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K Niimi

Publications and source records attributed to K Niimi.

At least 19 recordsLinked to original sources
PubMed1998

Candida albicans HEX1 gene, a reporter of gene expression in Saccharomyces cerevisiae.

The Candida albicans HEX1 gene was examined as a reporter of gene expression in Saccharomyces cerevisiae. The galactose-inducible S. cerevisiae GAL1-GAL10 promoter was inserted upstream of the C. albicans HEX1 gene, which encodes N-acetylglucosaminidase. The gene was introduced into S. cerevisiae AH22, which has no background N-acetylglucosaminidase activity. Expression of HEX1 in transformed cells was induced significantly by galactose and was repressed by glucose. The HEX1 gene product was functional in S. cerevisiae cells and was targeted to the periplasm. Both untransformed S. cerevisiae cells and cells expressing HEX1 had similar growth curves and cell morphology indicating that expression of N-acetylglucosaminidase was not toxic to the host strain. These results demonstrate that the HEX1 gene can be a useful reporter of gene expression in S. cerevisiae.

Acetylglucosaminidase↗
PubMed1998

Drug pumping mechanisms in Candida albicans.

Multiple drug resistance is becoming a major problem in the treatment of AIDS patients with oropharyngeal candidosis. Candida albicans strains isolated from candidosis patients who do not respond to fluconazole therapy often show azole drug resistance which usually correlates with the expression of C. albicans CDR1, CDR2 or BENr genes, encoding potential drug efflux pumps. The objective of this study was to develop a yeast secretory vesicle transport assay and use this system to study the pumping function of Cdr1 and Benr. The C. albicans CDR1 and BEN r genes were cloned separately into plasmid pVT101-U, to form plasmids pKY1011 and pKN5001 respectively. Plasmids pVT101-U, pKY1011 and pKN5001 were transformed into Saccharomyces cerevisiae SY1, a sec6-4 mutant with a temperature-sensitive mutation in the secretory pathway. SY1 cells transformed with pKY1011 or pKN5001, were more resistant to fluconazole (MICs in both cases 64 microg/ml) than SY1 cells (MIC 32 microg/ml). In addition, cells transformed with pKY1011 were more resistant to cycloheximide (MIC 16 microg/ml) than SY1 cells (MIC 2 microg/ml). Intact secretory vesicles were isolated from SY1 cells expressing Cdr1 and these vesicles accumulated fluconazole in a time dependent manner. These experiments demonstrated that S. cerevisiae secretory vesicles can be used to examine the mechanism of fluconazole transport by putative C. albicans membrane pumps.

Antifungal Agents↗
PubMed1997

Temperature-related expression of the vacuolar aspartic proteinase (APR1) gene and beta-N-acetylglucosaminidase (HEX1) gene during Candida albicans morphogenesis.

Expression of the Candida albicans vacuolar aspartic proteinase (APR1) and beta-N-acetylglucosaminidase (HEX1) genes was studied when carbon-starved cells of strains ATCC 10261 and A72 were induced to grow as yeast or as germ tube-forming cells. Amounts of APR1 mRNA were similar under yeast or germ tube growth conditions. However, more APR1 mRNA was present in cells grown at 28 degrees C than in cells grown at 37 degrees C. The Apr1 enzyme activity of cell-free extracts was not affected by cellular morphology, culture pH or growth temperature. Amounts of HEX1 mRNA were also higher in N-acetylglucosamine (GlcNAc)-induced cells grown at 28 degrees C than in cells grown at 37 degrees C. There was slightly more HEX1 mRNA in cells grown at pH 4.5 than in cells grown at pH 6.7. The beta-N-acetylglucosaminidase activities of GlcNAc-grown cells correlated with the amounts of HEX1 mRNA and were higher when cells were grown at a lower temperature and at a lower pH. Although a similar temperature- and pH-dependent pattern of HEX1 mRNA expression was seen in cells grown on glucose, the enzyme activities in cell-free extracts were all very low. These data indicate that the APR1 and HEX1 genes play no direct role in the dimorphic transition of C. albicans and that transcription of both genes appears to be temperature regulated when the cells are released from carbon starvation. The expression of HEX1 mRNA is in part under the control of culture pH and translation of HEX1 mRNA seems to be regulated by glucose.

Acetylglucosaminidase↗
PubMed1997

Regulation of N-acetylglucosaminidase production in Candida albicans.

The N-acetylglucosaminidase of Candida albicans is a secreted hydrolytic enzyme that contributes to the yeast's virulence. There was a significant increase in the N-acetylglucosaminidase activity of C. albicans cells released from carbon starvation in medium containing N-acetylglucosamine. The increased enzyme activity in N-acetylglucosamine-grown cells correlated with increased transcription of the HEX1 gene, which encodes C. albicans N-acetylglucosaminidase. In contrast, glucose repressed HEX1 transcription, and glucose-grown cells had on average 94-fold lower N-acetylglucosaminidase activities than did N-acetylglucosamine-grown cells. N-acetylglucosaminidase induction in cells grown on N-acetylglucosamine was also repressed by fructose, mannose or galactose, although to a lesser extent than by glucose, and sucrose repressed enzyme production by only 10%. Eighty-eight percent of the enzyme in N-acetylglucosamine-grown cells was localised in the periplasm, and after incubation for 5 h, 30 or 70% of the total enzyme activity was secreted into the medium by yeast or mycelial cells, respectively. The cellular location of the enzyme and the regulation of production by the carbon source indicate a scavenging role for C. albicans N-acetylglucosaminidase.

Acetylglucosamine↗
PubMed1996

Role of catalase in retinal antioxidant defence system: its comparative study among rabbits, guinea pigs, and rats.

The role of catalase in the retinal antioxidant defence system was examined in rabbits, guinea pigs, and rats with and without prolonged administration of a diet containing 0.4% 3-aminotriazole (3-AT), a catalase inhibitor. When weanling rabbits, guinea pigs, and rats we administered 3-AT for 8, 7, and 10 weeks, respectively, retinal catalase activity was reduced by approximately 50% in all these animals. In the retina of rabbits with 3-AT administration, a decrease in superoxide dismutase (SOD) activity and an increase in lipid peroxide (LPO) concentration occurred. while glutathione peroxidase (GSH-px) activity did not change. In the retina of guinea pigs with 3-AT administration, an increase in LPO concentration occurred, while SOD and GSH-px activities did not change. In the retina of rats with 3-AT administration, a decrease in GSH-px activity and an increase in LPO concentration occurred, while SOD activity did not change. An increase in serum LPO concentration was found in rats with 3-AT administration, while the concentration did not change in rabbits and guinea pigs. These results indicate that catalase plays an important role in the retinal antioxidant defence system, but that the way catalase contributes to the maintenance of the retinal antioxidant defence system is different among these animals. The present results suggest that under the prolonged inhibition of catalase, the retina of rats, but not of rabbits and guinea pigs, may suffer from the influence of systemic oxidative stress.

Amitrole↗
PubMed1995

Impact of uraemia on food efficiency and the pulsatile mode of growth hormone secretion in rats.

In view of the profound growth failure resulting from renal insufficiency and uraemia, the present studies were designed to specifically investigate food efficiency and the pattern of GH secretion under these conditions. Animals were made uraemic by 5/6 nephrectomy (Nx) and feeding a high-protein diet. Three groups of animals were studied: uraemic (Ur); sham-operated, fed ad libitum (Sh); and sham-operated pair-fed with the uraemics (PF). Food intake per 100 g body weight and food efficiency (g weight gained per g food consumed) were calculated. Fourteen days after 5/6 Nx, blood samples were taken via intra-atrial catheters at 10-min intervals over a period of 6 h. GH was measured in plasma by radioimmunoassay. GH pulsatility was analysed by multiple parameter deconvolution. The growth rate of Ur animals was significantly lower than that of Sh. The body weights of the Ur animals were also lower than PF due to an initial period of weight loss. Both Sh and PF animals showed the typical negative slope of food intake as body weight increased. In contrast, the Ur animals showed a positive slope of food intake. The lower rate of growth and the elevated food intake corresponded to a decreased food efficiency for the Ur group. Deconvolution analysis of pulsatile GH release demonstrated a significant increase in GH half-life in the Ur animals. The amplitude and mass of GH secretory pulses were decreased, whereas the number of detectable secretory bursts was increased. These changes were specific to uraemia with respect to half-life and number of pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1994

Molecular cloning and expression of the Candida albicans beta-N-acetylglucosaminidase (HEX1) gene.

beta-N-Acetylglucosaminidase was purified from the spent culture medium of Candida albicans A72 grown in the presence of N-acetylglucosamine (GlcNAc). The N-terminal amino acid sequence of the protein was determined, two degenerate oligonucleotide probes were constructed, and a 3.9-kb BamHI fragment of DNA that hybridized to both probes was subcloned from a lambda EMBL4 library of C. albicans A72 genomic DNA. This fragment of DNA contained the entire beta-N-acetylglucosaminidase (HEX1) gene, which consisted of an open reading frame coding for a polypeptide precursor of 562 amino acids with a putative 22-amino-acid leader sequence. The deduced HEX1 amino acid sequence showed similarity to hexosaminidases from a variety of organisms. Growth of C. albicans on GlcNAc induced transcription of HEX1, resulting in increased specific beta-N-acetylglucosaminidase activity. HEX1 mRNA (2.35 kb) from GlcNAc-grown cells was approximately 200 bp larger than HEX1 mRNA from cells grown on glucose. This size difference was suggested to result from the use of alternative transcription termination sites. The cloned HEX1 gene introduced into C. albicans SGY-243 on a plasmid also responded to GlcNAc induction.

Acetylglucosaminidase↗
PubMed1993

Glucocorticoid-induced changes in the quantity and secretory capacity of individual rat somatotropes.

Chronic glucocorticoid treatment is complicated by growth failure. The study presented here was designed to investigate the effect of cortisone on growth hormone (GH) secretion by individual pituitary cells in young male rats. Beginning at 37 days of age, animals were injected sc with cortisone acetate (CORT; 5.0 mg/rat per day) or the same volume of saline (SAL) for 8 days. At 45 days of age, the body weights of the CORT animals (134.5 +/- 5.5 g) were significantly less (P < 0.0005) than those of SAL controls (179.3 +/- 4.2 g). The secretory capacity of dispersed pituitary cells was assessed by the reverse hemolytic plaque assay. Cells were exposed to six concentrations of GH-releasing hormone (GHRH) ranging from 0.01 to 3.0 nM. CORT treatment significantly decreased the absolute number of somatotropes per pituitary gland (CORT, 1.23 +/- 0.03 x 10(6); SAL, 1.57 +/- 0.09 x 10(6); P = 0.025). Conversely, the mean plaque areas were significantly greater for CORT animals at all concentrations of GHRH tested, indicating that the amount of GH secreted by individual somatotropes was significantly increased by CORT. It was concluded that the paradoxical increase in the in vitro GHRH responsiveness, which is commonly observed after glucocorticoid treatment, was due to an increase in the capacity of fewer individual somatotropes to secrete GH.

Animals↗
PubMed1993

[Cataract].

Explore the source record for details and available documents.

Adult↗
PubMed1992

The effect of growth hormone on the growth failure of chronic renal failure.

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX, n = 40), GH-treated nephrectomized rats (NX+GH, n = 18), sham-operated rats fed ad libitum (SHAMAL, n = 27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF, n = 10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean +/- SEM) 49 +/- 3 and 54 +/- 4 mg/dl, respectively, compared with 16 +/- 4 and 19 +/- 0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0 +/- 3.3 g) and length (3.5 +/- 0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2 +/- 4.0 g, P less than or equal to 0.0001 and 4.1 +/- 0.2 cm, P less than or equal to 0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2 +/- 5.0 g) and length (3.4 +/- 0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81 +/- 2 mg/dl versus 55 +/- 3 mg/dl in SHAMAL (P less than or equal to 0.0001), was not increased in the NX+GH group, 87 +/- 3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.

Animals↗
PubMed1992

Growth hormone secretion from pituitary cells in chronic renal insufficiency.

To examine whether growth hormone (GH) secretion is adversely affected by chronic renal insufficiency (CRI), the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (CRI, N = 18) and sham-operated (N = 18) rats. Two weeks after nephrectomy, during a period of stable uremia, CRI rats had significantly higher serum concentrations (mean +/- SEM) of urea nitrogen and creatinine than sham rats, 16.8 +/- 1.4 mmol/liter (47 +/- 4 mg/dl) and 79.6 +/- 0.0 mumol/liter (0.9 +/- 0.0 mg/dl) versus 6.1 +/- 0.4 mmol/liter (17 +/- 1 mg/dl) and 35.4 +/- 0.0 mumol/liter (0.4 +/- 0.0 mg/dl), respectively (P less than 0.0001). Incremental gains in body weight and nose to tail-tip length of CRI rats over two weeks were also significantly depressed, 53.3 +/- 5.38 g (CRI) versus 87.0 +/- 3.78 g (sham; P less than 0.0001) and 3.2 +/- 0.2 cm (CRI) versus 3.6 +/- 0.1 cm (sham; P less than 0.05). The cumulative food intake as well as food efficiency (g food consumed/g weight gain) were also adversely influenced by the uremic state: food intake 304 +/- 1 g (CRI) versus 397 +/- 6 g (sham; P less than 0.0001) and food efficiency 0.173 +/- 0.013 g/g of weight gain (CRI) versus 0.219 +/- 0.008 g/g of weight gain (sham). No significant difference in GH secretory rate (ng/min/10(7) cells) was found between the uremic and sham animals under basal conditions, 65.2 +/- 2.1 (CRI) and 67.9 +/- 2.2 (sham) or in response to GH-releasing hormone, 282.8 +/- 42.4 (CRI) versus 306.2 +/- 42.6 (sham).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Growth hormone secretory capacity of individual somatotropes in rats with chronic renal insufficiency.

Growth failure is a common consequence of chronic renal insufficiency (CRI) in children and may be due to a number of factors. With regard to growth hormone (GH), regulation is often abnormal in CRI patients. The present study investigated the effect of CRI on the GH secretory responsiveness to GH-releasing hormone in individual rat pituitary somatotropes. Male Sprague-Dawley rats underwent a 5/6 nephrectomy to produce CRI. Control rats (SHAM) received sham operations, which included kidney decapsulation but not removal. Two wk later, during a period of stable uremia, serum creatinine [CRI: 1.1 +/- 0.08 mg/dL (97 +/- 7 mumol/L); SHAM: 0.4 +/- 0.04 mg/dL (35 +/- 4 mumol/L)] and serum urea nitrogen [CRI: 60.7 +/- 8.3 mg/dL (21.7 +/- 3.0 mmol/L); SHAM: 15.8 +/- 1.2 mg/dL (5.6 +/- 0.4 mmol/L)] were significantly elevated in the CRI rats (p less than 0.0005). Weight gain (p less than 0.0005), length gain (p less than 0.0005), food intake (p less than 0.0005), and food efficiency (p less than 0.005) were all significantly lower in the CRI rats. The GH secretory capacity of individual somatotropes was determined using the reverse hemolytic plaque assay technique. Plaque areas were measured to assess relative amounts of GH secreted. The total number of pituitary cells per rat, the percentage of somatotropes, and the mean plaque areas were similar for the two groups. These findings compare favorably with our in vitro study of GH responsiveness in perifused rat pituitary cells under conditions of mild uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hypercholesterolemia in rats with chronic renal insufficiency not aggravated by recombinant human growth hormone.

The lipid metabolic disorders in chronic renal insufficiency (CRI) are related to increased hepatic lipid synthesis, reduced triglyceride removal coupled with insulin insensitivity and impaired lipoprotein lipase activity. Growth hormone is lipolytic, and the effects of recombinant human growth hormone (rhGH) on the hypercholesterolemia of CRI are unsettled. To test this question, we gave rhGH for 14 days at a dosage of 3 units/day intraperitoneally to two-stage, 5/6 nephrectomized, male Sprague-Dawley rats (n = 18) compared to sex- and age-matched control (n = 27) and CRI (n = 40) rats. At the end of the study, CRI rats and those treated with rhGH had a similar degree of renal impairment, as assessed by serum concentrations (mean +/- SEM) of urea nitrogen (49 +/- 3 vs. 54 +/- 4 mg/dl), creatinine (0.9 +/- 0.0 vs. 1.0 +/- 0.1 mg/dl) and cumulative food intake (311 +/- 8 vs. 290 +/- 12 g). Serum urea nitrogen (16 +/- 4 mg/dl) and creatinine (0.4 +/- 0.1 mg/dl) concentrations as well as food intake (412 +/- 9 g) of control rats were significantly (p < 0.0001) different. Serum cholesterol concentration of CRI rats treated with rhGH (87 +/- 3 mg/dl) was not higher than those of CRI rats (81 +/- 2 mg/dl, p < 0.1338) but was significantly higher than in control rats (55 +/- 3 mg/dl, p < 0.0001). CRI rats treated with rhGH showed a similar serum albumin concentration and lower serum glucose than CRI rats (0.9 +/- 0.1 vs. 0.9 +/- 0.0 g/dl and 144 +/- 4 vs. 163 +/- 3 mg/dl, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

X-linked hypophosphatemia. Genetic and clinical correlates.

X-linked hypophosphatemia is a hereditary form of rickets that results from an isolated renal tubular wasting of phosphate. The clinical features unique to this disorder, and the recent advances in our understanding of vitamin D metabolism and molecular genetics in X-linked hypophosphatemia are reviewed. Finally, a succinct critique of the controversial treatment modalities round up this review.

Animals↗
PubMed1991

Peutz-Jeghers syndrome associated with adenocarcinoma of the cecum and focal carcinomas in hamartomatous polyps of the colon: a case report.

We report herein a case of Peutz-Jeghers syndrome associated with an adenocarcinoma of the cecum and four focal cancers arising in hamartomatous polyps of the colon. There were a total 27 polyps in the intestine; 4 in the small intestine and the rest in the large intestine. The hamartomatous polyps in which the 4 focal cancers were found showed no component of adenoma, and the other polyps removed from the colon and small intestine at the same time were all hamartomas with no evidence of dysplasia or malignancy. This case was rare in that multiple focal cancers may have arisen directly from the hamartomous polyps of the colon.

Adenocarcinoma↗
PubMed1991

Cortisone effects on growth, food efficiency, and in vitro growth hormone release.

These studies were designed to investigate the cause of growth retardation during glucocorticoid treatment in rats. In young animals, body weights and amounts of food consumed were measured at two-day intervals, beginning at 29 days of age. Average food intake and food efficiency were calculated. Animals were treated with cortisone (CORT, 5 mg/rat/day, s.c.) or saline (SAL) for eight days between 37 and 44 days. Growth hormone (GH) release by dispersed pituitary cells in response to nine concentrations of GH-releasing hormone (GHRH) were tested by in vitro perifusion at 45 and 73 days. As previously shown, CORT caused a cessation of growth during the treatment period, and body weight failed to catch up. Food efficiency was decreased during CORT treatment. All parameters of in vitro GH release including basal GH secretory rate, overall GH response to GHRH, and the GHRH concentration-response curves were significantly increased by CORT in the 45-day-old animals. An age-related increase in GH release was also observed between the 45 and 73 day saline-treated animals. These results support the hypothesis that glucocorticoids inhibit growth by induction of changes in food metabolism and GH secretion. The effect on the pituitary gland itself paradoxically involves an increase in GH secretory capacity in response to GHRH.

Animal Nutritional Physiological Phenomena↗
PubMed1990

[A calcified mucinous adenocarcinoma of the stomach--case report].

The paper discusses the case of a 44-year-old woman with an epigastric discomfort at Hiroshima University Hospital. A barium study of the stomach showed rigidity and a giant fold. A subsequent abdominal roentgenogram and CT disclosed calcification throughout the stomach wall. Thus, is hopes of effecting a cure, a total gastrectomy, a partial resection of transverse colon, a splenectomy and a pancreatic tail resection were performed. A surgical specimen macroscopically presented an inelastic and thickened wall of the entire stomach, and deposits of whitish calcium were visible within the gastric wall. The pathological diagnosis indicated a mucinous adenocarcinoma, se, INF alpha, v2, ly3, n4 (No. 221), with calcification of this mucinous adenocarcinoma in the stomach.

Adenocarcinoma, Mucinous↗