Biomedical subjects
Publications and source records attributed to K Oba.
We report a case of transitional cell carcinoma of the renal pelvis with vena caval tumor thrombus. To our knowledge only 14 cases of transitional cell carcinoma of the renal pelvis protruding into the vena cava have been reported. The literature regarding these cases is reviewed, and the differential diagnosis of this tumor from renal cell carcinoma is discussed.
To determine whether urinary albumin to creatinine ratio (Albumin index) and urinary N-acetyl-beta-D-glucosaminidase (NAG) to creatinine ratio (NAG index) in random spot urine samples can be sued to predict the early stage of diabetic nephropathy in the elderly non-insulin dependent diabetic patients, we measured these concentrations in 150 non-diabetics, 61 diabetics without retinopathy and 56 diabetics with retinopathy. All patients with Albustix-positive urine were excluded. Subjects divided into two groups according to whether they were < 60 years (adult group) or > or = 60 years old (old group). Multiple regression analysis was used to investigate the relationship between NAG index or Albumin index (dependent variable) and independent variables (age, systolic blood pressure, duration of diabetes. HbA1c) in diabetic patients. Diabetic patients with retinopathy showed the highest mean Albumin index, followed by diabetic patients without retinopathy and then non-diabetic patients both in adult group and in old group (p < 0.001, p < 0.001, respectively). Diabetic patients with retinopathy showed the highest mean NAG index, followed by diabetic patients without retinopathy and then non-diabetic patients both in adult group and in old group (p < 0.001, p < 0.001, respectively). Albumin index positively correlated with systolic blood pressure, duration of diabetes and HbA1c (r = 0.18, r = 0.35, r = 0.18, respectively). NAG index positively correlated with age, duration of diabetes and HbA1c (r = 0.18, r = 0.25, r = 0.29, respectively). These results suggest that both NAG index and Albumin index in random spot urine samples may serve as early functional indicators of diabetic nephropathy in elderly diabetics.
We studied concentrations of serum ferritin, glycosylated ferritin, and non-glycosylated ferritin in elderly patients with diabetes. The subjects were 111 people who were at least 60 years old: 54 healthy controls, 14 diabetic patients without retinopathy, and 43 diabetic patients with retinopathy. The mean levels of ferritin, glycosylated ferritin, and non-glycosylated ferritin in serum were significantly higher in the patients with retinopathy than in healthy controls. The mean percent glycosylated ferritin did not differ between patients with retinopathy and healthy controls. The mean levels of serum ferritin, glycosylated ferritin, and non-glycosylated ferritin, and the percent glycosylated ferritin did not differ significantly between patients without retinopathy and health controls. None of these values differed between subjects with macroangiopathy and those without macroangiopathy, in both groups of patients. In patients with diabetes, none of the values measured was significantly related to fasting plasma glucose, HbA1c, or the duration of diabetes. These results suggest that diabetic microangiopathy is associated with abnormally high levels of ferritin in serum.
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Ad4BP (or steroidogenic factor 1, SF-1) has been implicated to be an essential transcriptional factor for steroidogenesis as well as for the development of the reproductive axis. We elucidated the structure of the human Ad4BP gene. The gene is about 30 kb long and is split into 7 exons including a non-coding exon 1. The deduced amino acid sequence of the human Ad4BP consists of 461 amino acid residues and was highly homologous to those of other mammalian species.
Congenital adrenal hypoplasia, an X-linked disorder, is characterized by primary adrenal insufficiency and frequent association with hypogonadotropic hypogonadism. The X-chromosome gene DAX-1 has been most recently identified and shown to be responsible for this disorder. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. In a family containing several affected individuals, the proband male patient had a stop codon (TGA) in place of tryptophan (TGG) at amino acid position 171. As expected, his mother was a heterozygous carrier for the mutation, whereas his father and unaffected brother did not carry this mutation. In another male patient with noncontributory family history, sequencing revealed a 1-bp (T) deletion at amino acid position 280, leading to a frame shift and, subsequently a premature stop codon at amino acid position 371. The presence of this mutation in the patients' genome was further confirmed by digestion of genomic PCR product with MspI created by this mutation. Family studies using MspI digestion of genomic PCR products revealed that neither parent of this individual carried the mutation. These results clearly indicate that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene.
We studied age-related changes in the concentrations in serum of ferritin, glycosylated ferritin, and non-glycosylated ferritin. The concentrations were determined in 95 healthy subjects: 39 men and 56 women, aged from 22 to 94 years. In the men, age correlated significantly with serum ferritin (r = 0.332, p < 0.05) and non-glycosylated serum ferritin (r = 0.628, p < 0.001) but not with glycosylated serum ferritin. In the women, age correlated significantly with serum ferritin (r = 0.456, p < 0.001), non-glycosylated serum ferritin (r = 0.439, p < 0.001), and glycosylated serum serum ferritin (r = 0.415, p < 0.01). The ratio of glycosylated serum ferritin to serum ferritin correlated negatively with age both in men and in women (men: r = -0.661, p < 0.001; women: r = -0.411, p < 0.01). Serum non-glycosylated ferritin levels were higher in older men. Both serum glycosylated ferritin and non-glycosylated ferritin levels were higher in older women, but this phenomenon was more pronounced with respect to the non-glycosylated form. These results suggest that hyperferritinemia in the elderly is mainly caused by an increase in the concentration of non-glycosylated ferritin, both in men and in women.
OBJECTIVES: During the long-term follow-up of chronic hepatitis C patients treated with interferon alpha-2b, we have identified some patients who had continuous normalization, or transient elevation of the serum alanine aminotransferase levels within the first 6 months of follow-up and subsequent normalization, but HCV RNA was still found to be positive during the follow-up period (incomplete responder; ICR). We wished to clarify the characteristics of these patients, and to investigate the factors predictive of the response to interferon. METHODS: Seventy patients were treated with 6 MU of rIFN alpha-2b, three times weekly for 24 wk. Sixty-six patients (94%) completed the entire therapy and 2-yr follow-up protocol. RESULTS: Twenty-four months after cessation of IFN treatment, 24 patients (36%) were defined as complete responders (CR; continuously normal alanine aminotransferase levels, and HCV RNA negative). Nine patients (14%) were defined as ICR. Thirty-three patients (50%) were defined as nonresponders (NR). Compared with the CR or NR groups, the patients in the ICR group tended to have the mildest histological severity and lowest histological activity index scores, but there were no significant differences in any of the other histological features. The complete response rate was significantly higher in patients with low concentration of HCV RNA, and genotypes other than type II. CONCLUSIONS: After long-term follow-up of the 66 patients, 24 patients (36%) were CR, nine (14%) were ICR, and 33 (50%) were NR. The histological stage and indices of chronic hepatitis may help to predict a patient's response to IFN therapy.
Glucose tolerance has been shown to decline with age. Mechanisms of this phenomenon are not yet completely defined. The insulin response to glucose shows little change with age. The primary cause results from resistance to the ability of insulin to stimulate glucose uptake. Many factors, including composition of diet with regard to both caloric adequacy and carbohydrate content, decreased physical activity and decreased lean body mass, probably contribute to the insulin resistance. Mild glucose intolerance in the elderly, as in young adults, increases the risk for the development of overt diabetes mellitus and is a risk factor for the development of atherosclerotic diseases.
L-Galactono-gamma-lactone dehydrogenase (L-galactono-gamma-lactone:ferricytochrome c oxidoreductase [EC 1.3.2.3], GLDHase) which catalyzes the terminal step in the biosynthesis of L-ascorbic acid (AsA) has been purified from roots of sweet potato (Ipomoea batatas L., cv. Kintoki). Highly purified preparation of the GLDHase was obtained by three column chromatography steps with a recovery of ca. 1%, after solubilization from mitochondria in sweet potato roots. SDS-PAGE exhibited a single band at 56 kDa. In the native state, the apparent molecular mass of the enzyme was 56 kDa, based on a Sephadex G-100 gel filtration. The pI and optimum pH values were 5.8 and 7.9, respectively. The Km value for L-galactono-gamma-lactone was 0.12 mM. Substrate inhibition was obtained at concentrations greater than 4.2 mM. The enzyme was inhibited by p-chloromercuribenzoate (PCMB) and acriflavine, and the inhibition of acriflavine was diminished by the addition of FAD or FMN. The only effective substrate for the GLDHase was L-galactono-gamma-lactone.
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OBJECTIVES: The efficacy of three different dose treatments of interferon (IFN) was evaluated in patients with chronic hepatitis C (HCV). METHODS: Ninety-one patients with chronic hepatitis C were allocated to receive 3, 6, or 10 U of recombinant IFN-alpha 2b three times weekly for 24 wk. The number of patients was 26, 35, and 30 in the low, middle, and high dose groups, respectively. Treatment was discontinued, however, in four patients (one in the middle dose group and three in the high dose group) because of depression occurring 1-3 months after therapy began. A total of 87 patients, therefore, was analysed and was comprised of 26 patients in the low dose group, 34 in the middle dose group, and 27 in the high dose group. RESULTS: At the end of treatment, serum levels of ALT were normal in 50% (13/26) of patients in the low dose group, 70% (24/34) in the middle dose group, and 74% (20/27) in the high dose group. Patients with persistent normalization of ALT for 12 months of follow-up were defined as sustained responders. Twelve months after treatment cessation, the percentage of sustained responders was 23% (6/23) in the low dose group, 44% (15/34) in the middle dose group, and 41% (11/27) in the high dose group. Including the four patients who required discontinuation of IFN administration, the percentage of sustained responders was 43 and 37% in the middle and high dose groups, respectively. The clearance of HCV RNA was 40% in the middle dose group and 33% in the high dose group. This decrease in the clearance of HCV RNA was prominent in the high dose group. The percentage tended to be higher in the middle dose group, but the differences were not significant. CONCLUSIONS: The results suggest that a regimen of recombinant IFN-alpha 2b in a dose of 6 U three times weekly for 24 wk may be appropriate for the treatment of chronic HCV.
Blood glucose levels were continuously monitored in 70 subjects during a 75 g oral glucose tolerance test (OGTT). Subjects were divided into normal (N = 15), borderline (N = 31), diabetes with fasting glucose levels below 140 mg/dl (DM1) (N = 15) and diabetes with levels above 140 mg/dl (DM2) (N = 9). Three patterns of blood glucose curves were observed in each subject group; domed, biphasic and upward. The frequency of blood glucose patterns in each class of glucose tolerance group was as follows: in the normal group; domed 33.3%, biphasic 66.7%; in the borderline group; domed 67.7%, biphasic 29.0%, upward 3.2%; in the DM1 group; domed 66.7%, biphasic 13.3%, upward 20.0%; in the DM2 group; domed 77.8%, upward 22.2%. The frequency of patients with a biphasic pattern was significantly higher in the normal group than in the other groups. In the borderline group, almost all patients with a biphasic pattern were young or middle aged (< 60 years old). When the patients with fasting glucose levels below 140 mg/dl were analyzed, the mean peak time and peak value of blood glucose levels were significantly higher in patients with domed patterns than those with biphasic patterns. Indices of early insulin response to glucose load were significantly lower in patients with domed patterns than in those with a biphasic pattern. In conclusion, the pattern of the glucose curve in an OGTT is mainly dependent on the patient's early insulin response. Glucose intolerance with aging resembles diabetes from the standpoint of the pattern of glucose tolerance curves.
In order to determine whether amelanotic melanocytes are present in senile white hair, we attempted to detect tyrosinase mRNA and its protein using in situ hybridization and immunohistochemical staining. Specifically stained cells containing tyrosinase mRNA or its protein were detected by each technique in 7/23 (30.4%) or 4/14 (28.6%) senile white hairs, respectively. These cells were located in the outer root sheath between the hair-bulb and the infundibulum. Silver staining was used to determine whether melanin was present within the outer root sheath of the senile white hair. Because none of the 21 white hairs tested showed specific staining within the outer root sheath, the absence of melanin was confirmed. Thus our results suggest the presence of amelanotic melanocytes within the outer root sheath of senile white hair.
A 42-year-old male was admitted with subarachnoidal hemorrhage. Dexamethasone 224 mg was used to reduce brain edema. His operation was successful without blood transfusion. No remarkable signs and symptoms were found except HBsAg positive and mild GPT elevation during his admission. He was discharged on the 33rd day. But 2 weeks later, he felt general fatigue and became worse day by day. He was re-admitted on the 75th day. Several therapies were given but he died of hepatic failure on the 85th day. The autopsy showed liver cirrhosis with massive necrosis. We believed that the steroid-withdrawal-phenomenon caused excessive immunological response and this process caused his hepatic failure leading to death.
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