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Biomedical subjects

D Stein

Publications and source records attributed to D Stein.

At least 163 records · Page 9Linked to original sources

A cloned regulatory gene of Streptomyces lividans can suppress the pigment deficiency phenotype of different developmental mutants.

We report here the cloning of a Streptomyces lividans gene that when introduced on a multicopy plasmid vector reversed the pigment deficiency phenotype of several distinct mutants blocked in development, pigment production, or both. Although this gene was shown by restriction enzyme analysis to be similar to a previously cloned afsB-complementing gene of Streptomyces coelicolor, we show that it does not correspond to the S. coelicolor chromosomal locus designated afsB. Thus, the cloned locus, which we propose to rename afsR, appears to complement the AfsB- phenotype by pleiotropic regulatory effects.

Blotting, Southern↗

ACTH receptors in nervous tissue. High affinity binding-sequestration of [125I]Phe2,Nle4]ACTH 1-24 in homogenates and slices from rat brain.

We have demonstrated specific, high affinity binding of a biologically active Tyr23-monoiodinated derivative of ACTH, [125I][Phe2,Nle4]ACTH 1-24, in rat brain homogenates. Similarly, in metabolically inhibited and noninhibited rat whole brain slices there is a specific "binding-sequestration" process that is dependent on time, protein concentration, and pH. In homogenates, binding curves were best described by a two-site model and provided the following parameters: Kd1 = 0.65 +/- 0.47 nM, Bmax1 = 21 +/- 41 fmol/mg protein; Kd2 = 97 +/- 48 nM, Bmax2 = 3.5 +/- 1.8 pmol/mg protein. In metabolically viable brain slices, concentration-competition curves of [125I][Phe2,Nle4]ACTH 1-24 binding-sequestration can be described by three components (Kd1 = 14 +/- 24 nM, Bmax1 = 50 +/- 95 fmol/mg protein; Kd2 = 2.4 +/- 1.9 microM, Bmax2 = 44 +/- 49 pmol/mg protein; Kd3 = 0.16 +/- 1.0 mM, Bmax3 = 5.3 +/- 54 nmol/mg protein). Metabolic inhibition, by removal of glucose and addition of 100 microM ouabain, abolishes the lowest affinity, highest capacity binding-sequestrian component only (Kd1 = 7.1 +/- 14 nM, Bmax1 = 8.7 +/- 16 fmol/mg protein; Kd2 = 7.4 +/- 4.49 microM, Bmax2 = 37 +/- 27 pmol/mg protein). The two binding-sequestration parameter estimates obtained from metabolically inhibited tissue slices are not significantly different from those of the two higher affinity components obtained with noninhibited tissue. Thus, metabolic inhibition permits demonstration of ACTH receptor binding only, unconfounded by sequestration or internalization of ligand:receptor complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Prevention of diabetes in BB/Wor rat by single transfusion of spleen cells. Parameters that affect degree of protection.

Previous studies have shown that multiple transfusions of spleen cells from histocompatible nondiabetic donors prevent autoimmune diabetes mellitus in diabetes-prone (DP) BioBreeding/Worcester (BB/Wor) rats. In this study, a single transfusion of greater than or equal to 50 x 10(6) cells from either diabetes-resistant (DR) BB/Wor or Wistar-Furth (WF) rats substantially reduced the incidence of diabetes when given to DP rats 27 or 46 days old but not 61 days old. Transfusion and protection were associated with the appearance of RT6+ donor lymph node cells in recipient rats. In vivo depletion of RT6+ T-lymphocytes in 150-day-old protected animals did not produce diabetes. DR BB/Wor and WF spleen cells were equally efficacious when given either intraperitoneally or intravenously. Mitogen-activated spleen cells were relatively less effective than untreated cells. We conclude that BB rat diabetes can be prevented by one transfusion of spleen cells from histocompatible DR and WF donors, and that the protective effect is dependent on recipient age and cell dose. The effect may be mediated by a population of RT6+ T-lymphocytes that, during a critical developmental period, regulate the expression of autoimmunity in these animals.

Age Factors↗

Determination of alfentanil in serum by radioimmunoassay or capillary column gas-liquid chromatography. A comparison of the assays.

In view of recent controversies about the specificity and accuracy of radioimmunoassays (RIA) for morphine and alfentanil, we assessed the validity of an RIA for alfentanil by comparing it with a novel capillary column gas-liquid chromatographic (GLC) assay. The coefficients of variation for eight determinations of alfentanil in plasma or serum were approximately 2% at 2, 20, and 400 ng/ml with both assays. The assay comparison was done using 85 serum samples from patients given intravenous alfentanil. There was an excellent correlation between the assay results obtained by RIA and by GLC in the range of 10-1 825 ng/ml. The two assays can therefore be used interchangeably in pharmacokinetic studies.

Alfentanil↗

Adolescent attitudes toward suicide.

Jewish Israeli adolescent attitudes toward suicide were studied and overall demonstrated a positive approach. Adolescents related to suicide as representing a crisis rather than a mental disorder. Nearly half the subjects did not regard suicide as a shameful act, and approximately two-thirds considered it justifiable under certain conditions. The majority stated they would not punish a suicidal person, nor expel a suicidal adolescent from school. Approximately two-thirds said they would not change their attitude toward a suicidal friend. Female subjects consistently demonstrated a more accepting attitude, regardless of their religious beliefs, however, religious male adolescents consistently demonstrated a more negative attitude than nonreligious males.

Adolescent↗

Prospective study of lower respiratory tract infections in an extended-care nursing home program: potential role of oral ciprofloxacin.

PURPOSE: Infections of the lower respiratory tract pose an important problem in nursing homes. Despite the magnitude of this problem, few, if any, antibiotic studies have been targeted specifically at nursing home-acquired bronchopulmonary infections. Following the establishment of a teaching Extended-Care Nursing Home Program, which facilitated the early diagnosis and therapy of bronchopulmonary infections, a comparative trial of oral ciprofloxacin and intramuscular cefamandole was initiated in elderly patients with lower respiratory tract infections. In addition to assessing the relative efficacy and safety of ciprofloxacin and cefamandole, our goals were to identify problems and pitfalls associated with conducting clinical research in this nursing home setting, evaluate selected clinical and laboratory features of lower respiratory tract infection in this patient population, and measure outcomes in all study groups. PATIENTS AND METHODS: During a 20-month period, 40 patients with pneumonia and 20 patients with acute bronchitis were enrolled in this randomized study. Sixty-three patients with pneumonia who were ineligible for the randomized study were also followed prospectively. The mean age of the 111 participants (123 cases) was 80.8 years; all patients had at least one chronic medical condition. RESULTS: Although Streptococcus pneumoniae was the single most common isolate, gram-negative bacteria were cultured from 81 percent of the cases that yielded pathogens from a satisfactory sputum specimen. The in-hospital mortality rate was strikingly low (6.5 percent), and a large majority of patients in all study groups were discharged safely back to their nursing homes well within the Diagnosis-Related Group length of stay. CONCLUSION: Ciprofloxacin appeared to be as safe and effective as cefamandole in this nursing home program; however, additional studies are needed to determine its role in the treatment of elderly patients with bronchopulmonary infections.

Administration, Oral↗

Thyroid hormones in the treatment of affective disorders.

The experience of using thyroid hormones in affective disorders is summarized. This includes: 1) Using thyroid hormones alone in depression; 2) their combined use with tricyclic antidepressants; 3) addition of thyroid hormones to nontricyclic antidepressants; 4) the use of thyroid stimulating hormone; and 5) thyrotropin releasing hormone in depression. Suggested mechanisms of action are discussed. A special attention is paid to the place of thyroid hormones in the treatment of rapid cycling affective disorder.

Antidepressive Agents, Tricyclic↗

Site-specific insertion of biologically functional adventitious genes into the Streptomyces lividans chromosome.

We report that transformation of Streptomyces lividans with cloned DNA of the SLP1 genetic element results in integration of the element at the same chromosomal locus (attB) normally occupied by SLP1 in its original host, Streptomyces coelicolor, and in S. lividans that has received SLP1 by mating. We constructed SLP1 derivatives that can integrate foreign DNA at the attB site and used these to introduce adventitious DNA sequences into the S. lividans chromosome. We also identified three regions of SLP1 essential for its integration and demonstrated that integration of the SLP1 element does not require expression of functions necessary for stable maintenance or transfer of extrachromosomal forms of SLP1.

Cloning, Molecular↗

Single and multiple dose pharmacokinetics of oral ciprofloxacin in elderly patients.

The pharmacokinetics of oral ciprofloxacin were evaluated in 20 elderly patients with serious respiratory tract or musculoskeletal infections after single and multiple dose regimens of 750 mg of drug every 12 h. The single dose phase evaluations were performed on day 1 of therapy (n = 20) while the multiple dose phase evaluations were performed at the end of therapy (n = 11). Serum and urine ciprofloxacin concentrations were determined using high-performance liquid chromatography. Peak serum concentration (Cmax), terminal elimination half-life (t1/2 beta), apparent total body clearance (CL/f) and apparent volume of distribution (Vd/f) were 6.58 +/- 2.88 mg/l, 4.99 +/- 1.79 h, 6.69 +/- 3.73 ml/kg/min, and 2.87 +/- 1.86 l/kg, respectively, during the single dose phase. Only the Vd/f increased significantly during the multiple dose phase (4.40 +/- 3.32 vs. 2.71 +/- 1.53 l/kg, p = 0.047). Although Cmax increased and CL/f decreased markedly after multiple doses (8.83 +/- 2.79 vs. 6.65 +/- 2.28 mg/l, p = 0.057 and 5.61 +/- 2.53 vs. 6.53 +/- 3.03 ml/kg/min, p = 0.074, respectively), these changes were not statistically significant. The results of this study are consistent those previously derived from single dose studies in healthy and mildly-ill elderly subjects, but are markedly different from previous observations in young adult volunteers. Thus, acute illness does not significantly alter the pharmacokinetics of ciprofloxacin in the elderly suggesting that dosage adjustments based on the presence of acute illness do not appear warranted.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Fasting- and meal-stimulated peptide hormone concentrations before and after gastric surgery for morbid obesity.

The influence of morbid obesity and of gastric surgery operation in circulating peptide hormone concentrations was studied in 26 patients. Plasma hormone levels were determined in the fasting state and after a standardized test meal before and six to nine months after gastric surgery. Before surgery fasting and postprandial blood glucose and hormone levels did not significantly differ in morbidly obese subjects from those in obese or normal subjects, except that in morbidly obese subjects, postprandial gastrin concentration remained at peak levels and did not return to fasting levels 120 minutes after the test meal. An average weight loss of 92 lb following the gastric surgery operation was accompanied by a decrease of fasting glucose and insulin levels and a decreased postprandial insulin response. There were no significant differences in plasma levels of pancreatic glucagon, of pancreatic polypeptide in the basal state, or of pancreatic glucagon after the test meal between the preoperative and postoperative groups. As compared to preoperative values, fasting gastrin levels decreased after surgery, the postprandial release of gastrin was virtually absent, and that of pancreatic polypeptide reduced. The significance of altered postprandial pancreatic polypeptide response and of the reversal of prolonged postprandial hypergastrinemia to a state of low circulating gastrin levels following gastric surgery on gastrointestinal secretion and mucosa remain to be determined.

Adult↗

Pancreatic polypeptide, pancreatic glucagon and enteroglucagon in morbid obesity and following gastric bypass operation.

The influence of morbid obesity and gastric bypass operation on pancreatic polypeptide (PP), pancreatic glucagon and enteroglucagon was studied in six morbidly obese patients before and 6-9 months after surgery. Hormone plasma levels were determined in the fasting state and after a standardized test meal. Fasting levels of PP, pancreatic glucagon and enteroglucagon were not significantly different between the pre- and post-operative state as well as compared to normal controls. The postprandial response showed a significant reduction of PP, a significant increase of enteroglucagon and no change of pancreatic glucagon after surgery compared with the preoperative values.

Adult↗

Leptomeningeal metastases: reduction in regional cerebral blood flow and cognitive impairment.

Twenty-six patients with recently diagnosed leptomeningeal metastases underwent multiple diagnostic procedures in order to assess possible cerebral parenchymal involvement. Pretreatment studies included detailed neurological examination, computed tomographic scan, electroencephalogram, neuropsychological assessment, psychiatric evaluation, and measurement of regional cerebral blood flow (rCBF) using the xenon 133 inhalation technique. At diagnosis 50% of the patients had symptoms and signs of cerebral dysfunction. Computed tomographic scanning and electroencephalography detected abnormalities in 42% and 58%, respectively. Scoring was abnormally low on at least three neuropsychological tests in 93% of the patients. The mean rCBF was reduced in 88% of patients by 16.1 +/- 2.5% (mean +/- SEM; range, 8 to 45%) compared with age-matched controls (p less than 0.001). rCBF was reduced and cognition was impaired in patients with or without overt cerebral manifestations. Neuropsychological testing and rCBF measurement may be helpful in early detection of cerebral dysfunction in patients with leptomeningeal metastases.

Adolescent↗

Rapid recovery from aphasia: a detailed language analysis.

The paper presents a daily analysis of the language recovery of a patient who was globally aphasic at the time of her first observation and who had recovered language, as measured by the Western Aphasia Battery, at the time of her discharge 14 days later. The paper emphasizes the relatively regular growth of normal syntactic, lexical, and pragmatic features coupled with similar regular decreases in aphasic features. Observations of both phenomena are necessary to describe language recovery.

Adult↗