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Biomedical subjects

K Negishi

Publications and source records attributed to K Negishi.

At least 19 recordsLinked to original sources
PubMed2005

Supplement nephropathy due to long-term, high-dose ingestion of ascorbic acid, calcium lactate, vitamin D and laxatives.

A 48-year-old Japanese woman previously in good health was found to have severe proximal tubular dysfunction with a high serum level of ascorbic acid (57.3 microg/ml, reference range: 1.9 - 15.0 microg/ml). Renal biopsy specimen showed marked tubulointerstitial damage, i.e. tubular atrophy, dilatation of tubular lumen with flattened tubular epithelial cells, vacuolization of proximal and distal tubular epithelial cells, and severe interstitial fibrosis with mild infiltration of mononuclear cells. Calcified lesions, which caused tubular obstruction or stenosis, were also seen in interstitial area adjacent to degenerated proximal tubuli. Hypokalemic nephropathy, probably due to long-term use of laxatives, was clearly shown. However, calcified lesions seemed to be caused by inappropriate excessive daily ingestion of ascorbic acid (6 000 mg/day), calcium lactate, and vitamin D because of the patient's misunderstanding that these supplements could keep her in a good health. This condition may be clinically called "supplement nephropathy".

Ascorbic Acid↗
PubMed2001

Effect of chromatic aberration on contrast sensitivity in pseudophakic eyes.

OBJECTIVE: To evaluate the effect of chromatic aberrations in pseudophakic eyes with various types of intraocular lenses (IOLs). PATIENTS AND METHODS: The study included 51 eyes of 33 patients who underwent cataract surgery. The eyes were divided into 3 groups according to the material from which their IOL was made: group 1, polymethyl methacrylate; group 2, silicone; and group 3, an acrylate/methacrylate copolymer. Ten normal phakic control eyes (group 4) underwent the same examination. Best-corrected distance visual acuity and contrast sensitivity were measured under white light and monochromatic light with wavelengths of 470 nm, 549 nm, and 630 nm, with the best correction under white light. RESULTS: There were no significant differences in best-corrected visual acuity and contrast sensitivity under the 549-nm monochromatic light in any group. However, under both white multichromatic light and 470- and 630-nm monochromatic light, the mean contrast sensitivity in group 3 tended to be lower, sometimes significantly, than in the other IOL groups. CONCLUSIONS: Our results showed that longitudinal chromatic aberrations of some IOLs may degrade the quality of the retinal image. Attention must be paid to the detailed optical performance of IOL materials to achieve good visual function.

Acrylates↗
PubMed2001

Diabetic ketoacidosis in a case of pheochromocytoma.

A 31-year-old woman was admitted to our hospital because of diabetic ketoacidosis (DKA). Ultrasound sonography revealed the existence of the left adrenal tumor and endocrinological examinations established a diagnosis of pheochromocytoma. She had been healthy and there was no evidence for gestational diabetes in her personal history. Characteristic features were not found in her tumor size and the catecholamine levels as compared with typical cases of pheochromocytoma. An overwhelming secretion of catecholamine might suppress insulin secretion, as evidenced by the improvement after the resection of the tumor. However, a significant insulin resistance continued after tumor resection. Obesity and the heterozygosity of beta3-adrenergic receptor gene (Try64Arg) might play a role in insulin resistance, which resulted in DKA at least in part. Literature survey revealed four cases of DKA in the patients with pheochromocytoma including ours, three of which were Japanese. Pancreatic capacity to secrete insulin has been reported to be less than Caucasians, which might be another reason for DKA. Thus, we speculate that both suppressed insulin secretion and insulin resistance deteriorated by obesity or other factor(s) such as abnormality in beta3 adrenergic receptor probably depress beta-cell function resulting in abnormal metabolic imbalance such as DKA.

Adrenal Gland Neoplasms↗
PubMed2001

Photorejuvenation for Asian skin by intense pulsed light.

BACKGROUND: Dermabrasion and deep chemical peeling are used in the treatment of photoaged skin. These ablative procedures are effective enough to produce a certain improvement but have often caused postinflammatory hyperpigmentation among Asian patients. To avoid such adverse effects, a new, nonablative procedure has been sought. OBJECTIVE: To determine the effectiveness of photorejuvenation for Asian skin using intense pulsed light (IPL). The specific parameters used, improvement ratios, side-effects, and downtime required are also discussed. METHODS: Ninety-seven patients were treated for photoaging using IPL. The cutoff filters of 550 nm and 570 nm were utilized for three to six treatments at intervals of 2 to 3 weeks. RESULTS: Treatment results were evaluated and rated by both patients and physicians at the end of the third treatment based on improvement in pigmentation, telangiectasia, and skin texture. A combined rating of "good" or "excellent" was given to more than 90% of the patients for pigmentation, more than 83% for telangiectasia, and more than 65% for skin texture. There were some minor complications in four cases: one had erythema that continued to the next day and three had minor blisters leaving no marks. CONCLUSION: Photorejuvenation using IPL is a completely safe and effective procedure even for Asian skin. It will be increasingly used for skin rejuvenation in the future.

Adult↗
PubMed2001

Highly efficient random mutagenesis in transcription-reverse-transcription cycles by a hydrogen bond ambivalent nucleoside 5'-triphosphate analogue: potential candidates for a selective anti-retroviral therapy.

The nucleoside P can base pair with both A and G. We evaluated the mutation frequency induced by the 5'-triphospbate of the ribonucleoside P (PTP) in an in vitro retroviral replication model. After 4 cycles of replication in the presence of PTP, the mutation frequency was raised to 3.8 x 10(-2) per nucleotide and C-to-U and U-to-C mutations were dominantly observed. These results suggest that ambivalent NTP analogues, like PTP, could induce mutations beyond the error threshold of retroviruses.

Antiviral Agents↗
PubMed2001

Binding specificities of the mismatch binding protein, MutS, to oligonucleotides containing modified bases.

We have studied the effects of DNA mismatch repair on mutagenesis induced by nucleoside analogs. Among them, the mutagenic action of 3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one 2'-deoxyriboside (dP) showed high susceptibility to the mismatch repair system, while mutagenesis by N4-aminocytidine and N4-hydroxycytidine was only weakly affected. 2-Aminopurine mutagenesis showed intermediate susceptibility. MutS protein specifically bound to an oligonucleotide duplex containing a dP-dG pair, while the dP-dA pair was bound only weakly. The binding to the dP-dG pair was as strong as binding to a dA-dC mismatch. These specific binding properties can explain the effective avoidance of dP-induced mutagenesis by the mismatch repair system. We have also studied the effects of the repair system on mutagenesis induced by methylating and ethylating agents.

2-Aminopurine↗
PubMed2001

Reverse transcriptional mutagenesis induced by ribonucleoside triphosphate analogue, PTP and its availability for anti-HIV-1 therapy.

The bicyclic pyrimidine analogue, 3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one (P) can base pair with both A and G. The riboside 5'-triphsophate of P (PTP) efficiently induces mutation during in vitro transcription and reverse transcription cycles using a phage promoter. In the present study, we have constructed an in vitro transcription system promoted by the human immunodeficiency virus type 1 (HIV-1) 5'-long terminal repeat (LTR) using HeLa nuclear extract supplemented with HIV-1 Tat protein. Using this system, the effects of mutagenic ribonucleotide analogues were studied.

Anti-HIV Agents↗
PubMed2001

Inhibition of DNA adduct formation and mutagenic action of 3-amino-1-methyl-5h-pyrido[4,3-b]indole by chlorophyllin-chitosan in rpsL transgenic mice.

We have studied the inhibitory effect of chlorophyllin-chitosan (Chl-Chi) complex, an insoluble form of chlorophyllin, on the DNA adduct formation and mutagenesis by a heterocyclic food mutagen-carcinogen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in mice carrying the E. coli rpsL gene as a mutagenesis reporter. Upon administration of a diet containing 0.002% or 0.01% Trp-P-2, DNA adducts were formed in various tissues in a dose-dependent manner, with the maximum level observed in the liver. Addition of 3% Chl-Chi to the diet reduced the Trp-P-2 adduct by up to 90%. The rpsL mutant frequencies increased significantly in both the liver and spleen upon administration of a 0.01% Trp-P-2 diet. Addition of Chl-Chi to the diet decreased these induced mutant frequencies to the background level. No harmful effect of Chl-Chi was detected during these experiments. The results show that Chl-Chi may be a candidate chemopreventive agent against the genotoxic action of Trp-P-2, and possibly also other aromatic carcinogens in the diet.

Animals↗
PubMed2000

Retrovirus-specific random mutagenesis by a nucleoside 5'-triphosphate analogue, PTP.

In a retrovirus replication model system, which consists of in vitro transcription and reverse transcription cycles, 6-(beta-D-ribofuranosyl)-3,4- dihydro-8H-pyrimido[4,5-c][1,2]oxazin-7-one-5'-triphosphate (PTP) induced highly efficient random mutations and this was due to the ambiguous incorporation of PTP by RNA polymerases. The types of mutations were mainly C-to-U or U-to-C transition mutations and the frequency was about 4 x 10(-2)/nucleotide during four cycles of the replication. Since a high mutation rate is harmful to species, PTP may be new candidate for anti-retroviral drugs. N4-aminoCTP and N4-hydroxyCTP were also incorporated ambiguously by RNA polymerase. These compounds may have a potential to induce mutation by the same mechanism as PTP.

Mutagenesis↗
PubMed2000

DNA lesion and mutagenesis induced in phageM13mp2 by UVA, UVB and UVC irradiation.

Sunlight is carcinogenic and mutagenic and its genotoxic effects are believed to be the result of UV light-induced lesions in DNA. These lesions include pyrimidine dimers and (6-4) photoproducts, but it is uncertain whether the pyrimidine modifications are the sole pre-mutagenic lesions induced by UV light. Previous studies indicate that some sunlight-induced mutations in the single-stranded DNA phage M13mp2 may not be caused by these photoproducts. In this work, purified single-stranded phage DNA was exposed to UVA, UVB and UVC and the induced mutations were analyzed. All 3 types of UV light increase the mutation frequency. The mutants were sequenced and the results suggest that UVA exposure may induce formation of a non-dipyrimidine lesion in DNA.

Bacteriophage M13↗
PubMed2000

Insulin levels during fasting and the glucose tolerance test and Homa's index predict subsequent development of hypertension.

OBJECTIVE: To determine whether there is a longitudinal relationship between hypertension and hyperinsulinemia and to find the most useful parameter(s) for predicting the subsequent development of hypertension. SUBJECTS AND METHODS: The oral glucose (75 g) tolerance test (OGTT) was performed in 313 patients, who were divided into three groups according to glucose tolerance based on the WHO criteria: normal, borderline and diabetes mellitus. The fasting insulin (IRI) levels, sigmaIRI (the sum of the insulin levels 0, 30, 60 and 120 min after the OGTT), insulinogenic index and Homa's index, a candidate for the simple assessment of insulin sensitivity, of the normotensive and hypertensive subjects in each subgroup were compared. In addition, 145 normotensive subjects were followed up for over 3 years and observed for the development of hypertension. RESULTS: Hypertensive diabetic subjects had not only higher fasting IRI levels and sigmaIRI values, but they also had higher Homa's indices than normotensive diabetics. Normotensive subjects with normal glucose tolerance (n = 20) did not develop hypertension. However, 16 out of 94 patients with borderline glucose tolerance and five out of 31 diabetics became hypertensive. The incidence of hypertension in the group with fasting IRI > or = 15, sigmaIRI > or = 150 or Homa's index > or = 4 was between 5 and 9 times higher than that in the group with fasting IRI < 10, sigmaIRI < 100 or Homa's index < 2. This difference was still significant when multivariate analysis, including various factors such as age, body mass index (BMI) and sex, was performed. CONCLUSIONS: These results suggest that higher plasma IRI levels and/or insulin resistance are closely related to the pathogenesis of hypertension in patients with diabetes mellitus. Homa's index, fasting and sigmaIRI may be useful predictors of the subsequent development of hypertension.

Adult↗
PubMed1999

Sunlight mutagenesis: changes in mutational specificity during the irradiation of phage M13mp2.

We reported previously that the mutations in phage M13mp2, a single-stranded DNA phage, induced by sunlight exposure are predominated by G-to-C transversions. We have now made an unexpected observation that an exposure to sunlight for a short period of time results in induction mainly of C-to-T transitions while a longer exposure results in the induction of G-to-C transversions. This peculiar phenomenon suggests that DNA damage formed by initial sunlight exposure can be transformed during an elongated exposure. 7, 8-Dihydro-8-oxoguanine (8-oxoG) in DNA might be involved in the shift of the mutational specificity, as 8-oxoG was formed in the phage DNA upon the sunlight exposure. We also compared the mutagenic activity of UVB irradiation with that of sunlight exposure. The results demonstrate that the genotoxic properties of sunlight and UVB in phage M13mp2 mutagenesis are different. The shift in the mutational specificity associated with the dose of the sunlight may call for general cautions in the studies of agent-induced mutagenesis.

Bacteriophage M13↗
PubMed1999

Neurohumoral activations in congestive heart failure: correlations with cardiac function, heart rate variability, and baroreceptor sensitivity.

BACKGROUND: The clinical significance of the determination of heart rate variability and baroreceptor sensitivity relating to cardiac function and neurohumoral factors remains to be established. METHODS AND RESULTS: We investigated the relation between conventional clinical variables and frequency domain analysis of heart rate variability and baroreceptor sensitivity in 146 patients with heart failure. Cardiac function including left ventricular ejection fraction, left ventricular dimensions, and left atrial size was different by the plasma atrial natriuretic peptide level but not by the norepinephrine level. The total power and low-frequency power were correlated with plasma norepinephrine, whereas baroreceptor sensitivity was correlated with plasma atrial natriuretic peptide. None of the frequency domain variables and baroreceptor sensitivity was correlated with cardiac function. There was a positive correlation between the low-frequency power and baroreceptor sensitivity. CONCLUSIONS: Heart rate variability and baroreceptor sensitivity, which reflect autonomic regulation, may be an indicator independent from cardiac function in patients with heart failure.

Atrial Natriuretic Factor↗
PubMed1999

Disturbance of genetic information by a ribonucleotide analogue.

The synthetic base analogue, 6H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one (P), can efficiently base pair with A and G. We have previously demonstrated that the deoxyribonucleoside of P (dP) is highly mutagenic and that this is due to the ambiguous base pairing ability of P. In this work, we have shown that the ribonucleoside triphosphate of P (rPTP) induces C to U mutation on an in vitro model of retroviral genomic RNA replication pathway. This mutation induction by rPTP may be specific to retroviruses, since host genomic DNA should not be affected by such a ribonucleotide analogue, although temporary transcription-translation errors may occur.

Adenine↗
PubMed1999

Troglitazone and metformin, but not glibenclamide, decrease blood pressure in Otsuka Long Evans Tokushima Fatty rats.

To determine whether hypoglycemic agents such as sulfonylureas, biguanides and the newly developed insulin sensitizers such as troglitazone, have hypotensive effects in an animal model of non-insulin-dependent diabetes mellitus associated with insulin resistance, male Otsuka Long Evans Tokushima Fatty (OLETF) rats aged 12 weeks were administered following hypoglycemic agents or vehicle by gavage for 26 weeks; glibenclamide (5 mg/kg/day), metformin (100 mg/kg/day) and troglitazone (70 mg/kg/day). The gain in body weight was similar in the different groups. At 36 weeks of age, troglitazone significantly decreased fasting plasma glucose levels when compared to controls. The area under the curve (AUC) for insulin during glucose loading (2 g/kg, i.p.) was 50% lower in the group treated with troglitazone. Serum triglyceride levels in troglitazone-treated rats were also significantly lower than in the glibenclamide-treated group. Plasma membrane GLUT4 protein content was significantly augmented by a factor of 1.48-fold (p<0.02) in the glibenclamide-treated group and tended to be increased 1.32 times by administration of metformin (p=0.06). The systolic blood pressure increased with age in controls and the glibenclamide-treated group. In contrast, treatment with either metformin or troglitazone significantly decreased systolic blood pressure after the age of 29 weeks. Plasma norepinephrine and epinephrine concentrations did not show a significant decrease in the treated group when compared with the control group. These results suggest that metformin and troglitazone, but not glibenclamide, lower blood pressure in an animal model of insulin resistance, providing further evidence of the beneficial effect of insulin sensitizing hypoglycemic agents on blood pressure.

Animals↗