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Biomedical subjects

A Adam

Publications and source records attributed to A Adam.

At least 91 records · Page 5Linked to original sources
PubMed1997

Tay-Sachs disease and HEXA mutations among Moroccan Jews.

Moroccan Jewry (N>750,000) is the only non-Ashkenazi Jewish community in which Tay-Sachs disease (TSD) is not extremely rare. Previous studies among Moroccan Jewish TSD families identified three HEXA mutations. In this study, extended to enzyme-defined and new obilgate TSD carriers, we found four additional mutations. One of them is a novel, IVS5-2(A-->G) substitution, resulting in exon skipping, and it was found only among enzyme-defined carriers. The seven HEXA identified mutations among Moroccan Jews are: deltaF(304/305), R170Q, IVS-2(A-->G), Y180X, E482K, 1278+TATC, and IVS12+1(G-->C). Their respective distribution among 51 unrelated enzyme-defined and obligate carriers is 22:19:6:1:1:1:1. The mutation(s) remain unknown in only three enzyme-defined carriers. Five of the seven Moroccan mutations, including the three most common ones, were not found among Ashkenazi Jews. Compared with the much larger and relatively homogeneous Ashkenazi population, the finding among Moroccan Jews probably reflects their much longer history.

Heterozygote↗
PubMed1997

Molecular basis of heat labile hexosaminidase B among Jews and Arabs.

Genotyping individuals for Tay-Sachs disease (TSD) is mainly based on the heat lability of beta-hexosaminidase (Hex) A (alphabeta) and the heat stability of Hex B (betabeta). Mutations in the HEXB gene encoding the beta-subunits of Hex that result in heat-labile Hex B thus may lead to erroneous enzymatic genotyping regarding TSD. Utilizing single strand conformation polymorphism (SSCP) analysis for all 14 exons of HEXB followed by direct sequencing of aberrant fragments, we screened individuals whose Hex B was heat labile. A novel heat labile mutation, previously concluded to exist in the HEXB gene, was identified among Jews and Arabs as 1627 G-->A. One individual with heat labile Hex B (HLB) was negative for this novel mutation and for the known 1514 G-->A HLB mutation, proving that there exists at least one other unidentified HLB mutation. Based on these results, it is advisable to perform DNA tests for 1627 G-->A mutation in suspected HLB individuals.

Arabs↗
PubMed1997

Involvement of endogenous kinins in the pathogenesis of peptidoglycan-induced arthritis in the Lewis rat.

OBJECTIVE: To investigate the pathophysiologic roles of endogenous bradykinin (BK) and des-Arg9-BK on local and systemic inflammatory responses in a rat model of acute arthritis induced by peptidoglycan-polysaccharide (PG-APS). METHODS: Female Lewis rats were injected intraperitoneally with PG-APS. Selective antagonists of B1 (Lys-[Leu8]-des-Arg9-BK) and B2 (Hoe 140) receptors were infused at 500 microg/kg and 5 mg/kg per day for 6 days, starting 3 days before induction of inflammation, with subcutaneous micro-osmotic pumps. The local inflammatory response was assessed by paw edema, joint swelling, and tissue content of BK and des-Arg9-BK. These peptides were measured by highly sensitive and specific chemiluminescent enzyme immunoassays. Systemic inflammatory reaction was evaluated by the hepatic concentration of the type 2 acute-phase protein T-kininogen. RESULTS: PG-APS induced significant paw edema and joint swelling 24-72 hours after intraperitoneal injection. The maximal responses to PG-APS observed at 72 hours were significantly reduced (31-38%) by the combination of both B1 and B2 receptor antagonists at 5 mg/kg per day. PG-APS induced a significant increase of BK (up to 5.3-fold) and des-Arg9-BK (up to 4.1-fold) 72 hours after challenge. Liver T-kininogen content was increased by 5.3-, 7.7-, and 5.8-fold at 24, 48, and 72 hours, respectively, after PG-APS injection. At 24 hours, Hoe 140 and Lys-[Leu8]-des-Arg9-BK increased liver T-kininogen content by 43% and 45%, respectively, but they had no effect at 72 hours. CONCLUSION: The results indicate that endogenous kinins are involved in local and systemic acute inflammatory responses, through both B1 and B2 kinin receptors, in the model of PG-APS-induced arthritis.

Acute Disease↗
PubMed1997

Speech perception abilities of adult and pediatric Nucleus implant recipients using the Spectral Peak (SPEAK) coding strategy.

A series of 73 postlinguistically deafened adults and 34 prelinguistically deafened children were evaluated with the Spectral Peak (SPEAK) coding strategy of the Nucleus 22-channel cochlear implant. The adults who received consecutive implants demonstrated rapid acquisition of open-set speech recognition skills in the initial postoperative period. Group mean sentence recognition improved to 53.5% (n = 52) after 2 weeks, 62.1% (n = 55) after 1 month, 69.8% (n = 57) after 3 months, and 74.4% (n = 42) after 6 months of use. At the 6-month evaluation interval, 43% of subjects scored greater than 90% on sound-alone sentence recognition in quiet and only one patient (2.4%) scored less than 10%. Mean monosyllabic word recognition was 35.6% after 6 months of use. The 34 prelinguistically deafened children were converted from the Multipeak strategy to Spectral Peak strategy at four large pediatric implant centers. After 6 months of using the new coding strategy, the children demonstrated significant improvements in their speech perception abilities.

Adult↗
PubMed1997

Radioimmunoassay of meterelin and pharmacokinetics after single injection and implant administration in dogs.

A sensitive and specific radioimmunoassay for a novel luteinizing-hormone-releasing-hormone (LHRH) agonist, [2-Me-D-Trp6, DesGly10]LHRH ethylamide (meterelin), was developed for documenting the pharmacokinetic parameters of this peptide following its intravenous (iv) and subcutaneous (sc) administration in dogs. The assay was also used for monitoring meterelin in plasma following its release from d,l-lactide-glycolide implants in the same species. Rabbit antisera generated against [DespyroGlu1] meterelin and conjugated to bovine serum albumin with glutaraldehyde showed high specificity, whereas crossreactivity to LHRH and its fragments and to analogs with substitutions at residues 6 and 10 was found insignificant. The assay was validated in terms of accuracy (recovery range, 94.0-105.4%), in terms of precision (intra- and interassay variations of 10.0-12.4% and 8.6-11.3%, respectively), and in terms of sensitivity (minimum detectable dose of 2.7 pg/assay). Following iv acute administration, a biexponential decline of plasma meterelin levels was observed, with distribution and elimination half-lives of 5.9 +/- 2.5 and 106 +/- 22 min, respectively. After sc acute administration, the elimination half-life was in the range of 103 to 173 min. The systemic clearance (CLT) ranged from 1.6 to 2.6 mL/min/kg, and the volume of distribution at steady state (Vdss) varied from 285 to 438 mL/kg. The elimination half-life (T1/2 beta), Vdss, and ClT were not significantly different after both routes of administration over the 1-100-microgram/kg dose range of peptide studied. Castrate levels of testosterone were attained 10 days after sc administration of the implant, lasted for up to 247 days, and were well correlated with plasma levels of meterelin.

Amino Acid Sequence↗
PubMed1997

Palliation of inoperable esophageal carcinoma: a prospective randomized trial of laser therapy and stent placement.

PURPOSE: A prospective, randomized comparison of the result of endoscopic laser therapy and that of placement of self-expandable metallic endoprostheses was performed to determine which method provides the best palliation of dysphagia in patients with inoperable esophageal carcinoma. MATERIALS AND METHODS: Sixty patients participated in the study. Twenty-three were randomly assigned to undergo plastic-covered stent placement, 19 to undergo uncovered stent placement, and 18 to undergo laser therapy. The quality of swallowing was assessed with the dysphagia score, which ranged from 0 for normal swallowing to 4 for complete dysphagia. RESULTS: The mean improvement in dysphagia score was 2 and ranged from -1 to 3 in patients who underwent placement of plastic-covered stents, was 2 and ranged from 0 to 4 in those who underwent placement of uncovered stents, and was 1 and ranged from 0 to 2 in those who underwent laser therapy. Six of 23 (26%) plastic-covered stents migrated, whereas none of the uncovered stents did so (P < .02). Tumor ingrowth through uncovered stents occurred in five of 19 patients (26%). CONCLUSION: Placement of metallic esophageal endoprostheses is substantially better than endoscopic laser therapy for palliation of dysphagia in patients with inoperable esophageal carcinoma. Use of uncovered and plastic-covered metallic stents provides equal palliation in patients with dysphagia.

Adult↗
PubMed1997

Malignant esophageal fistulas and perforations: management with plastic-covered metallic endoprostheses.

PURPOSE: To evaluate prospectively the efficacy of plastic-covered metallic endoprostheses in patients with malignant esophageal fistulas and perforations. MATERIALS AND METHODS: Thirty-nine patients with incurable esophageal carcinoma who developed esophagorespiratory fistulas (n = 20) or perforations (n = 19) were treated with plastic-covered metallic stents. RESULTS: Covered Wallstent endoprostheses were placed in 36 patients and covered Gianturco stents in three. All 19 perforations and 18 of 20 fistulas were successfully closed (clinical success rate, 95%). Symptoms of aspiration or dysphagia improved in all successfully treated patients. Mean survival was 81.8 days (range, 1-370 days). One patient with a closed perforation developed a fistula 16 weeks later and was treated with a second, overlapping stent; three patients with recurrent fistulas were treated with additional esophageal stents (one patient) or tracheal stents (two patients). In four patients, stent migration (two Gianturco and two Wallstent endoprostheses) necessitated placement of an additional stent. CONCLUSION: Covered metallic stents offer effective treatment for perforations and fistulas in patients with esophageal malignancy. Patients with recurrent fistulas can be treated with additional stents. Fistulas close to the upper esophageal sphincter may be closed with placement of parallel covered metallic stents in the esophagus and trachea.

Aged↗
PubMed1997

Contribution of angiotensin-converting enzyme to the cardiac metabolism of bradykinin: an interspecies study.

The role of angiotensin-converting enzyme (ACE) in the metabolism of bradykinin (BK) has been studied in several tissues. However, and contrary to angiotensin I, the metabolism of BK at the cardiac level has not been investigated. In this study, we define the participation of ACE in the carboxy-terminal degradation of BK in heart membranes of the dog, human, rabbit, and rat. The calculation of the kinetic parameters characterizing the metabolism of BK and the generated des-Arg9-BK can be summarized as follows: the half-life (t1/2) of BK [dog (218 +/- 32 s) > human (143 +/- 9 s) = rat (150 +/- 4 s) > rabbit (22 +/- 2 s)] and of des-Arg9-BK [dog (1,042 +/- 40 s) > human (891 +/- 87 s) > rat (621 +/- 65 s) > rabbit (89 +/- 8 s)] both showed significant differences according to species. Enalaprilat, an ACE inhibitor, significantly prevented the rapid degradation of BK and des-Arg9-BK in all species studied, whereas retrothiorphan, a neutral endopeptidase inhibitor, and losartan, an angiotensin II type I receptor antagonist, did not affect this metabolism. The relative importance of ACE in the cardiac metabolism of BK was species related: dog (68.4 +/- 3.2%) = human (72.2 +/- 2.0%) > rabbit (47.7 +/- 5.0%) = rat (45.3 +/- 3.9%). ACE participation in the metabolism of des-Arg9-BK was as follows: rabbit (57.0 +/- 4.0%) > dog (39.9 +/- 8.8%) = human (25.4 +/- 5.5%) = rat (36.0 +/- 7.0%). The participation of cardiac kininase I (carboxypeptidase M) in the transformation of BK into des-Arg9-BK was minor: human (2.6 +/- 0.1%) > dog (0.9 +/- 0.1%) = rabbit (1.0 +/- 0.1%) = rat (1.0 +/- 0.1%). These results demonstrate that ACE is the major BK-degrading enzyme in cardiac membranes. However, the metabolism of exogenous BK by heart membranes is species dependent. Our observations could explain some discrepancies regarding the contribution of kinins in the cardioprotective effects of ACE inhibitors.

Amino Acid Sequence↗
PubMed1997

Dr Francis Adams of Banchory (1796-1861). "Doctissimus medicorum Britannorum".

Dr Francis Adams practised medicine in Banchory from 1819-1861. At that time there was no translation in English of the classic medical literature of the Greeks, Romans and Arabians. Almost entirely self-taught, and in spite of the demands of a large scattered practice, Dr Adams found time to remedy this deficiency.

History, 19th Century↗
PubMed1997

The role of metallic stents in malignant duodenal obstruction.

Malignant duodenal obstruction is a common complication of carcinoma of the head of the pancreas. We report successful palliative treatment of malignant duodenal strictures by the peroral placement of metallic endoprostheses in two patients in whom palliative surgery was not possible.

Aged↗
PubMed1997

Digoxigenin-labeled peptides for the immunological quantification of intracellular signaling proteins: application to the MAP kinase kinase isoform MEK2.

Two competitive enzyme immunoassays using digoxigenin-labeled peptides have been developed for the quantification of the protein kinase MEK2 in cell extracts. Rabbit polyclonal antibodies directed against either the amino-terminal or proline-rich amino acid sequences of MEK2 were used for the immunoconcentration of the protein. Anti-digoxigenin Fab fragments labeled with horseradish peroxidase allowed the detection of the immune complexes. Amino-terminal and proline-rich enzyme immunoassays exhibited a sensitivity level of 63 and 71 fmol/mL, respectively, and displayed a half-maximal saturation value of 1320 and 1780 fmol/mL. The intra- and inter-assay coefficients of variation for both assays assessed at three different concentrations of MEK2 were lower than 6% and 12%, respectively. The amount of MEK2 measured by the two methods demonstrated an excellent correlation with the expression level of the protein detected by immunoblot analyses when tested on different cell lysates.

Animals↗
PubMed1997

Using uncovered metallic endoprostheses to treat recurrent benign esophageal strictures.

OBJECTIVE: The management of recurrent benign esophageal strictures is a difficult clinical problem, especially in patients who are not surgical candidates. We evaluated the role of uncovered metallic endoprostheses in four patients who had strictures that were resistant to repeated balloon dilatation. CONCLUSION: Our preliminary experience indicates that uncovered metallic endoprostheses can be effective in treating a select group of patients who have benign esophageal strictures and for whom multiple dilatations have failed. It is also important to note that epithelial hyperplasia can result in stenoses and recurrent dysphagia.

Aged↗
PubMed1997

The oral and intratracheal toxicities of ROUNDUP and its components to rats.

The toxicities of ROUNDUP and its component chemicals, glyphosate (N-phosphonomethylglycine) and polyoxyethyleneamine (POEA), were determined at 0, 1, 3, 6 and 24 h following administration to rats. The intratracheal administration of glyphosate (0.2 g/kg), POEA (0.1 g/kg), a mixture of glyphosate (0.2 g/kg) + POEA (0.1 g/kg), or ROUNDUP (containing 0.2 g/kg glyphosate and 0.1 g/kg POEA) elicited immediate respiratory effects which were more severe and which lasted longer in the groups receiving the POEA-containing preparations than in the glyphosate alone group. By 1 h, all test preparations had caused deaths, but more occurred from the POEA-containing preparations than from glyphosate. The po administration of POEA (1 g/kg), the mixture of glyphosate (2 g/kg) +POEA (1 g/kg), or ROUNDUP (containing 2 g/kg glyphosate and 1 g/kg POEA) produced diarrhea and blood-stained weeping from noses. Death was only seen from POEA at 24 h. Glyphosate (2 g/kg po) produced transient diarrhea without nose bleeds; POEA caused diarrhea at 1 h; and the mixture of POEA + glyphosate produced diarrhea later that increased in severity with time. Bloody nose secretions were seen only with the preparations that contained POEA. No deaths, respiratory effects or bloody nose secretions occurred in controls given saline. Both POEA and glyphosate caused lung hemorrhages and lung epithelial cell damage with po or intratracheal exposures. These results indicate POEA and preparations that contained POEA were more toxic than glyphosate.

Administration, Oral↗
PubMed1997

UV irradiation of a B-cell hybridoma increases expression of alkaline phosphatase: involvement in apoptosis.

Expression of alkaline phosphatase (APase) by 7TD1 B-cell hybridoma was amplified by ultraviolet irradiation; cell growth was inhibited and cell death by apoptosis was increased. Irradiation induced high levels of APase activity in cycling as well as in apoptotic cells. In contrast, APase activity faded with time in nonirradiated cells and was no longer expressed in spontaneous apoptotic cells appearing after several days in culture. This was demonstrated by cell morphology, DNA fragmentation, and flow cytometry after simultaneous staining of DNA with Hoechst 33342 and APase with naphthol AS-TR phosphate--fast red RC fluorescent reagent. Levamisole, a specific inhibitor of APase activity, almost totally abrogated apoptosis induced by ultraviolet irradiation at doses that failed to affect 7TD1 cell survival. These data suggest that APase could play a role in the signalling cascade that mediates apoptosis in irradiated cells.

Alkaline Phosphatase↗
PubMed1996

Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in Lewis rat.

A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroArg (P8720), was used to define the relationship between the kallikrein-kinin (K-K) system and acute intestinal inflammation induced by bacterial peptidoglycan-polysaccharide (PG-APS) in Lewis rats. Group I received human serum albumin (HSA) intramurally in the intestine and was treated with HSA. Group II received PG-APS and was treated with P8720. Group III received PG-APS and was treated with HSA. P8720 attenuated the decrease of high-molecular-weight kininogen and factor XI activity (group II vs group III, P < 0.01). P8720 therapy significantly but modestly decreased acute intestinal inflammation measured by gross gut score (P < 0.01) and more dramatically reduced the tissue myeloperoxidase activity (P < 0.05), a measure of granulocyte recruitment, in group II compared with group III. We conclude that the K-K system is directly involved in the pathogenesis of the acute phase of experimental acute inflammation. A specific inhibitor may modulate inflammatory bowel disease.

Acute Disease↗