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Biomedical subjects

Kozo Hashimoto

Publications and source records attributed to Kozo Hashimoto.

At least 73 records · Page 4Linked to original sources
PubMed2003

Effect of stress and adrenalectomy on urocortin II mRNA expression in the hypothalamic paraventricular nucleus of the rat.

Urocortin II (Ucn II) is a novel corticotropin-releasing hormone (CRH)-related peptide discovered as a selective agonist for type-2 CRH receptor. In the rat or mouse brain, Ucn II mRNA shows weak expression mainly in the hypothalamic paraventricular nucleus (PVN) and the locus coeruleus (LC). Understanding the regulation of Ucn II mRNA expression under varying conditions provides new insights into central stress response. We examined expression of Ucn II mRNA in the PVN and LC following immobilization stress, water deprivation, and adrenalectomy. Rats subjected to immobilization stress exhibited a dramatic induction of Ucn II mRNA expression in the parvocellular part of the PVN at the end of 2 h of immobilization. In contrast, water deprivation for 3 days induced Ucn II mRNA expression mainly in the magnocellular part of the PVN. Although water-deprived rats showed a marked decrease in their food intake, pair-fed rats failed to alter PVN Ucn II mRNA expression, suggesting that osmotic stimuli per se, but not reduced food consumption during water deprivation, caused Ucn II mRNA induction in the magnocellular part of the PVN. Adrenalectomized rats failed to show an increase in Ucn II mRNA in the PVN when compared to sham-operated rats. Double-label in situ hybridization revealed colocalization of Ucn II mRNA in approximately 45% of the CRH mRNA-expressing cells in the parvocellular part of the PVN following immobilization, or colocalization in most of the vasopressin mRNA-expressing cells in the magnocellular part of the PVN following water deprivation. In the LC, no induction of Ucn II mRNA was observed in any of the three experimental conditions, indicating that the regulation of Ucn II mRNA expression was site-specific. The results show a stressor-specific regulation of Ucn II mRNA expression in the PVN and raise the possibility that Ucn II mRNA plays a modulatory role in stress-induced alteration of anterior and posterior pituitary function, depending on the type of stress.

Adrenalectomy↗
PubMed2003

Frequent appearance of autoantibodies against prohormone convertase 1/3 and neuroendocrine protein 7B2 in patients with nonfunctioning pituitary macroadenoma.

Among pituitary disorders having mass effect of the pituitary gland, nonfunctioning pituitary macroadenoma and lymphocytic hypophysitis are difficult to differentiate without histological examination. In order to efficiently distinguish lymphocytic hypophysitis and pituitary tumors, we studied the presence of autoantibodies against prohormone-processing enzymes, prohormone convertase (PC) 1/3, PC2, carboxypeptidase E (CPE), and PC2 regulatory protein, 7B2, by radioligand assay using recombinant human 35S-labeled protein in patients with clinically nonfunctioning pituitary macroadenoma, lymphocytic hypophysitis, and other pituitary diseases. The indexes for anti-PC1/3 antibodies (Ab) were significantly higher in patients with nonfunctioning pituitary macroadenoma than in patients with lymphocytic hypophysitis. Patients positive for either anti-PC1/3 or anti-7B2 Ab were significantly frequent among patients with nonfunctioning pituitary macroadenoma than in other pituitary diseases and healthy controls. None of the patients was positive for anti-PC2 Ab or anti-CPE Ab. These results suggest that autoantibodies against PC1/3 and 7B2 are novel tumor-associated autoantibodies and can be helpful in the diagnosis of clinically nonfunctioning pituitary macroadenoma.

Adenoma↗
PubMed2003

Anti-alpha-enolase antibodies in pituitary disease.

A previous study reported a high prevalence of autoantibodies to alpha-enolase in lymphocytic hypophysitis and these antibodies efficiently distinguished lymphocytic hypophysitis from pituitary tumors. To confirm this, we examined autoantibodies to alpha-enolase in patients with lymphocytic hypophysitis (n = 17), pituitary non-functioning adenoma (n = 13), other pituitary diseases (n = 17) and other autoimmune diseases (n = 30), and compared to healthy controls (n = 46). Autoantibodies were found in 41.2%, 46.2%, 23.5%, 20.0% and 4.3%, respectively. Our findings indicate that detection of anti-alpha-enolase antibodies is not suitable for specific diagnosis of lymphocytic hypophysitis.

Adenoma↗
PubMed2003

A case of anterior hypopituitarism showing recurrent pituitary mass associated with central diabetes insipidus.

We report a case of anterior hypopituitarism showing recurrent pituitary mass associated with central diabetes insipidus. A 76-year old woman was hospitalized with general fatigue and 5 kg body weight loss. Endocrinological examinations and pituitary provocative tests demonstrated hypopituitarism and central diabetes insipidus. T1-weighted image of magnetic resonance imaging (MRI) revealed an intrasellar cystic mass with ring enhancement suggesting pituitary abscess. MRI films subsequently obtained from another hospital and studied retrospectively showed intrasellar cystic mass with ring enhancement 4 years earlier, and a mass shape that was decreased after 2 years. Over the subsequent years, the patient has remained asymptomatic with hormone replacement therapy only. Cystic pituitary adenoma or Rathke's cleft cyst with repeated infection may be involved in the repeated change of pituitary mass shape although neither pituitary surgery nor a pituitary biopsy was performed because of the patient's age and condition. It is reported that apparent recurrence of Rathke's cleft cysts after initially successful surgery was higher than suggested by previous reports, and that long-term follow-up with pituitary imaging and neuroophthalmological assessment is essential. Careful evaluation by follow-up brain MRI is needed in the present case to prevent future recurrence of pituitary abscess.

Aged↗
PubMed2003

[Successful treatment of combination therapy using an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker in a patient with IgA nephropathy].

A 24-year-old Japanese woman with IgA nephropathy was admitted to our hospital due to the development of proteinuria and pretibial edema while on glucocorticoids and an angiotensin-converting-enzyme(ACE) inhibitor. She had been on both medications for more than 2 years. Urinary protein excretion was 2.53 g/day and renal function laboratory data were within the normal range. Plasma aldosterone concentration was high at 248 pg/ml, with normal plasma renin activity. The renal biopsy specimens showed prominent glomerular hypertrophy. Four weeks after the addition of valsartan, an angiotensin II receptor blocker(ARB), urinary protein excretion was remarkably reduced to 0.6 g/day without adversely affecting blood pressure. During the treatment period, proteinuria was maintained at less than 0.6 g/day and renal function remained normal. We propose that glomerular hypertension caused by insufficient suppression of the renin-angiotensin system was an essential factor underlying the increased urinary protein excretion in this patient. Combination therapy of an ARB and an ACE inhibitor appears to have a beneficial effect in patients with IgA nephropathy patients with persistent glomerular hypertension.

Adult↗
PubMed2002

Down-regulation of corticotropin-releasing hormone receptor type 2beta mRNA expression in the rat cardiovascular system following food deprivation.

The present study was conducted to assess the effect of nutritional stress induced by food deprivation on expression of messenger ribonucleic acid (mRNA) for corticotropin-releasing hormone receptor type 2beta (CRH-R2beta) in the rat cardiovascular system in the presence or absence of changes in circulating corticosterone. Food deprivation for 96 h caused a robust increase in plasma corticosterone levels and a significant decrease in CRH-R2beta mRNA expression in the rat heart. Starvation for 48 and 96 h decreased CRH-R2beta mRNA expression in the atria, ventricle as well as aorta of sham-adrenalectomized (sham) rats. Surprisingly, clamping plasma glucocorticoids at low levels by adrenalectomy with corticosterone pellet replacement (ADX+B) did not completely prevent starvation-induced decreases of CRH-R2beta mRNA expression in the rat cardiovascular system. Urocortin (Ucn) mRNA expression was increased significantly by food deprivation in the heart of sham as well as ADX+B rats. We speculate that food deprivation may increase urocortin, which in turn down-regulates CRH-R2beta mRNA expression in cardiovascular system. These data indicate that food deprivation despite the presence or absence of changes in circulating corticosterone may have an inhibitory effect on CRH-R2beta mRNA expression in the rat cardiovascular system.

Adrenal Glands↗
PubMed2002

Biallelic inactivation by somatic mutations of the MEN1 gene in sporadic parathyroid tumors.

We report three sporadic parathyroid tumors with biallelic inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene. Three parathyroid tumors had two somatic mutations (K119del and 864del8, 363insT and 1767delT, and 508del33 and W341X, respectively). The mutations in both alleles detected by long-range polymerase chain reaction and subcloning in three tumors would likely result in a nonfunctional menin protein in parathyroid glands. These results show that the MEN1 gene is inactivated not only by a combination of somatic mutations and loss of heterozygosity, but also by somatic double mutations located on different alleles. The results directly confirmed the participation of MEN1 in the tumorigenesis of sporadic parathyroid tumors.

Adult↗
PubMed2002

Multiple feedback mechanisms activating corticotropin-releasing hormone system in the brain during stress.

Stress-associated disorders such as melancholic depression are characterized by persistent hypothalamic-pituitary-adrenocortical (HPA) axis activation and intensive anxiety. Corticotropin-releasing hormone (CRH) appears to play an essential role in pathophysiology of such disorders. In an attempt to elucidate possible mechanisms underlying persistent activation of CRH in the central nervous system (CNS), we examined responses of hypothalamic and extrahypothalamic CRH systems to the stressors (immobilization stress or psychological stress) and interactions between these CRH systems and glucocorticoids in rats. We propose multiple feedback loops activating central CRH system: (1) attenuation of glucocorticoid-induced negative feedback on the activity of the hypothalamic and brainstem nuclei during chronic stress, (2) autoregulation of CRH biosynthesis in the hypothalamic paraventricular nucleus (PVN) through up-regulation of Type-1 CRH receptor (CRHR-1), and (3) glucocorticoid-mediated positive effects on the amygdaloid CRH system. Stress initially activates the hypothalamic CRH system, resulting in the hypersecretion of glucocorticoids from the adrenal gland. In addition, the psychological component of the stressor stimulates the amygdaloid CRH system. In the chronic phase of stress, down-regulation of GR in the PVN and other brain structures such as the locus coeruleus (LC) fails to restrain hyperfunction of the HPA axis, and persistent activation of the HPA axis further up-regulates the amygdaloid CRH system. Thus, the hypothalamic and the amygdaloid CRH systems cooperatively constitute stress-responsive, anxiety-producing neurocircuitry during chronic stress, which is responsible for the clinical manifestations of stress-associated disorders. Effects of tricyclic antidepressants (TCAs), which appear to mitigate the above mentioned multiple feedback loop forming the vicious circle to activate central CRH systems, will also be discussed.

Animals↗
PubMed2002

A case of lymphocytic infundibuloneurohypophysitis associated with systemic lupus erythematosus.

A 27-year-old man was admitted to our hospital with facial erythema and general malaise. He had previously suffered from orbital myositis, central diabetes insipidus (DI), peripheral neuritis, and hypogonadotropic hypogonadism. Physical and immunological examinations revealed that he was suffering from systemic lupus erythematosus (SLE). Magnetic resonance imaging of the hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk and posterior pituitary. Endocrinological examinations showed that he had not only DI and hypogonadotropic hypogonadism but also hypoadrenalism and hypothyroidism, which were ascribed to the pituitary stalk lesion. Lymphocytic infundibuloneurohypophysitis associated with SLE was diagnosed. Administration of 30 mg/day of prednisolone for one month resulted in a marked reduction of the pituitary stalk thickening and posterior pituitary. It is recommended that a pharmacological dose of glucocorticoid be used in the treatment of lymphocytic hypophysitis patients who show significant thickening of the pituitary stalk and/or a large pituitary mass.

Adrenal Insufficiency↗
PubMed2002

Detection of autoantibodies against the pituitary-specific proteins in patients with lymphocytic hypophysitis.

OBJECTIVE: Several reports have described antipituitary antibodies by immunofluorescent or immunoblotting methods in patients with lymphocytic hypophysitis. However, with the exception of the pituitary hormones, individual antigens specific for the pituitary gland have not been studied. To understand the pathogenesis of lymphocytic hypophysitis and to diagnose this disease efficiently, we studied the presence of autoantibodies against three pituitary-specific proteins, GH and two novel pituitary-specific proteins, namely, pituitary gland specific factor 1a (PGSF1a) and PGSF2. DESIGN: Seventeen patients with lymphocytic hypophysitis, all of whom had pituitary enlargement (5 with lymphocytic adenohypophysitis and 12 with lymphocytic infundibuloneurohypophysitis, including 3 of the latter group proven by biopsy), and 14 patients with hypopituitarism without pituitary enlargement (10 with isolated ACTH deficiency and 4 with idiopathic TSH deficiency) were studied, and compared with 11 patients with non-functioning pituitary macroadenoma, 31 patients with other autoimmune diseases, and 36 healthy controls. METHODS: The presence of each antibody was studied by radioligand assay using recombinant human (35)S-labeled protein. RESULTS: Three (18%) patients with lymphocytic hypophysitis having pituitary enlargement, five (36%) patients with hypopituitarism without pituitary enlargement and three (9.7%) patients with other autoimmune diseases were positive for one or more of the antibodies studied. CONCLUSIONS: Anti-human GH, anti-PGSF1a, and anti-PGSF2 antibodies were detected in patients with lymphocytic hypophysitis and other hypopituitarism, but were not detected in patients with non-functioning pituitary macroadenoma. Detection of these antibodies may be useful for the diagnosis of lymphocytic hypophysitis.

Adolescent↗
PubMed2002

Chronic lupus peritonitis with massive ascites at elderly onset: case report and review of the literature.

A 77-year-old Japanese woman with massive painless ascites caused by chronic lupus peritonitis is reported. Peritoneal effusion had been resistant to the administration of steroids during the whole treatment period. It was characteristic that the titers of anti-DNA antibodies and the level of immune complex were elevated in the peritoneal fluid with suppressed levels of complements in ascites, although serum immunological markers reflecting the activity of SLE presented improvement after initiation of the treatment. Fifteen patients with chronic lupus peritonitis were reported previously. We reviewed the literature and suggest that chronic lupus peritonitis at elderly onset may demonstrate a poor response to the glucocorticoid therapy because of persistent inflammation in the peritoneum and the presence of impaired vascular circulation in addition to immunological mechanisms.

Age Factors↗
PubMed2002

Diabetes mellitus associated with Klinefelter's syndrome: a case report and review in Japan.

We report a case of Klinefelter's syndrome in a 48-year-old man who had diabetes mellitus associated with severe insulin resistance. We diagnosed him with Klinefelter's syndrome from his atrophic testicles, primary hypogonadism in hormonal examination, and a chromosomal aberration of 47,XXY. He showed severe decreased insulin sensitivity in a hyper-insulinemic euglycemic clamp test. He had injected over 100 units of insulin per day, however, testosterone replacement and administration of pioglitazone improved his glycemic control, which resulted in a decrease of insulin dose to less than 50 units per day. Here, we discuss the characteristics of diabetes mellitus associated with Klinefelter's syndrome in Japanese patients including this case.

Blood Glucose↗
PubMed2002

Acute-phase, but not constitutive serum amyloid A (SAA) is chemotactic for cultured human aortic smooth muscle cells.

The human serum amyloid A (SAA) protein family is subclassified as acute phase SAA (A-SAA), which comprises the SAA1 and SAA2 allelic variants, and constitutive SAA (C-SAA), which is the SAA4 isoform. Extrahepatic production of A-SAA occurs in many organs and tissues of the body, including smooth muscle cells (SMC) of the aorta. A-SAA has been shown to act locally as a chemoattractant for neutrophils, monocytes and lymphocytes via the N-formyl peptide receptor-like (fPRL1). In order to gain further understanding of the physiological significance of local production of A-SAA by SMC, the effect of exogenous A-SAA on the in vitro migration of human aortic SMC was investigated. Increased SMC migration in the presence of A-SAA was detectable after six hours and continued to increase up to 24 hours after incubation. The increased migration was dose-dependent over the concentration range 10 to 100 micrograms/ml. The mode of A-SAA stimulated SMC migration was by chemotaxis not chemokinesis. Exogenous constitutive SAA (C-SAA) did not affect SMC migration. Stimulation of SMC migration by A-SAA was inhibited by both polyclonal and monoclonal antibodies to human SAA1 and also by the inhibitors of fPRL1 signaling, wortmannin, bisindolylmaleimide and pertussis toxin. The results herein indicate that A-SAA, but not C-SAA, may serve as an autocrine factor to influence SMC migration in situations of aortic tissue injury and inflammation.

Amino Acid Sequence↗
PubMed2002

Proinflammatory cytokines but not acute phase serum amyloid A or C-reactive protein, downregulate paraoxonase 1 (PON1) expression by HepG2 cells.

The expression of paraoxonase1 (PON1) during inflammation has been investigated in vitro. The alteration of steady state PON1 mRNA in HepG2 cells by interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), was investigated relative to acute-phase serum amyloid A (A-SAA) mRNA. PON1 mRNA expression by HepG2 cells was decreased within three hours of stimulation by IL-1beta or TNF-alpha. Relative to PON1 mRNA expression, the pattern of steady state A-SAA mRNA expression was altered reciprocally and inversely by IL-1beta. These findings suggested that the decrease in serum PON activity after abdominal surgery in our previous clinical study may be ascribed to a decrease in steady state PON1 mRNA expression by liver with proinflammatory cytokines.

Apolipoproteins↗
PubMed2002

Serum paraoxonase (PON1) concentration in patients undergoing hemodialysis.

Cardiac death from atherosclerosis is common in patients undergoing hemodialysis. Although the enzymic activity of human serum paraoxonase (PON1) has been reported to be decreased in such patients, serum PON1 concentrations have not been measured. We investigated serum PON1 concentrations in 81 patients undergoing hemodialysis and 103 age-matched healthy subjects using an enzyme immunoassay. The PON1 concentration was significantly lower in the patient group than the control group (mean +/- SD: 6.78 +/- 3.56 vs 18.01 +/- 4.55 U/ml, respectively. p < 0.0001). There were no significant relationships between serum PON1 concentrations and the PON1 genetic polymorphisms, 55Leu/Met (L/M) and 192Gln/Arg (Q/R). The concentration adjusted for HDL-cholesterol or apolipoprotein A-I was also lower in the patient group. However, the specific activities (enzyme activity divided by the PON1 concentration) of paraoxonase and arylesterase were increased in the patient group compared with the control group. In the male patients, but not the female patients, PON1 concentrations were significantly lower in subjects with than without coronary heart disease (CHD) (mean +/- SD: 4.48 +/- 2.77 vs 7.34 +/- 3.22 U/ml, respectively. p < 0.01). In conclusion, the serum PON1 concentration in hemodialyzed patients was significantly decreased, resulting in an attenuation of PON1 enzymic activity. This decrease may be in part involved in the development of cardiovascular disease.

Aged↗
PubMed2002

Aberrant responsiveness to RANTES in synovial fluid T cells from patients with rheumatoid arthritis.

OBJECTIVE: To study expression and function of the chemokine receptor CCR5 in synovial fluid (SF) T cells from patients with rheumatoid arthritis (RA). METHODS: Expression of CCR5 was studied by flow cytometry and immunoblotting. The chemotactic response of T cells to chemokines was studied in cell migration assay. Tyrosine phosphorylation of Crk-associated substrate lymphocyte-type (CasL) was evaluated in immunoprecipitation and immunoblotting. RESULTS: SF T cells showed an increase in the population of CCR5, CXCR4, and CD45RO positive cells and exhibited an increase in chemotactic activity, which was not augmented with RANTES but stromal cell-derived factor-1alpha. Tyrosine phosphorylation per CasL molecule was markedly enhanced in SF T cells. In H9 cells, tyrosine phosphorylation of not only focal adhesion kinase but also CasL was induced after treatment with RANTES. Downmodulation of CCR5 by RANTES was decreased and recycling of CCR5 was accelerated in SF T cells when compared with peripheral blood (PB) T cells. When CD45RO positive PB T cells were cultured with interleukin 2, blunted responsiveness to RANTES-induced chemotaxis was reproduced as well as spontaneous chemotaxis, increased expression of CCR5, and aberrant receptor dynamics, after RANTES stimulation as observed in SF T cells. CONCLUSION: Synovial fluid T cells highly positive for CCR5 show aberrant characteristics; resistant to RANTES in terms of migration, but responsive in terms of dynamics of CCR5.

Arthritis, Rheumatoid↗