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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 379 records · Page 21Linked to original sources
PubMed1987

Decreased deoxyribonucleic acid binding of glucocorticoid-receptor complex in cultured skin fibroblasts from a patient with the glucocorticoid resistance syndrome.

A patient with the syndrome of glucocorticoid resistance was studied. A 27-yr-old woman initially was diagnosed as having Cushing's disease, based on the findings of high plasma ACTH and serum cortisol levels, increased urinary cortisol secretion, resistance to adrenal suppression with dexamethasone, and bilateral adrenal hyperplasia by computed tomography and scintigraphy of the adrenal glands. However, she had no signs or symptoms of Cushing's syndrome. During a 5-yr follow-up, no clinical abnormalities developed, although hypercortisolism persisted. End-organ resistance to cortisol was suspected. To explain the end-organ resistance to cortisol, the glucocorticoid receptors (GR) in peripheral mononuclear leukocytes and cultured skin fibroblasts from a forearm skin biopsy were characterized and compared with the results of similar studies in normal subjects. The patient's GR in whole cell assays had an increased dissociation constant (Kd). In the cytosol of cultured skin fibroblasts from the patient, there was also decreased binding capacity. The thermal stability and the sedimentation coefficient in a sucrose density gradient of the receptors in the cytosol of cultured skin fibroblasts from the patient and normal subjects were similar. GR complex activation, analyzed by DEAE-cellulose chromatography, was decreased in the patient. DNA binding of the GR complex after temperature-induced activation was lower in the patient than in normal subjects. Nuclear translocation of GR complexes from the patient was also slightly decreased. These results suggest that the patient's glucocorticoid resistance was due to a decrease in the affinity of the receptor for glucocorticoids and a decrease in the binding of the GR complex to DNA.

Adrenocortical Hyperfunction↗
PubMed1987

A molecular-pathologic approach to murine senile amyloidosis. Serum precursor-apolipoprotein A-II variant (Pro5----Gln) presents only in the senile amyloidosis-prone SAM-P/1 and SAM-P/2 mice.

Murine apolipoprotein (apo) A-II is a serum precursor of murine senile amyloid protein. We determined the primary structures of apo A-II in accelerated senescence-prone mice (SAM-P) characterized by a high frequency of age-associated systemic amyloidosis and accelerated senescence-resistance mice (SAM-R) in which senile amyloidosis occurred with a low incidence. Apo-A-II variant (Pro5----Gln) was found to be present only in the serum of SAM-P and not in that of SAM-R or other random bred slc:ICR mice. The apo A-II variant in the serum of SAM-P is identical to the murine senile amyloid fibril protein (ASSAM) derived from amyloid-deposited tissues of SAM-P. These findings proved that apo A-II deposits in tissues without degradation and this mutation (Pro5----Gln) probably have significant effects on the structure and function of apo A-II and would play a critical role in murine senile amyloidogenesis.

Aging↗
PubMed1987

Immune responses in newly developed short-lived SAM mice. I. Age-associated early decline in immune activities of cultured spleen cells.

Using a cell culture system, age-associated changes in immune activities were investigated in newly developed, short-lived mouse strains. These SAM-P strains of mice (H-2k), which have a remarkably short life span (around 9 months) under conventional breeding conditions, showed an age-associated early decline in several immune functions, as compared to ordinary strains of AKR/J (H-2k) and C3H/He (H-2k) mice. Their antibody-forming capacity to T-independent antigen, DNP-Ficoll, and natural killer (NK) cell activity showed a markedly early onset of regression and a sharp decline from the level of control mice at 2 months of age. SAM-P strains of mice have a profound defect in antibody response to a T-dependent (TD) antigen, such as sheep red blood cells (SRBC), thus there was only a feeble antibody response to SRBC as early as the age of 2 months, and a negligible response at a later age. In contrast, the allo-specific cytotoxic T lymphocyte (CTL) response of the mice was as high as that of control mouse strains at 2 months of age and declined little until at least 6 months of age. The early age-related functional decline in the immune system of SAM-P mice suggests that these new inbred strains are appropriate models for investigating the age-related appearance of immune dysfunctions.

Aging↗
PubMed1987

[Tubular damage in toxemia of pregnancy using urinary trehalase as a marker].

We proved reversible tubular damage in edema and in toxemia of pregnancy using urinary trehalase as a marker. 1. Urinary trehalase activity in mild toxemia (edema: more than 0.5 kg body weight gain per week) was significantly increased as compared with normal pregnancy (less than 0.5 kg body weight gain per week) (p less than 0.02). Urinary albumin content, however, was not significantly changed with edema. 2. Toxemia of pregnancy showed significantly high urinary trehalase activity, NAG activity and beta 2-MG content as compared with the 3rd trimester of pregnancy. Urinary trehalase activity of severe toxemia was significantly higher than that of mild toxemia. Urinary NAG and beta 2-MG showed similar results to urinary trehalase. On the 5th and 30th puerperal days there was significantly lower trehalase activity than in the 3rd trimester. Urinary beta 2-MG in toxemia was significantly decreased at the 30th puerperal day as compared with the 3rd trimester and 5th puerperal day. However, no significant decrease was observed in urinary NAG. 3. Urinary trehalase activity in superimposed toxemia of pregnancy was significantly increased as compared with the 3rd trimester of pregnancy. However, urinary trehalase activity on the 5th puerperal day was significantly decreased, but was still significantly high. These results show that pregnancy with edema and pure toxemia of pregnancy cause renal tubular damage and this damage is reversible. In the stage of edema, no remarkable glomerular damage, but tubular damage could occur.

Female↗
PubMed1986

The single proline-glutamine substitution at position 5 enhances the potency of amyloid fibril formation of murine apo A-II.

The primary structure of murine apolipoprotein A-II (apo A-II) has been determined. Apo A-II consists of a single polypeptide chain of 78 amino acid residues, of which the amino-terminus is pyrrolidone carboxylic acid. Except for residues 5 and 38, the amino acid sequence is identical to that of murine senile amyloid protein (ASSAM), which has a common antigenicity with apo A-II. Substitution of glutamine (ASSAM) for proline (apo A-II) at position 5 is distinct and may possibly be related to murine senile amyloid-ogenesis.

Amino Acid Sequence↗
PubMed1986

Purification and characterization of a senile amyloid-related antigenic substance (apoSASSAM) from mouse serum. apoSASSAM is an apoA-II apolipoprotein of mouse high density lipoproteins.

Two putative serum precursors which cross-react with antiserum against murine senile amyloid protein (ASSAM) were isolated from the high density lipoprotein (HDL) of normal mouse serum. Apolipoproteins designated "apoSASSAM-1" and "apoSASSAM-2" have the same molecular weight as tissue amyloid fibril protein. ApoSASSAM-1 and apoSASSAM-2 migrate to an intermediate position between apoA-I and apoC on alkaline-urea polyacrylamide gel electrophoresis and are present mainly in HDL apoproteins and to a slight extent in very low density lipoprotein apoproteins when compared to apoC. ApoSASSAM-1 and apoSASSAM-2 are polymorphic; there are two apparent isoproteins of apoSASSAM-1 with isoelectric points of 4.72 and 4.79 and two major isoproteins of apo-SASSAM-2. Subunit bands of ASSAM separated by alkaline-urea polyacrylamide gel electrophoresis and that migrated to the same positions as apoSASSAM-1 and apoSASSAM-2 were labeled by anti-apoSASSAM-1 antiserum. The amino acid compositions of apoSASSAM-1 and apoSASSAM-2 were much the same and closely resembled those of ASSAM and mouse apoA-II. Sequence analysis of apoSASSAM and ASSAM revealed a blocked amino terminus. ApoSASSAM is considered to be a mouse apoA-II and probably transforms to amyloid fibril "ASSAM" in tissues through a process yet to be clarified.

Amino Acids↗
PubMed1986

High homology is present in the primary structures between murine senile amyloid protein (ASSAM) and human apolipoprotein A-II.

The primary structure of a murine senile amyloid protein (ASSAM) was determined. The protein consists of a single polypeptide chain of 78 amino acid residues. The amino-terminus is blocked with pyrrolidone-carboxylic acid. The sequence differs from that of the known murine amyloid A protein and is highly homologous to human apolipoprotein (apo) A-II. The result indicates that the putative precursor of the senile amyloid protein is apo A-II in mice.

Amino Acid Sequence↗
PubMed1986

Molecular cloning and nucleotide sequence of cDNA for murine senile amyloid protein: nucleotide substitutions found in apolipoprotein A-II cDNA of senescence accelerated mouse (SAM).

cDNA clones encoding the murine senile amyloid protein (ASSAM) have been isolated from animal models of accelerated senescence (SAM-P/1) and from normal aging (SAM-R/1). Immunochemical and protein sequence studies revealed that apolipoprotein (apo) A-II is a serum precursor of ASSAM. A 17-base synthetic oligonucleotide based on residues 39-44 of ASSAM was used as a hybridization probe for screening newly constructed SAM-P/1 and SAM-R/1 liver cDNA libraries. The structure of murine apo A-II cDNA is of interest because of the amino acid substitution found in ASSAM and serum apo A-II of SAM-P; in SAM-R or other random bred slc:ICR mice, amino acid residue 5 of mature apo A-II is proline but, in SAM-P, this amino acid is changed to glutamine. This amino acid replacement is caused by two nucleotide substitutions (CCA for proline codon to CAG for glutamine codon). The third base mutation may not be relevant to the substitution of amino acid. Attention is directed to the relation of this amino acid substitution to the specific deposition of apo A-II, as a tissue amyloid fibril.

Aging↗
PubMed1986

Alpha-human natriuretic polypeptide (alpha-hANP) specific binding sites in bovine adrenal gland.

The effects of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. alpha-hANP did not inhibit basal aldosterone secretion. alpha-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of ACTH (10(-8) M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of [125I]alpha-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of alpha-hANP.

Adrenal Cortex↗
PubMed1986

Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived amino acid sequence.

Human apolipoprotein B-100 (apoB-100), the ligand on low density lipoproteins that interacts with the low density lipoprotein receptor and initiates receptor-mediated endocytosis and low density lipoprotein catabolism, has been cloned, and the complete nucleic acid and derived amino acid sequences have been determined. ApoB-100 cDNAs were isolated from normal human liver cDNA libraries utilizing immunoscreening as well as filter hybridization with radiolabeled apoB-100 oligodeoxynucleotides. The apoB-100 mRNA is 14.1 kilobases long encoding a mature apoB-100 protein of 4536 amino acids with a calculated amino acid molecular weight of 512,723. ApoB-100 contains 20 potential glycosylation sites, and 12 of a total of 25 cysteine residues are located in the amino-terminal region of the apolipoprotein providing a potential globular structure of the amino terminus of the protein. ApoB-100 contains relatively few regions of amphipathic helices, but compared to other human apolipoproteins it is enriched in beta-structure. The delineation of the entire human apoB-100 sequence will now permit a detailed analysis of the conformation of the protein, the low density lipoprotein receptor binding domain(s), and the structural relationship between apoB-100 and apoB-48 and will provide the basis for the study of genetic defects in apoB-100 in patients with dyslipoproteinemias.

Amino Acid Sequence↗
PubMed1986

An autoradiographic study of changes in the uptake of tritiated estradiol in the anterior hypothalamus during the estrous cycle of the rat.

In cycling rats exposed to a controlled light schedule of 12 h of light daily from 22.00 to 10.00 h the concentration of estradiol in the anterior hypothalamus at 5.00-6.00 h on the day of proestrus was significantly higher than those at 0.00-1.00 h on day 1 of diestrus and estrus, and was about twofold higher than serum estradiol concentration, which reached a peak at 5.00-6.00 h on the same day. Autoradiographically, the uptake of tritiated estradiol by the nuclei of neurons in the nucleus (n.) preopticus, pars suprachiasmatica (POSC), n. preopticus periventricularis (POP), and anterior part of n. anterior hypothalami (AAH) was significantly higher at 1.00 h on the day of diestrus 1 than at 6.00 h on the day of proestrus and at 1.00 h on the day of estrus. These results suggest that the POSC, POP and AAH may be target sites in the anterior hypothalamus of estradiol for its feedback action.

Animals↗
PubMed1986

Alpha-human atrial natriuretic polypeptide inhibits steroidogenesis in cultured human adrenal cells.

The ability of synthetic alpha-human atrial natriuretic polypeptide-(1-28) (alpha hANP) to alter steroidogenesis by human adrenal glands was investigated in primary human adrenal cell cultures. alphahANP (10(-9)-10(-7) M) inhibited basal and ACTH (10(-8) M)-stimulated aldosterone, cortisol, and dehydroepiandrosterone (DHEA) secretion in a dose-dependent manner. alpha hANP inhibited aldosterone (IC50, 1.3 X 10(-8) M) and cortisol (IC50, 0.7 X 10(-8) M) secretion more potently than it did DHEA (IC50, 7.5 X 10(-8) M) secretion. ACTH dose-dependent (10(-10)-10(-8) M) increases in aldosterone, cortisol, and DHEA secretion were significantly inhibited by alpha hANP (10(-8) M). In addition, alpha hANP enhanced the accumulation of intracellular cGMP in a dose-dependent manner. As aldosterone, cortisol, and DHEA secretion from cultured human adrenal cells was inhibited by alpha hANP, the site of inhibition of steroidogenesis by alpha hANP is probably localized in the early pathway of steroidogenesis in human adrenal cells. The results also suggest a link between inhibitory effects of alpha hANP and accumulation of intracellular cGMP.

Adrenal Cortex↗
PubMed1986

Lack of inhibitory effect of alpha-human atrial natriuretic polypeptide on aldosteronogenesis in aldosterone-producing adenoma.

The effects of synthetic alpha-human atrial natriuretic polypeptide (alpha hANP) on aldosteronogenesis in normal and aldosterone-producing adenoma cells (APA cells) in primary monolayer cultures were studied. alpha hANP significantly inhibited aldosterone secretion from normal adrenal cells in culture, but had no inhibitory effect on aldosterone secretion from APA cells in the presence or absence of 10(-8) M ACTH. alpha hANP enhanced the accumulation of intracellular cGMP in normal adrenal cells in culture, but not in APA cells. Visualization of [125I]iodo-alpha hANP-specific binding sites in APA and adjacent normal adrenal tissues by an in vitro receptor autoradiographic technique showed that these sites were localized only in normal adrenal tissue, but not in APA tissue. These results suggest that the lack of an inhibitory effect of alpha hANP on aldosteronogenesis in APA cells may be due to the absence of alpha hANP-specific receptor sites in APA cells.

Adenoma↗