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Biomedical subjects

J Simon

Publications and source records attributed to J Simon.

At least 433 records · Page 24Linked to original sources

Covalent labeling of opioid receptors with 3H-D-Ala2-Leu5-enkephalin chloromethyl ketone. II. Binding characteristics in frog brain membranes.

3H-D-Ala2-Leu5-enkephalin chloromethyl ketone (3H-DALECK) was used to label opioid receptors of frog brain membranes. We have previously shown (15) that 70% of the opioid receptors are of kappa type in this preparation. The binding of 3H-DALECK was of high affinity, half maximal binding being achieved by 0.9 nM of the radioligand. The number of sites labeled was calculated to be 108 fmol/mg protein. Opioid ligands, incubated with the membranes prior to the label, inhibited 3H-DALECK binding with the following rank order:etorphine greater than EKC greater than DAGO greater than DALECK greater than DADLE. Dissociation experiments showed that 70% of the binding is irreversible. Fluorography performed after SDS-PAGE revealed specific covalent labeling of protein subunits of 90, 58 and 20 kD molecular weights. Results will be compared to those obtained in rat brain (13). Our two studies demonstrate that 3H-DALECK is a useful probe for investigation the subunit structure of opioid receptors.

Amino Acid Chloromethyl Ketones↗

[Neoplastic jaundice. Percutaneous transhepatic approach to biliary endoprosthesis. 39 cases].

Over a 5-year period attempts at transhepatic introduction of a biliary endoprosthesis were made in 39 inoperable patients. The procedure was in 3 stages: transhepatic cholangiography, passage through the stenosis and positioning of the prosthesis. Stenosis was intrapancreatic in 20 cases, pedicular in 9 cases and hilar in 10 cases. The endoprosthesis was successfully set in 20 cases (51%), the success rate being related to the level of the obstacle: intrahepatic 60%, hilar 30%. Failure was more frequent in patients with right liver metastasis, cholangitis or prior unsuccessful palliative surgery. The prosthesis was effective for 1 month in 17 patients and for 6 months or more in 7 patients, two of whom were followed up for 14 and 18 months respectively. Provided patients are better selected and the procedure is used mainly for cholangiocarcinomas, we see no reason why the transhepatic route (combined, if necessary, with endoscopy) should no longer be used to introduce biliary endoprostheses.

Aged↗

Role of growth hormone in regulating T-dependent immune events in aged, nude, and transgenic rodents.

Growth hormone (GH) appears to play a major role in a reciprocal axis that has been postulated between the thymus and pituitary glands. Our previous studies showed that thymic structure, as well as T-cell proliferation and IL-2 synthesis, could be restored in aged female Wistar-Furth rats by the implantation of GH3 pituitary adenoma cells. These cells secrete GH and some prolactin. We have now used three different approaches to determine whether GH affects a variety of immune events in vivo in both old and young rodents, and whether GH3 cells can directly affect progenitor T-cells in nude rats that congenitally lack a thymus gland. To test the effects of GH in aged rats, 750 micrograms of pituitary-derived ovine GH was injected 2 x daily into 26-month-old Fischer 344 rats for 5 weeks. This approach demonstrated that GH augments splenocyte proliferation to T-cell lectins as well as natural killer (NK) activity at low effector:target ratios even though morphologic characteristics of the thymus were not altered. To assess the effect of GH in young rodents, mice were studied that were transgenic for the rat metallothionein-GH gene. Histologic evaluation of thymus glands revealed that the amount of adipose tissue and the number of epithelial cells and Hassall's corpuscles are augmented in transgenic mice. Splenocyte proliferation at suboptimal mitogen doses is greater in transgenic than in control littermate mice, but neither IL-2 synthesis nor antibody synthesis to sheep erythrocytes is affected. The role of pituitary hormones on progenitor T-cells was then explored by implanting GH3 cells into Rowett nude rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effects of high-frequency jet ventilation on intracranial pressure in experimental head-brain injury.

Based on experimental studies, ventilation with small volumes of gas and rates of up to 100-400/minute, high-frequency jet ventilation (HFJV), seems to present a true alternative to conventional intermittent positive pressure ventilation (IPPV), especially in patients with multiple organ damage. In order to determine the effects of high-frequency jet ventilation on intracranial pressure, we examined the effects of the HFJV in comparison to conventional ventilation in experimental balloon brain trauma. Ten young pigs were studied using continuous invasive hemodynamic, pulmonary, and intracranial pressure monitoring. There was no increase in brain pressure over normal ventilation. As a matter of fact, there was a temporary decrease of the intracranial pressure by about 5 mmHg, which returned to the initial pre-HFJV value after 5 minutes. In contrast to conventional ventilation, HFJV allows for tracheobronchial suctioning and interruption of ventilation without any noticeable increase of ICP.

Animals↗

Transitional cell papillary carcinoma of the bladder in a child.

We report a rare case of transitional cell papillary carcinoma of the bladder in a 10-year-old girl who had hematuria. The tumor was diagnosed and assessed through VCUG and ultrasound. The tumor protruded into the urethra during micturition and its mobility was observed by both diagnostic procedures.

Carcinoma, Papillary↗

Characterization of the chicken muscle insulin receptor.

Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens.

Animals↗

Tyr-D-Ala-Gly-(Me)Phe-chloromethyl ketone: a mu specific affinity label for the opioid receptor.

An alkylating tetrapeptide enkephalin derivative, Tyr-D-Ala-Gly-(Me)Phe-chloromethyl ketone (DAMK) was synthesized, and its binding characteristics on rat brain membranes were evaluated. In competition experiments, the product shows high affinity for the mu opioid binding site of the rat brain membranes, whereas its binding to the delta and kappa subtypes is weak. Micromolar concentrations of this ligand produce a dose-dependent, apparently irreversible inhibition of /3H/-naloxone binding, with apparent IC50 value of 1-5 uM. Neither reversibly binding opioids nor tosyl-amino acid chloromethyl ketones show these effects. Saturation binding analysis with /3H/-naloxone of membranes preincubated with Tyr-D-Ala-Gly-(Me)Phe-CH2Cl reveal a selective and irreversible inhibition of the high affinity /3H/-naloxone binding site. Irreversible blockade of mu-selective /3H/-ligand binding by Tyr-D-Ala-Gly-(Me)Phe-CH2Cl is much more effective than that of the binding of /3H/-enkephalin or /3H/-ethylketocyclazocine. The mu-selective binding properties of this new irreversible enkephalin analogue suggest that it could serve as an affinity label for the mu opioid receptor subtype.

Affinity Labels↗

Purification of a kappa-opioid receptor subtype from frog brain.

A kappa-opioid receptor subtype was purified from a digitonin solubilized preparation of frog brain membranes using affinity chromatography. The affinity resin was prepared by coupling D-Ala2-Leu5-enkephalin to Sepharose-6B matrix. After elution of the receptor by 50 mumol naloxone, the kappa-subtype was separated from the mu- and delta-subtypes by gel permeation chromatography on Sepharose-6B. The purified receptor binds 3,900 pmol [3H]-ethylketocyclazocine per mg protein (a 4,300-fold purification over the membrane-bound receptor) with a KD of 8.3 nM. The purified receptor protein exhibits high affinity for kappa-selective ligands. The purified fraction shows two bands (Mr 65,000 and 58,000) in sodium dodecyl sulfate gel electrophoresis.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Endoscopic treatment of vesicoureteral reflux in children.

We treated 35 children with different grades of vesicoureteral reflux with endoscopic injection of polytetrafluoroethylene (Teflon) behind the intravesical ureter. A total of 51 refluxing ureters was treated. In all cases absence of reflux was noted on a cystogram performed immediately after the procedure. At 3 to 12-month followup reflux was absent in 32 ureters and it recurred in 4, including 3 ureters with low grade reflux. A second injection of polytetrafluoroethylene in 3 ureters resulted in its absence, while in 1 case reimplantation was performed. The procedure is simple and reliable. An operation is avoided, hospital stay is reduced and no complications have occurred.

Adolescent↗

Effect of exogenous corticosterone in genetically fat and lean chickens.

1. The effects of daily injections of corticosterone (1 or 5 mg/bird) on growth, fat deposition, liver lipid and plasma concentrations of uric acid, glucose, insulin and growth hormone were studied using genetically selected lines of fat (FL) and lean (LL) chickens. 2. Both doses of corticosterone depressed body weight gain and increased the liver lipid and the abdominal fat to the same extent in both lines. 3. In both lines, corticosterone caused a dose-dependent increase in the plasma concentrations of uric acid, glucose and insulin in the fasted and refed states. 4. In untreated birds, plasma concentrations of growth hormone (GH) were slightly higher in FL than in LL chickens and slightly decreased during refeeding. The response was not modified by injection of 1 mg corticosterone. Injections of 5 mg decreased plasma GH in both lines in the fasting state and in LL chickens during refeeding. In contrast, the same dose increased GH in FL chickens during refeeding. This contradiction remains unexplained. 5. The results suggest that corticosterone sensitivity is not involved in difference of fattening between FL and LL chickens.

Adipose Tissue↗

Effects of selection for high and low plasma glucose concentration in chickens.

1. Two lines of broilers exhibiting low (LG) or high (HG) plasma glucose concentrations were selected from a pure line of White Rock chickens. 2. Realised heritabilities were close to 0.25 in both lines. 3. The LG line was significantly fatter than the HG line; this difference was more pronounced in females than in males. 4. Food was utilised less efficiently by the LG line than by the HG one.

Animals↗

Malignant lymphomas involving the central nervous system--a morphological and immunohistochemical study of 32 cases.

The morphological features of 32 cases of malignant lymphomas involving the central nervous system presenting over a 32 year period were reviewed and the lymphomas redefined using current classifications. Twenty-four cases (75%) of non-Hodgkin's lymphomas were reclassified using the Kiel classification. There were 18 low grade non-Hodgkin's lymphomas (comprising 11 lymphoplasmacytoid, five lymphocytic and two centroblastic-centrocytic) and six high grade tumours (comprising two centroblastic, two immunoblastic, one unclassifiable and one lymphoblastic lymphoma). Cytologically the great majority of non-Hodgkin's lymphomas were B-cell lymphomas. The eight cases (25%) of Hodgkin's disease were classified by the Rye subtype and consisted of three mixed cellularity, two lymphocyte depletion, two lymphocyte predominant and one nodular sclerosis. The presence of intracytoplasmic immunoglobulins as well as markers for histiocytic cells were studied by the immunoperoxidase technique using polyclonal antisera. A monoclonal staining pattern, as revealed by light chain restriction, was found in nine cases (38%) of the non-Hodgkin's lymphomas confirming their B-cell origin. With the Marshall's metalophil method and the other histiocytic markers, scattered reactive microglial cells and histiocytic reticulum cells were found throughout the tumours in most cases. No histiocytic lymphomas were present in the series.

Central Nervous System Diseases↗

Fracture of the penis: conservative versus surgical treatment.

Four patients with penile rupture were treated by a surgical procedure without any complications. Three patients with a history of penile fracture consulted for sexual problems; 2 of them had a penile curvature and the other presented an arteriovenous fistula. We discuss immediate treatment of penis rupture by comparing our results and those reported in the literature.

Adult↗

Medicaid recipients in intermediate care facilities for the mentally retarded.

In this study, we examined Medicaid utilization and expenditure patterns of Medicaid recipients in intermediate care facilities for the mentally retarded (ICF's/MR) in three States: California, Georgia, and Michigan. Data were obtained from uniform Medicaid data files (Tape-to-Tape project). Most recipients in ICF's/MR were nonelderly adults with severe or profound mental retardation who were in an ICF/MR for the entire year. The average annual cost of care ranged from $26,617 per recipient in Georgia to $36,128 per recipient in Michigan. The vast majority of recipients were low utilizers of other Medicaid services. Approximately one-third of the recipients were also covered by Medicare.

Adult↗