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Biomedical subjects

B Greenberg

Publications and source records attributed to B Greenberg.

At least 19 recordsLinked to original sources
PubMed1992

Correlates of aortic distensibility in chronic aortic regurgitation and relation to progression to surgery.

Aortic distensibility decreases with increasing age. Patients with chronic aortic regurgitation eject a large stroke volume into the proximal aorta. A decrease in distensibility of the aorta may impose a higher afterload on the left ventricule and may contribute to deterioration of left ventricular function over time. Accordingly, aortic distensibility was measured in 33 patients aged 13 to 73 years who had chronic isolated aortic regurgitation with minimal or no symptoms. Ascending aortic diameter was measured 4 cm above the aortic valve by two-dimensional echocardiography and pulse pressure was measured simultaneously by sphygmomanometry. Aortic distensibility was calculated as (Change in aortic diameter between systole and diastole/End-diastolic diameter)/Pulse pressure. Left ventricular systolic wall stress and mass were derived from standard M-mode echocardiographic measurements. Left ventricular volumes and ejection fraction were measured by radionuclide ventriculography. Aortic distensibility decreased logarithmically with increasing age (r = -0.62, p less than 0.001) and also correlated inversely with systolic wall stress, left ventricular mass and end-diastolic volume. Patients who eventually underwent aortic valve replacement for symptoms of left ventricular dysfunction had significantly lower aortic distensibility than did those who did not yet require valve replacement: 0.09 +/- 0.08 vs. 0.22 +/- 0.19 x 1/100 (1/mm Hg) (p less than 0.05). Thus, the reduced aortic distensibility that occurs with increasing age may contribute to the gradual left ventricular dilation and dysfunction seen in patients with chronic aortic regurgitation.

Adult↗
PubMed1992

Abortions and HIV-1 infection in New York City, 1987-1989.

OBJECTIVE: This serologic survey was performed to determine rates of HIV-1 infection among New York City (NYC) women seeking abortions. DESIGN: Anonymous unlinked blood samples were collected and analyzed for the presence of HIV-1 antibodies. Abortion clinics were chosen for the representativeness of their patient population to all women obtaining abortions in NYC. SETTING: Blood samples and demographic information, including age group, race/ethnicity, borough of residence and type of payment were obtained from 15 abortion sites (11 clinics, four hospitals) in NYC between 1987 and 1989. PARTICIPANTS: A total of 5889 blood samples were collected from women seeking abortions. Twelve of the 15 facilities were sampled in all 3 years. MAIN OUTCOME MEASURES: We determined HIV infection rates in the overall sample and in selected subpopulations, and assessed temporal trends. Stepwise logistic regression was applied to identify factors independently associated with HIV-1 infection. RESULTS: The rate of HIV-1 infection in the overall sample was 1.19% (70 out of 5889) and remained stable in the 12 facilities sampled during all 3 years: 1987 (1.42%, 17 out of 1200); 1988 (1.67%, 20 out of 1200); and 1989 (0.90%, 27 out of 2989) (P = 0.09). Logistic regression identified receiving Medicaid and being aged between 25 and 35 years to be independently associated with HIV-1 infection. CONCLUSION: Approximately 1200 women seeking abortions annually in NYC are infected with HIV-1. If accessibility to elective abortion is curtailed, the number of children born to HIV-1 infected mothers will increase.

Abortion Applicants↗
PubMed1992

Genetic analysis of atopy in three large kindreds: no evidence of linkage to D11S97.

Both genetic and environmental influences have been implicated in the pathogenesis of atopic disease. A recent report suggested that a major gene providing susceptibility to atopy was transmitted in a pattern consistent with autosomal dominant inheritance and evidence was presented that places the disease locus near the D11S97 marker on human chromosome 11q. In this report, we present three large, highly characterized pedigrees in which atopy is transmitted in a pattern consistent with autosomal dominant inheritance. Genotypes at the D11S97 and HLA loci were evaluated using both lod score and sib pair methods of analysis. In these pedigrees, we reject close moderate linkage (up to 10 cM) of atopy with both D11S97 and HLA.

Genetic Linkage↗
PubMed1992

Effects of stopping long-term vasodilator therapy in patients with chronic aortic insufficiency.

We studied the effects of stopping long-term vasodilator therapy in 17 patients with chronic stable aortic insufficiency. These patients received hydralazine for 37 +/- 15 months (mean +/- SD) and, as a result, had experienced a significant decrease in left ventricular volumes. All patients were followed clinically and ten of the patients underwent serial radionuclide evaluation at baseline, while receiving drug, and at 20 +/- 7 months after stopping drug therapy. No patient showed evidence of acute clinical deterioration when drug therapy was stopped. The rate of progression to valve replacement due to onset of symptoms or left ventricular dysfunction was not significantly different from that previously reported in a population with similar characteristics. Left ventricular size, however, returned to levels similar to baseline after drug therapy was stopped. We conclude that long-term vasodilator therapy may be discontinued in patients with chronic stable aortic insufficiency without causing clinical deterioration or significant alteration in rate of progression to valve replacement.

Adult↗
PubMed1992

Zinc deficiency reduces hepatic cellular retinol-binding protein in rats.

Hepatic cellular retinol-binding protein (cRBP) levels were measured from the livers of four groups of Sprague-Dawley rats after three weeks of dietary treatment. The experimental group (n = 8) received a zinc-deficient (2.3 mg/kg dry powder) liquid diet ad libitum. A pair-fed control group (n = 8) received the same amount of liquid diet with supplemental zinc (60 mg/kg dry powder). Another control group (n = 8) received liquid diet ad libitum with supplemental zinc (60 mg/kg powder). A third control group (n = 7) received a pellet diet which also contained the same amount of zinc as the other control groups (60 mg/kg). Hepatic cRBP was reduced by more than 50% in the experimental group as compared to each of three control groups. It appears that zinc may be an essential element for the intra-cellular transport of vitamin A, in addition to its well-established role in the intercellular transport of vitamin A.

Animals↗
PubMed1991

Effects of long-term vasodilator therapy on electrocardiographic abnormalities in chronic aortic regurgitation.

Electrocardiographic abnormalities develop in patients with chronic aortic regurgitation (AR). Although vasodilator drugs may reduce left ventricular (LV) volume overload, the effects of such therapy on electrocardiographic abnormalities have not been previously evaluated. Accordingly, electrocardiograms were analyzed before and after double-blind, randomized administration of either hydralazine or placebo in 54 patients with chronic AR. These patients were without limiting symptoms and had preserved ejection fraction on entry in the study. The magnitude of ST-segment depression and Romhilt-Estes point score for LV hypertrophy were assessed. Baseline ST depression and LV hypertrophy scores in the placebo and hydralazine groups were not significantly different. At follow-up, after a mean of 19 +/- 6 months, there was a significant reduction in ST depression in patients taking hydralazine (n = 28) compared with patients given placebo (n = 26): -0.023 +/- 0.044 vs 0.029 +/- 0.055 mV, respectively (p = 0.0001); and in the LV hypertrophy score (-1.1 +/- 2.2 vs 0.9 +/- 2.3 points, respectively; p = 0.002). Hydralazine-treated patients also had significant decreases in LV end-diastolic and end-systolic volume indexes, and a significant increase in ejection fraction. These results suggest that such vasodilator therapy may be beneficial in patients with chronic AR.

Adult↗
PubMed1991

Dystrophic neurites infiltrate extracellular neurofibrillary tangles in Alzheimer disease.

The neurotrophic activity of beta-amyloid protein (beta-AP) has been suggested to be responsible for the dystrophic neurites that surround beta-AP deposits in senile plaques of Alzheimer disease. The recent finding that neurofibrillary tangles (NFT) that remain as remnants in the extracellular space (E-NFT) after the death of the neuron contain beta-AP, suggested that dystrophic neurites might also be associated with E-NFT. In this study, we use a probe for E-NFT, basic fibroblast growth factor (bFGF)-binding to show that E-NFT do contain dystrophic neurites. Since these neurites contain the amyloid precursor protein whose cleavage can lead to beta-AP, they may also play a role in further beta-AP deposition in the E-NFT.

Aged↗
PubMed1991

Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

Senile plaques are polymorphous beta-amyloid protein deposits found in the brain in Alzheimer disease and normal aging. This beta-amyloid protein is derived from a larger precursor molecule of which neurons are the principal producers in brain. We found that amyloid precursor protein (APP)-immunoreactive neurites were involved in senile plaques and that only a subset of these neurites showed markers for the abnormal filaments characteristic of neurofibrillary pathology. In the neocortex of nondemented individuals with senile plaques but spared of neurofibrillary pathology, dystrophic neurites in senile plaques showed only APP accumulation. In contrast, in the brains of Alzheimer patients, virtually all APP-immunoreactive neurites also showed immunoreactivity with ubiquitin, tau, and phosphorylated neurofilaments. The presence of tau and neurofilament epitopes in dystrophic neurites in senile plaques was correlated with the extent of neurofibrillary pathology in the surrounding brain tissue. Accumulation of APP and the formation of neurofibrillary pathology in senile plaque neurites are therefore distinct phenomena. Our findings suggest that APP accumulation in senile plaque neurites occurs prior to tau accumulation and is therefore more closely related to appearance of neuritic dystrophy.

Aged↗
PubMed1991

Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus.

We show here for the first time that actin, troponin C, Alzheimer amyloid precursor protein (AAP), and pro-interleukin 1 beta (pro-IL-1 beta), are substrates of the protease encoded by the human immunodeficiency virus (HIV) type-1. As has been seen in other non-viral protein substrates of the HIV protease, the presence of Glu residues in the P2' position appears to play an important role in substrate recognition. Three of the four bonds cleaved in actin, two of the three in troponin C, and all of the bonds hydrolyzed in AAP and pro-IL-1 beta have a P2' Glu residue. In fact, Glu residues are accommodated in all positions from P4 to P4' surrounding the scissile bond in substrates of the HIV proteases, and as many as 4 adjacent Glu residues were seen in one of the bonds cleaved in AAP. This study of non-viral protein substrates has also revealed unexpected amino acids such as Gly, Arg, and Glu in the scissile bond itself rather than the more conventional hydrophobic amino acids. The HIV-2 protease hydrolyzed actin in a manner similar to that of the HIV-1 enzyme, but its cleavage of troponin C was distinct in that it split a bond adjacent to a triplet of Glu residues in P2, P3, and P4 that was refractory to the HIV-1 enzyme. Documentation of cleavage sites in the several important cellular proteins noted above has extended our understanding of the features in a substrate that are recognized by these multi sub-site proteases of retroviral maturation. Moreover, the present work adds to an accumulating body of evidence which demonstrates that these enzymes can damage crucial structural and regulatory cellular proteins if ever their activity is expressed outside the viral particle itself.

Actins↗
PubMed1991

Sequential cloning by a vector walking along the chromosome.

A procedure was devised for sequential cloning of chromosomal DNA by cyclical integration and excision of a plasmid vector so that slightly overlapping chromosomal segments are successively cloned. The method depends on circular integration of the vector into the chromosome of a host nonpermissive for its replication, and on excision and reduction of a recombinant plasmid by use of an appropriately designed set of restriction enzyme sites in the vector. A vector suitable for cloning in Escherichia coli was constructed by combining a segment of pBR322 with a gene encoding chloramphenicol resistance expressible in many species. Sequential cloning was demonstrated in Streptococcus pneumoniae by extending a previously cloned segment of the region of the chromosome encoding maltosaccharide utilization by 8 kb in three cycles of cloning. Accuracy of the method was confirmed by hybridization of cloned DNA with chromosomal restriction fragments. It is pointed out that the similarity of the requisite genetic processes in bacteria and yeasts should allow use of the method for sequential cloning of yeast chromosomal DNA and of human or other mammalian DNA in artificial chromosomes of yeast.

Animals↗
PubMed1991

High affinity interactions between the Alzheimer's beta-amyloid precursor proteins and the basement membrane form of heparan sulfate proteoglycan.

High affinity interactions were studied between the basement membrane form of heparan sulfate proteoglycan (HSPG) and the 695-, 751-, and 770-amino acid Alzheimer amyloid precursor (AAP) proteins. Based on quantitative analyses of binding data, we identified single binding sites for the HSPG on AAP-695 (Kd = 9 x 10(-10) M), AAP-751 (Kd = 10 x 10(-9) M), and AAP-770 (Kd = 9 x 10(-9) M). It is postulated that the "Kunitz" protease inhibitor domain which is present in AAP-751 and -770 reduces the affinity of AAPs for the HSPG through steric hindrance and/or conformational alteration. HSPG binding was inhibited by heparin and dextran sulfate, but not by dermatan or chondroitin sulfate. HSPG protein core, obtained by heparitinase digestion, also bound to the beta-amyloid precursor proteins with high affinity, indicating that the high affinity binding site is constituted by the polypeptide chain rather than the carbohydrate moiety. The effects of various cations on these interactions were also studied. Our results suggest that specific interactions between the AAP proteins and the extracellular matrix may be involved in the nucleation stages of Alzheimer's disease type amyloidogenesis.

Alzheimer Disease↗
PubMed1991

Flies as forensic indicators.

Synanthropic flies, particularly calliphorids, are initiators of carrion decomposition and, as such, are the primary and most accurate forensic indicators of time of death. The relevant biology and forensic applications of the egg, larva, pupa, and young adult are discussed for various species, with emphasis on thermal history and age markers.

Animals↗
PubMed1991

Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure.

Abnormalities in vasomotor tone, including enhanced vasoconstriction at rest and diminished vasodilation in response to various stimuli, develop as a consequence of chronic heart failure. This study was undertaken to evaluate whether a specific local mechanism, namely endothelium-derived relaxing factor (EDRF) activity, might be impaired in an experimental model of chronic heart failure. Segments of thoracic aorta (TA) and pulmonary artery (PA) were isolated from a group of rats that had hemodynamic evidence of heart failure 10 weeks after ligation of the left coronary artery (n = 25) and from a group of sham-operated control rats (n = 18). Both endothelium-dependent and endothelium-independent vascular responses were assessed by exposing arterial segments to increasing concentrations of agonists. All studies were performed in the presence of 10 microM indomethacin to avoid the influence of vasoactive prostanoids. The dose-response curve for EDRF-mediated relaxation to acetylcholine was shifted rightward in rats with heart failure, and the concentrations of acetylcholine required to achieve 50% maximal relaxation (EC50) were increased compared with those of control rats in both TA and PA segments. Additionally, the dose-response curve for relaxation to ADP was shifted rightward with significantly increased EC50 in PA segments from rats with heart failure. In contrast, EDRF-mediated relaxation to the calcium ionophore A23187 was similar in the groups. Endothelium-independent relaxation to nitroglycerin was slightly increased in TA but not PA segments in the heart-failure group. Basal EDRF activity, as assessed by the increase in force after exposure to hemoglobin, was diminished in PA segments from rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Genetic and structural characterization of endA. A membrane-bound nuclease required for transformation of Streptococcus pneumoniae.

The endA gene encoding the membrane nuclease of Streptococcus pneumoniae, which is necessary for DNA uptake in genetic transformation, was cloned in a streptococcal vector. This was accomplished by insertional mutagenesis of the gene, cloning of the mutant allele, and substitution of the wild-type allele by chromosomal facilitation of plasmid establishment. Plasmids carrying the endA+ gene complemented cells with endA- in the chromosome to restore DNAase activity and transformability. Determination of its DNA sequence showed the gene to encode a 30 kDa protein, EndA, with a typical signal sequence for membrane transport at its amino end. In vitro synthesis of EndA showed the initial translation product to be enzymatically active without further processing. Comparison with EndA found in cell membranes indicated that the enzyme retained its signal sequence, which apparently anchored the otherwise hydrophilic protein to the membrane. From the nucleotide sequence in the vicinity of endA and the effect of various insertions and deletions, it appears that endA is the last gene in an operon containing at least two other genes. Neither of these upstream genes, nor the downstream gene, are essential for either cell viability or transformability.

Amino Acid Sequence↗
PubMed1990

Nocturnal oviposition behavior of blow flies (Diptera: Calliphoridae).

It is widely held that blow flies, in general, and Phaenicia sericata (Meigen), in particular, are not active at night and do not lay eggs during that time. P. sericata is thought to require sunlight and warmth for oviposition. Three common and forensically important flies--Calliphora vicina (Robineau-Desvoidy), P. sericata, and Phormia regina (Meigen)--oviposited during the dark hours of the night during the summers of 1988 and 1989. Nocturnal oviposition can alter the usual estimate of the postmortem interval in homicide cases by as much as 12 h. Cases are presented that serve to change our concept of P. sericata from an obligate heliophile to a facultative heliophile that has a willingness to enter dim or dark places to oviposit.

Adult↗
PubMed1990

Neural networks in radiologic diagnosis. II. Interpretation of neonatal chest radiographs.

A neural network (NN) system was trained to choose one or more diagnoses from a list of 12 possible diagnoses, based on 21 radiographic observations made on each of a series of neonatal chest radiographs. Initially, an experienced pediatric radiologist provided both the radiographic observations and ranked differential diagnoses for each of 77 neonatal chest radiographs in the preliminary phase used to train the NN. Subsequently, two pediatric radiologists (one of whom provided the initial training-phase data) independently read a series of 103 neonatal chest radiographs (different from the training set) and compiled a list of radiographic findings and differential diagnoses for each radiograph. The trained NN was then asked to provide a list of differential diagnoses for each case from the radiologists' lists of findings. Agreement between the network and each radiologist independently was greater than between the two radiologists. Both the positive and negative agreement between the network and either radiologist was greater than the inter-radiologist agreements for most of the diagnostic endpoints.

Artificial Intelligence↗