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Biomedical subjects

J Rosa

Publications and source records attributed to J Rosa.

At least 37 records · Page 2Linked to original sources
PubMed1993

Unstable alpha-chain hemoglobin variants with factitious beta-thalassemia biosynthetic ratio: Hb Questembert (alpha 131[H14]Ser-->Pro) and Hb Caen (alpha 132[H15]Val-->Gly).

Hb Questembert [alpha 131(H14)Ser-->Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an alpha-/beta-labeling ratio similar to that of beta-thalassemia trait. Hb Caen [alpha 132(H15) Val-->Gly] is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled beta-chains from the abnormal hemoglobin, thus leading to an apparent suppression of beta-chain synthesis, or 3) to a modified stability of the abnormal alpha-globin mRNA.

Adult↗
PubMed1993

Growth failure in pediatric inflammatory bowel disease.

To assess whether children with inflammatory bowel disease (IBD) develop permanent impairment of linear growth, we analyzed records from 48 young adults who had IBD during childhood or early adolescence (Tanner I-III; 11.8 +/- 2.4 years old at diagnosis). All were fully grown (Tanner V; 21.1 +/- 3.0 years) at last examination. Adult heights were predicted from data obtained at or shortly after the diagnosis of IBD by three methods: height for age percentile, the Bailey-Pinneau (BP), and Roche-Wainer-Thissen (RWT) methods. Predicted adult heights were then compared with the actual ultimate height of each subject. Permanent growth failure occurred in 19-35% of subjects, depending upon the method used to assess growth. Overall, 31% (15 of 48) of the subjects had deficits of adult height identified by two or more methods, including 14 of 38 (37%) of those with Crohn's disease but only one of 10 with ulcerative colitis. Age at diagnosis of IBD, age at last examination, age at cessation of linear growth, and site of IBD did not differ between impaired and normal growth groups. Duration of corticosteroid use was longer (p < 0.05) in growth-impaired subjects. In addition, although 60% of all subjects had periods of poor growth that put them in height-for-age percentiles two or more major growth channels below previous percentiles, only 19% remained at these levels upon achieving their final adult heights. Permanent impairment of linear growth leading to clinically meaningful deficits of ultimate adult height is common in patients with IBD in childhood or early adolescence. New therapeutic approaches are needed to address this problem.

Adolescent↗
PubMed1993

Acquired unbalanced hemoglobin chain synthesis during HIV infection.

Few abnormalities have been described up to know in the red cell lineage of HIV patients except for a slight anemia. To better interpret this, a hemoglobin study was performed in a group of 71 HIV infected patients. By contrast to patients at stage II or III, those at stage IV of the disease had moderate elevation of HbA2 level. A second group of ten patients being at stage IV of HIV infection and having moderate increase in HbA2 level were found to have beta thalassemia-like unbalanced biosynthetic globin ratio, unlike a control group with chronic inflammation condition. The observed abnormality may be a feature reflecting the peculiar disordered erythropoiesis seen in the late stage of this disease.

Adult↗
PubMed1992

Compound heterozygosity in a complete erythrocyte bisphosphoglycerate mutase deficiency.

Erythrocyte bisphosphoglycerate mutase (BPGM) deficiency is a rare disease associated with a decrease in 2,3-diphosphoglycerate concentration. A complete BPGM deficiency was described in 1978 by Rosa et al (J Clin Invest 62:907, 1978) and was shown to be associated with 30% to 50% of an inactive enzyme detectable by specific antibodies and resulting from an 89 Arg-->Cys substitution. The propositus' three sisters exhibited the same phenotype, while his two children had an intermediate phenotype. Samples from the family were examined using polymerase chain reaction and allele-specific oligonucleotide hybridization and sequencing techniques. Amplification of erythrocyte total RNA from the propositus' sister around the 89 mutation indicated the presence of two forms of messenger RNAs, a major form with the 89 Arg-->Cys mutation and a minor form with a normal sequence. Sequence studies of the propositus' DNA samples indicated heterozygosity at locus 89 and another heterozygosity with the deletion of nucleotide C 205 or C 206. Therefore, the total BPGM deficiency results from a genetic compound with one allele coding for an inactive enzyme (mutation BPGM Créteil I) and the other bearing a frameshift mutation (mutation BPGM Créteil II). Examination of the propositus' two children indicated that they both inherited the BPGM Créteil I mutation.

Arginine↗
PubMed1992

[Health policies and sickle cell disease].

Issues of public health raised by sickle cell disease and available solutions vary greatly between countries. Two main variables lead the choices: the affordable health resources, and the distribution of the abnormal genes in the population. Three examples have been chosen to illustrate these challenges. 1. In continental France, the level of health resources is good but the distribution of sickle traits is very heterogeneous among the population. Health policies against sickle cell disease aim at organizing screening and care to reach populations at risk, and concentrate the efforts upon them. This task is made difficult by two usual characteristics of these minorities: their rather poor social condition, and their cultural isolation. 2. In Guadeloupe (French West Indies) available health resources are similar to those of France but the sickle trait is common and has a homogeneous distribution in the population (14% carriers). Sickle cell disease is a health priority. Such conditions have recently favoured the organization of an efficient program for prevention and care of the disease. 3. In Benin (West Africa) a very high prevalence of sickle trait (more than 30% individuals are carriers, and about 4% have the disease) comes along with quite precarious resources that have to be shared with several other health priorities. An efficient and sustained policy against sickle cell disease has not yet been developed, which impedes a rational use of the few available resources, and creates much distress for diseased individuals.

Anemia, Sickle Cell↗
PubMed1992

Inhibition by noradrenaline and adrenaline of the increase in glucose and lactate output and decrease in flow after sympathetic nerve stimulation in perfused rat liver: possible involvement of protein kinase C.

In perfused rat liver stimulation of the hepatic nerve plexuses increased via alpha 1-receptors glucose and lactate output decreased flow and caused an overflow of noradrenaline into the hepatic vein. Infusion of noradrenaline and adrenaline also elicited similar metabolic and hemodynamic alterations via alpha 1-receptors, whereas infusion of isoproterenol via beta 2-receptors enhanced glucose output and slightly reduced lactate release without affecting flow. The influence of circulating catecholamines on the nerve stimulation-dependent changes was investigated. Noradrenaline (100 nmol/L) or adrenaline (40 nmol/L) but not isoproterenol (1 mumol/L), which themselves caused about half-maximal alterations, strongly inhibited the nerve stimulation-induced increase in glucose and lactate output and decrease in flow but had no effect on noradrenaline overflow. The protein kinase C activator (4 beta)phorbol 12-myristate, 13-acetate (100 nmol/L) but not its analog (4 alpha)phorbol 12,13-didecanoate (100 nmol/L) strongly inhibited the metabolic and hemodynamic changes caused by nerve stimulation or noradrenaline infusion. The protein kinase C inhibitor H7 (20 mumol/L) partially prevented the inhibition of the nerve actions by noradrenaline. The results lead us to conclude that noradrenaline and adrenaline inhibited the metabolic and hemodynamic nerve actions by means of a mechanism involving protein kinase C rather than presynaptic alpha-receptors or beta-receptors. The catecholamines apparently increased via alpha 1-receptors inositol 1,4,5-trisphosphate, which in turn enhanced cytosolic Ca2+ and thus altered metabolism and in part hemodynamics, and diacylglycerol, which in turn activated protein kinase C and thus feedback inhibited the signal chain from alpha 1-receptors via G proteins to phospholipase C.

Animals↗
PubMed1992

Effects of somatostatin on glucagon-stimulated glycogenolysis and gluconeogenesis in hepatocytes cultured in vitro.

The effects of somatostatin (SS-14) on glycogenolysis and gluconeogenesis in rat hepatocytes cultured in vitro in a serum-free medium were investigated. Somatostatin (122 nmol l-1) did not significantly change the basal glucose production with or without pyruvate (10 mmol l-1). Glucagon strongly (over 100%) increased the glucose production in hepatocytes incubated in a medium supplemented with 10 mmol l-1 pyruvate. This increase in glucose production is the result of increased rates of gluconeogenesis and glycogenolysis. Somatostatin partially inhibited the glucagon stimulated increase in glucose production. Glucagon also significantly increased the glucose production in a glucose-free medium without pyruvate, which resulted from an increase of glycogenolysis. Somatostatin did not inhibit the increase in glucose production in these conditions. After a 4 h 'fast', glycogen in hepatocytes fell to a very low level. Glucose production was minimal. After the addition of pyruvate, there was a increase in gluconeogenesis and glucose production. Glucagon stimulated the rate of gluconeogenesis. Somatostatin completely inhibited this glucagon-stimulated increase in gluconeogenesis.

Animals↗
PubMed1992

Thiazide-induced pulmonary edema: a case report.

A 42-year-old white female developed severe respiratory distress 30 minutes following the ingestion of hydrochlorothiazide. On her arrival at the emergency room, pulmonary edema was evident by physical examination and chest radiograph. She presented without evidence of a gallop, jugular venous distention, or history suggesting cardiac disease. Normal electrocardiogram (ECG) and echocardiogram, and a radionuclide ventriculogram showing normal systolic and diastolic functions supported the noncardiac origin. The patient responded to supportive treatment within hours although the radiographic abnormalities persisted for several days. A review of the literature revealed that at least 12 other cases have been described of this unusual but life threatening idiosyncratic reaction to hydrochlorothiazide.

Adult↗
PubMed1991

Structure of the human adult hemoglobin minor fraction A1b by electrospray and secondary ion mass spectrometry. Pyruvic acid as amino-terminal blocking group.

Hemoglobin A1b is a minor hemoglobin component from human hemolysate (less than 0.5% of total hemoglobin) whose structure has never been established. It was purified and studied by mass spectrometry. Electrospray ionization of its abnormal beta-chain indicated a 70-Da mass increase. Separation of the trytic digest by reversed-phase liquid chromatography revealed an abnormal beta T1 peptide. Cesium ion bombardment ionization produced a protonated molecular ion at m/z 1022.516, showing an additional C3H2O2 residue to normal beta T1. The amino acid sequences of both abnormal and normal beta T1 peptides were found identical by comparison of their collision activation spectra. Time course hydrolysis of abnormal beta T1 indicated a rapid loss of the modifying group, leading to normal beta T1. At least, mild treatment with acidic methanol showed an additional methylated site, comparatively with normal beta T1. All these results are consistent with a ketimine-linked pyruvic acid at the amino end of the beta-chain of hemoglobin.

Amino Acid Sequence↗
PubMed1991

Crystallization and preliminary X-ray diffraction studies of the human erythrocyte bisphosphoglycerate mutase.

Bisphosphoglycerate mutase (EC 2.7.5.4) catalyzes the synthesis and breakdown of 2,3-diphosphoglycerate in red cells. The human enzyme, cloned and expressed in Escherichia coli has been crystallized in the rhombohedral space group R32 with a = b = c = 100.4 A and alpha = beta = gamma = 81.2 degrees. The asymmetric unit contains either a dimeric enzyme molecule, or a monomer.

Bisphosphoglycerate Mutase↗
PubMed1991

Is DNA ploidy and proliferative activity of prognostic value in advanced gastric carcinoma?

We analyzed the DNA content of 116 gastric carcinomas and lymph node metastasis in 53 of these using flow cytometry on archival material. DNA index and proliferative activity (% S-phase) values were obtained in 111 and 76 tumors, respectively, and survival rates were obtained for 108. Tumor classification was based on histologic type, grade, and growth pattern and stage. All were advanced gastric carcinomas. Fifty four tumors (47%) were aneuploid. In single variable analysis, survival was related to stage (muscularis propria versus serosa P = .002) and lymph node metastasis (P = .04). Infiltrative tumor growth had a slightly worse prognosis (P = .06). In multifactorial analysis, tumor stage was the only independent prognostic factor. Neither DNA ploidy nor % S-phase values had any effect on survival, although, patients with tumors with higher DNA indexes (greater than 1.7) showed a tendency toward worse survival rates. We failed to prove the prognostic value of DNA ploidy in gastric carcinoma. Before its effect is ruled out, some factors have to be considered: (1) all tumors were in advanced stage and the true effect of ploidy on survival may have been diluted, (2) quality of fixation--near diploid aneuploid populations may have been overlooked, and (3) intratumoral DNA ploidy heterogeneity can cause sample discrepancy (20% in our series).

Adenocarcinoma↗
PubMed1991

Sickle cell anemia in the Tunisian population: haplotyping and HB F expression.

Thirty-three Tunisian patients, homozygous for Hb S, were examined. Haplotyping using nine restriction sites in the beta-globin gene cluster revealed that the most common type is the Benin type [---- + - + - +] which occurs at a frequency of 0.94% (31 cases); only one patient was homozygous for an atypical haplotype which shows some differences with the Benin haplotype at sites 1, 5, 6, and 8 [+ ---- + + + +]; the two remaining patients were assumed to be double heterozygotes for the Benin and atypical haplotypes. The presence of the atypical haplotype suggested a double origin of the beta S gene in Tunisia. Moreover, a heterogeneity in the Hb F production was observed, ranging between 2 to 16%, whereas the G gamma-globin expression was remarkably homogeneous in our patients with a normal amount approaching 40%. These results suggested the presence of a combination of several control factors.

Adolescent↗
PubMed1990

Long-term 6-mercaptopurine treatment in adolescents with Crohn's disease.

Although 6-mercaptopurine is often used to treat adolescents with intractable Crohn's disease, its long-term efficacy has not yet been studied in this population. This study shows data derived from 36 adolescents (mean age +/- SD, 16.5 +/- 3.3 years; 27 males, 9 females) treated at least 6 months with 6-mercaptopurine (1.5 mg.kg-1.day-1, maximum of 75 mg/day). Sites of Crohn's disease at the start of 6-mercaptopurine therapy included 17 ileocolic, 9 pancolic, 7 small bowel, and 3 partial colon. All had received corticosteroids, sulfasalazine, antibiotics, and nutritional support for 5.0 +/- 3.0 years before administering 6-mercaptopurine, but intractable symptoms persisted. Disease activity lessened during the first year of 6-mercaptopurine, reflected by a higher Lloyd-Still disease activity score (pre, 64 +/- 9 vs. 6-mercaptopurine, 72 +/- 11; P less than 0.0001). General activity, physical examination, nutrition, and laboratory subscores all improved (P less than 0.004). Lessened disease activity occurred despite concomitant decrease in duration of prednisone use (pre, 9.5 +/- 4.2 vs. 6-mercaptopurine, 6.6 +/- 4.9 months/year; P less than 0.001) and cumulative annual prednisone exposure (pre, 3672 +/- 2106 vs. 6-mercaptopurine, 1964 +/- 1460 mg; P less than 0.0007). The frequency of perianal fistulae and abscesses also decreased (P less than 0.01) during treatment. Annual rates of hospitalization decreased in 44% of subjects during 6-mercaptopurine treatment, while increasing in only 22%. Follow-up beyond 1 year of 6-mercaptopurine treatment showed continued remission in 23 of 30 subjects. No serious complications were seen. 6-mercaptopurine is an effective long-term therapy for adolescents with intractable Crohn's disease. While inducing remission, it also has a significant steroid-sparing effect which may be of particular benefit to this population.

Abscess↗
PubMed1990

Human bisphosphoglycerate mutase expressed in E coli: purification, characterization and structure studies.

Bisphosphoglycerate mutase (EC 5.4.2.4.) is an erythrocyte-specific enzyme whose main function is to synthesize 2,3-diphosphoglycerate (glycerate-2,3-P2) an effector of the delivery of O2 in the tissues. In addition to its main synthase activity the enzyme displays phosphatase and mutase activities both involving 2,3-diphosphoglycerate in their reaction. Using a prokaryotic expression system, we have developed a recombinant system producing human bisphosphoglycerate mutase in E coli. The expressed enzyme has been extracted and purified to homogeneity by 2 chromatographic steps. Purity of this enzyme was checked with sodium dodecyl sulfate polyacrylamide gel and Cellogel electrophoresis and structural studies. The bisphosphoglycerate mutase expressed in E coli was found to be very similar to that of human erythrocytes and showed identical trifunctionality, thermostability, immunological and kinetics' properties. However, the absence of a blocking agent on the N-terminus results in a slight difference of the electrophoretic mobility of the enzyme expressed in E coli compared to that of the erythrocyte.

Amino Acid Sequence↗
PubMed1990

Nucleolar organizer regions in gastric carcinoma and its precursor stages.

A silver technique for nucleolar organizer regions (AgNOR) was applied to sections from 156 gastric biopsies and gastrectomy specimens. These included normal controls, normal gastric mucosa from carcinoma-bearing stomachs, intestinal metaplasia types I and III, dysplasia and carcinoma. AgNOR counts gradually increased from normal, through intestinal metaplasia, to carcinoma. This finding supports the chronic atrophic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence concept for gastric carcinogenesis. Normal gastric mucosa was different from all lesions, including normal mucosa from carcinoma-bearing stomachs. Significantly higher AgNOR counts were observed in tumours compared to all other lesions except dysplasia. Dysplasia differed from intestinal metaplasia type I but not from type III. Eighty-five per cent of metaplasia cases overlapped with carcinoma and 19% with normal controls. The spread of AgNOR values in intestinal metaplasia reinforces the concept that this lesion is a heterogeneous entity reflecting a dynamic and continuous process. The AgNOR technique may contribute to the assessment of the stage of evolution of 'borderline' lesions.

Biopsy↗