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Biomedical subjects

M Ujihara

Publications and source records attributed to M Ujihara.

At least 19 recordsLinked to original sources
PubMed2002

Dowling-Degos disease associated with squamous cell carcinomas on the dappled pigmentation.

We report the first case of Dowling-Degos disease associated with squamous cell carcinomas (SCCs) in the pigmented area of Dowling-Degos disease. A 64-year-old Japanese man manifested dappled pigmentation unusually localized to the buttocks, and two pigmented adenoid SCCs had developed on his left pigmented buttock. The other findings of Dowling-Degos disease were comedone-like lesions on the face and back, a finger-like fibroma in the right popliteal fossa, dystrophic fingernails, and a large number of seborrhoeic keratosis-like lesions predominantly on the flexural areas. Another unique clinical feature was the lack of vellus hair on the whole body surface. In addition to thin branching and elongation of rete ridges with basal hyperpigmentation, immature hair follicles surrounded by fibrosis and a lace-like pattern of the hair follicle epithelia were observed histologically. These epithelial hamartomatous features were consistent with Dowling-Degos disease. We speculate that the SCCs developed in relation to an underlying naevoid anomaly in pilosebaceous epithelia of Dowling-Degos disease.

Buttocks↗
PubMed2001

Granulocyte-macrophage colony-stimulating factor ensures macrophage survival and generation of the superoxide anion: a study using a monocytic-differentiated HL60 subline.

A large number of constituents, such as growth factors, cytokines, and vasoregulatory molecules, contribute a network of cellular interactions to atherosclerotic lesions, and current evidence suggests that granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of these constituents. We conducted this study to determine whether GM-CSF has an effect on the fate and function of macrophages. We examined the effect of GM-CSF on macrophages in vitro with a highly inducible HL60 subclone (HL60/DU-1) that we recently established. HL60 cells have been reported to preserve functional GM-CSF receptors, but a GM-CSF allele was rearranged and partially deleted. HL60/DU-1 cells were devoid of GM-CSF immunoreactivity and of autocrine stimulation of GM-CSF. HL60/DU-1 cells fated to die soon after terminal differentiation of macrophages by 1, 25-dihydroxy vitamin D(3) treatment. We found cell death to be mediated mainly by necrosis, not apoptosis, as confirmed by DNA fragmentation in agarose gel electrophoresis, morphological observation under a fluorescence microscope, and assay of lactate dehydrogenase release. Exogeneously administered GM-CSF rescued cells from necrotic death and caused them to survive and generate superoxide anions. We also conducted immunohistochemical analysis on an atherosclerotic human artery. Macrophages, endothelial cells, and smooth muscle cells were found to be GM-CSF positive in an atherosclerotic lesion. In summary, GM-CSF, which is produced by macrophages, endothelial cells, and smooth muscle cells, is thought to act in an autocrine and a paracrine fashion as a necrosis-inhibiting factor against arterial macrophages. This unique function may play an important role in ensuring survival and promoting function in atherosclerotic lesions.

Aorta↗
PubMed2001

Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives.

An aldosterone-producing adenoma causes surgically correctable hypertension. Screening tests should be assessed for their accuracy and ability to detect aldosterone-producing adenoma in an appropriate population. This study aims to validate the accuracy and efficacy of the basal plasma aldosterone concentration (picomoles per liter) to PRA (nanograms per liter/sec) ratio and of combined stimulation of PRA by the furosemide and upright posture test in screening for aldosterone-producing adenoma in hypertensives with PRA less than 0.28 ng/liter.sec (1 ng/ml.h). Thirty-five aldosterone-producing adenoma and 79 nonaldosterone-producing adenoma patients were retrospectively selected from among 159 patients examined with the furosemide and upright posture test between 1989 and 1999. Selection criteria were based on blood pressure, PRA, and plasma aldosterone concentration. Diagnosis was based on surgical outcome, computed tomography scans with adrenal scintigraphy, or venous sampling. The accuracy and efficacy of basal (aldosterone/PRA ratio) and dynamic (postfurosemide and upright posture PRA) screening tests were assessed based on test sensitivity, specificity, likelihood ratio, and receiver operating characteristics. At a cut-off value of 3,200, the aldosterone/PRA ratio had a high sensitivity of 1.0 and a low specificity of 0.61. The importance was strengthened by using a multilevel likelihood ratio, i.e. positive (aldosterone/PRA ratio >10,000), negative (aldosterone/PRA ratio <3,200), and neutral (intermediate aldosterone/PRA ratio) levels. Patients with a positive level had a likelihood ratio of 7.1 and were likely to have an aldosterone-producing adenoma. The aldosterone/PRA ratio enclosed a larger area under the receiver operating characteristics curve (0.905) than did postfurosemide and upright posture PRA (0.826). In conclusion, the plasma aldosterone concentration to PRA ratio is an effective screening and diagnostic test when a triple level likelihood ratio is applied. The furosemide and upright posture test did not raise the posttest probability over that obtained using the aldosterone/PRA ratio.

Adenoma↗
PubMed2001

Ectopic adrenocorticotropin syndrome exhibiting paradoxical adrenocorticotropin responsiveness to gonadotropin-releasing hormone.

In a 37-year-old man who had Cushing's syndrome, investigations, including overnight dexamethasone suppression test, corticotropin-releasing hormone (CRH) test, pituitary MRI and inferior petrosal sinus sampling suggested the presence of ectopic adrenocorticotropin (ACTH) production. Interestingly, gonadotropin-releasing hormone (GnRH) increased plasma ACTH from 73 pg/ml to 708 pg/ml at 15 min. Furthermore, desmopressin also increased plasma ACTH whereas CRH and thyrotropin-releasing hormone (TRH) had no effect. Such paradoxical responses of plasma ACTH were observed repeatedly. A thoracic CT scan revealed a right anterior mediastinal mass, which was surgically resected. Histological and immunohistochemical examination confirmed that the tumor was an ACTH-producing carcinoid. ACTH and cortisol decreased immediately following surgery. Neither desmopressin nor GnRH administration resulted in elevation of plasma ACTH while ACTH-responsiveness to dexamethasone and CRH was restored. To our knowledge, this is the first report documenting GnRH responsiveness in ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗
PubMed1999

An additional exon of stress-inducible heat shock protein 70 gene (HSP70-1).

The HSP70-1 gene, reportedly a single exon, encodes a major stress-inducible 72-kDa heat shock protein (HSP70). We recently demonstrated that patients with major depression had a 162-base pair (bp)-deletion in the 5'-flanking sequence of HSP70-1 mRNA in their peripheral blood mononuclear cells. Present study has been conducted to clarify how this short mRNA is generated, and demonstrated that a novel 385 bp sequence is located 1.1 kb upstream from the HSP70-1 gene of normal subjects. Except for the 162 bp deletion, it is compatible with part of the 5'-flanking sequence of the HSP70-1 gene, and contains another exon of 358 bp (exon 1) that may be connected to the 3'-terminus (exon 3) of the conventional HSP70-1 gene. Alternative transcription of exons 1 and 3 may cause the short mRNA. It is concluded that HSP70-1 gene is constituted of three exons and may cause alternative splicing.

Alternative Splicing↗
PubMed1999

Surgical stress increases renal glutathione content via increased glucocorticoid, and resistance to subsequent oxidative injury in the rat: significant link between endocrine response and cell defense system under the stress.

Systemic and nonspecific stress response effects on the cellular defense mechanism were studied in the male rat kidney. Two days after laparotomy-induced surgical stress, rats showed increased serum corticosterone and renal cortical reduced glutathione (GSH). Rats were then injected s.c. with mercuric chloride (HgCl2) to oxidatively injure renal tubuli. Increased serum creatinine levels indicated that laparotomy pretreatment lessened renal damage. To study the effects of the activated pituitary-adrenal axis on renal cortical GSH content and vulnerability to subsequent oxidative injury, rats were injected s.c. with ACTH on two consecutive days. ACTH administration increased both corticosterone and aldosterone. These rats showed increased, dose-dependent renal cortical GSH content, i.e., controls (n=7): 1.25 +/- 0.23 micromol/g tissue, daily dose of 10 microg/100 gBW (n=7): 1.53 +/- 0.24 micromol/g tissue, and daily dose of 40 microg/100 gBW (n=7): 2.31 +/- 0.23 micromol/g tissue. Rats receiving daily doses of 40 microg of ACTH/100 gBW acquired resistance to oxidative injury, indicated by serum creatinine levels: controls (n=6), 22 +/- 4 micromol/L; HgCl2 (n=6), 145 +/- 88 micromol/L; ACTH and HgCl2 (n=6), 37 +/- 11 micromol/L. Morphological evidence indicated that ACTH pretreatment in HgCl2-injected rats prevented renal tissue from inflammatory cell infiltration but not from tubular degeneration. Cellular GSH content of LLC-PK1 cells, porcine renal-tubule-derived culture cells, increased significantly in incubation with dexamethasone or aldosterone, suggesting that adrenal steroids directly stimulate renal cell GSH. We demonstrated that stress or ACTH administration activates the defense mechanism in the kidney via increased GSH. This stress-activatable defense system may therefore indicate a connection between endocrine stress response and the cellular defense mechanism.

Adrenocorticotropic Hormone↗
PubMed1998

Establishment of a stable HL60 subline having the potential for monocytic differentiation using granulocyte-macrophage colony-stimulating factor: possible use for the study of monocytic differentiation and oxidative stress.

A stable HL60 subline having the potential for monocytic differentiation was established by use of GM-CSF. HL60, a human promyelocytic cell line, has frequently been employed for research in the fields of monocytic differentiation and atherosclerosis because of its potential to differentiate into either granulocytes or monocytes. However, HL60 are frequently seen to change their phenotype during long-term culture. To date, many sublines or variants of HL60 cells have been established. However, most of them display diminished or complete loss of activities that characterize parental cells. The present study was conducted to establish a stable HL60 subline with the potential for monocytic differentiation. Firstly, a single HL60 cell was isolated by limiting dilution, and was successfully proliferated by incubation with GM-CSF. Secondly, from this population, cells were selected that had the ability to generate superoxide after VD-induced monocytic differentiation. Cells obtained in this manner (designated HL60/DU-1) exhibited expression of CD14 and CD11b and suppression of CD3 expression after monocytic differentiation. NBT positivity showed a consistent level of over 971% after a 6-day challenge with VD throughout the experimental period of 12 months. HL60/DU-1 cells, which were cryopreserved in liquid nitrogen for 6 months, thawed and re-cultured, exhibited over 97% NBT positivity. Carvedilol and probucol, which exhibit antioxidative activity, inhibited superoxide release from the differentiated HL60/DU-1 cells. HL60/DU-1 cell line is a promising model for the study of monocytic differentiation and the effects of oxygen radicals.

Calcitriol↗
PubMed1998

Down-regulation of telomerase activity is an early event of cellular differentiation without apparent telomeric DNA change.

With the use of three different hematopoietic cell lineages, the downregulation of telomerase activity was found to be a general response to the induction of differentiation. The decrease in telomerase activity occurred as early as 24 h when HL-60 and K562 cells were cultured in the presence of 1alpha, 25 dihydroxyvitamin D3 (VD3), all-trans-retinoic acid (ATRA) and hemin, and completely disappeared after 3 days. On the other hand, MEG-01 cells showed a marked inhibition of telomerase activity after 6 days of culture with 12-0-tetradecanoylphorbal 13-acetate (TPA). The analysis of telomeric DNA in the HL-60 cells and K562 cells demonstrated no detectable loss of telomeric DNA with cellular differentiation, with a loss of telomerase activity. The repression of telomerase is a common molecular event during leukemic cell differentiation.

Base Sequence↗
PubMed1998

Age-dependent decline in cortisol levels and clinical manifestations in patients with ACTH-independent Cushing's syndrome.

OBJECTIVE: Adrenocortical cells change with age in both subcellular morphology and level of steroidogenesis. This study evaluates the influence of aging on hypercortisolism and clinical manifestations in patients with ACTH-independent Cushing's syndrome due to a cortisol-secreting adrenal adenoma (CS). DESIGN: Restrospective study. PATIENTS: Thirty-six (33 females and 3 males) with CS. 31 healthy controls were age- and sex-matched to CS patients. MEASUREMENT: Patient age at diagnosis was compared to the degree of hypercortisolism and clinical manifestations. The degree of hypercortisolism was estimated using serum cortisol levels and urinary free cortisol excretion. Positive clinical manifestations were quantified using 12 symptoms and signs which resulted in a clinical score for each patient. Endogenous creatinine clearance, estimated disease duration and gender were analysed as possible factors affecting adenoma-secreated cortisol. RESULTS: Patient age correlated negatively with serum cortisol level (r = -0.417, P = 0.0107, n = 36) and urinary excretion of free cortisol (r = -0.613, P = 0.0002, n = 31). Analysis of Spearman's rank correlation showed that the clinical score decreased with age (rho = -0.631, P = 0.0004, n = 33). Oedema, weakness/myopathy, hirsutism, striae and psychological changes were infrequent symptoms in the elderly. Using stepwise multiple regression analysis, we estimated the clinical score (Y) by factors of serum cortisol levels (X1:nmol/l), age (X2: years of age) and gender (X3: gender; female = 1, male = 0), i.e. Y = 4.771 + 0.004 X1 - 0.064 X2 + 2.548 X3 (r = 0.743, P < 0.0001, n = 33). Results suggested that aging both suppressed cortisol secretion and repressed manifestations directly as an independent factor, although its direct effect may be weak. CONCLUSIONS: Our findings indicated the importance of age as a factor modulating hormonal levels and possible clinical manifestations in patients with cortisol-secreting adenomas.

Adenoma↗
PubMed1997

A case of recessive X-linked ichthyosis: scale-specific abnormalities of lipid composition may explain the pathogenesis of the skin manifestation.

We analyzed the lipid content of the scales, red blood cells, and plasma from a recessive X-linked icthyosis patient. The patient's scales accumulated cholesterol sulfate, had decreased levels of free sterols, sterol esters and sphingolipids, and lacked phospholipids. Although the accumulation of cholesterol sulfate was found in the patient's red blood cells and plasma as well as in the scales, other lipid composition abnormalities were specific for scales. Such scale-specific abnormal lipid composition may explain the pathogenesis of generalized hyperkeratosis and abnormal scaling of the disease.

Adult↗
PubMed1996

An allel-specific abnormal transcript of the heat shock protein 70 gene in patients with major depression.

Stress-inducible 72-kDa heat shock proteins (HSP70) were encoded on genes in multiple chromosomes. The expression of mRNA transcribed from the gene (HSP70-1) on chromosome 6 was studied using reverse transcript polymerase chain reaction in peripheral blood mononuclear cells of patients with different diseases. The deletion of 29 bp occurred in 5' noncoding and subsequent 133 bp in coding sequences of HSP70 mRNA in patients with major depression (n = 18), while normal subjects (n = 10) and patients with schizophrenia (n = 5), essential hypertension (n = 3), rheumatoid arthritis (n = 7), and Graves' disease (n = 3) had normal mRNA. No such deletion occurred in genomic DNA and no protein was translated from deleted mRNA. The allel-specific abnormal transcript of the HSP70 gene on chromosome 6 thus may underlie the altered stress and/or immune response in major depression.

Alleles↗
PubMed1996

Tissue manganese levels and liver pyruvate carboxylase activity in magnesium-deficient rats.

To investigate the manganese status in magnesium deficiency, 40 male Wistar rats, 3 wk old, were divided into two groups and fed a magnesium deficient diet or a normal synthetic diet for 2 wk. Dietary magnesium depletion decreased magnesium levels in brain, spinal cord, lung, spleen, kidney, testis, bone, blood, and plasma, while it elevated the magnesium level in liver. In magnesium-depleted rats, calcium concentration was increased in lung, liver, spleen, kidney, and testis, while it was decreased in tibia. In magnesium-depleted rats, manganese concentration was decreased in plasma and all tissues except adrenal glands and blood. Dietary magnesium depletion diminished pyruvate carboxylase (EC 6.4.1.1) activity in the crude mitochondrial fraction of liver. Positive correlation was found between the liver manganese concentration and the pyruvate carboxylase activity. In the magnesium-depleted rats, glucose was decreased while plasma lipids (triglycerides, phospholipids, and total cholesterol) were increased. These results suggest that dietary magnesium deficiency changes manganese metabolism in rats.

Animals↗
PubMed1996

Clinical implications of renal cyst in primary aldosteronism.

The present study surveyed 69 patients with aldosteronoma to study the clinical implications of renal cysts demonstrated in computed tomography. Patients who had cysts (n = 16, 23.2%) were older and had a longer duration of hypertension and more severe hypokalemia than those without cysts (n = 53). Patients with cysts therefore had longer-term, more severe hypokalemia than those without cysts. Endogeneous creatinine clearance (Ccr), measured in 61 patients, was significantly lower in patients with cysts (58.4 +/- 7.1 ml/min, n = 16) than in those without cysts (77.3 +/- 7.1 ml/min, n = 45, P = 0.0039). This significant difference was observed even after adjusting for covariables (age, duration of hypertension, and serum potassium) between the two groups by analysis of covariance (ANCOVA). No significant difference was observed in gender, blood pressure, serum creatinine, plasma aldosterone, or PRA. Age, serum potassium levels, and systolic and diastolic blood pressure were the significant determinants in predicting Ccr in a backward stepwise multiple regression analysis (r = 0.505, n = 61, P = 0.0025). Cysts were graded into four classes on the basis of number and size. Cyst grading correlated negatively with Ccr at a Spearman rank correlation (rho = -0.33, n = 61, P = 0.0103). The incidence of chronic renal failure was significantly higher in patients with cysts (18.8%) than in patients without (0%) in a Fischer's exact probability test (P = 0.0107). Thus, both renal cysts and dysfunction arose and/or developed from common roots, i.e., the duration and severity of hypokalemia, in primary aldosteronism. In addition, we surveyed 27 patients with pheochromocytoma. Patients with renal cysts (n = 8) had a significantly longer duration of hypertension than those without cysts. No significant difference was observed in Ccr between patients with and those without cysts. Thus, a significant link between renal cysts and Ccr was a specific feature of primary aldosteronism, but not of pheochromocytoma. In summary, the renal cysts in primary aldosteronism should be recognized as a significant complication representing the extent of renal injury and dysfunction.

Adolescent↗
PubMed1996

LH and testosterone modulate mercuric chloride-induced acute renal failure in male rats: the implication of stress-induced hypogonadism.

The significance of stress-induced hypogonadism remains unclear. Since plasma testosterone and LH have renotropic activity that is other than reproductive, we hypothesize that stress-induced hypogonadism is an adaptive response to protect the kidney. To examine this hypothesis, we prepared hypogonadal male rats with different levels of LH and testosterone through orchiectomy (castration), through chronic treatment with a slowly secreted form of gonadotropin-releasing hormone agonist (GnRHA; GnRHA pretreatment), or through both treatments concomitantly (castration with GnRHA pretreatment). Castrated rats had undetectable plasma testosterone and high plasma LH. GnRHA-pretreated rats had low plasma testosterone and normal plasma LH. Castrated rats with GnRHA pretreatment had undetectable plasma testosterone and normal plasma LH. We compared their sensitivity to HgCl2 nephrotoxicity and found that, when a low dose of HgCl2 (1.5 mg/kg body weight (BW)) was injected s.c. to induce acute renal failure, endogenous creatinine clearance (Ccr) decreased from 390 +/- 30 to 94 +/- 17 ml/h per kg BW in intact (unpretreated) rats. Such a decrease in Ccr was completely prevented in castrated rats (388 +/- 30 ml/h per kg BW) and partially prevented in GnRHA-pretreated rats (216 +/- 40 ml/h per kg BW). When a high dose of HgCl2 (2.25 mg/kg BW) was injected, half of the eight intact rats died but castrated rats and GnRHA-pretreated rats survived (P < 0.05). The elevated resistance in castrated rats was reduced when plasma LH was reduced with GnRHA pretreatment, but was restored by additional pretreatment with ovine LH (40 micrograms/day), as evidenced by changes in Ccr. Elevated resistance in castrated rats was also reduced by the administration of testosterone propionate. In conclusion, hypogonadism activated the preventive and defensive mechanisms that protect the kidney through both decreased plasma testosterone and high or even normal plasma LH.

Acute Kidney Injury↗
PubMed1995

A case of multiple eccrine porocarcinoma with stepping-stone distribution on the foot.

An 89-year-old woman had three tumors of several years' duration in a stepping-stone distribution on the dorsum of her right foot. The two larger ones were diagnosed histologically as eccrine porocarcinomas, and the smallest of the three shared many clinical similarities with them. Eccrine porocarcinoma is a rare malignant tumor. We describe this peculiar case in which three tumors developed in the same region and discuss how they might have occurred. It is most likely that the three tumors of this case originated from nevoid tumors, and that the individual lesions exhibited malignant changes.

Acrospiroma↗
PubMed1994

Pemphigus vulgaris associated with autoimmune hemolytic anemia and elevated TNF alpha.

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNF alpha detected significantly in the blister fluid of this patient.

Aged↗