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Biomedical subjects

M Carmel

Publications and source records attributed to M Carmel.

At least 19 recordsLinked to original sources
PubMed2005

Multi-centre study of intraurethral valve-pump catheter in women with a hypocontractile or acontractile bladder.

OBJECTIVES: To compare the safety, effectiveness and patient satisfaction of an intraurethral valve-pump catheter (In-Flow) versus the current standard of care, clean intermittent catheterization (CIC), for females with hypocontractile or acontractile bladder. MATERIALS AND METHODS: The study was a multi-centre, prospective, single-arm crossover study. Eligible patients underwent a 1-week In-Flow tolerability trial. Successful patients then continued through an 8-week baseline phase using CIC, followed by a 16-week In-Flow treatment phase, and a final 4-week treatment withdrawal phase. Outcome measures included post-void residual (PVR), Wagner incontinence-specific quality of life (I-QOL), rate of urinary tract infection and adverse events. At study completion, open enrollment was offered. RESULTS: A total of 273 women with a mean age of 48.9 years using CIC entered the study in 18 centres under either the original (n=88) or revised protocols (n=185). The revised protocol included the addition of a 1-week tolerability trial. The reasons for the large early withdrawal of subjects (169/273) were mainly related to initial discomfort and leakage. A total of 77 patients completed the In-Flow treatment phase. PVR was comparable during baseline CIC phase and In-Flow treatment phase (20.3 ml vs. 16.1 ml), with significantly improved quality of life (QOL; mean improvement of I-QOL score +25.9; p<0.001). CONCLUSION: The In-Flow catheter appears to be a viable alternative to CIC. A subgroup of patients, mainly those unsatisfied with the currently available treatments, was more likely to tolerate In-Flow catheters, and they may achieve enhanced independence and QOL.

Adult↗
PubMed2001

The I1307K APC polymorphism: prevalence in non-Ashkenazi Jews and evidence for a founder effect.

A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (approximately 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

Adenocarcinoma↗
PubMed2000

Role of positive and negative regulation in modulation of the Fer promoter activity.

p94(fer) is a cytoplasmic and nuclear tyrosine kinase whose function has been linked to cell growth. p94(fer) accumulates at different levels in various cell types and is not detected in pre-B, pre-T and T-cells (Halachmy, S., Bern, O., Schreiber, L., Carmel, M., Sharabi, Y., Shoham, J., Nir, U., 1997. p94(fer) facilitates cellular recovery of gamma irradiated pre-T cells. Oncogene 14, 2871-2880). The fer RNA, encoding p94fer, is transcribed from the FER locus in human rat and mouse. In the present work, a Fer gene transcription initiation point was determined, and the Fer promoter was cloned. A DNA genomic fragment, extending 3698bp upstream of the fer RNA start site, was isolated, sequenced and functionally characterized. A transient transfection assay, carried out in fibroblastic cell lines, revealed the presence of the Fer promoter within the cloned genomic fragment. The Fer promoter contains neither an obvious 'TATA' element nor a putative initiator sequence, but is composed of positive and negative, cis-acting elements. Negative regulation was found to be the main cause for dysfunctioning of the Fer promoter in a T-cell leukemia cell line (Jurkat). The minimal Fer promoter that is still active in fibroblasts consists of an AP1 binding site located 14bp upstream of the fer transcription initiation point. This minimal promoter was not active in the Jurkat T-cell leukemia cells and did not bind AP1 in these cells. Three additional AP1 sites were identified in functional sequences of the Fer promoter. Thus, the availability of AP1 activity may contribute as well to the modulation of the Fer promoter activity. The presumed regulatory role of AP1 in modulating the Fer promoter activity implies a link between cell growth and the Fer gene expression level. Indeed, exposure of fibroblasts to low serum growth conditions reduced the cellular level of the fer RNA.

3T3 Cells↗
PubMed1998

Regional library and information services in the NHS--why, where, what and whither?

A general introduction showing the need for a regional structure, how the regional networks were set up, what they do and how they facilitate better library and information services (LIS) for their users, is followed by descriptions of the setting up, work and development of four different regions; South West England, Midland, Wales and Scotland. A list with contacts is given for all the regional networks, the NHS Regional Librarians Group (RLG) and the LINC Health Panel.

Information Centers↗
PubMed1997

p94fer facilitates cellular recovery of gamma irradiated pre-T cells.

p94fer is a ubiquitous, nuclear and cytoplasmic tyrosine kinase, whose accumulation has been demonstrated in all mammalian cell lines analysed. In the present work, the p94fer expression profile was determined in cell lines which were not tested before. While being present in several hematopoietic and non hematopoietic cell lines including thymic stromal cells, the p94fer kinase could not be detected in pre-T and T cell lines. p94fer was also absent in pre-B line, but accumulated in these cells upon their induced development to antibody producing cells. This is in agreement with the absence of p94fer in primary thymic and splenic T lymphocytes and its induced accumulation in stimulated B cells. Relatively high p94fer levels were detected in primary thymic and splenic stromal cells. Ectopic expression of p94fer in pre-T cells slightly affected their cell cycle profile but it did not affect their apoptotic death which was induced by ionizing radiation. However, p94fer facilitated dramatically, the cellular recovery of gamma irradiated pre-T cells which have escaped the apoptotic death. The enhanced recovery of the irradiated, p94fer expressing pre-T cells, resulted most probably from their increased survival, rather than from a prominent change in their proliferation rate. The absence of p94fer from pre-B and pre-T cells, may thus contribute to the relative sensitivity of these cells to ionizing radiation and to their dependence on the functioning of other nuclear tyrosine kinasese.

3T3 Cells↗
PubMed1996

Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes.

The human erythropoietin receptor (EpoR) gene has been cloned and characterized. Very few EpoR genetic abnormalities have been reported so far. Polycythemia vera (PV) is characterized by low/normal serum erythropoietin (Epo) levels with proposed Epo hypersensitivity. Myelodysplastic syndromes (MDS) are characterized by refractory anemia with variable serum Epo levels. Several reports have suggested EpoR abnormalities in both types of stem cell disorders. We analyzed DNA obtained from peripheral blood mononuclear cells of seven healthy controls, 20 patients with myeloproliferative disorders (MPD, 11 patients with PV, five agnogenic myeloid metaplasia with myelofibrosis, four essential thrombocytosis) and eight patients with refractory anemia with ringed sideroblasts (RARS), an MDS variant. The DNA was digested with four restriction enzymes (BamHI, Bgl II, Sacl and HindIII), followed by Southern blot, using a 32P radiolabeled probe, containing 1.5 kb of the human EpoR cDNA. All 20 MPD patients and seven out of the eight MDS patients demonstrated a restriction pattern which was identical to the seven normal controls, as well as to the erythroid cell line K562, and also consistent with the expected restriction map, for all four enzymes tested. One RARS patient had a normal pattern with three enzymes but a different one with HindIII. The HindIII 12 kb large band was replaced by a faint 12 kb band and a new (about 9 kb) band appeared. The EpoR restriction map and the normal pattern obtained with the other three enzymes suggest that this patient has a 3 kb upstream deletion in one allelic EpoR gene. The same molecular pattern was detected in the patient's sister, who suffers from anemia with mild bone marrow (BM) dyserythropoiesis and plasmacytosis. Northern blot analysis showed that the patient's BM RNA carried normal EpoR message. This familial pattern may represent polymorphism. However, the patient's very high serum Epo level, her resistance to treatment with recombinant Epo, and the abnormally low growth rate of in vitro erythroid cultures, suggesting poor response to Epo in this MDS patient as well as the hematological abnormalities in her sister, support the speculation that the different EpoR gene might serve as a genetic predisposing marker and potentially could be involved (probably via post-transcriptional mechanisms and by an interaction with other factors or cytokines) in the pathogenesis. Our data suggest that the EpoR is intact in MPD and in most patients with RARS. One RARS patient had a familial different genetic structure, which could represent polymorphism. However, we can speculate also that it might be involved in the pathogenesis of the disease.

Aged↗
PubMed1994

[A simple alteration in a ureteral double J stent to improve its clinical acceptability].

The authors describe a modification of the classical double J stent designed to improve its clinical acceptability. It consists of cutting the lower J so that the catheter, inserted in the ureter, does not protrude into the bladder. A loop of nonresorbable suture attached to the lower extremity of the stent is passed through the ureteric orifice, allowing its easy extraction. This procedure has been used in eight patients with no complications.

Cystoscopes↗
PubMed1993

ferT encodes a meiosis-specific nuclear tyrosine kinase.

ferT is a mouse testis-specific mRNA, shown previously to potentially encode a 51 kilodalton tyrosine kinase termed p51ferT. The accumulation of ferT RNA is restricted to primary spermatocytes that are at the prophase stage of the first spermatogenic meiotic division. By using antibodies raised against a synthetic peptide which was designed according to a putative p51ferT unique amino acid sequence, we have shown that testicular cells indeed contain a 51 kilodalton protein that is recognized by the anti-p51ferT antibodies. The protein was not detected in six nontesticular mouse tissues, nor was it detected, like the ferT RNA, in the testes of 14-day-old mice. These findings strongly suggest that the 51 kilodalton protein is p51ferT. Immunohistochemical staining localized p51ferT to meiotically dividing spermatocytes. Transfection experiments in CHO cells confirmed the nuclear localization of p51ferT in eukaryotic cells. p51ferT seems thus to be the first meiosis-specific nuclear tyrosine kinase described to date.

Animals↗
PubMed1991

Management by agreement: contracting for library services in South West Thames.

On 1 April 1991, the financial base of the NHS underwent its most dramatic change since its inception in 1948. All NHS services are now based on contracts and this has major implications for library services. This change was perceived by the South West Thames Regional Library Service as presenting a unique opportunity and the paper outlines the background to the thinking and the strategy adopted to meet the challenges. Sources of library funding and precise spending details were identified by means of a survey and contracts agreed covering all NHS staff in each of the 13 districts. The contracts are operating as 'shadow contracts' for 1991-92 allowing a valuable period of evaluation and monitoring before any money actually changes hands. The survey form for collecting library budgetary information and the service agreement are included as Appendices to the article.

Budgets↗
PubMed1991

Assisted erection follow-up with couples.

Erection obtained with a vacuum pump can be a solution for the impotent man. In this study it was proposed to and discussed with couples, eleven of whom chose it as treatment. The mean age of the men was 54 years and 8 months. The estimated etiology of their erectile disorder was: biogenic, 4, mixed, 7. A 25-item questionnaire was administered to each couple. Results show that the device was a good solution and improved the sex life of both partners. They manifested a fair degree of satisfaction with its use. The presence and the participation of the female partner should be considered in therapeutic recommendations for erectile disorders.

Erectile Dysfunction↗
PubMed1989

Studies on the characterization of rat prostate androgen receptors.

In the presence of sodium molybdate and protease inhibitors, two forms of androgen-receptor complexes were observed which sedimented in the areas of 8-9S and 5-7S by SDG centrifugation. The intermediary 5-7S form was better seen when complexes were incubated at low KCl concentrations. The sedimentation coefficient of this form fluctuated between 5 and 7S depending on the KCl concentration. At high ionic strength (0.6M KCl) in all media, one form only was observed having a sedimentation coefficient value of 4.3S. By gel exclusion chromatography, we also observed two specific entities at 75A and 68A; in the presence of 0.6M KCl, however, two entities were found at 68A and 43A. The constant presence of protease inhibitors in all buffers was necessary to separate the intermediary 68A form. We calculated molecular weights of about 270 kDa, 190 kDa, and 80 kDa respectively for these three forms. [3H]R1881-receptor complexes bound to DEAE-cellulose and were eluted in the absence of glycerol at 0.1M and 0.2M KCl. Material found at 0.1M KCl sedimented in the areas of 5-7S and 8-9S in nearly equal proportion, and that found at 0.2M KCl sedimented in the 8-9S area only. When the cytosol was chromatographed at a fast flow rate (4 ml/min), untransformed 8-9S receptors did not bind to phosphocellulose, but transformed complexes were retained, could be eluted with 0.4M KCl and sedimented in the 4S area on KCl free SDG centrifugation. When the excluded untransformed 8-9S complexes were re-chromatographed at a slow flow rate (1 ml/min), they were retained on phosphocellulose, and could be eluted with 0.3M KCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Action of clonidine on micturitional reflexes in decerebrate cats.

We explored the urodynamic action of clonidine (preferential alpha 2-agonist) and yohimbine (preferential alpha 2-blocker) in decerebrate cats. These animals retain catecholaminergic fibers from the complex of the locus coeruleus to the spinal cord and have synergic and faster micturition cycles than normal cats. Twenty-nine male cats were made decerebrate at intercollicular level under ether anesthesia. Voiding, vesical, urethral and blood pressures, and the EMG of the external sphincter-pelvic floor and leg muscles were studied. Preparations with the urethrovesical junction opened and closed were used. Control activity was characterized by two types of vesical pressure waves: (1) low frequency, high intensity, and (2) high frequency, low intensity. Type-2 preceded Type-1 waves. Clonidine caused: (A) reduction of Type-1 and enhancement of Type-2 Pves waves; (B) diminution of vesical capacity; (C) facilitation of external sphincter relaxation; (D) inhibition of skeletal muscle activity; (E) systemic hypotension and bradycardia. Yohimbine inhibited clonidine's actions. When injected alone, it inhibited vesical and increased sphincteric activities. It also produced systemic hypertension and enhanced crisis of autonomic dysreflexia. The overall effect of clonidine on urodynamics in acute decerebrate cats was to bring about an active, small (normotonic) bladder with urinary frequencies. We suggest that clonidine: (1) inhibited Type-1 waves by inhibiting cellular activity in the locus coeruleus. As a result, the vesico-vesical contraction long loop reflex was abolished; (2) facilitated Type-2 waves by inhibiting inhibitory interneurons in the sacral parasympathetic center. As a result, the vesicovesical contraction short loop reflex was facilitated.

Adrenergic alpha-Agonists↗
PubMed1989

Characteristics of the rat prostate androgen receptors analyzed by sucrose density gradient and high-performance liquid chromatofocusing.

Rat prostate cytosolic androgen-receptor complexes were analyzed by sucrose density gradient (SDG) centrifugation and by high-performance liquid chromatofocusing (HPCF). Without protecting agents, these complexes were resolved by HPCF at basic (8.25-7.1), intermediary (7.0-5.0) and acidic (4.6-4.2) pH. Sodium molybdate stabilized labeled complexes which migrated in the 8-9S and 3.5-6S areas on SDG. These were further stabilized by the presence of sodium molybdate and four protease inhibitors: complexes then sedimented mainly in the 8-9S area with a shoulder at 6-7S. Forms eluting at acidic pH on HPCF were favored by the presence of sodium molybdate and further enhanced by the addition of inhibitors, to the detriment of basic ones. Furthermore, when chromatographed on phosphocellulose (P-c), unretained complexes sedimented as a symmetrical peak on SDG centrifugation in the 8-9S area, but were eluted from HPCF columns as two entities at pH 4.1 and 4.6. The P-c retained complexes subsequently detached by 0.6 M KCl, were resolved into three entities by HPCF with a major component at pH 8.2, which sedimented in the 4S areas. These results demonstrate that the gradual decrease in the negative net charge of androgen receptor correlates with the gradual reduction in mass of the androgen-receptor complex. Moreover, this can be interpreted as further evidence for a heterogeneity of androgen receptor population in rat prostate, suggesting the involvement of a multistep mechanism preceding the induction of specific gene transcription by the hormone.

Animals↗