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Biomedical subjects

S Kaplan

Publications and source records attributed to S Kaplan.

At least 343 records · Page 19Linked to original sources
PubMed1984

Sites of lead localization in embryonic chick tissues following treatment.

Lead treatment by subgerminal injection causes rupture of embryonic chick dorsal aortae during early morphogenesis, followed by localized caudal hematoma formation. Shortly thereafter, damaged tissues are resorbed, leading to a condition known as rumplessness (caudal dysplasia syndrome in humans). We have studied this process by light microscopy and have found that the caudal dorsal aortae exhibit morphological alterations as early as 4 hr after injection. Further, we used energy dispersive X-ray analysis (EDXA) to establish the precise localization and distribution of lead in the developing embryo, 4 hr after Pb(NO3)2 treatment. Embryos treated with NaNO3 were used as controls. The hierarchy of lead concentrations was endothelium of the caudal dorsal aortae greater than caudal endoderm greater than blood cells. The surrounding mesenchyme, neural tube, and notocord, as well as all control embryonic tissue, exhibited no detectable lead levels. These results suggest that lead has a high degree of specificity for entering and damaging the developing caudal dorsal aortae. A possible mechanism for this phenomenon is that lead gains access to the vascular net surrounding the caudal region of the embryo at the time of injection. Parts of this vascular net including the lead are then incorporated into the developing caudal dorsal aortae as they grow distally, thus further concentrating the lead.

Animals↗
PubMed1984

Phase I trial of 4'-deoxydoxorubicin given weekly.

Twenty-six patients with various solid tumors entered a Phase I trial with 4'-Deoxydoxorubicin (Esorubicin, IMI-58), a new doxorubicin analogue. The drug was administered weekly i.v. for 3-4 weeks. Leukopenia proved to be dose limiting. The maximum tolerated dose (MTD) was reached at 20 mg/m2 weekly for 3 weeks. For Phase II trials, a weekly dose of 15 and 17.5 mg/m2 can be proposed for poor and good risk patients respectively. Non-hematologic toxicity was minimal. Phase II trials with this new anthracycline are warranted.

Adult↗
PubMed1984

Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses.

Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and vomiting. Sixty mg/m2 was found to be the maximum tolerated dose in patients with fair tolerance to chemotherapy and normal liver function. Similar hematologic toxicity was reported in patients with very extensive prior chemotherapy or diffuse bone and/or liver metastases receiving 50 mg/m2. However, the wide range of the WBC nadirs reported with the same dose in 'good risk' cases, suggest that 40 mg/m2, increased up to 50 mg/m2 in the absence of significant myelotoxicity, could be more safely proposed as starting dose for Phase II trials. Pharmacokinetic studies were performed in five patients given a single dose of 40-60 mg/m2. IMI-30 (NSC 256439) appears to be rapidly absorbed and rapidly eliminated from plasma by means of a rapid and extensive biotransformation to 13-OH-idarubicin. The 13-dihydroderivative was present at higher and more prolonged levels than the parent compound, with an elimination half-life of about 40 hours.

Administration, Oral↗
PubMed1984

A phase I trial of cis-diammine-1,1-cyclobutane dicarboxylate platinum II (Carboplatin, CBDCA, JM-8) with a single dose every five week-schedule.

Carboplatin, a new platinum analogue, was administered intravenously on a schedule of a single dose every five weeks to 23 patients with advanced malignant solid tumors. Patients were treated at six dosage levels ranging from 200-550 mg/m2 every five weeks. Thrombocytopenia was dose-limiting. At 550 mg/m2 Carboplatin, the median platelet nadir was 65 000/mm3. Leukopenia was common, but usually of mild to moderate degree. Gastrointestinal upset was commonly seen at all dose levels, but 35% of the patients experienced no vomiting. No significant increase of the serum creatinine following Carboplatin was seen. In 16 patients serial determinations of the creatinine clearance were performed. The median base line creatinine clearance was 87 (50-155) ml/min and dropped to a median lowest creatinine clearance of 69 (23-171) ml/min on day four (p less than 0.05). The median creatinine clearance before the next Carboplatin treatment was 89 (42-155) ml/min. No significant proteinuria or electrolyte disturbances were noted. Carboplatin exhibited antitumor activity in ovarian, endometrial, thyroid and gastric carcinomas. The maximally tolerated dose appears to be 550 mg/m2 every five weeks. A starting dose of 450 mg/m2 seems to be appropriate for Phase II studies. In patients with impaired renal function and/or prior cis-Platin chemotherapy, Carboplatin at doses of 200-500 mg/m2 induced renal and severe hematological toxicity.

Adult↗
PubMed1984

Maximal exercise in children with aortic regurgitation: an adjunct to noninvasive assessment of disease severity.

Twenty-five asymptomatic children with chronic aortic regurgitation were evaluated by graded bicycle exercise testing and standard resting M-mode echocardiogram. These results were compared to those of 35 normal controls matched for age and body surface area. Twenty-one patients underwent cardiac catheterization to rule out associated lesions. Patients fell into two groups based upon the left ventricular end-diastolic volume per body surface area (LVEDVI): group I (n = 10) had LVEDVI less than or equal to 2 SD from the mean of normal; group II (n = 15) had LVEDVI greater than or equal to 4 SD from the mean of normal. All had normal shortening fraction and velocity of circumferential fiber shortening. At maximal exercise, patients in group I were found to have no significant differences from normals in maximal workload, total work, percent maximal oxygen consumption, heart rate, blood pressure, or ST segment depression. However, patients in group II had blunted mean maximal exercise heart rate (p less than 0.001), systolic hypertension (p less than 0.05), and increased frequency and maximal amplitude of ST depression (p less than 0.01, p less than 0.001, respectively) compared to normal controls. Within group II the mean maximal amplitude of ST depression was significantly related to increasing LVEDVI (r = 0.53, p less than 0.05). The mean maximal exercise heart rate, systolic blood pressure, and maximal amplitude of ST segment depression were significantly related to LVEDVI for patient groups and normal controls together (r = -0.384, p less than 0.01; r = 0.28, p less than 0.05; r = 0.70, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Plasmid distribution and analyses in Rhodopseudomonas sphaeroides.

Ten strains of Rhodopseudomonas sphaeroides were analyzed by agarose gel electrophoresis for plasmid DNA content and, by filter-hybridizations, for their molecular relationships. All strains examined contained at least one plasmid. Several strains carried as many as six different plasmid species with sizes ranging from 42 to 140 kilobases (kb). Those larger than 89 kb showed extensive homology with each other; the 42-kb plasmid of R. sphaeroides strain 2.4.1 was homologous to the smaller plasmid DNA of three other strains. A partial map of the 42-kb plasmid derived from R. sphaeroides 2.4.1 was prepared by analysis of restriction endonuclease digests. Cross-hybridization among the large plasmids indicated that those present in any one strain of R. sphaeroides showed homology to one or more of the large plasmids detected in strains L and 2.4.1.

Chromosome Mapping↗
PubMed1984

Aspirin therapy in small-caliber arterial prostheses: long-term experimental observations.

To study the therapeutic effects of 3 mg/kg aspirin given at the time of surgery and postoperatively, Dacron carotid grafts with an internal diameter of 4 mm and a length of 6 cm were implanted bilaterally in mongrel dogs. Sixteen control grafts in eight subjects and 20 grafts in 10 subjects treated with aspirin were followed by serial angiograms until consecutive studies showed stable patency rates in both groups. Platelet aggregations, malondialdehyde production, serum salicylate levels, and thromboxane A2 and prostacyclin secretion (measured as thromboxane B2 and 6-keto-prostaglandin F1 alpha) were monitored prior to and throughout the experiment. Surface mapping, indium-111 uptake, factor VIII-related antigen staining, and scanning and transmission electron microscopy were performed on the grafts at sacrifice. This study demonstrates a protective effect on the early patency of small-caliber prostheses in the canine model with daily oral aspirin administration. The degree and duration of this effect depends on the preoperative baseline ratio of thromboxane to prostacyclin in each subject.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Plasmid rearrangements in the photosynthetic bacterium Rhodopseudomonas sphaeroides.

Mu d1(Ap lac) was introduced into the photosynthetic bacterium Rhodopseudomonas sphaeroides 2.4.1. via the R-plasmid R751 in an attempt to isolate fusion derivatives involving photosynthetic operons. The selection system is potentially very powerful since R. sphaeroides is normally Lac negative. Among the exconjugants, photosynthesis-deficient mutants were recovered, some of which had elevated beta-galactosidase levels. Among the mutants examined, beta-galactosidase expression was linked exclusively to R751 . Many of the photosynthesis-deficient mutants were found to have alterations in their indigenous plasmids which apparently involved the exchange of DNA from one plasmid to another. Southern blot analysis revealed that there are extensive DNA sequences which are shared by the two plasmids that are involved in the rearrangements and that no exogenous DNA sequences appear to be involved. It was further discovered that plasmid rearrangement is a general phenomenon which can occur spontaneously in R. sphaeroides 2.4.1 and shows a high correlation with a photosynthesis minus phenotype.

Coliphages↗
PubMed1984

Induction of the photosynthetic membranes of Rhodopseudomonas sphaeroides: biochemical and morphological studies.

Cells of Rhodopseudomonas sphaeroides grown in a 25% O2 atmosphere were rapidly subjected to total anaerobiosis in the presence of light to study the progression of events associated with the de novo synthesis of the inducible intracytoplasmic membrane (ICM). This abrupt change in physiological conditions resulted in the immediate cessation of cell growth and whole cell protein, DNA, and phospholipid accumulation. Detectable cell growth and whole cell protein accumulation resumed ca. 12 h later. Bulk phospholipid accumulation paralleled cell growth, but the synthesis of individual phospholipid species during the adaptation period suggested the existence of a specific regulatory site in phospholipid synthesis at the level of the phosphatidylethanolamine methyltransferase system. Freeze-fracture electron microscopy showed that aerobic cells contain small indentations within the cell membrane that appear to be converted into discrete ICM invaginations within 1 h after the imposition of anaerobiosis. Microscopic examination also revealed a series of morphological changes in ICM structure and organization during the lag period before the initiation of photosynthetic growth. Bacteriochlorophyll synthesis and the formation of the two light-harvesting bacteriochlorophyll-protein complexes of R. sphaeroides (B800-850 and B875) occurred coordinately within 2 h after the shift to anaerobic conditions. Using antibodies prepared against various ICM-specific polypeptides, the synthesis of reaction center proteins and the polypeptides associated with the B800-850 complex was monitored. The reaction center H polypeptide was immunochemically detected at low levels in the cell membrane of aerobic cells, which contained no detectable ICM or bacteriochlorophyll. The results are discussed in terms of the oxygen-dependent regulation of gene expression in R. sphaeroides and the possible role of the reaction center H polypeptide and the cell membrane indentations in the site-specific assembly of ICM pigment-protein complexes during the de novo synthesis of the ICM.

Aerobiosis↗
PubMed1984

The dexamethasone suppression test in adolescent psychiatric patients.

The authors administered a structured psychiatric interview, the Kiddie-SADS, and the dexamethasone suppression test (DST) to 42 adolescent psychiatric inpatients. Of the 26 adolescents diagnosed as depressed, nine (36.4%) failed to suppress cortisol, and of the 16 nondepressed adolescents, three (18.8%) also failed to suppress cortisol. There was no significant association between the diagnosis of depression and the failure to suppress cortisol during the DST. The use of the DST to diagnose endogenous major depressive illness in adolescents seems to be a premature clinical application of an important investigative finding.

Adolescent↗
PubMed1984

Recurrence of patency of the ductus arteriosus after surgical ligation in premature infants.

Two premature infants who had surgical ligation of their patent ductus arteriosus are described. These infants initially did well postoperatively but then developed congestive heart failure. Both infants had echocardiographic evidence of recurrence of their patent ductus arteriosus. One of the infants required a repeat ligation procedure. It is important to continue to monitor premature infants for the return of clinical signs of a patent ductus arteriosus after surgical ligation.

Ductus Arteriosus, Patent↗
PubMed1983

The lactose carrier of Escherichia coli functionally incorporated in Rhodopseudomonas sphaeroides obeys the regulatory conditions of the phototrophic bacterium.

Rhodopseudomonas sphaeroides was provided with the ability to transport lactose via conjugation with a strain of Escherichia coli bearing a plasmid containing the lactose operon (including the lac Y gene, coding for the lactose carrier or M protein) and subsequent expression of the lac operon in Rps. sphaeroides (Nano, F.E. and Kaplan, S. submitted). The initial rate of lactose transport in Rps. sphaeroides was studied as a function of the light intensity and the magnitude of the proton-motive force. The results demonstrate that lactose transport is regulated by the rate of cyclic electron transfer in the same way as the endogenous transport systems.

Alanine↗
PubMed1983

Aortic valve replacement in childhood: evaluation of left ventricular function by electrocardiography, echocardiography and graded exercise testing.

Preoperative and postoperative left ventricular (LV) performance was evaluated noninvasively in 15 children who survived aortic valve replacement (AVR). The noninvasive evaluation included electrocardiography, M-mode echocardiography, and graded exercise testing. Clinically, there was dramatic improvement postoperatively: All but 2 patients were asymptomatic. No conduction defects or arrhythmias were detected preoperatively; however, in the late postoperative period there was a variety of intraventricular conduction abnormalities, myocardial infarctions, and ventricular or supraventricular arrhythmias. On M-mode echocardiography, children with aortic stenosis continued to have increased LV mass postoperatively. Shortening fraction and left-sided systolic time intervals returned to normal. The children with aortic regurgitation also had persistently abnormal LV mass on echocardiography postoperatively. Exercise data indicated no improvement in working capacity after AVR. Also, 9 children (63%) continued to have ST-segment depression with maximal exercise. These data indicate that AVR does not result in a return to normal of myocardial performance in children with severe aortic valve disease.

Adolescent↗
PubMed1983

Vaginal delivery after cesarean section. Experience in private practice.

To test whether vaginal delivery after cesarean section (VDAC) is a safe alternative to repeated section, a retrospective chart review of 2,350 deliveries during a ten-year period in a private practice group committed to VDAC was studied. Eighty-five parturients met six predetermined safety criteria and were permitted a trial of labor. These criteria were (1) prior low-segment transverse uterine incision; (2) vertex presentation; (3) carefully monitored labor with obstetrician present; (4) availability of emergency facilities; (5) no administration of oxytocin; and (6) patients' consent and desire to pursue VDAC. Seventy-six labors (89%) managed expectantly were successful in VDAC. No maternal or fetal morbidity was detected. No uterine ruptures were detected on postpartum examination or at the time of cesarean section. These results support the 1980 report of the National Institute of Child Health and Human Development recommending that labor and VDAC are of low risk to mother and fetus in properly selected cases.

Cesarean Section↗
PubMed1983

Solubilization, isolation, and immunochemical characterization of the major outer membrane protein from Rhodopseudomonas sphaeroides.

Solubilization of the major outer membrane protein of Rhodopseudomonas sphaeroides, and subsequent isolation, has been achieved by both non-detergent- and detergent-based methods. The protein was differentially solubilized from other outer membrane proteins in 5 M guanidine thiocyanate which was exchanged by dialysis for 7 M urea. The urea-soluble protein was purified to homogeneity by a combination of DEAE-Sephadex chromatography and preparative electrophoretic techniques. Similar to the peptidoglycan-associated proteins of other Gram-negative bacteria, the protein was also purified by differential temperature extraction of the outer membrane in the presence of sodium dodecyl sulfate (SDS) followed by preparative SDS-polyacrylamide gel electrophoresis. Immunochemical analysis of the proteins isolated by the two techniques established the immunochemical identity and homogeneity of each preparation. Immunoblots of SDS-polyacrylamide gels revealed that antibody directed against the major outer membrane protein reacted with the three high molecular weight aggregates present in the outer membrane which we have previously shown to be composed of the major outer membrane protein and three nonidentical small molecular weight proteins.

Bacterial Proteins↗
PubMed1983

Physical and chemical characterization of the major outer membrane protein of Rhodopseudomonas sphaeroides.

The characterization of the major outer membrane protein of Rhodopseudomonas sphaeroides is described. Molecular weight estimations using Ferguson plots derived from sodium dodecyl sulfate and urea-polyacrylamide gels were 39,500 and 32,200, respectively, in good agreement with the value of 33,800 obtained from amino acid compositional studies. NH2-terminal amino acid determinations of the major outer membrane protein revealed a blocked NH2 terminus. Gas chromatography of the acid-hydrolyzed protein confirmed the presence of fatty acid covalently associated with the protein presumably through an amino linkage. Peptide mapping of tryptic and chymotryptic digestions of the protein led to the identification of one peptide in each digest containing fatty acid. Digestion of the fatty acid-containing peptide with pronase resulted in the fatty acid together with L-alanine becoming extractable into hexane. We conclude that the major outer membrane protein of R. sphaeroides is a proteolipid containing at least 1 mol of fatty acid/mol of protein in amide linkage to the NH2-terminal L-alanine of the protein.

Amino Acids↗