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Biomedical subjects

R Feinstein

Publications and source records attributed to R Feinstein.

At least 19 recordsLinked to original sources

Long-term testosterone stimulation induces hyperplasia in the guinea-pig prostate.

The relation between supraphysiologic circulating testosterone levels and prostatic diseases is unclear and difficult to study in men. Animal models may be advantageous. Based on a pilot study, testosterone enantate 50 mg (n=12) or 25 mg (n=12) was administered to guinea-pigs intramuscularly every 3 weeks, for either 7 or 14 months. The histopathology of the prostate was described. Epithelial hyperplasia was found in 14/21 animals receiving testosterone and in 7/12 very old animals, but no such changes were found in the sham or castrated animals. Testosterone stimulation seems to induce epithelial hyperplasia, but not cancer, in the guinea-pig prostate.

Animals↗

Microbial cell wall product contamination of bedding may induce pulmonary inflammation in rats.

To test the hypothesis that airborne microbial cell wall components could induce an inflammatory response in the lungs, measurements were made of the amounts of bacterial endotoxin and (1-->3)-beta-D-glucan in laboratory animal bedding materials. Groups of rats were exposed by inhalation to airborne endotoxin, (1-->3)-beta-D-glucan or a combination of the two for 5 weeks. The results demonstrated that measurable amounts of endotoxin and (1-->3)-beta-D-glucan could be detected in the different bedding materials. In contrast to animals at delivery, those kept on bedding for 5 weeks showed moderate inflammatory reactions in the lung. These were most pronounced among animals exposed to endotoxin and (1-->3)-beta-D-glucan. The results suggest that further studies need to be undertaken to elucidate the role of microbial cell wall products in the development of inflammatory lung responses among research animals.

Administration, Inhalation↗

Classification of Brachyspira spp. isolated from Swedish dogs.

Brachyspira spp. were isolated from 21 of 32 sampled dogs (66%) in a colony of Swedish beagle dogs with a history of diarrhea and from 3 of 17 Swedish pet dogs (17%) with diarrhea. All Swedish isolates were weakly beta-hemolytic and gave a negative indole reaction. Eighty-eight percent showed negative alpha-galactosidase and hippurate reactions, but a positive beta-glucosidase reaction. Two isolates were hippurate positive with a negative beta-glucosidase reaction. One additional German isolate diverged by showing a positive indole reaction in combination with a positive hippurate reaction. Sequencing of 16S rDNA indicated that the hippurate-positive isolates belonged to the species Brachyspira pilosicoli. Four representative isolates were examined using pulsed-field gel electrophoresis (PFGE) and compared with six reference strains and five porcine isolates of Brachyspira spp. The canine isolates clustered together in the PFGE analysis. Necropsy examination of a culture-positive B. pilosicoli colony-raised beagle dog revealed macro- and microscopical lesions of colitis with numerous spiral-shaped bacteria in the lumens of the crypts, in goblet cells and within the colonic epithelium.

Animals↗

Targeted disruption of the mouse phospholipase C beta3 gene results in early embryonic lethality.

In order to investigate the biological function of phosphatidylinositol-specific phospholipase C (PLC) we generated mutant mice by gene targeting. Homozygous inactivation of PLCbeta3 is lethal at embryonic day 2.5. These mutants show poor embryonic organization as well as reduced numbers of cells. Identical phenotypes were recorded in homozygous mutants generated from two independently targeted embryonic stem cell clones. Heterozygous mutant mice, however, are viable and fertile for at least two generations. We also showed that mouse PLCbeta3 is expressed in unfertilized eggs, 3-cell and egg cylinder stages of embryos. In conclusion, these results indicate that PLCbeta3 expression is essential for early mouse embryonic development.

Animals↗

B cell-deficient muMT mice as an experimental model for Mycoplasma infections in X-linked agammaglobulinemia.

B cell-deficient muMT mice were investigated as an experimental model for human X-linked agammaglobulinemia (XLA). Mice were intranasally infected with Mycoplasma pulmonis and in 16 out of 17 muMT mice, dissemination of the bacteria from the airways was observed. More than 50% of these mice developed arthritis and/or changes in periarticular tissues. Mycoplasmal infection in muMT mice thus resembles the disease seen in XLA patients implying the usefulness of the model.

Agammaglobulinemia↗

Clinical degradation and biocompatibility of different bioabsorbable interference screws: a report of six cases.

The clinical biocompatibility and degradation of bioabsorbable interference screws of different polymer composition is described in this report for six patients who underwent repeat arthroscopy after anterior cruciate ligament (ACL) reconstruction. Bioabsorbable interference screws were used for bone plug fixation of bone--patellar tendon--bone (BPTB) autografts. Poly (L-lactide) (PLLA) interference screws were used in one case, poly (D,L-lactide-co-glycolide) (PDLLA-co-PGA) in two cases and poly (D,L-lactide) (PDLLA) in three cases. The patients either underwent removal of the femoral screw or had a biopsy taken from the screw site during re-arthroscopy. Large fragments of the PLLA screw were still present 20 months postoperatively. In one case, the PDLLA-co-PGA screw was extruded spontaneously from the tibial bone tunnel 3 weeks after the operation. In the second PDLLA-co-PGA screw case, there was no evidence left of the screw material on biopsy 12 months after implantation. The PDLLA screw in one patient was removed 6 weeks after implantation without any signs of degradation. No traces of the PDLLA screws were found in the two other patients, 10 or 14 months postoperatively. There were no clinical signs of foreign-body reactions in all cases.

Adult↗

Differential susceptibility to Mycoplasma pulmonis intranasal infection in X-linked immunodeficient (xid), severe combined immunodeficient (scid), and immunocompetent mice.

Mice with the scid mutation are highly susceptible to Mycoplasma pulmonis infection and develop a disseminated disease. In order to study the contribution of humoral immunity to the immune response, M. pulmonis was inoculated intranasally to X-linked immunodeficient (xid) mice. Severe combined immunodeficient (scid) and immunocompetent CBA mice were used as controls. The mice were killed and necropsied at day 30 or 37 post-infection. Samples from the nose, lungs and joints were taken for bacteriological and histological examination. Rhinitis was observed in all mouse strains. Chronic purulent bronchopneumonia was diagnosed in some of the CBA mice. Xid mice did not show severe lung lesions, despite the presence of numerous mycoplasma organisms in the lungs, in contrast to immunocompetent mice, which developed lung pathology. Scid mice showed less signs of pneumonia, but unlike in xid and CBA mice, there was spread of mycoplasmas from the respiratory tract and severe pathological changes in the joints. Our results indicate that B and/or T lymphocytes protect against dissemination of M. pulmonis from the airways. Innate immune reactions and/or bacterial virulence factors seem to contribute to the development of joint lesions, whereas IgG3 and IgM antibodies might be involved in lung pathology.

Animals↗

Annexin II is a novel player in insulin signal transduction. Possible association between annexin II phosphorylation and insulin receptor internalization.

Annexin II is a Ca2+-, phospholipid-, and actin- binding protein that was implicated in the regulation of vesicular traffic and endosome fusion. It is a known substrate for protein kinases including the platelet-derived growth factor receptor, src protein-tyrosine kinase, and protein kinase C. In the present study we investigated the possible involvement of annexin II in insulin signal transduction. Phosphorylation of annexin II in response to insulin treatment of intact Chinese hamster ovary (CHO)-T cells was detected by 5 min and reached maximal levels after a 2-3-h incubation with the hormone. However, unlike other receptor substrates, annexin II failed to undergo insulin-induced Tyr phosphorylation under conditions where receptor internalization was inhibited. This was evident in CHO cells, overexpressing the insulin receptor, in which internalization was inhibited either by tyrosine kinase inhibitors or by lowering the temperature to 4 degrees C, and in CHO cells overexpressing various insulin receptor mutants in which normal internalization was impaired. Hence, Tyr phosphorylation of annexin II could be part of the internalization and sorting mechanism of the insulin receptor.

Androstadienes↗

Differential activation of mitogen-activated protein kinase and S6 kinase signaling pathways by 12-O-tetradecanoylphorbol-13-acetate (TPA) and insulin. Evidence for involvement of a TPA-stimulated protein-tyrosine kinase.

AG-18, an inhibitor of protein-tyrosine kinases, was employed to study the role of tyrosine-phosphorylated proteins in insulin- and phorbol ester-induced signaling cascades. When incubated with Chinese hamster ovary cells overexpressing the insulin receptor, AG-18 reversibly inhibited insulin-induced tyrosine phosphorylation of insulin receptor substate-1, with minimal effects either on receptor autophosphorylation or on phosphorylation of Shc64. Under these conditions, AG-18 inhibited insulin-stimulated phosphorylation of the ribosomal protein S6, while no inhibition of insulin-induced activation of mitogen-activated protein kinase (MAPK) kinase or MAPK was detected. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced activation of MAPK kinase and MAPK and phosphorylation of S6 were inhibited by AG-18. This correlated with inhibition of TPA-stimulated tyrosine phosphorylation of several proteins, the most prominent ones being pp114 and pp120. We conclude that Tyr-phosphorylated insulin receptor substrate-1 is the main upstream regulator of insulin-induced S6 phosphorylation by p70s6k, whereas MAPK signaling seems to be activated in these cells primarily through the adaptor molecule Shc. In contrast, TPA-induced S6 phosphorylation is mediated by the MAPK/p90rsk cascade. A key element of this TPA-stimulated signaling pathway is an AG-18-sensitive protein-tyrosine kinase.

Animals↗

Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1.

Tumor necrosis factor-alpha (TNF) has been suggested to be the mediator of insulin resistance in infection, tumor cachexia, and obesity. We have previously shown that TNF diminishes insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). The current work examines potential mechanisms that mediate this event. TNF effect on IRS-1 in Fao hepatoma cells was not associated with a significant reduction in insulin receptor tyrosine kinase activity as measured in vitro but impaired the association of IRS-1 with phosphatidylinositol 3-kinase, localizing TNF impact to IRS-1. TNF did not increase protein-tyrosine phosphatase activity and protein-tyrosine phosphatase inhibition by vanadate did not change TNF effect on IRS-1 tyrosine phosphorylation, suggesting that protein-tyrosine phosphatases are not involved in this TNF effect. In contrast, TNF increased IRS-1 phosphorylation on serine residues, leading to a decrease in its electrophoretic mobility. TNF effect on IRS-1 tyrosine phosphorylation was not abolished by inhibiting protein kinase C using staurosporine, while inactivation of Ser/Thr phosphatases by calyculin A and okadaic acid mimicked it. Our data suggest that TNF induces serine phosphorylation of IRS-1 through inhibition of serine phosphatases or activation of serine kinases other than protein kinase C. This increased serine phosphorylation interferes with insulin-induced tyrosine phosphorylation of IRS-1 and impairs insulin action.

Alkaloids↗

Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy.

There is controversy as to whether zidovudine (ZDV) induces a mitochondrial myopathy that is distinguishable from human immunodeficiency virus (HIV)-associated myopathy in ZDV-naive patients. Mitochondrial abnormalities were evaluated in skeletal muscle obtained from 18 HIV-positive, ZDV-exposed patients, and 9 who were drug naive. All patients had clinical myopathy, and underwent neuromuscular evaluation with information recorded on timing and dosage of ZDV. All underwent muscle biopsies and samples were examined without knowledge of clinical history or ZDV status. Biopsy samples were evaluated by light and electron microscopy. Mitochondrial abnormalities were seen in ZDV-treated and -naive groups, and did not correlate with ZDV exposure or cumulative ZDV dosage. Mitochondrial abnormalities displayed significant correlation with the presence and severity of myofiber degeneration on biopsy, regardless of ZDV status. As mitochondrial abnormalities reflect myofiber degeneration, present in both patient groups, they may not be used as evidence of primary mitochondrial dysfunction. The etiology of myofiber degeneration in patients with HIV infection, whether ZDV-exposed or -naive, remains unclear.

Adult↗

Radiology on the information superhighway.

PURPOSE: To explore the potential for the information superhighway to provide radiologists with new opportunities. MATERIALS AND METHODS: The Internet was used as the communication and distribution medium. MOSAIC, a graphical interface, provided access for clients, and a computer was used to serve text, images, sound, and cine onto the Internet. RESULTS: The system can be used to send reports and images to referring physicians or consulting radiologists; to provide a large database that is constantly available; to provide an increasing collection of teaching files; and to distribute interactive, multimedia teaching tools that can be used on any computer system. The use of the MOSAIC interface facilitates interaction, which allows users with limited computer experience to access the system. CONCLUSION: The Internet can dramatically expand the ways radiologists interact with their colleagues. These preliminary results indicate that there will be great challenges and opportunities for improving care and teaching in the future.

Computer Communication Networks↗

Characterization of a chicken cDNA encoding the retinoblastoma gene product.

We have isolated a chicken cDNA that encodes the retinoblastoma susceptibility gene product (RB). The predicted amino acid sequence of the chicken RB protein is highly similar to that of the mouse, human and Xenopus RB proteins in regions of known functions; however, chicken RB has distinct species-specific differences, including a shorter N-terminal region as compared to the mouse and human RB proteins. In vitro-translated chicken RB co-migrates on SDS-polyacrylamide gels with endogenous RB synthesized in transformed chicken spleen cells. Finally, chicken RB is located in the nucleus of chicken embryo fibroblasts when overexpressed from a retroviral vector.

Amino Acid Sequence↗

Intranasal inoculation of Mycoplasma pulmonis in mice with severe combined immunodeficiency (SCID) causes a wasting disease with grave arthritis.

Mycoplasma pulmonis or Myc. pneumoniae were inoculated intranasally to C.B-17 scid/scid mice (severe combined immunodeficient (SCID) mice). Immunocompetent C.B-17 mice were inoculated as controls. During the observation period of 5 weeks the mice were killed and necropsied. Mycoplasma pulmonis was recovered from all of the inoculated mice, and dissemination to various tissues increased with time. SCID mice, unlike immunocompetent mice, did not show lung lesions but exhibited severe inflammatory changes of the joints. Mycoplasma pulmonis, however, was isolated both from the lungs and the articular lesions. In addition, SCID mice infected for more than 3 weeks suffered from a pronounced loss of weight and emaciation. In the experiment with Myc. pneumoniae the agent could be reisolated, but lesions were not found in any of the infected mice. Mycoplasma pulmonis infection in SCID mice may be useful as a model of arthritis in immunodeficient humans.

Administration, Intranasal↗

Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates.

Tumor necrosis factor-alpha (TNF) has recently been shown to induce insulin resistance. We have examined the possible effect of TNF on the early events in insulin transmembrane signaling. Incubation of the insulin-sensitive rat hepatoma Fao cells with 5 nM TNF for 1 h led to a 65% decrease in insulin-induced tyrosine phosphorylation of both the insulin receptor beta-subunit and IRS-1, its major cytosolic substrate. TNF-induced impairment of tyrosine phosphorylation was maximal at 0.5 nM and was not accompanied by any reduction in insulin binding. Sixteen hours of TNF incubation led to further impairment in insulin-induced tyrosine phosphorylation of these proteins. Our findings suggest that TNF may exert its anti-insulin effect by interrupting the early insulin-stimulated tyrosine phosphorylation events, which are crucial to insulin transmembrane signaling.

Animals↗

Effects of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy.

Ketorolac, a nonsteroidal anti-inflammatory drug, is alleged to produce postoperative analgesia without opioid-related side effects. Patients undergoing laparoscopic cholecystectomy were assigned randomly to receive either ketorolac or a placebo (saline) according to a double-blind protocol. Preoperative (baseline) pulmonary function was evaluated using a Respiradyne II monitor. Patients received midazolam, 2 mg, and 2 mL of either ketorolac, 60 mg (n = 31), or saline (n = 29), 20-40 min before surgery. Anesthesia consisted of thiopental, 4-5 mg/kg, and vecuronium, 0.1 mg/kg, for induction, and isoflurane, 0.5%-2.0%, with 67% nitrous oxide in oxygen for maintenance. A second 2-mL dose of the same study medication (ketorolac, 60 mg, or saline) was administered 4 h after the initial dose. Postoperatively, 66% of patients in the saline group complained of pain requiring treatment with fentanyl compared to 32% in the ketorolac group (P < 0.05). There were no significant differences between the two groups with respect to postoperative sedation, anxiety, pain, or nausea visual analog scores. Compared to the preoperative values, significant decreases in pulmonary function tests were noted in both groups at 4 h after the operation and the following morning (P < 0.01). In the ketorolac group, only values of forced expiratory volume at 1 s and forced expiratory flow at 25%-75% of the forced vital capacity at 4 h after the operation were significantly higher than those in the saline group (P < 0.05). Incidences of nausea (45% vs 52%) and vomiting (10% vs 10%) were similar in both groups. In conclusion, ketorolac decreased the postoperative requirement for opioid analgesic medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗