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Biomedical subjects

M Lambert

Publications and source records attributed to M Lambert.

At least 271 records · Page 15Linked to original sources
PubMed1992

Genetic epidemiology of lipoprotein lipase deficiency in Saguenay-Lac-St-Jean (Québec, Canada).

Familial hyperchylomicronemia due to the lipoprotein lipase (LPL) activity deficiency (Type I hyperlipoproteinemia) is an autosomal recessive disorder with a prevalence estimated at one case per million. Thirty-four type I individuals are known in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec. The prevalence of type I and LPL deficient heterozygote in this region was estimated at 1/6382 and 1/46 inhabitants respectively. The mean inbreeding coefficient was slightly elevated in the type I group compared with three control groups. The mean kinship coefficient was 15.1 times higher in the type I group than in the control groups. The high prevalence of type I in SLSJ appears to be the result of the emigration of carriers of LPL deficiency from Charlevoix, another isolated region of quebec to the SLSJ region. Endogamy also played a crucial role in increasing the prevalence of type I in SLSJ.

Child↗
PubMed1991

A mutation in the human lipoprotein lipase gene as the most common cause of familial chylomicronemia in French Canadians.

BACKGROUND: Lipoprotein lipase hydrolyzes the triglyceride core of chylomicrons and very-low-density lipoproteins and has a crucial role in regulating plasma lipoprotein levels. Deficiencies of lipoprotein lipase activity lead to aberrations in lipoprotein levels. Worldwide, the frequency of lipoprotein lipase deficiency is highest among French Canadians. We sought to determine the molecular basis of the disorder in this population. METHODS: The entire coding sequence of the lipoprotein lipase gene from one French Canadian patient was amplified by the polymerase chain reaction and sequenced. Exon 5 from 36 other French Canadian patients was amplified and analyzed by dot blot hybridization with allele-specific oligonucleotides. RESULTS: Sequence analysis revealed a missense substitution of leucine (CTG) for proline (CCG) at residue 207 in exon 5. This mutation was found on 54 of the 74 mutant alleles (73 percent) in the patients. Studies of site-directed in vitro mutagenesis have confirmed that this mutation generates inactive lipoprotein lipase and is the cause of lipoprotein lipase deficiency. CONCLUSIONS: We have identified a missense mutation at residue 207 of the lipoprotein lipase gene that is the most common cause of lipoprotein lipase deficiency in French Canadians. This mutation can be easily detected by dot blot analysis, providing opportunity for definitive DNA diagnosis of the disorder and identification of heterozygous carriers.

Base Sequence↗
PubMed1991

Functional and molecular characterization of CCK receptors in the rat pancreatic acinar cell line AR 4-2J.

Competitive inhibition binding studies on membranes from the rat pancreatic AR 4-2J cell line revealed the predominance (80%) of low selectivity CCK receptors (KD of 1 nM and 4 nM for, respectively, CCK-8 and gastrin-17I (G-17I] over selective receptors (20% with a KD of 1 nM and 1 microM for, respectively, CCK-8 and G-17I). Amylase secretion was stimulated by low concentrations of CCK-8, G-17I and CCK-4. G-17I-induced amylase secretion was unaffected by 100 nM of the selective peripheral CCK-A receptor antagonist L-364,718, suggesting that amylase hypersecretion followed non-selective CCK receptor activation, a function normally assumed by selective CCK-A receptors in rat pancreatic acini. Direct ultraviolet irradiation of AR 4-2J cell membranes preloaded with 125I-BH-CCK-33 or 125I(Leu)G(2-17)I resulted in covalent cross-linking with, respectively, a 90 kDa protein and a 106 kDa protein, both distinct from the 81 kDa CCK binding species revealed in normal rat pancreatic membranes. Gpp[NH]p increased the dissociation rate of CCK-8 and G-17I from AR 4-2J cell membranes, indicating a coupling of receptors with guanyl nucleotide regulatory protein(s) G. [32P]ADP-ribosylation of AR 4-2J cell membranes allowed to detect the presence of two Gs alpha (the 50 kDa form predominating over the 45 kDa form) and one Gi alpha (41 kDa). However, Gi and Gs may not be involved in gastrin stimulation of amylase secretion, as Bordetella pertussis toxin and cholera toxin pretreatment of cells did not suppress G-17I-dependent amylase secretion.

Amylases↗
PubMed1991

Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: their characterization and delineation of defects in pregnancies at risk.

During a follow-up study of 19,790 pregnancies at risk for a genetic disease, from 1968 to 1989, 1083 fetuses were found to have an anomaly during the second trimester, leading to 977 terminations of pregnancy. Neural tube defects (31.4 per cent), chromosomal disorders (27.1 per cent), and Mendelian or multifactorial diseases (10.6 per cent) were the main causes of fetal anomaly. More than half (52.9 per cent) of the fetal anomalies were detected by routine ultrasound examination. Forty-two per cent of cystic hygromas were secondary to a chromosomal defect. We stress the importance of a comprehensive fetal and newborn examination to ensure an accurate diagnosis so that subsequently accurate counselling can be provided.

Abdominal Muscles↗
PubMed1991

Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo.

We transferred the complementarity determining regions from a murine monoclonal antibody that neutralizes infection by respiratory syncytial virus (RSV) to a human IgG1 monoclonal antibody. The resulting reshaped human antibody lost affinity for RSV, but an additional alteration to one of the framework regions restored binding affinity and specificity. This second generation reshaped human monoclonal antibody cross-reacted with all clinical isolates of RSV tested and both prevented disease and cured mice even when administered four days after infection. We expect the antibody will prove useful in the management of this major childhood disease.

Amino Acid Sequence↗
PubMed1991

[Type I neurofibromatosis (von Recklinghausen's disease) associated with abdominal neurofibrosarcoma and pheochromocytoma. Apropos of a case].

Neoplasia and endocrine disorders are common complications of neurofibromatosis 1 (NF1--von Recklinghausen disease). We report here a case of NF1 in a 31-year-old woman presenting simultaneously with an abdominal neurofibrosarcoma and a pheochromocytoma. The prevalence of secondary neoplasia and endocrine tumors in NF1 is also discussed.

Abdominal Neoplasms↗
PubMed1991

Captopril renography in the diagnosis of renovascular disease.

Several investigators have reported methods for the use of renal scintigraphy in the diagnosis of renal artery stenosis. We report the experience of Duke University Medical Center, and offer some suggestions for standardizing and optimizing the use of this potential screening tool. We evaluated 140 clinically selected hypertensive adults with postcaptopril renal scintigraphy (renography), pre- and postcaptopril peripheral renin activity, and conventional renal arteriography. Postcaptopril renography (using 99mTc-diethylenetriaminepentaacetic acid (DTPA) to measure glomerular filtration and [131I]iodohippurate to measure renal plasma flow) was considered abnormal if one kidney contributed 47% or less of total activity. Postcaptopril renin was considered elevated if it was at least 4 ng/mL/h. Renovascular disease was defined as 50% or greater main renal artery stenosis. Of 140 subjects, 31 (22%) had significant renovascular disease. Captopril-stimulated DTPA renography suggested asymmetric function in 24 (74%) of these, but was also abnormal in 61 of 109 (56%) with normal renal arteries. Captopril-stimulated hippuran renography performed in a similar manner. Captopril-stimulated renin activity was elevated in only 58% of subjects with renal artery stenosis, and had a false positive rate of 24%. These data differ from reports from other centers, perhaps due to differences in renography methods, criteria for interpretation of renography, and/or patient selection criteria.

Adult↗
PubMed1991

Open evaluation of amlodipine in the monotherapeutic treatment of systolic hypertension in the elderly.

The antihypertensive efficacy and safety of amlodipine (5-10 mg once daily for 10 weeks) was assessed in elderly patients with primary systolic hypertension (average sitting and standing systolic blood pressure > or = 160 mm Hg and diastolic blood pressure < or = 95 mm Hg). Interim analysis of data from 25 patients shows that amlodipine treatment produced significant decreases in sitting blood pressure (-26.8/-11.4 mm Hg; p < 0.05). Efficacy assessments after 8 weeks of therapy showed 15 of 21 (71.4%) evaluable patients were considered therapeutic successes with amlodipine (defined as a fall from baseline in sitting systolic blood pressure of > or = 20 mm Hg or to < or = 150 mm Hg with a fall of > or = 10 mm Hg). Of the six evaluable patients who were not considered therapeutic successes using this definition, three had clinically beneficial falls in systolic blood pressure of 16-18 mm Hg. Fourteen patients were considered therapy successes on the basis of assessments taken 48 h postdose at the end of the study. Investigators' overall impression of efficacy was excellent or good in 21 patients (84%). Amlodipine treatment had no significant effect on heart rate. Amlodipine was generally well tolerated, with no patients being withdrawn due to side effects. Investigators' evaluation of toleration was excellent or good in 22 patients (88%).

Aged↗
PubMed1991

Resonant frequency at the wrist in hypermobile women.

The resonant frequency of the wrist has been measured in sixteen hypermobile and nine normal women at ten levels of peak torque. At the lowest level the results were identical but at the others the hypermobile values were lower. Damping and thixotropy appeared to be normal. In another group the grip strength of hypermobile subjects was similar to that of controls. The possibility that the connective tissue of the musculature of hypermobile subjects is of enhanced compliance is discussed.

Adult↗
PubMed1991

Similar prevalence of renovascular hypertension in selected blacks and whites.

Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation.

Adolescent↗
PubMed1991

Illegitimate transcription. Application to the analysis of truncated transcripts of the dystrophin gene in nonmuscle cultured cells from Duchenne and Becker patients.

We have previously demonstrated that there is a low level of transcription of tissue-specific genes in every cell type. In this study, we have taken advantage of this phenomenon, called illegitimate transcription, to analyze the muscle-type dystrophin mRNA in easily accessible cells such as lymphoid cells, fibroblasts, and peripheral blood cells from Duchenne and Becker muscular dystrophies with known internal gene deletion. The results showed that, in the studied regions surrounding the deletions, processing of truncated transcripts is identical in specific (muscle tissue) and in nonspecific cells (lymphoid cells). In Becker cases with out-of-frame deletions, the already described alternatively spliced species found in muscle samples were also found in nonspecific cells. These results demonstrate that illegitimate transcripts are a bona fide version of tissue-specific mRNA, and that they represent a useful material to investigate the qualitative consequences of gene defects at the mRNA level.

Base Sequence↗
PubMed1991

Importance of accurate employment histories of patients admitted to units of internal medicine.

A study was undertaken to assess the importance of systematically recording occupational histories of patients admitted to an internal medicine unit of a university hospital. Detailed information on current and past employment was obtained with questionnaires and in personal interviews from 200 inpatients over a 12-month period. Twenty-one patients (10.5%) were considered to have a "primary illness" (condition causing hospital admission) probably (4.5%) or possibly (6%) related to their current or previous occupation. From the 786 primary and secondary illness and medical antecedents diagnosed for the 200 patients examined, 70 illnesses of 55 patients were considered probably or possibly related to current or previous occupation. This pilot study emphasizes the need for accurate occupational records for patients in an internal medicine ward. This task is best performed by an appropriately trained occupational physician.

Adult↗
PubMed1991

Metabolic rate, not percent dehydration, predicts rectal temperature in marathon runners.

This study was designed to determine the factors predicting the post-race rectal temperature in marathon runners. Post-race rectal temperatures of 30 recreational runners (maximum oxygen consumption (VO2max) = 58.3 +/- 5.9 ml O2.kg-1.min-1; mean +/- SD) who completed a 42.2 km marathon at 75.8% (+/- 9.3%) VO2max were measured and related to their levels of dehydration (percent mass loss), their running velocities (km.h-1), and their estimated absolute metabolic rates (1 O2.min-1) for different segments of the 42.2 km race. The influence of certain anthropometric variables was also determined. Percent mass loss during the race (2.5 +/- 1.4%), post-race rectal temperatures (38.9 +/- 0.6 degrees C), and rates of sweat loss (1.0 +/- 0.3 1.h-1) were low. There was no statistical relationship between percent mass loss and post-race rectal temperature. Post-race rectal temperatures were significantly related to the metabolic rates for the full 42.2 km and for the last 21.1 and 6 km of the race, and to the average running velocity for the last 6 km (P less than 0.05 and P less than 0.01). Average sweat rates were related to metabolic rates for 42.2 km and for the last 6 km of the race (P less than 0.05) but were unrelated to running velocity. We conclude that metabolic rate sustained during the latter section of the race, and not the level of dehydration, is the principal determinant of the post-race rectal temperature in marathon runners.

Adult↗
PubMed1990

Effect of dystrophin gene deletions on mRNA levels and processing in Duchenne and Becker muscular dystrophies.

Muscle dystrophin mRNAs from Duchenne (DMD) and Becker (BMD) patients with internal deletion of the DMD gene were quantitated and sequenced. In all cases (eight DMD and three BMD), truncated mature transcripts were found, and their amount was correlated to the clinical phenotype and to the reading frame. We focused on four cases that were apparently not in agreement with the reading frame rule. In two DMD cases, slightly reduced amounts of in-frame truncated mRNA are present but no dystrophin is detected, suggesting impaired translation and/or instability of the protein. In two BMD patients with out-of-frame deletions, the presence of minor in-frame alternatively spliced mRNA species is congruent with the observed truncated dystrophin and the mild phenotype.

Base Sequence↗
PubMed1990

Internalization-sequestration and degradation of cholecystokinin (CCK) in tumoral rat pancreatic AR 4-2 J cells.

Cholecystokinin (CCK) receptors were investigated in the tumoral acinar cell line AR 4-2 J derived from rat pancreas, after preincubation with 20 nM dexamethasone. At steady state binding at 37 degrees C (i.e., after a 5 min incubation), less than 10% of the radioactivity of [125I]BH-CCK-9 (3-(4-hydroxy-[125I]iodophenyl)propionyl (Thr34, Nle37) CCK(31-39)) could be washed away from intact cells with an ice-cold acidic medium, suggesting high and rapid internalization-sequestration of tracer. By contrast, more than 85% of the tracer dissociated rapidly after a similar acid wash from cell membranes prelabelled at steady state. In intact AR 4-2 J cells, internalization required neither energy nor the cytoskeleton framework. Tracer internalization was reversed partly but rapidly at 37 degrees C but slowly at 4 degrees C. In addition, two degradation pathways of the tracer were demonstrated, one intracellular and one extracellular. Intracellular degradation occurred at 37 degrees C but not at 20 degrees C and resulted in progressive intracellular accumulation of [125I]BH-Arg that corresponded, after 1 h at 37 degrees C, to 35% of the radioactivity specifically bound. This phenomenon was not inhibited by serine proteinase inhibitors and modestly only by monensin and chloroquine. Besides, tracer degradation at the external cell surface was still observable at 20 degrees C and yielded a peptide (probably [125I]BH-Arg-Asp-Tyr(SO3H)-Thr-Gly). This degradation pathway was partly inhibited by bacitracin and phosphoramidon while thiorphan, an inhibitor of endopeptidase EC 3.4.24.11, was without effect.

Animals↗