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Biomedical subjects

H Morio

Publications and source records attributed to H Morio.

11 recordsLinked to original sources

Renal expression of serum-type mannan-binding protein in rat.

Mannan-binding proteins (MBPs) occur as liver and serum forms, which are encoded by separate genes and synthesized by the liver. Serum MBP plays a role in the first defense against a variety of pathogens. We found in this study, by reverse-transcriptional PCR, that rat serum MBP mRNA but not liver MBP is also expressed in the kidney. The level of the serum mRNA expression in the kidney as estimated by competitive PCR was about one-eighth that of the liver. Transcripts of serum MBP were detected in the renal corpuscles and distal convolutions by in situ hybridization. Affinity chromatography of the extract of rat kidney on a column of Sepharose-4B-mannan isolated a 29-kDa protein. These results indicate that serum MBP is synthesized in the kidney as well as in the liver. The kidney protein may be associated with local host defense around the kidney.

Animals

Pituitary adenylate cyclase-activating polypeptide protects rat-cultured cortical neurons from glutamate-induced cytotoxicity.

We have investigated the effects of pituitary adenylate cyclase-activating polypeptide with 38 residues (PACAP38) on glutamate-induced neuronal cell death in rat-cultured cortical neurons. The rat-cultured neurons were obtained from E17 day-old embryos and cultured in a chemically defined medium without serum for 10 days, after which more than 95% of the cells were stained by a specific antibody against MAP-2, a specific marker for neurons. The number of viable neurons was identified by the mitochondrial conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to formazan, which was detected by the associated change in optical density at 570 nm. Glutamate-induced neuronal cell death was suppressed by PACAP38 at concentrations as low as 10(-13) M, and at 10(-11) M maximally suppressed half of the amount of glutamate-induced cell death seen in a control situation (no PACAP38). The dose-response curve was bell-shaped. Dibutyryl cAMP (dbcAMP) also increased the number of neurons that were protected from damage with a bell-shaped dose-response curve suggesting that PACAP exerts its neuroprotective effect through the activation of a cAMP signal transduction system. However, cAMP accumulation in the media of neurons was stimulated by PACAP38 at concentrations as low as 10(-11) M, a much higher concentration than the minimal effective dose of PACAP38 required for protection against glutamate-induced neuronal cell death. Among the three neuropeptides of PACAP38, arginine vasopressin (AVP) and C-type natriuretic peptide (CNP), only PACAP38 exhibited a neurotrophic effect in the glutamate-induced neuronal cell death at the indicated concentrations. These data indicate that PACAP38 is one of the more important neuroprotective factors. The kind of intracellular signal transduction system involved in the neuroprotective effect of PACAP38 still remains to be established.

Animals

Serum levels of dehydroepiandrosterone sulfate in patients with asymptomatic cortisol producing adrenal adenoma: comparison with adrenal Cushing's syndrome and non-functional adrenal tumor.

The reported number of adrenal incidentalomas has been increasing because of wider application of imaging techniques. Patients with asymptomatic cortisol producing adrenal adenoma (ASCA) which secretes cortisol without clinical evidence of Cushing's syndrome has been more frequently observed than previously assumed, and they have a risk of adrenal insufficiency after adrenalectomy. Therefore patients with incidentalomas should be screened for cortisol overproduction. The aim of this study is to discover an easy screening test to uncover ASCA. We investigated the hormone profiles of 4 patients with ASCA in comparison with 11 patients with non-functional adrenal tumor and 10 patients with adrenal Cushing's syndrome. We also investigated the expression of dehydroepiandrosterone sulfotransferase (DHEA-ST) in surgically removed attached non-neoplastic adrenal tissues by immunostaining, which was considered to represent the degree of suppression of the hypothalamo-pituitary-adrenal axis. Serum dehydroepiandrosterone sulfate (DHEA-S) levels of all the patients with ASCA and adrenal Cushing's syndrome were lower than those of healthy subjects of corresponding age, but they were within the normal range in the patients with non-functional adrenal tumors. The serum DHEA-S level reflects the degree of suppression of the normal adrenal gland by cortisol hypersecretion from adrenal tumors. But the serum level of DHEA-S decreases with age, and because the normal range of serum DHEA-S is low in elderly subjects, we should be careful to evaluate the level of DHEA-S in elderly patients with adrenal Cushing's syndrome or ASCA. The immunohistochemical study showed DHEA-ST expression was noticeably suppressed in the adjacent adrenal cortex in ASCA and adrenal Cushing's syndrome. The decreased expression of DHEA-ST may reflect autonomous neoplastic cortisol secretion and subsequent ACTH suppression in ASCA and adrenal Cushing's syndrome. A single measurement of plasma ACTH or measurement of ACTH response to corticotropin-releasing hormone was not enough to screen for ASCA because of the wide variation among the cases. Dexamethasone suppression test is essential in identifying ASCA and also a single determination of serum DHEA-S is easy and may be useful for the screening of ASCA in adrenal incidentalomas in young and middle aged subjects, and is especially useful for outpatients.

Adenoma

Effect of modified LDL on the release of NO and PGI2 from rat peritoneal macrophages.

Nitric oxide (NO) and prostacyclin (PGI2) have vasodilative and anti-proliferative effects on smooth muscle cells (SMC) and an anti-aggregating action on platelets. The present study was designed to elucidate the influence of modified low density lipoprotein (LDL) on the release on NO and PGI2 from rat peritoneal macrophages. Cholesteryl ester (CE) content in macrophages markedly increased on incubation with acetylated LDL (ac-LDL), while NO release did not change. Although incubation with mildly oxidized LDL (m-ox-LDL) and highly oxidized LDL (h-ox-LDL) increased CE content in macrophages, only incubation with h-ox-LDL reduced NO release. PGI2 release from macrophages was not affected by incubation with ac-LDL, m-ox-LDL or h-ox-LDL. These results indicate that the degree of suppression of NO release in macrophages by modified LDL is related to the extent of oxidative modification of LDL itself, but not to the extent of the accumulation of CE in macrophages. Although the role of NO released from macrophages in atherosclerosis is still unclear, the observation of reduced production of NO from macrophages in response to ox-LDL may provide new insight into the role of ox-LDL in the pathogenesis of atherosclerosis.

Animals

Effect of the infusion of OKY-046, a thromboxane A2 synthase inhibitor, on urinary metabolites of prostacyclin and thromboxane A2 in healthy human subjects.

The influence of OKY-046, a selective thromboxane synthase inhibitor, on prostanoid formation in healthy human subjects was studied. Vehicle (5% glucose solution) or OKY-046 in 5% glucose solution at 15 micrograms kg-1 min-1 was intravenously administered to five male healthy volunteers for 6 h. Platelet aggregation and thromboxane B2 (TXB2) formation induced by collagen and arachidonic acid were suppressed by the infusion of OKY-046, while both were not affected by the infusion of vehicle. Urinary excretion of 11-dehydro-thromboxane B2, one of major urinary metabolites of thromboxane A2 (TXA2) was decreased by the infusion of OKY-046, while that of 2,3-dinor-6-keto-prostaglandin F1 alpha, one of major urinary metabolites of prostacyclin (PGI2) was increased. The present study demonstrated that the infusion of OKY-046 improved the balance of TXA2/PGI2 into antithrombotic state in healthy subjects. It was also suggested that endogenously produced (probably platelet-derived) endoperoxides could be redirected into prostacyclin in vivo.

6-Ketoprostaglandin F1 alpha

Malignant exophthalmos associated with multiple myeloma.

We report a patient with malignant exophthalmos associated with multiple myeloma which showed no evidence of direct orbital involvement of plasma cells. This exophthalmos had similarities with Graves' ophthalmopathy, but the patient had no detectable autoimmune thyroid diseases. Plasmapheresis was effective not only for the treatment of heart and renal failure due to the myeloma kidney but also for the malignant exophthalmos. As the serum monoclonal IgG level was decreased by plasmapheresis, the improvement of proptosis, visual acuity, and hypertrophy of the extraocular muscle as measured by magnetic resonance imaging were observed. It is suggested that humoral factors removed by plasmapheresis might be involved in the pathogenesis of this nonendocrine exophthalmos.

Aged

[Effect of ethanol injection in tracheal large cell carcinoma--a case report].

A 66-year-old woman was admitted with dyspnea. A tracheal tumor was found by bronchofiberscopy, and histological examination revealed large cell carcinoma. The tumor obstructed nearly 90% of her tracheal lumen, so we performed intratumoral ethanol injection. The tumor became almost completely necrotic, and obstruction of her airway markedly improved. No serious complication was found. Intratumoral ethanol injection was very effective and safe in this case. This is the fifth report of undifferentiated carcinoma of the trachea in Japan.

Aged