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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 253 records · Page 14Linked to original sources
PubMed1991

Structural and functional organization of the human neutrophil 60 kDa bactericidal/permeability-increasing protein.

We have isolated, after limited proteolysis of the bactericidal/permeability-increasing protein (BPI) of human polymorphonuclear leukocytes (PMN), two fragments representing roughly the two halves of the BPI molecule. The 25 kDa N-terminal fragment possesses all the antibacterial activities of the 60 kDa parent protein, while the ca. 30 kDa C-terminal fragment has no detectable activity. The 25 kDa fragment is as potent on a molar basis as holo-human BPI against rough Escherichia coli, is more potent than holo-BPI against more resistant smooth E. coli, and retains the specificity of BPI toward Gram-negative bacteria. The findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the N-terminal half of the molecule, implying a novel structural/functional organization for a cytotoxic protein.

Antimicrobial Cationic Peptides↗
PubMed1991

Neuroendocrine control of human reproduction in the male.

The traditional difficulty in studying the neuroendocrine control of reproduction in the human male has been the inability to tease out the hypothalamic from the pituitary component of this neuroendocrine system. The use of multiple models, each with its own strength and weakness, represents an overlapping approach that has permitted further insights to be gained into the hypothalamic control of the neuroendocrine regulation of gonadotropin secretion in the human. Such an insight is an important prerequisite to the understanding of the pathophysiology of various disease states, the unraveling of a control of FSH secretion by GnRH vs other modulators, and the subsequent design of rational therapies for male reproductive disorders.

Follicle Stimulating Hormone↗
PubMed1991

Normal sequence of the gonadotropin-releasing hormone gene in patients with idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) results from absent or greatly diminished secretion of GnRH. Defects in the GnRH gene have been identified in an animal model of IHH and have been hypothesized as a possible basis for GnRH deficiency in humans. In this study, we used the polymerase chain reaction to clone and sequence the coding regions, promoter, and 3' untranslated tract of the GnRH genes from both alleles of four unrelated patients with IHH. One of the patients studied is a member of a kindred in which X-linked inheritance has been excluded by father-to-son transmission of the disease. No DNA sequence mutations were found. We conclude that most cases of IHH in humans do not involve mutations in the GnRH gene and are presumably caused by mutations at one or more other genetic loci that are required for normal function of GnRH-producing neurons.

Adolescent↗
PubMed1991

High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia.

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.

Adult↗
PubMed1991

Preterm birth prevention: an evaluation of programs in the United States.

During the last decade several programs were established to prevent the onset of preterm labor and facilitate its early identification and treatment. Although these prevention programs shared a similar goal, they varied in their primary outcome focus, target populations, study designs, and specific intervention components. Their initial reports were promising; however, subsequent evaluations of efforts in the United States produced mixed results. The current literature is suggestive of the benefits of programs to prevent preterm labor and delivery, but methodologic differences among them and deficiencies in the reported evaluations have rendered a final verdict equivocal. Many studies using historical or geographic controls found positive results, whereas randomized, controlled trials did not find a significant impact. Positive results were found in studies using low-risk populations, but investigations of high-risk patients noted little effect. Together with continued research on the factors that underlie the onset of labor, additional assessment of these programs and their individual intervention components appears to be necessary.

Bed Rest↗
PubMed1991

Cerebral regional capillary perfusion and blood flow after carbon monoxide exposure.

Alterations in regional cerebral blood flow (rCBF) and percent perfused capillaries (indicative of functional intercapillary distance) were determined in conscious male Long-Evans rats after reducing their blood O2-carrying capacity by exposing them to 1% CO for 12 min. rCBF was determined by the iodoantipyrine method. rCBF increased from a mean of 106 +/- 8 (SE) ml.min-1.100 g-1 before CO exposure to 173 +/- 14 ml.min-1.100 g-1 after CO exposure. There was a greater flow increase (126%) in the cerebral cortex than in the lower brain stem [pons (45%), medulla (39%)]. Presence of fluorescein isothiocyanate-labeled dextran identified the perfused capillaries before and after CO exposure. The volume fraction (Vv) and number/mm2 (Na) of all capillaries (perfused and nonperfused) in a given area of brain were determined after staining for alkaline phosphatase. The percent Vv and percent Na of perfused capillaries increased uniformly (from approximately 50% to approximately 80%) in all parts of the brain after CO exposure. In the presence of tissue hypoxia with undiminished plasma PO2, the brain vasculature allowed greater flow of blood while the microvasculature adjusted to reduce the diffusion distance for O2.

Alkaline Phosphatase↗
PubMed1991

Malignant melanoma in southern Germany: different predictive value of risk factors for melanoma subtypes.

The presented case-control study with 204 melanoma patients and 200 control persons assesses the significance of melanoma risk factors for an ethnically homogeneous population from a geographically small region. In a multivariate analysis of the data the total number of benign naevi proved to be the most predictive parameter with a relative risk (RR) of 14.9 (total number of naevi higher than 50). The constitutional factors red hair colour and skin type 1 were less predictive with an RR of 2.9 and 4.9, respectively. Occupational and recreational sun exposure were of ancillary importance (RR 1.8 and 2.1). The assessment of the risk for the subtypes of melanoma however showed a clear difference in the predictive value of the mentioned risk factors. The risk of developing superficial spreading melanoma is nearly exclusively defined by the number of benign naevi (RR 24.8), red hair colour was of subordinate importance (RR 4.2), whereas the risk of lentigo maligna melanoma is dependent on skin type 1 (RR 12.9) and sun exposure (RR 3.4).

Case-Control Studies↗
PubMed1991

Source of bias in prenatal care utilization indices: implications for evaluating the Medicaid expansion.

BACKGROUND: Recent expansions in eligibility for coverage of prenatal care services by the Medicaid program reflect national initiatives to improve pregnancy outcomes. This study investigates the potential impact that completeness of reporting of prenatal care and gestational age variables and strategies to impute missing data may have on evaluations of the Medicaid expansion. METHODS: This study, examining 15 years of vital record data from a single state and comparing 1 year of data from four mid-Atlantic states, selected single live births to resident mothers for analyses. The "day 15" and the "preceding case" methods were used to impute missing gestational age data. RESULTS: Considerable temporal and geographic variation was detected in completeness of reporting of variables used to construct prenatal care indices. After imputing values for cases with missing data, the proportion of cases for which adequacy of prenatal care utilization could not be determined ranged from 3% to 24% among the states investigated. For those cases where gestational age data could be imputed, the distribution of prenatal care utilization was not markedly disparate from those cases with complete reporting of gestational age. CONCLUSIONS: The results indicate that variations in reporting, decisions regarding the treatment of missing data, and the choice of the denominator can alter prenatal care utilization percentages and have implications for evaluations of the impact of the recent Medicaid expansion on prenatal care utilization.

Bias↗
PubMed1991

Prevention of pedestrian injuries to children: effectiveness of a school training program.

Pedestrian injuries are a complex problem for which no single intervention will be completely effective. One component of a community-wide program, training of schoolchildren in street-crossing skills, is evaluated. The program targeted public school students in grades K through 4 with an eight-session training program by a single teacher, cross-age teaching, videotape feedback, and in 1990 parent-child activity workbooks. Children's street crossing was observed pretraining and posttraining and graded on four behaviors: WALKING on sidewalk/shoulder vs in the street; STOPPING at the curb; LOOKING L-R-L before crossing; KEEP LOOKING while crossing. Analysis was conducted on matched pairs in which observations pretraining were compared with those posttraining on same child. Observations were completed on 137 children in 1989 and 92 in 1990. Nearly all children walked on the side of the road; however, fewer than 50% of children STOPPED, 25% LOOKED, and fewer than 20% KEPT LOOKING before training. Training did not improve the performance on the first two behaviors in either year, significantly increased LOOKING in 1990, and increased KEEP LOOKING by twofold in 1989 and threefold in 1990. It is concluded that pedestrian skills of children can be improved but that such a program must be part of a broader effort if pedestrian injuries are to decrease.

Accidents, Traffic↗
PubMed1990

Isolation of two isoforms of a novel 15-kDa protein from rabbit polymorphonuclear leukocytes that modulate the antibacterial actions of other leukocyte proteins.

We have recently reported the use of the highly selective and reversible binding of the potent bactericidal/permeability-increasing protein (BPI) to target Gram-negative bacteria (Escherichia coli) for its isolation from crude extracts of human polymorphonuclear leukocytes (PMN). We now report the use of the same procedure for the purification from rabbit PMN of BPI and also of a novel 15-kDa species that consists of two nearly identical isoforms. These 15-kDa proteins have no demonstrable antibacterial activities by themselves. However, one isoform (p15A) potentiates strongly and the other (p15B) weakly the early antibacterial effects of both rabbit and human BPI. Both isoforms inhibit the late lethal action of BPI. Whereas the potentiating effect is specific for BPI the inhibitory effect is seen also with another antibacterial protein of PMN granules, azurocidin. Thus, we have identified in rabbit PMN a previously unrecognized 15-kDa protein species that may modulate during phagocytosis the antimicrobial effects of BPI (and other granule proteins).

Amino Acid Sequence↗
PubMed1990

Purification of a cellular (granulocyte) and an extracellular (serum) phospholipase A2 that participate in the destruction of Escherichia coli in a rabbit inflammatory exudate.

A granule-associated phospholipase A2 from rabbit polymorphonuclear leukocytes and a closely similar phospholipase A2 from rabbit serum have been purified to near homogeneity by ion-exchange and reverse-phase chromatography. The cellular (polymorphonuclear leukocyte) phospholipase A2 has been purified greater than 100,000-fold and the extracellular (serum) phospholipase A2 approximately 60,000-fold. The NH2-terminal amino acid sequence of the ascitic fluid phospholipase A2 that we have recently purified from inflammatory exudates produced in rabbits is nearly identical (15 of 16 residues) to that of the polymorphonuclear leukocyte phospholipase A2 and completely identical (19 of 19 residues) to that of the purified serum phospholipase A2. The functional properties of these three phospholipases A2 are indistinguishable. Each enzyme is active against Escherichia coli killed by the bactericidal/permeability-increasing protein of polymorphonuclear leukocyte, a property shared only by a subset of phospholipases A2. The presence of structurally and functionally very closely similar phospholipases A2 in the cellular and extracellular compartments of an inflammatory exudate is consistent with the apparent role of these enzymes in the destruction of certain microbial invaders during the acute inflammatory response.

Amino Acid Sequence↗
PubMed1990

Facilitation of ventricular tachycardia initiation by procainamide during programmed ventricular stimulation in patients with heart failure.

Antiarrhythmic drugs occasionally facilitate, rather than prevent, ventricular tachycardia. The purpose of this study was to assess the incidence of procainamide facilitation of ventricular tachycardia initiation during programmed electrical stimulation in patients with no history of spontaneous sustained ventricular tachycardia but who are at high risk. Twenty patients with advanced heart failure (mean left ventricular ejection fraction 0.19 +/- 0.09) and nonsustained ventricular tachycardia and in whom sustained ventricular tachycardia was not inducible by programmed electrical stimulation in the basal state were studied. Six patients had coronary artery disease, 13 had idiopathic dilated cardiomyopathy, and 1 had valvular heart disease. All patients received programmed stimulation from the right ventricular apex with one to three extra-stimuli before and after the intravenous infusion of 10 mg/kg of procainamide (serum level 6.6 +/- 2.4 mcg/l). In two patients (10%) sustained monomorphic ventricular tachycardia was initiated only after the administration of procainamide. One of these patients later died in ventricular tachycardia during hyperkalemia. Of the noninducible patients, during a follow-up period of 6 +/- 5 months, two died suddenly and one developed symptomatic ventricular tachycardia. Thus, procainamide can unmask potential reentry circuits in some patients who have not had spontaneous sustained ventricular tachycardia. In patients with heart failure, this risk, as assessed by programmed stimulation after a single dose of procainamide, appears to be low.

Adult↗
PubMed1990

Behavior and physiological effects of supplemental episodes of testosterone, its precursors and metabolite in rats.

Androgen-sensitive behavior and physiology were examined in gonadally intact male rats receiving daily injections of steroids (0.4 mg/kg) in two pharmaceutical forms for one month. When steroids were injected as aqueous solutions of hydroxypropyl-beta-cyclodextrin complexes, a form which insures a rapid distribution through the organism, testerosterone strongly increased behavioral parameters, while testosterone precursors (dehydroepiandrosterone and 4-androstene-3, 17-dione) and metabolite (5-alpha-dihydrotestosterone) decreased them. These results suggest that it is not possible to produce an effective testosterone pulse by metabolic conversion through supplemental pulses of precursors. The treatments did not affect sperm counts in epididymis. The size of ventral prostate was increased only after the administration of 4-androstene-3,17-dione or 5-alpha-dihydrotestosterone, not after testosterone or dehydroepiandrosterone. When steroids were injected in oil, a pharmaceutical form which distributes steroids slowly and in a protracted manner, testosterone led to an enlargement of the prostate in addition to the increase in behavioral parameters seen with the complexed form. The suppression in behavior and prostate enlargement by other steroids were more pronounced than when these were administered in complexed forms. Obviously, some of the adverse effects of the presently used depot steroid preparations are of pharmacokinetic origin.

Androstenedione↗
PubMed1990

Characterization of infectious transcripts from a potato virus X cDNA clone.

A full-length cDNA clone of potato virus X (PVX) has been constructed and fused to the bacteriophage T7 promoter in an in vitro transcription vector. Transcripts derived from this template (pMON 8660) were infectious when inoculated onto the local lesion host, Chenopodium amaranticolor. The infectivity of these transcripts was approximately 0.2% that of authentic PVX RNA. Lesions sampled from plants inoculated with these transcripts contained virus particles and virus aggregates typically observed in lesions from plants inoculated with authentic PVX RNA, as evidenced by electron microscopy. In addition, progeny virus isolated from these lesions was as infectious as progeny virus from an authentic PVX RNA infection when inoculated onto new local lesions plants. Infectious transcripts derived from PVX cDNA clones will facilitate analysis of the molecular aspects of PVX infection.

Antigens, Viral↗
PubMed1990

Selecting therapy for sustained ventricular tachycardias: importance of the sensitivity and specificity of programmed electrical stimulation for predicting arrhythmia recurrences.

Antiarrhythmic therapy for prevention of sustained ventricular tachycardia is commonly guided by programmed electrical stimulation, and the persistent ability to initiate ventricular tachycardia during drug therapy often leads to the use of nonpharmacologic therapies such as surgery. Prior studies suggest that programmed stimulation has a high sensitivity but a lower specificity for predicting recurrences of ventricular tachycardia during drug therapy. We constructed a model to evaluate the impact of various programmed stimulation specificities and sensitivities on total mortality when patients with inducible ventricular tachycardia during drug therapy proceed to arrhythmia surgery. Assumptions for this model included an 11.5% surgical mortality, a 13% risk of arrhythmia recurrence for surgery survivors, and that 33% of ventricular tachycardia recurrences are fatal. In this model the relative impact of test sensitivity and specificity on total population mortality depended on the pretest probability that drug therapy would be effective. When this probability was high, variations in test sensitivity had relatively little impact on mortality, but a low specificity increased mortality by increasing the number of false positive patients treated surgically who then suffered the surgical mortality. When the probability of effective drug therapy was low, varying test specificity had relatively little impact on mortality, but a low sensitivity increased mortality by increasing the number of patients with a false negative test who suffered fatal arrhythmia recurrences. If the specificity of programmed stimulation is low and the probability that drug therapy will be effective is high, the total population mortality can exceed the mortality expected from drug therapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗