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Biomedical subjects

R Stein

Publications and source records attributed to R Stein.

At least 235 records · Page 13Linked to original sources
PubMed1989

A comparison of fine needle aspiration and core biopsy in diagnosis and preoperative grading of prostate cancer.

Fine needle aspiration biopsy has been documented to be safe and accurate for the diagnosis of prostate cancer. A study was done based on 3 objectives to determine 1) whether performing core biopsies and fine needle aspiration in each patient with a prostate nodule increases the detection rate of prostate cancer, 2) the accuracy of preoperative grading by fine needle aspiration in predicting the final pathological grade in radical prostatectomy specimens and 3) the usefulness of fine needle aspiration in screening for unsuspected stage A prostate cancer. Of 203 consecutive patients undergoing prostate biopsies core and fine needle aspiration biopsies were performed in 121. An additional 58 patients underwent prostate biopsies just before transurethral resection of the prostate and 24 underwent radical prostatectomy. The diagnostic accuracy of fine needle aspiration was superior to that of core biopsy (82 versus 74 per cent). Performance of both biopsies yielded a higher percentage of positive diagnoses than either biopsy alone (32.2 per cent versus 24 and 28 per cent). Except in poorly differentiated cancers, fine needle aspiration is a poor predictor of final pathological grade. Fine needle aspiration is not useful in detecting stage A1 prostate cancer. Although fine needle aspiration has several distinct advantages over core biopsies, there is a definite learning curve before its use can be fully exploited. It is important to have an experienced pathologist and to perform both biopsies at each center until sufficient experience is accumulated.

Biopsy↗
PubMed1989

The mortality of childhood falls.

Falls accounted for 5.9% of the childhood deaths due to trauma in a review of the medical examiner's files in a large urban county. Falls represented the seventh leading cause of traumatic death in all children 15 years of age or younger, but the third leading cause of death in children 1 to 4 years old. The mean age of those with accidental falls was 2.3 years, which is markedly younger than that seen in hospital admission series, suggesting that infants are much more likely to die from a fall than older children. Forty-one per cent of the deaths occurred from "minor" falls such as falls from furniture or while playing; 50% were falls from a height of one story or greater; the remainder were falls down stairs. Of children falling from less than five stories, death was due to a lethal head injury in 86%. Additionally, 61.3% of the children with head injuries had mass lesions which would have required acute neurosurgical intervention. The need for an organized pediatric trauma system is demonstrated as more than one third of the children were transferred to another hospital, with more than half of these deteriorating during the delay. Of the patients with "minor" falls, 38% had parental delay in seeking medical attention, with deterioration of all. The trauma system must also incorporate the education of parents and medical personnel to the potential lethality of "minor" falls in infants and must legislate injury prevention programs.

Accidental Falls↗
PubMed1989

Pancreatic beta-cell-type-specific expression of the rat insulin II gene is controlled by positive and negative cellular transcriptional elements.

The insulin gene is expressed almost exclusively in pancreatic beta-cells. The DNA sequences that control cell-specific expression are located upstream of the transcription initiation site. To identify the cis-acting transcriptional control regions within the rat insulin II gene that are responsible for this tissue-specific expression pattern, we constructed a series of 5'-flanking deletion mutants and analyzed their expression in vivo in transfected insulin-producing and -nonproducing cell lines. Pancreatic beta-cell-specific expression was shown to be controlled by enhancer sequences lying between nucleotides -342 and -91 relative to the transcription start site. The rat insulin II enhancer appears to be a chimera, composed of a number of distinct cis-acting DNA elements. Both positive and negative transcriptional regulatory elements appear to be responsible for this cell-type-specific expression. We have shown that expression from one element within the enhancer, which is found between nucleotides -100 and -91, is regulated by both positive- and negative-acting cellular transcription factors. Expression from chimeras containing only the enhancer element sequences from -100 to -91 were active only in insulin-producing cells, indicating that the positive-acting factor(s) required for this activity may be active only in beta-cells. In contrast to the enhancer region, the rat insulin II gene promoter did not appear to require cell-specific transcription factors. Promoter mutants with 5'-flanking sequences extending to nucleotides -90 and -73 were constitutively active in both insulin-producing and -nonproducing cells. These results suggest that rat insulin II gene transcription in pancreatic beta-cells is imparted by a combination of both negative- and positive-acting cellular factors interacting with the gene enhancer.

Animals↗
PubMed1989

Blood pressure, heart rate, and heart rhythm changes in patients with heart disease during talking.

Blood pressure and heart rate were recorded in 37 patients with cardiac disease while they were resting quietly and talking. Heart rate, systolic blood pressure, and diastolic blood pressure were all significantly greater while the patients were speaking than while they were resting silently. In addition, ventricular and atrial arrhythmias were more frequent while they were talking than while they were quiet. Higher resting systolic blood pressure levels also were associated with larger blood pressure increases while the patients were speaking. Older patients exhibited significantly greater systolic pressure increases while talking than younger patients. Therapeutic doses of antihypertensive medications, including beta-blockers, calcium channel blockers, and diuretics did not block the heart rate and blood pressure increases while the patients were talking. These findings suggest that more attention needs to be paid to the hemodynamic consequences of communication in patients with coronary heart disease. Coupled with previous research findings, these data also suggest that clinicians need to attend to verbal communications during routine diagnostic procedures for evaluating cardiovascular function.

Adult↗
PubMed1989

Postnatal changes in muscarinic receptor subtype mRNAs in rat brain and heart.

Expression of mRNAs for the muscarinic acetylcholine receptor subtypes in various brain regions and in the heart of male rats was examined during postnatal development. The mRNAs for the four subtypes displayed different developmental patterns in the different regions, depending both on the cell type composition and on the age of the brain region examined.

Aging↗
PubMed1989

Severe acute asthma in a pediatric intensive care unit: six years' experience.

The management of children with severe acute asthma who required admission to the intensive care (ICU) of this hospital during 1982 to 1988 was reviewed retrospectively. A total of 89 children were admitted to the ICU on 125 occasions. During the study period, 24% of the patients were admitted to the ICU on more than one occasion. Prior to admission to this hospital, patients had been symptomatic for a mean of 48 hours. Although all patients had received bronchodilators before admission to hospital, only 23% of patients had received oral corticosteroids. According to initial arterial blood gas values determined in the ICU, 77% of the patients had hypercapnia (PaCO2 greater than 45 mm Hg). The pharmacologic agents used in the ICU included nebulized beta 2-agonists (100% of admissions), theophylline (99%), steroids (94%), nebulized ipratropium bromide (10%), IV albuterol (38%), and IV isoproterenol (10%). Mechanical ventilation was necessary in 33% of admissions; the mean duration of ventilation was 32 hours. Ten patients had pneumothorax; in six cases, these were related to mechanical ventilation. Three of the patients who received mechanical ventilation died, representing a mortality of 7.5%. In each of these patients, sudden, severe asthma episodes had developed at home, resulting in respiratory arrest. They had evidence of hypoxic encephalopathy at the time of admission to the ICU and eventually were declared brain dead. It was concluded that delay in seeking medical care and underuse of oral corticosteroids at home may have contributed to the need for ICU admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Monoclonal and oligoclonal gammopathy after bone marrow transplantation.

Serial serum protein electrophoreses were performed on 60 patients undergoing allogeneic and syngeneic bone marrow transplantation (BMT). More than 50% of patients (31 of 60) developed transient oligoclonal and monoclonal gammopathies that appeared an average of 84 days posttransplantation (range 27 to 336 days) and persisted an average of 175 days (range 14 to 652 days). Immunofixation analysis revealed 82% of the M components to be of the immunoglobulin G (IgG) type and 18% to be IgM; 56% were kappa and 44% were lambda. A strong correlation between development of graft versus host disease (GVHD) and appearance of M components was observed (73% incidence in GVHD patients v 27% in non-GVHD patients, P = .0003). Two of the three syngeneic graft recipients also developed monoclonal gammopathies. Evidence of oligoclonal circulating B-cell populations was found in 68% of patients posttransplantation by flow cytometric B-cell clonal excess assay. No correlation of recovery of particular B- or T-lymphocyte subsets and development of M components was seen. The development of transient oligoclonal and monoclonal gammopathies after transplantation may be a ubiquitous finding reflecting recapitulation of early B-cell ontogeny.

B-Lymphocytes↗
PubMed1988

Cloned M1 muscarinic receptors mediate both adenylate cyclase inhibition and phosphoinositide turnover.

The rat M1 muscarinic receptor gene was cloned and expressed in a rat cell line lacking endogenous muscarinic receptors. Assignment of the cloned receptors to the M1 class was pharmacologically confirmed by their high affinity for the M1-selective muscarinic antagonist pirenzepine and low affinity for the M2-selective antagonist AF-DX-116. Guanylyl imidodiphosphate [Gpp(NH)p] converted agonist binding sites on the receptor, from high-affinity to the low-affinity state, thus indicating that the cloned receptors couple to endogenous G-proteins. The cloned receptors mediated both adenylate cyclase inhibition and phosphoinositide hydrolysis, but by different mechanisms. Pertussis toxin blocked the inhibition of adenylate cyclase (indicating coupling of the receptor to inhibitory G-protein), but did not affect phosphoinositide turnover. Furthermore, the stimulation of phosphoinositide hydrolysis was less efficient than the inhibition of adenylate cyclase. These findings demonstrate that cloned M1 receptors are capable of mediating multiple responses in the cell by coupling to different effectors, possibly to different G-proteins.

Acetylcholine↗
PubMed1988

The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable.

We describe features of the regulation of a neural-specific gene, SCG10, which is induced by nerve growth factor (NGF) during the neuronal differentiation of the rat pheochromocytoma cell line PC12. Induction of SCG10 mRNA occurs within 12-24 hr of exposure to NGF, is sustained in the continued presence of the neurotrophic factor, and involves a mechanism that is, at least in part, transcriptional. Unlike the rapid, transient transcriptional activations of genes such as c-fos, SCG10 induction requires ongoing protein synthesis, suggesting the participation of a de novo synthesized regulatory protein in mediating the effects of NGF on this gene. Although c-fos itself may play this role, its induction is clearly insufficient to cause an induction of SCG10. NGF, FGF, and, to a lesser extent, phorbol esters induced SCG10, whereas EGF and dibutyryl cAMP did not. In these characteristics, SCG10 induction appears to constitute a reliable molecular index of the transcription-dependent neuronal differentiation induced by NGF. Glucocorticoids, which inhibit NGF-induced neurite outgrowth from normal primary chromaffin cells, partially blocked SCG10 induction in PC12 cells. A reciprocal pattern of regulation by NGF and glucocorticoids was observed for tyrosine hydroxylase mRNA. These data suggest that environmental signals such as NGF may act on specific genes, both positively and negatively, to control the choice of alternative fates by developing neural crest cells.

Animals↗
PubMed1988

The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons.

We have characterized and sequenced cDNA clones corresponding to the neural-specific SCG10 mRNA. The predicted amino acid sequence is novel and not strongly homologous to that of any known polypeptide. The protein is encoded by two mRNAs that differ in their choice of polyadenylation site. Immunocytochemical localization experiments using an affinity-purified antibody (against an SCG10-TrpE fusion protein) reveal accumulations of punctate staining in the perinuclear cytoplasm, axons, and growth cones of cultured neurons. SCG10 levels are maximal in the embryonic CNS but are dramatically reduced in the adult. Preliminary cell fractionation experiments suggest that the protein is tightly associated with membranes but is not itself an integral membrane protein. The apparent localization and timing of expression of the SCG10 protein are reminiscent of GAP-43, but the sequences of the two polypeptides are unrelated. Cross-hybridizing mRNAs and antigenically related proteins are found in several nonneuronal cell lines that do not express SCG10.

Aging↗
PubMed1988

A murine monoclonal antibody raised against human non-small cell carcinoma of the lung.

Murine monoclonal antibodies (MAbs) reactive with human non-small cell carcinoma of the lung (NSCCL) were produced following immunization with a membrane preparation of Calu-3, a human adenocarcinoma of the lung cell line grown in nude mice. Positive hybrids unreactive with normal liver membranes and human peripheral white blood cells were selected for further testing. One MAb (RS5-4H6) recognized an antigen expressed in a variety of lung and other carcinoma cell lines as detected by flow cytometry. Immunohistology showed a selectivity for normal and neoplastic lung epithelium, as well as other cancers. The antigen was detected by immunohistology in 87% of tumor specimens derived from the lung, breast, colon, kidney, and ovary. Most other normal human tissues were not stained but occasional cells of the stomach, salivary and other glands, as well as kidney tubules were reactive. This MAb is an IgG1. Western blot analysis indicated that the antibody reacts selectively with an antigen greater than 300 kD. The antigen is resistant to neuraminidase treatment and periodate oxidation, but sensitive to pronase treatment, suggesting that the epitope is peptide in nature. This antibody may be potentially useful as a targeting agent for radioimmunodetection and immunoconjugate therapy.

Adenocarcinoma↗
PubMed1988

Purification of complexes of nuclear oncogene p53 with rat and Escherichia coli heat shock proteins: in vitro dissociation of hsc70 and dnaK from murine p53 by ATP.

Oligomeric protein complexes containing the nuclear oncogene p53 and the simian virus 40 large tumor antigen (D. I. H. Linzer and A. J. Levine, Cell 17:43-51, 1979), the adenovirus E1B 55-kilodalton (kDa) tumor antigen, and the heat shock protein hsc70 (P. Hinds, C. Finlay, A. Frey, and A. J. Levine, Mol. Cell. Biol. 7:2863-2869, 1987) have all been previously described. To begin isolating, purifying, and testing these complexes for functional activities, we have developed a rapid immunoaffinity column purification. p53-protein complexes are eluted from the immunoaffinity column by using a molar excess of a peptide comprising the epitope recognized by the p53 monoclonal antibody. This mild and specific elution condition allows p53-protein interactions to be maintained. The hsc70-p53 complex from rat cells is heterogeneous in size, with some forms of this complex associated with a 110-kDa protein. The maximum apparent molecular mass of such complexes is 660,000 daltons. Incubation with micromolar levels of ATP dissociates this complex in vitro into p53 and hsc70 110-kDa components. Nonhydrolyzable substrates of ATP fail to promote this dissociation of the complex. Murine p53 synthesized in Escherichia coli has been purified 660-fold on the same antibody affinity column and was found to be associated with an E. coli protein of 70 kDa. Immunoblot analysis with specific antisera demonstrated that this E. coli protein was the heat shock protein dnaK, which has extensive sequence homology with the rat hsc70 protein. Incubation of the immunopurified p53-dnaK complex with ATP resulted in the dissociation of the p53-dnaK complex as it did with the p53-hsc70 complex. This remarkable conservation of p53-heat shock protein interactions and the specificity of dissociation reactions suggest a functionally important role for heat shock proteins in their interactions with oncogene proteins.

Adenosine Triphosphate↗
PubMed1987

Modification of an amidolytic heparin assay to express protein-bound heparin and to correct for the effect of antithrombin III concentration.

A modification of an anti-Xa assay for plasma heparin has been devised using a low molecular weight dextran sulfate that competitively binds protein heparin neutralizers and displaces masked heparin. The addition of 0.12 mg dextran sulfate per ml of plasma permits heparin, neutralized by the products of platelet aggregation, to recover full functional activity against Xa. The assay will permit a more accurate assessment of both exogenous plasma heparin and endogenous heparin-like activity in blood samples collected with varying techniques. A further modification is proposed employing polybrene to neutralize the plasma heparin-like material providing a concurrent control for each sample that increases accuracy by eliminating the effect of varying AT-III levels which have anti-Xa activity.

Antithrombin III↗
PubMed1987

Amphotericin-B nephrotoxicity in humans decreased by sodium supplements with coadministration of ticarcillin or intravenous saline.

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Amphotericin B↗