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Biomedical subjects

B Greenberg

Publications and source records attributed to B Greenberg.

At least 127 records · Page 7Linked to original sources
PubMed1988

Decreased gastric acid secretion and bacterial colonization of the stomach in severely malnourished Bangladeshi children.

To assess the effect of malnutrition on gastric acidity and gastric bacterial colonization, we studied 35 severely malnourished Bangladeshi children before (0 wk) and after (3 wk) they received nutritional rehabilitation for 3 wk. These results were compared with those obtained from a similarly examined group of 20 better-nourished Bangladeshi children. Gastric acid output, both basal and after betazole stimulation, was significantly lower in the malnourished group at 0 wk compared with the better-nourished children (p less than 0.01): basal 0.22 vs. 0.52 mEq HCl/h and stimulated 0.90 vs. 2.5 mEq HCl/h. Both the concentration of acid and the rate at which gastric juice was secreted were decreased in the malnourished group but serum gastrin levels were not significantly different. After 3 wk, the malnourished children had improved from 61% (+/- 9.0%; SD) to 81% (+/- 8.1%) of expected weight-for-height and were not significantly different than the better-nourished group (86% +/- 11%). Nevertheless, gastric acid concentration remained depressed in the 3-wk group, although the rate of gastric juice secretion equaled levels observed in the better-nourished group. None of the better-nourished children had detectable gram-negative bacterial colonization of their gastric juice. In contrast, 26 of 32 (81%) malnourished children at 0 wk were colonized--even after betazole stimulation, 11 of 33 (33%) gastric juice samples yielded viable organisms--suggesting that the decrease in gastric acid output greatly reduced the gastric acid barrier. Interestingly, only 9 of 20 (45%) better-nourished children had gastric juice with basal pH values below 4.0, suggesting that the gastric acid barrier may be an intermittent defense factor in Bangladeshi children.

Age Factors↗
PubMed1988

Nucleotide sequence of the hexA gene for DNA mismatch repair in Streptococcus pneumoniae and homology of hexA to mutS of Escherichia coli and Salmonella typhimurium.

The Hex system of heteroduplex DNA base mismatch repair operates in Streptococcus pneumoniae after transformation and replication to correct donor and nascent DNA strands, respectively. A functionally similar system, called Mut, operates in Escherichia coli and Salmonella typhimurium. The nucleotide sequence of a 3.8-kilobase segment from the S. pneumoniae chromosome that includes the 2.7-kilobase hexA gene was determined. An open reading frame that could encode a 17-kilodalton polypeptide (OrfC) was located just upstream of the gene encoding a polypeptide of 95 kilodaltons corresponding to HexA. Shine-Dalgarno sequences and putative promoters were identified upstream of each protein start site. Insertion mutations showed that only HexA functioned in mismatch repair and that the promoter for hexA transcription was located within the OrfC-coding region. The HexA polypeptide contains a consensus sequence for ATP- or GTP-binding sites in proteins. Comparison of the entire HexA protein sequence to that of MutS of S. typhimurium, which was determined by Haber et al. in the accompanying paper (L. T. Haber, P. P. Pang, D. I. Sobell, J. A. Mankovitch, and G. C. Walker, J. Bacteriol. 170:197-202, 1988), showed the proteins to be homologous, inasmuch as 36% of their amino acid residues were identical. This homology indicates that the Hex and Mut systems of mismatch repair evolved from an ancestor common to the gram-positive streptococci and the gram-negative enterobacteria. It is the first direct evidence linking the two systems.

Amino Acid Sequence↗
PubMed1988

Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial.

Although vasodilator drugs acutely reduce regurgitation and improve cardiac performance in aortic insufficiency, their long-term effects on left ventricular size and function are uncertain. Consequently, we performed a double-blinded, placebo-controlled trial using hydralazine in 80 minimally symptomatic patients who had clinically stable, moderate-to-severe aortic insufficiency. Patients randomized to hydralazine displayed a progressive reduction in left ventricular end-diastolic volume index (LVEDVI) measured by radionuclide angiography, the predetermined end point of the study. At 24 months, mean LVEDVI had been reduced by 30 +/- 38 ml/m2, an 18% reduction from baseline. In contrast, LVEDVI changed minimally in patients randomized to placebo, and the intergroup differences over time were statistically significant (p less than 0.03). The hydralazine group also experienced reductions in left ventricular end-systolic volume index and increases in ejection fraction that were significantly different (both p less than 0.01) from changes in placebo-treated patients. These findings show that long-term treatment with hydralazine reduces the volume overload in aortic insufficiency and suggest that such therapy may have a beneficial effect on the natural history of the disease.

Administration, Oral↗
PubMed1988

Variability of the thymidine labeling index in squamous cell carcinoma of the head and neck.

Tritiated thymidine (3HTdR) labeling is the standard technique for determining the kinetic activity of tumors. This method has been used to label multiple sections of tumor specimens obtained from seven patients with advanced squamous cell carcinoma of the head and neck. Considerable variability was observed in the labeling index in different sites from the same specimen. To reduce the large sampling error due to heterogeneity, we recommend that an average value be determined from multiple sections when employing this technique.

Carcinoma, Squamous Cell↗
PubMed1987

Neoadjuvant therapy for advanced head and neck cancer with allopurinol-modulated high dose 5-fluorouracil and cisplatin. A phase I-II study.

The combination of cisplatin (100 mg/m2) and 5-fluorouracil (5-FU) by continuous infusion (1 g/m2/day for 5 days) has been reported to produce a high response rate as neoadjuvant therapy for advanced squamous cell head and neck cancer. We sought to improve the response rate by increasing the dose of 5-FU to 1.5 g/m2/day and 2.0 g/m2/day with allopurinol modulation to reduce toxicity. The overall response rate in the 30 patients who received three courses of chemotherapy was 100% with a 50% complete response (CR) rate. A 50% CR rate was observed in patients with T3 (six of 12) and N3 (four of eight) disease. Six patients (four with CR) did not complete subsequent treatment as planned. Seven of 11 (63.6%) chemotherapy complete responders and three of 12 (25%) partial responders (one lost to follow-up) who received all planned treatment are free of disease. The major toxicity encountered was stomatitis (severe in 32%) followed by leukopenia. The maximum tolerated dose of 5-FU in this combination with allopurinol protection was 1.5 g/m2/day. Cisplatin plus high dose 5-FU does not appear to be associated with a higher CR rate than that reported with conventional doses of 5-FU and is more toxic.

Adult↗
PubMed1987

Reproducibility of rest and exercise left ventricular ejection fraction and volumes in chronic aortic regurgitation.

To assess the variability of rest and exercise radionuclide ventriculography in patients with aortic regurgitation (AR), 22 patients in stable condition with chronic AR underwent radionuclide ventriculography at rest and during exercise for measurement of left ventricular volumes and ejection fraction (EF) on 2 occasions 3 months apart. For the group, there were no significant differences between the findings of the 2 studies except for a slightly lower exercise end-systolic volume on the second study. The inter-study differences and variabilities (expressed as the standard deviation of differences) for rest and exercise EF and change in EF were 0 +/- 0.04, +0.02 +/- 0.05 and +0.01 +/- 0.05, respectively. Thus, although mean differences were minor, considerable individual variability occurred, the magnitude of which was similar to that reported for other patient populations. In 3 patients who had an initial normal response to exercise (increase in EF greater than or equal to 0.05), the response became abnormal and in 2 who initially had an abnormal response, the response normalized. This variability must be considered in clinical decision-making or in research study design for patients with chronic AR.

Adult↗
PubMed1987

Hemodynamic effects of PN 200-110 (isradipine) in congestive heart failure.

PN 200-110 (isradipine), a dihydropyridine derivative, is a newly available calcium antagonist with potent vasodilatory properties. To determine if PN 200-110 might benefit patients with congestive heart failure (CHF), its acute hemodynamic effects were evaluated in a group of 12 patients with severe CHF. Measurements of cardiac performance were obtained after oral administration of placebo and 15 mg of PN 200-110. Placebo resulted in no significant changes in any of the variables. PN 200-110 decreased mean arterial pressure from 94 +/- 14 (mean +/- standard deviation) to 77 +/- 7 mm Hg (p less than 0.001) and increased both cardiac index from 2.1 +/- 0.4 to 2.8 +/- 0.6 liters/m2 (p less than 0.01) and stroke volume index from 26 +/- 7 to 36 +/- 10 ml/m2 (p less than 0.001). Systemic vascular resistance was reduced from 1,726 +/- 563 to 1,099 +/- 370 dynes s cm-5 (p less than 0.01). Neither heart rate nor pulmonary artery wedge pressure changed significantly. Of the 7 patients discharged receiving PN 200-110, 6 improved clinically and there was evidence of a substantial reduction in cardiothoracic ratio on chest x-ray in some patients. No serious side effects were encountered. Vasodilation with PN 200-110 can improve cardiac performance acutely in patients with CHF. Although this clinical experience is encouraging, carefully performed long-term trials must be done to determine the value of this drug in the management of patients with CHF.

Adult↗
PubMed1987

Application of magnetic resonance imaging technique in determining canine muscle and human free-flap viability.

Magnetic resonance imaging technique is an exciting, new, safe clinical tool that provides a noninvasive way to monitor free-tissue transfers. Magnetic resonance imaging (MRI) produces a cross-sectional tomographic image at higher resolution than conventional CAT scans and provides a dynamic and physiologic assessment of transferred tissue. We first studied ischemic muscle in the beagle hindlimb gracilis muscles and found an incremental and definitive increase in signal strength both over time and in comparing complete devascularization to partial devascularization. In the right hindlimb (partially devascularized), there was an average increase in T2 (measured in milliseconds) of 2.5 percent at 1 hour, 16.72 percent at 3 hours, and 16.45 percent at 12 hours as compared to normal undisturbed muscle. Similarly, the left hindlimb (completely devascularized) measurements increased from 10.97 percent at 1 hour to 24.02 percent at 3 hours to 47.75 percent at 12 hours. Possible explanations for T2 increases include an increase in intercellular and intracellular water, a change in pH, and possible protein metabolism changes. Clinical studies in seven patients with free flaps have shown "normal" T2 values in healthy tissue comparable to undisturbed canine gracilis muscle and the change in contour and composition of tissue over time. The clinical usefulness of these data is apparent.

Adolescent↗
PubMed1987

Calcitonin gene-related peptide (CGRP) is a potent non-endothelium-dependent inhibitor of coronary vasomotor tone.

1 Ring segments of bovine left circumflex coronary artery were pre-contracted with 5-hydroxytryptamine or phenylephrine and then exposed to increasing concentrations of calcitonin gene-related peptide (CGRP) and other drugs. 2 CGRP administration resulted in dose-dependent inhibition of induced tone. Maximal relaxation to CGRP was 89 +/- 5% and the concentration required to achieve 50% maximal relaxation (EC50) was 2.11 +/- 1.35 X 10(-9)M. 3 CGRP-induced relaxation was not affected by removal of endothelial cells nor was it significantly altered by incubation of coronary vessels with atropine, propranolol, phentolamine (all 10(-6)M) or indomethacin (10(-5)M). 4 From these data we conclude that CGRP is a potent inhibitor of coronary artery vasomotor tone which appears to act directly on vascular smooth muscle rather than through the release of a secondary mediator. These data support the possibility that CGRP may play a role in non-adrenergic, non-cholinergic regulation of coronary artery tone.

Animals↗
PubMed1987

Sulfonamide resistance in Streptococcus pneumoniae: DNA sequence of the gene encoding dihydropteroate synthase and characterization of the enzyme.

A chromosomal gene of Streptococcus pneumoniae carrying a spontaneous mutation to sulfonamide resistance was identified. Comparison of its DNA sequence with the wild-type sequence showed that the mutation, sul-d, consisted of an insert of 6 base pairs, a repeat of an adjacent 6-base-pair segment. The gene encoded a 34-kilodalton polypeptide, SulA, which as a dimer or trimer constituted the enzyme dihydropteroate synthase. This was shown by enzyme activity measurements, expression in minicells of Bacillus subtilis, and the amino-terminal sequence of the polypeptide product. Subcloning of the gene in an Escherichia coli expression vector allowed purification of the enzyme to 80% homogeneity in a single step and at high yield. Although a deleted plasmid, pLS83, produced the mutant dihydropteroate synthase, it did not confer sulfonamide resistance in vivo. It is suggested that the SulA polypeptide is also a component of an enzyme that acts in another step of folate biosynthesis and that this step is inhibited in vivo by either free or conjugated sulfonamides.

Bacillus subtilis↗
PubMed1987

Endothelium-dependent relaxation of human pulmonary arteries.

Although endothelial cell (EC)-dependent relaxation has been described in most mammals, there have been no detailed reports of its existence in humans. Consequently, we evaluated human pulmonary artery segments taken from uninvolved regions of resected lung from 11 patients. EC removal did not significantly alter relaxation to vasoactive intestinal peptide (VIP). However, relaxation to acetylcholine (ACh) was observed only in segments with EC. Preincubation with either 1 microM propranolol or 10 microM indomethacin failed to block relaxation, but the addition of either 30 microM quinacrine hydrochloride or 100 microM nordihydroguaiaretic acid prevented it entirely. EC-dependent relaxation to ATP was also demonstrated. These data demonstrate that EC-dependent relaxation occurs in human pulmonary arteries. Neither beta-adrenergic pathways nor prostaglandin intermediaries are utilized. An oxidized breakdown product of arachidonic or some other fatty acid from EC phospholipid appears to be involved. These data suggest that interactions between endothelium and smooth muscle may be important in modulating tone in the vessel wall and that damage to the endothelium may play a role in the development of pulmonary hypertension in humans.

Acetylcholine↗
PubMed1987

Relaxant effects of vasoactive intestinal peptide and peptide histidine isoleucine in human and bovine pulmonary arteries.

We studied the functional effects of vasoactive intestinal peptide (VIP) and the structurally related peptide histidine isoleucine (PHI) in segments of bovine and human intrapulmonary artery. In both species, VIP caused nearly complete relaxation of precontracted vessel segments. The EC50 was 1.3 +/- 0.3 X 10(-9) M (mean +/- SD) in bovine and 3.4 +/- 0.4 X 10(-9) M in human pulmonary artery. The response to VIP was not endothelium-dependent and it was not affected by either adrenergic and cholinergic blockade or by cyclooxygenase inhibition. PHI also relaxed human and bovine vessels but this related peptide was significantly less effective than VIP. We conclude that VIP is a potent inhibitor of bovine and human pulmonary artery, which appears to act directly on vascular smooth muscle. These data support the concept that VIP may be a neurotransmitter which modulates pulmonary artery tone in both man and cow.

Adenosine Triphosphate↗
PubMed1987

High-dose cytosine arabinoside, daunomycin and 6-thioguanine in relapsed or refractory acute nonlymphocytic leukemia.

Fifteen patients with relapsed (10) or primarily refractory (5) acute nonlymphocytic leukemia were treated with a combination of cytosine arabinoside (3 g/m2 i.v. every 12 h, 12 doses, days 1-6), 6-thioguanine (100 mg/m2 orally every 12 h, 12 doses, days 1-6) and daunomycin (60 mg/m2 i.v. on days 5 and 6 only). Complete remission was achieved in 11 patients. Eight of 10 relapsed patients and 3 of 5 primarily refractory patients entered remission. Median remission duration was 7.5 months (2-36+ months). Ten of the 11 remissions resulted from a single induction course. The time to hematologic recovery was comparable to that seen with 'standard'-dose cytosine arabinoside regimens. Nonhematologic toxicity, although considerable, was not greater than that seen with high-dose cytosine arabinoside alone. The most significant problem was gastrointestinal toxicity with diarrhea occurring in the majority of patients. Mild neurologic toxicity (reversible cerebellar dysfunction) occurred in 2 patients.

Acute Disease↗
PubMed1987

Morphological evidence of an altered bone marrow microenvironment in patients with acute nonlymphoblastic leukemia and myelodysplastic disorders.

Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of type IV nuclear bodies in the in vitro bone marrow fibroblastic cells (FC) derived from eight nonleukemic subjects and 13 patients with acute nonlymphoblastic leukemia (ANLL) and myelodysplastic disorders (MDD). Patients with ANLL, MDD, and myelofibrosis, as a group, had four times as many type IV nuclear bodies as nonleukemic subjects. The mean frequency of type IV nuclear bodies for patients with ANLL and MDD was 2.68% +/- 3.27% as compared with 0.63% +/- 1.06% for the nonleukemic subjects (p less than 0.05). The mean maximum type IV nuclear body area of the ANLL and chronic myelomonocytic leukemia (CMML) patients as a group was 2.08 +/- 1.10 micron2, compared with a mean maximum area of 0.93 +/- 0.10 micron2 from nonleukemic subjects (p less than 0.05). The FC were otherwise morphologically indistinguishable and displayed the typical ultrastructural features of fibroblasts. These findings have provided the first morphologic evidence that supports the concept of an altered bone marrow microenvironment in patients with ANLL and MDD. Since type IV nuclear bodies are found in high frequency in virally infected tissues, our quantitative ultrastructural findings raise the possibility of a local viral infection that affects the bone marrow microenvironment of patients with ANLL and some MDD disorders.

Acute Disease↗
PubMed1986

Identification and analysis of genes for tetracycline resistance and replication functions in the broad-host-range plasmid pLS1.

The streptococcal plasmid pMV158 and its derivative pLS1 are able to replicate and confer tetracycline resistance in both Gram-positive and Gram-negative bacteria. Copy numbers of pLS1 were 24, 4 and 4 molecules per genome in Streptococcus pneumoniae, Bacillus subtilis and Escherichia coli, respectively. Replication of the streptococcal plasmids in E. coli required functional polA and recA genes. A copy-number mutation corresponding to a 332 base-pair deletion of pLS1 doubled the plasmid copy number in all three species. Determination of the complete DNA sequence of pLS1 revealed transcriptional and translational signals and four open reading frames. A putative inhibitory RNA was encoded in the region deleted by the copy-control mutation. Two putative mRNA transcripts encoded proteins for replication functions and tetracycline resistance, respectively. The repB gene encoded a trans-acting, 23,000 Mr protein necessary for replication, and the tet gene encoded a very hydrophobic, 50,000 Mr protein required for tetracycline resistance. The polypeptides corresponding to these proteins were identified by specific labeling of plasmid-encoded products. The tet gene of pLS1 was highly homologous to tet genes in two other plasmids of Gram-positive origin but different in both sequence and mode of regulation from tet genes of Gram-negative origin.

Bacillus subtilis↗
PubMed1986

Genetic basis of the complementary DpnI and DpnII restriction systems of S. pneumoniae: an intercellular cassette mechanism.

Cells of S. pneumoniae contain either DpnI, a restriction endonuclease that cleaves only the methylated DNA sequence 5'-GmeATC-3', or DpnII, which cleaves the same sequence when not methylated. A chromosomal DNA segment containing DpnII genes was cloned in S. pneumoniae. Nucleotide sequencing of this segment revealed genes encoding the methylase and endonuclease and a third protein of unknown function. When the plasmid was introduced into DpnI cells, recombination during chromosomal facilitation of its establishment substituted genes encoding the DpnI endonuclease and another protein in place of the DpnII genes. DNA hybridization and sequencing showed that the DpnI and DpnII segments share homology on either side but not between themselves or with other regions of the chromosome. Thus, the complementary restriction systems are found on nonhomologous and mutually exclusive cassettes that can be inserted into a particular point in the chromosome of S. pneumoniae on the basis of neighboring homology.

Base Sequence↗