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Biomedical subjects

M Haji

Publications and source records attributed to M Haji.

At least 55 records · Page 3Linked to original sources
PubMed1993

[The role of endothelin in adrenal medulla: identification of endothelin and its receptor in two cases of pheochromocytoma].

To clarify the role of a novel vasoactive peptide endothelin in endocrine hypertension, we examined endothelin (ET)-like immunoreactivity and the ET binding sites in the tissues of two pheochromocytoma. Case 1 was a 25-year-old woman who manifested multiple endocrine neoplasia (MEN) II b with left adrenal pheochromocytoma, and case 2 was a 48-year-old woman with familial bilateral pheochromocytoma. In both cases, fairly high amount of ET-like immunoreactivity was detected in the resected tumors. By competitive binding analysis, high affinity binding sites for 125I-ET-1 were also detected in the same resected tissues. Concomitant existence of ET and its receptor suggests that ET may play an important role in these tumors in modulating the secretion of catecholamines from the tumors by an autocrine/paracrine fashion.

Adrenal Gland Neoplasms↗
PubMed1992

Partial purification of phosphoramidon-sensitive endothelin converting enzyme in porcine aortic endothelial cells: high affinity for Ricinus communis agglutinin.

A membrane-bound endothelin converting enzyme (ECE) of porcine aortic endothelial cells (ECs) was solubilized with Lubrol PX with high efficiency and stability. The solubilized ECE was bound to Ricinus communis agglutinin (RCA) but not to peanut agglutinin (PNA) or wheat germ agglutinin (WGA), suggesting that the ECE has a galactosylated structure possessing a high affinity for RCA. The sequential chromatography on RCA-agarose, PNA-agarose and a TSKgel DEAE-5PW column attained 2,100-fold purification for the ECE over the membrane fractions. The purified ECE was sensitively inhibited by phosphoramidon but not by thiorphan. The present RCA and PNA affinity column procedures may be a powerful approach to isolation of ECE of EC origin.

Animals↗
PubMed1992

Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor.

We isolated a cDNA encoding type-1 angiotensin II receptor from a human liver cDNA library. The cDNA had an open reading frame encoding a protein of 359 amino acid residues with a relative Mr of 41,060. The deduced amino acid sequence of the human angiotensin II (Ang II) receptor was 95.3% and 94.2% identical to those of bovine and rat type-1 Ang II receptors, respectively, and had a significant similarity with the G protein-coupled receptor. The rank order of the binding to the receptor expressed in COS-7 cells was Ang II greater than Ang III greater than Ang I. The expression of the Ang II receptor mRNA was detected in human liver, lung, adrenal and adrenocortical adenomas but not in adrenomedullary tumor, pheochromocytoma, by Northern blot analysis.

Amino Acid Sequence↗
PubMed1992

A single amino acid substitution (Met786----Val) in the steroid-binding domain of human androgen receptor leads to complete androgen insensitivity syndrome.

Androgen receptors (ARs) in two Japanese siblings with complete androgen insensitivity syndrome were characterized, and their molecular bases were investigated. Androgen binding was undetectable in cultured pubic skin fibroblasts from the patients by whole cell assay. Sequence analysis of exons B-H, which encode the DNA- and steroid-binding domains, of the AR gene from these patients using polymerase chain reaction revealed a single nucleotide substitution in exon F, resulting in an amino acid change at 786 from methionine (ATG) to valine (GTG) within the steroid-binding domain of AR. Reconstruction of this mutation by site-directed mutagenesis into human AR cDNA followed by expression in COS-1 cells led to production of the same amount and the same molecular mass of immunodetectable AR protein as those found with expression of the normal human AR cDNA. However, in contrast to wild-type AR expressed in COS-1 cells, the mutant AR showed markedly low affinity of androgen binding by whole cell assay. These results suggest that androgen resistance in these patients is due to the point mutation in the steroid-binding domain of the AR.

Adult↗
PubMed1992

Disordered expression of adrenal steroidogenic P450 mRNAs in incidentally discovered nonfunctioning adrenal adenoma.

In order to elucidate the steroidogenesis of clinically nonfunctioning adrenocortical adenoma, we studied the aldosterone, cortisol (F) and dehydroepiandrosterone (DHEA) content and the expression of mRNA of cytochrome P450 for side chain cleavage (P450scc), 17 alpha-hydroxylase (P450c17). 21-hydroxylase (P450c21) and 11 beta-hydroxylase (P450c11) in four clinically nonfunctioning adrenocortical adenomas discovered incidentally in asymptomatic patients (Cases 1, 2, 3 and 4). The results were compared with those in normal adrenal glands. In the adenomas from cases 1 and 2, the abundance of steroidogenic P450s mRNA were similar to those in normal adrenal glands, except P450c11 mRNA expression in the adenoma from case 1 which was slightly higher than normal. The steroid content was normal level, except for higher F in the adenoma from case 1 and lower aldosterone in case 2 adenoma than normal. The adenoma from case 3 contained much less P450scc, P450c17 and P450c21 mRNA, while the amount of P450c11 mRNA was slightly greater than in normal adrenals. The adenoma showed normal aldosterone, high F and low DHEA content compared with normal adrenal glands. In the adenoma from case 4, the accumulation of all four P450 mRNAs decreased, whereas aldosterone, F and DHEA content in the adenoma was similar to that of normal adrenal glands. These data indicated that nonfunctioning adrenocortical adenoma showed similar or decreased expression of steroidogenic P450 mRNAs that the normal adrenal gland. This decreased expression of steroidogenic P450 mRNAs may be at least partly concerned with the absence of clinical symptoms in patients with nonfunctioning adenoma.

Adenoma↗
PubMed1992

Human recombinant activin-A modulates the steroidogenesis of cultured bovine adrenocortical cells.

The effect of human recombinant activin-A on adrenal steroidogenesis was studied in cultured bovine adrenocortical cells. Activin-A significantly reduced cortisol output from ACTH (10nmol/l)-stimulated adrenocortical cells incubated for 24 hours in a dose-dependent manner (10, 100 and 500ng activin-A/ml suppressed cortisol secretion by 19, 33 and 40%), although no significant effect was observed in the case of 3 h incubation. Dehydroepiandrosterone (DHEA) secretion from ACTH-stimulated adrenocortical cells incubated for 24 h was also decreased by the addition of activin-A in a dose-dependent manner. (10, 100 and 500ng activin-A/ml suppressed DHEA secretion by 22, 56 and 58%). These inhibitory effects of activin-A (100ng/ml) on cortisol and DHEA secretion were partially blocked by the addition of follistatin/FSH-Suppressing Protein (200ng/ml). In contrast, activin-A treatment resulted in no significant decrease in aldosterone secretion. There were no significant effects of activin-A on basal secretions of cortisol, DHEA or aldosterone from adrenocortical cells. These results suggest that activin-A has a direct inhibitory effect on ACTH-stimulated bovine adrenocortical steroidogenesis.

Activins↗
PubMed1992

Alterations in femoral bone histomorphometry and vitamin D metabolism in neonatal streptozotocin-induced diabetic rat.

Histomorphometric examination and histological observation of femoral bone were performed on long-standing neonatal streptozotocin-induced diabetic rats (n2STZ, n5STZ) as a human model of non-insulin-dependent diabetes mellitus. The growth and strength of femurs decreased in the STZ diabetic rats. Histomorphometric parameters such as cortical bone thickness, number of metaphysical trabeculae and percent trabecular volume of metaphysical area all significantly decreased in the STZ diabetic rats. There were no significant differences in parameters between the n2STZ and n5STZ diabetic rats. Histological findings demonstrated no significant change in the number of osteoclasts in femur nor change corresponding to osteomalacia. Bone absorption in the STZ diabetic rats appeared unchanged. The plasma calcium level did not change in the STZ diabetic rats, although their plasma phosphate or A1-p levels increased. Circulating 24, 25 (OH)2D3 was significantly lower in the STZ diabetic rats than the controls. However, 25 (OH) D3 or biologically active 1, 25 (OH)2D3 was not different between the controls and STZ diabetic rats. Osteopenia is thus present in the femurs of long-standing neonatal STZ diabetic rats, due in part to abnormal vitamin D metabolism.

Animals↗
PubMed1992

[Senile osteoporosis in normal women examination using dual energy X-ray absorptiometry].

Osteoporosis is now one of the most serious problems in aged Japanese women. We investigated bone mineral contents of the vertebrae of 132 adult women (28-94y.o.) using dual energy X-ray absorptiometry (DEXA) in order to clarify the change of the bone mineral densities (BMD) with aging, and the influences of a diet and exercise on osteoporosis. In the women, BMD of the vertebrae increase to maximum level in 3 rd or 4 th decade of life, and then reduce with aging. The level of BMD is well matched with the index of osteopenia using the lateral view of vertebral X-ray. According as the BMD reduce, the number of bone fractures and the number of patients with bone fractures increase. More than 80% of the women whose BMD are less than 0.7 g/cm2 have bone fractures. In aged women, over 65 year's old, exercise had significant positive effect with BMD, but that was no evidence for influence of calcium intake to BMD.

Absorptiometry, Photon↗
PubMed1992

[A case of the diabetic nephropathy without hyperglycemia].

We report a case of diabetic nephropathy with impaired glucose tolerance. A 52 year obese woman with nephrotic syndrome and hypertension showed severe and remarkable edema, as her legs were elephantiasis. To be clear the etiology of nephrotic syndrome, we performed renal biopsy. The histological findings of the specimen showed glomerulosclerosis. Additionally the examination of ocular fundus revealed microaneurysm and avascular area. We concluded that diagnosis of this case must be non-insulin-dependent diabetes mellitus.

Diabetes Mellitus, Type 2↗
PubMed1991

The modification and expression of 21-hydroxylase gene in normal human adrenal gland and adrenal cancer.

Genomic DNA and total RNA from three adrenal cancer tissues were analyzed by hybridization with human 21-hydroxylase gene. Southern blot analysis with restriction enzyme Eco RI revealed major fragments at 18, 13 and 9 kilobase (kb) in normal adrenal glands. In two of three adrenal cancers, however, the band at 18 kb was either absent or decreased and the 9 kb fragment showed an increase in its intensity. Normal liver, kidney and leucocytes has only 18 and 13 kb while lacking the 9 kb fragment. Using Taq I, Bam HI or Bgl II, we found no difference in restriction fragment patterns between adrenal cancer and normal tissues. Cleavage with Hpa II after digestion with Bgl II showed that significantly more DNA was digested into low-molecular weight fragments in adrenal cancer and the normal adrenal gland than those in other normal tissues. By Northern blot analysis, there was difference of signal intensity of hybridizing mRNA between the adrenal cancers and normal adrenal glands. These results suggest that the Eco RI site in the flanking region of the 21-hydroxylase gene may be modified in adrenal cancer tissue, and that inadequate 21-hydroxylase is present in some forms of adrenal cancers.

Adrenal Cortex Hormones↗
PubMed1991

Juvenile granulosa cell tumor in association with a high serum inhibin level.

Inhibin is a glycoprotein hormone produced mainly by ovarian granulosa cells. Recently measurement of serum inhibin levels was made possible by radioimmunoassay. We describe a patient with a juvenile granulosa cell tumor, a distinctive and rare form of granulosa cell tumor. This patient's serum inhibin level was extremely high preoperatively and returned to normal after the tumor was resected. This case suggests that serum inhibin level may be a useful marker of granulosa cell tumors.

Biomarkers, Tumor↗
PubMed1991

Markedly increased expression of cytochrome P-450 17 alpha-hydroxylase (P-450c17) mRNA in adrenocortical adenomas from patients with Cushing's syndrome.

We studied the contents of cortisol (F) and dehydroepiandrosterone (DHEA) and the expression of mRNA of cytochrome P-450 for side-chain cleavage (P-450scc), 17 alpha-hydroxylase (P-450c17), 21 alpha-hydroxylase (P-450c21) and 11 beta-hydroxylase (P-450c11) in adrenocortical adenomas from three patients with Cushing's syndrome. The F content was significantly higher in adrenocortical adenomas than in normal adrenal glands, while the DHEA level was similar to that in normal adrenal glands. The adrenal adenomas showed a markedly higher level of P-450c17 mRNA, and a slightly but not significantly increased level of P-450c21 mRNA, compared with normal adrenal glands. The expression of P-450scc and P-450c11 mRNA in the adenomas was similar to that in normal adrenal glands. These results suggest that the overproduction of cortisol in adrenocortical adenomas associated with Cushing's syndrome results from an increased expression of P-450c17 and P-450c21 mRNA.

Adenoma↗
PubMed1991

Expression of cytochrome P-450 mRNAs in steroidogenesis of adrenocortical adenomas from patients with primary aldosteronism.

We studied the contents of aldosterone and cortisol (F) and the expression of mRNA of cytochrome P-450 for side-chain cleavage (P-450scc), 17 alpha-hydroxylase (P-450c17), 21-hydroxylase (P-450c21) and 11 beta-hydroxylase (P-450c11) in adrenocortical adenomas from three patients with primary aldosteronism. The aldosterone content was significantly higher in adrenocortical adenomas than in normal adrenal glands, while F content in adenomas was similar to the level in normal adrenal glands. The aldosterone-producing adenomas showed a markedly higher level of P-450c11 mRNA, a slightly but not significantly increased level of P-450c21 mRNA and a significantly decreased level of P-450c17 mRNA, compared with those in normal adrenal glands. The expression of P-450scc mRNA in adenomas was similar to the level in normal adrenal glands. These results suggested that the renin-independent overproduction of aldosterone in adrenocortical adenomas from the patients with primary aldosteronism results from increasing expression of the mRNA for P-450c11 and decreasing expression of the mRNA for P-450c17.

Adenoma↗