2-day intervals. Six weeks later, we found by review of PAS-hematoxylin-stained 1-micron sections of plastic-embedded lung tissue that large intrapulmonary airways of animals given cathepsin B contained a significantly greater number of secretory cells per millimeter of airway (64.8 +/- 7.3 versus 47.5 +/- 10.3 for control animals, p less than 0.005) in association with a significant increase in the number of total cells per millimeter of airway, from 149 +/- 14 for control animals to 164 +/- 11 for cathepsin-B-treated animals (p less than 0.025). No change was observed in the number of ciliated cells (93.9 +/- 8.1/mm for control animals versus 94.8 +/- 10.3/mm for cathepsin-B-treated animals) or other cells (3.0 +/- 2.2/mm for control versus 4.3 +/- 4.1/mm for cathepsin B), indicating that selective expansion of the secretory cell population occurred. In contrast, in the main bronchi of animals given cathepsin B, no significant alterations were found in the number or percentage of secretory cells. The findings reveal that cathepsin B induces secretory cell hyperplasia in hamsters and suggest the possibility that cysteine proteinases may contribute to GCH in smokers.

Animals↗

PubMed1992

Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Genotyping for 10 mutations in the CYP21 gene was performed in 88 families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Southern blot analysis was used to detect CYP21 deletions or large gene conversions, and allele-specific hybridizations were performed with DNA amplified by the polymerase chain reaction to detect smaller mutations. Mutations were detected on 95% of chromosomes examined. The most common mutations were an A----G change in the second intron affecting pre-mRNA splicing (26%), large deletions (21%), Ile-172----Asn (16%), and Val-281----Leu (11%). Patients were classified into three mutation groups based on degree of predicted enzymatic compromise. Mutation groups were correlated with clinical diagnosis and specific measures of in vivo 21-hydroxylase activity, such as 17-hydroxyprogesterone, aldosterone, and sodium balance. Mutation group A (no enzymatic activity) consisted principally of salt-wasting (severely affected) patients, group B (2% activity) of simple virilizing patients, and group C (10-20% activity) of nonclassic (mildly affected) patients, but each group contained patients with phenotypes either more or less severe than predicted. These data suggest that most but not all of the phenotypic variability in 21-hydroxylase deficiency results from allelic variation in CYP21. Accurate prenatal diagnosis should be possible in most cases using the described strategy.

Adrenal Hyperplasia, Congenital↗

PubMed1992

Identification of two zinc metalloendopeptidases in alveolar macrophages of rats, guinea pigs, and human beings.

Neutral endopeptidases EC 3.4.24.11 and EC 3.4.24.15, widely distributed zinc metalloendopeptidases, degrade a number of biologically active peptides including substance P, bradykinin, neurotensin, and luteinizing hormone-releasing hormone. In this study we measured EC 3.4.24.11 and EC 3.4.24.15 activity in alveolar macrophages, key inflammatory cells in the lung that produce and respond to a large number of bioactive substances including chemotactic peptides, with the substrates glutaryl-ala-ala-phe-2-naphthylamide and tertiary butoxycarbonyl-phe-ala-ala-phe-paraaminobenzoate, respectively. We found that specific activity of EC 3.4.24.15, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-ala-ala-phe-paraaminobenzoate+ ++, was significantly higher (p < 0.001) in cells from Sprague-Dawley rats (485 +/- 123 nmol/mg protein.hr) than in cells from Hartley guinea pigs (138 +/- 94 nmol/mg protein.hr), healthy human male smokers (121 +/- 73 nmol/mg protein.hr) and healthy human male nonsmokers (94 +/- 12). In contrast, activity of EC 3.4.24.11, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]-phe-paraaminobenzoate, was significantly higher (p < 0.001) in cells from human smokers (689 +/- 167 nmol/mg protein.hr) and nonsmokers (762 +/- 136 nmol/mg protein.hr) than in cells from rats (52 +/- 12 nmol/mg protein.hr) and guinea pigs (34 +/- 14 nmol/mg protein.hr). An additional activity in alveolar macrophages toward tertiary butorycarbonyl-phe-ala-ala-phe-paraaminobenzoate was inhibited with L-3-carboxy-trans-2,3-epoxypropionyl-leucylamido-(4-guanido) butane, a specific inhibitor of cysteine proteinases, a finding of interest because in general enzymes in this class show little activity at neutral pH.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobenzoic Acid↗

PubMed1992

Interinstitutional variability of follicle-stimulating hormone and estradiol levels.

OBJECTIVE: To evaluate the variability of follicle stimulating hormone (FSH) and estradiol (E2) results from different laboratories. DESIGN: Prospective analyses of sera separated and frozen, obtained from 15 female patients in the follicular phase. All kits used for radioimmunoassay (RIA) for FSH were from the Second International Reference Preparation (IRP). Four different kits were used for FSH and three for E2. SETTING: Sera obtained from each patient were separated into five test tubes and frozen. Analysis of all samples was done on the same day in each one of five participating hospital-based RIA laboratories (North Shore, Cornell, Yale, Mount Sinai, and Norfolk). PARTICIPANTS: Fifteen consecutive patients from the assisted reproductive technology program at North Shore University Hospital participated in the study. MAIN OUTCOME MEASURES: After FSH and E2 levels were tabulated for each laboratory, mean levels were calculated. RESULTS: Using the Bonferroni adjusted pairwise multiple comparisons analysis, significant differences were found between three groups of laboratories within the FSH results and three different groups within the E2 results. CONCLUSIONS: [1] Different results may be obtained on the same sera for FSH and E2 at different laboratories; [2] for FSH, even though the same IRP is used, different results are reached; [3] for E2, even when the same kits are used, results may be significantly different. These results suggest that specific FSH and E2 levels used to predict chances for achieving a viable pregnancy through in vitro fertilization should be interpreted with caution across institutions.

Estradiol↗

PubMed1992

Degradation of rat lung collagens by cathepsin B.

The lysosomal proteinase cathepsin B degrades purified insoluble collagen in vitro. To determine whether the enzyme degrades collagens present in normal extracellular matrices, we quantitated release of hydroxyproline-containing peptides during incubation of rat lung explants with bovine spleen cathepsin B. Incubation of explants with cathepsin B at pH 5.9 caused significant release of hydroxyproline, indicating collagen degradation, without apparent injury to lung parenchymal cells, as determined by release of lactate dehydrogenase. Release of hydroxyproline was completely inhibited by E-64, a specific inhibitor of cysteine proteinases. Cathepsin B demonstrated significant collagenolytic activity over a range of pH values from 4.0 to 6.5. Little activity was present at pH 7.0 or above. The findings indicate that cathepsin B is capable of degrading collagens embedded in the complex extracellular matrix of the lung and suggest that the enzyme may contribute to collagen degradation in vivo.

Animals↗

PubMed1991

Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer.

The serum and cerebrospinal fluid (CSF) of 8 women with ataxia, 6 of whom also had eye movement abnormalities believed to be opsoclonus, were found to contain a highly specific antineuronal antibody we call anti-Ri. Seven of the 8 women also had or developed cancer: carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1, and carcinoma of the fallopian tube in 1. Four patients presented with the neurological disorder; the cancer was diagnosed first in the other 4. Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells; the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF. Biotinylated IgG from the patients' serum reacted with the tumors of 3 of 4 patients with anti-Ri antibody but not with breast cancers from patients without anti-Ri antibody. Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55-kd and 80-kd relative molecular mass. Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers, from 1:10 to 1:2,000. The relative amount of anti-Ri was always higher in CSF than in serum. The antibody was not present in sera from normal individuals; patients with breast cancer without opsoclonus; other patients with opsoclonus; or patients with other paraneoplastic syndromes related to breast, ovarian, or small-cell lung cancer. We conclude that the presence of anti-Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.

Aged↗

PubMed1991

Mortality in dialysis patients: analysis of the causes of death.

The objective of this study was to identify the causes of death in maintenance dialysis patients who survived at least 90 days and were monitored during a 16-year period. Of 532 patients starting dialysis, 222 died. The causes of death were grouped into six categories: cardiac, infectious, withdrawal from dialysis, sudden, vascular, and "other." The greatest number of deaths were due to infections, followed by withdrawal from dialysis, cardiac, sudden death, vascular, and other. The risk of dying increased for the first 4 years of dialysis, decreased in years 5 through 10, and had a second increase at 11 years. The mortality during the first 4 years consisted largely of infectious and cardiac deaths. The late peak of deaths was mainly due to infections and withdrawal from dialysis. Overall, infections accounted for more than 36% of all deaths. Withdrawal occurred in 21.2% of the patients and was most common in patients over age 61. Notably, cardiac deaths accounted for only 14.4% of all deaths and no patient died from a cardiac cause after surviving on dialysis more than 8.5 years. We conclude that infection is the leading cause of death in our dialysis patient population. Withdrawal from dialysis was a common cause of death, especially in older patients. Cardiac mortality was not as frequent as anticipated and occurred mainly in patients on dialysis less than 4 years, suggesting that it is the result of preexisting disease.

Adolescent↗

PubMed1991

Clinical significance of neutropenia in patients with human immunodeficiency virus infection.

OBJECTIVE: To determine the incidence of infection in human immunodeficiency virus (HIV)-infected patients during periods of neutropenia and non-neutropenia. To compare the infection rates in patients with HIV disease to those in a group hospitalized with neutropenia and hematologic malignancy. DESIGN: Prospective observational study conducted between December 1985 and December 1987 at a university teaching hospital. Thirty patients with documented acquired immunodeficiency syndrome (AIDS) and absolute T-helper cells less than 200 mm/mm3. All patients had a period of non-neutropenia following a neutropenic period (neutrophils less than 1000 cells/mm3). RESULTS: The rate of first infection during neutropenic and non-neutropenic periods for opportunistic infection and nonopportunistic infections were compared. There were no differences between infection rates for the two time periods for both types of infections. A subgroup of patient care days in which non-neutropenic days followed neutropenic days also was studied to eliminate selection bias. In this group, a comparison of infection rates also revealed no difference between neutropenic and non-neutropenic periods. An alternate analysis of the time until first infection during periods of neutropenia or non-neutropenia was done using the Kaplan-Meier product limit method. There was a longer infection-free period for the neutropenic group for opportunistic infections, but it was not statistically significant (p less than .1). In addition, we compared HIV-infected patients with a group of 37 patients with neutropenia from hematologic malignancy. There was a significantly higher rate of all infections, particularly bacteremias (p less than .001), in the group of patients with hematologic malignancies when compared with all subsets of patients with HIV disease. CONCLUSION: We conclude that patients with HIV disease and modest neutropenia do not have an increased risk of bacterial infection. The incidence of all infections is significantly greater in patients with neutropenia secondary to hematologic malignancy.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Suicidal children grow up: demographic and clinical risk factors for adolescent suicide attempts.

This longitudinal study reports rates and demographic and clinical risk factors for adolescent suicide attempts during a 6- to 8-year follow-up period of an initial sample of 106 preadolescent and young adolescent psychiatric inpatients and 101 preadolescent and young adolescent nonpatients. Survival analysis was used to evaluate risk for a first suicide attempt in the follow-up period for 133 subjects who were interviewed. No deaths occurred. Suicidal inpatients, compared with nonpatients, had earlier first suicide attempts in the follow-up period. Adolescents who attempted suicide in the follow-up period were seven times more likely to have a mood disorder during the follow-up period than those who did not attempt suicide. Implications for clinical practice and research are discussed.

Adolescent↗

PubMed1991

Lipopolysaccharide-induced pulmonary vascular sequestration of polymorphonuclear leukocytes is complement independent.

Lipopolysaccharide (LPS) injected intravenously produces leukopenia and sequestration of polymorphonuclear leukocytes (PMN) in the pulmonary vascular bed. To evaluate the role of complement in this process, we used C5-sufficient (B10.D2/nSn) and C5-deficient (B10.D2/oSn) mice and Sprague-Dawley rats depleted of complement with Naja naja cobra venom factor (CVF). We found a comparable increase in the number of PMN in lung tissue of C5-sufficient and C5-deficient mice given Escherichia coli LPS (0127:B8, 3 mg/kg), revealing that LPS acts independently of C5 and its biologically active fragments. Intravenous injection of LPS (3 mg/kg) into rats caused significant intravascular complement activation as assessed by serum CH50 and resulted in an almost 10-fold increase in numbers of PMN in lung tissue. Pretreatment of rats with CVF (50 U) did not reduce LPS-induced PMN sequestration, suggesting that the process is independent of C3. As reported previously, we found large numbers of PMN in bronchoalveolar lavage samples of 24 h after injection of LPS (3 mg/kg). Complement depletion did not prevent LPS-induced migration of PMN. No PMN migration occurred 2, 6, 12, 24, or 48 h after injection of CVF alone, indicating that complement activation is not sufficient to cause PMN migration. In contrast to our findings in rats, no PMN migrated into airspaces of C5-sufficient and C5-deficient mice 24 or 48 h after injection of LPS (3 to 20 mg/kg).

Animals↗

PubMed1991

Observations on the postpartum shivering phenomenon.

Fifty healthy, nonmedicated, laboring women who had normal spontaneous vaginal deliveries were studied to determine the incidence, time of onset, severity, duration, temperature patterns and relationship of various perinatal factors to the postpartum shivering phenomenon. Axillary temperature was recorded on admission, before delivery, at delivery and every 15 minutes postpartum for 75 minutes. The degree and duration of shivering were quantified visually. The environmental temperature was recorded. Of the 50 women, 22 (44%) commenced shivering during delivery or up to 30 minutes postpartum. Shiverers and nonshiverers exhibited a reduction in the mean axillary temperature during labor, with a rise post-partum (P less than .002). The median axillary temperature of the shiverers at all time points was higher than that of the nonshiverers and was statistically significant 30 (P less than .01), 45 (P less than .003), 60 (P less than .004) and 75 minutes (P less than .001) after delivery. The shiverers tended to raise their postdelivery temperature somewhat later than did the nonshiverers. The temperature pattern of both shiverers and nonshiverers fell during labor, and the temperature pattern of the shiverers differed from that of the nonshiverers postpartum. The mean delivery room temperature for shiverers was lower than for nonshiverers (P less than .009), as was the mean recovery room temperature (P less than .03). Environmental temperature may play a heretofore unsuspected role in the postpartum shivering phenomenon.

Adult↗

PubMed1991

Blood pressure values in 500- to 750-gram birthweight infants in the first week of life.

The means and standard deviations for systolic, mean, and diastolic blood pressure were noted in the first week after delivery for 12 hemodynamically stable infants by a retrospective chart review. Blood pressure taken by means of an umbilical artery transducer or an oscillometer were not statistically different. All blood pressure values increased during the first week after birth. A trend was noted toward increasing blood pressure with increasing gestational age for the first week after birth. We conclude that the range of blood pressure in 500- to 750-g birthweight infants is extremely wide and that it may be necessary to use other clinical criteria in conjunction with blood pressure to determine which infants require intervention for hypotension.

Blood Pressure↗

PubMed1990

Prognosis in infiltrating lobular carcinoma. An analysis of "classical" and variant tumors.

A precise histologic and clinical delineation of infiltrating lobular carcinoma, including its variant forms, has been elusive. We studied 230 patients with stage I and II infiltrating lobular carcinoma treated by mastectomy and axillary lymph node dissection. Included were 176 patients with the "classical" or "Indian-file" pattern (IFL) of infiltrating lobular carcinoma, and 54 patients with variant (VAR) histology [solid (SOL), alveolar (ALV), and mixed (MIX) patterns]. IFL patients were younger than VAR patients (52 versus 57 years; p = 0.004), and IFL patients were more likely to be premenopausal (p = 0.013). Microscopic multifocality and intraepithelial ductular extension of LCIS were both more frequent in the IFL group (p = 0.008 and 0.03, respectively). There was no significant difference in tumor size (T1 versus T2), axillary lymph node status, or TNM stage at presentation. Median survival time and time to recurrence was similar in the two groups. Although it was not statistically significant, median survival for stage I and low-axillary lymph node positive stage II IFL patients was better than that of VAR patients. One hundred forty of our 176 IFL patients (80%) could be matched with infiltrating duct carcinoma (IFDC) patients of similar age at diagnosis, menstrual status, tumor size, and axillary lymph node involvement. When stratified by stage, stage I IFL patients had a significantly higher disease-free survival (p = 0.02) than comparable patients with IFDC. There was not a significant difference in disease-free survival when stage II IFL and IFDC patients were compared. The unmodified term "infiltrating lobular carcinoma" should be restricted to lesions exhibiting the classical or Indian-file (IFL) microscopic architectural pattern in approximately 85% of the tumor. Patients with VAR forms of IFL may have a less favorable prognosis and should be distinguished from those with classical IFL for further characterization.

Breast Neoplasms↗