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Biomedical subjects

H Ikegami

Publications and source records attributed to H Ikegami.

At least 19 recordsLinked to original sources

A new highly sensitive immunoassay for cytokines by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA).

Non-isotopic immunoassays for human tumor necrosis factor alpha (TNF alpha) and human interleukin-6 (IL-6) were established by employing the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) system based on the time-resolved fluoroimmunoassay technique with europium-labeled antibody. Compared to enzyme-linked immunosorbent assays and bioassays, the sensitivity and range of measurement were significantly increased by applying the DELFIA systems to TNF alpha and IL-6. TNF alpha was measurable from 100 fg/ml to 10 ng/ml with the TNF alpha-DELFIA and IL-6 was measurable from 100 fg/ml to 1 ng/ml with the IL-6-DELFIA.

Antibodies, Monoclonal

Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer.

The expression of Ha-ras and fes oncogenes was investigated with the immunohistochemical method in formalin-fixed, paraffin-embedded tissue specimens of 147 lung carcinomas. Positive immunoperoxidase reactions for Ha-ras p21 were found in 80.5% of the adenocarcinomas, 39.5% of the squamous cell carcinomas, 21.4% of the large cell carcinomas, and 15.4% of the small cell carcinomas; those for fes P85 were found in 51.2% of the adenocarcinomas, 26.3% of the squamous cell carcinomas, 35.7% of the large cell carcinomas, and 15.4% of the small cell carcinomas. Both Ha-ras p21 and fes P85 were expressed most frequently and most strongly in adenocarcinoma. In addition, adenocarcinoma showed significantly higher incidence of concomitant expression of Ha-ras p21 and fes P85 as compared with other histologic types of lung cancer. Thus, the authors suggest that the cooperative effects of Ha-ras and fes oncogenes are especially important in the carcinogenesis of adenocarcinoma. In adenocarcinoma, the incidence and grade of Ha-ras p21 expression increased with the degree of histologic differentiation, suggesting that Ha-ras oncogene might be related to cellular differentiation. Papillary adenocarcinoma showed more frequent Ha-ras p21 expression in comparison with acinar adenocarcinoma. In well- or moderately differentiated adenocarcinoma, the incidence and grade of Ha-ras p21 immunoreactivity in the cases with poor prognosis were significantly higher than in those with good prognosis if other major prognostic factors were equivalent in the two groups. The authors propose that the expression of Ha-ras p21 may be one of the useful prognostic factors in such carcinomas.

Adenocarcinoma

Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen-DR9-linked susceptibility to insulin-dependent diabetes mellitus.

DNA sequence analysis of class II HLA from Caucasian and black patients with type 1 (insulin-dependent) diabetes mellitus has suggested that aspartic acid at position 57 (Asp 57) of the DQ beta chain provides protection against insulin-dependent diabetes mellitus (IDDM). In contrast, most Japanese patients with IDDM have Asp 57-positive alleles. To determine the reason for the differences and to localize the HLA-linked diabetogenic gene in Japanese, we studied the DQA1 and DQB1 genes of Japanese patients with IDDM and control subjects by the polymerase chain reaction in combination with restriction fragment length polymorphism analysis. Associations of DQA1*0301 and DQB1*0303 with IDDM were observed. DQA1*01 was associated negatively with IDDM. The HLA-DR9 haplotype, which is associated positively with IDDM in Japanese, was associated with DQA1*0301 and DQB1*0303, indicating that the Japanese DR9 haplotype is the same as that in caucasians but different from that in blacks. Of the loci on Japanese DR9 haplotypes, the DQA1*0301 allele showed the highest association with IDDM. DQB1*0303 was also positively associated with IDDM. Since DQB1*0303 is identical to DQB1*0302 except that it contains Asp 57, the data suggests that an Asp 57-positive allele confers susceptibility to IDDM when the whole molecule of the DQ beta chain is similar to other susceptible DQ beta chains. DQA1*0301 appears to be a marker of IDDM in all these populations: Japanese, caucasian, and black.

Adult

Intraventricular administration of thyrotrophin-releasing hormone (TRH) suppresses prolactin secretion and synthesis: a possible involvement of dopamine release by TRH from rat hypothalamus.

The administration of thyrotrophin-releasing hormone (TRH) causes a variety of dopamine-related biological events. To understand the specific role of TRH on rat hypothalamic dopamine neurones, we examined the in-vivo effects of intraventricular (i.c.v.) infusion of TRH on the release and synthesis of prolactin in the rat pituitary gland and on the changes in binding of [3H]MeTRH and dopamine turnover rates in rat hypothalamus. We have also examined the in-vitro effects of TRH on the release of [3H]dopamine from dispersed tuberoinfundibular dopamine neurones. Female rats were treated with i.c.v. infusions of 1 mumol TRH/1 daily for 1, 3 and 7 days using Alzet osmotic pumps. Following 7 days of treatment the serum prolactin concentrations were significantly decreased. A reduction in hypothalamic TRH-binding sites (Bmax) was also apparent but the dissociation constant (Kd) was unaffected. Northern blot analysis of total RNA isolated from the pituitary glands of control animals using 32P-labelled prolactin cDNA as a probe indicated the presence of three species of prolactin gene transcripts of approximately 3.7, 2.0 and 1.0 kb in size, and these were decreased by TRH treatment. We examined the turnover rate of dopamine in the rat hypothalamus when TRH was administered i.c.v. for 7 days. There was a significant increase in 3,4-dihydroxyphenylacetic acid/dopamine ratio with TRH treatment. Moreover, exposure to TRH stimulated [3H]dopamine release from rat tuberoinfundibular neurones in a time- and dose-dependent manner. Dopamine receptor antagonists such as SCH23390 and (-)sulpiride, and other neuropeptides such as vasoactive intestinal peptide and oxytocin did not affect TRH-stimulated [3H]dopamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid

An improved method for measurement of sweat expulsions during profuse sweating.

We present an improved ventilated-capsule method of recording for clear sweat expulsion patterns using nitrogen gas as a carrier gas heated to promote sweat evaporation. With this method, sweat expulsion patterns were more clearly recorded than with the conventional ventilated-capsule method. Taking the derivatives of these recordings of sweating expulsions could eliminate slow fluctuation components in the patterns of sweating. The results indicate that this method is useful in providing more-accurate measurements of sweat expulsion frequencies during profuse sweating.

Adult

Analysis of early-phase insulin responses in nonobese subjects with mild glucose intolerance.

OBJECTIVE: To study the possible contribution of a B-cell defect in the development of glucose intolerance in nonobese subjects. RESEARCH DESIGN AND METHODS: There were 41 normal, nondiabetic subjects; 18 subjects with IGT; and 21 patients with NIDDM. All subjects were nonobese (BMI < 27 kg/m2). Insulin secretory responses to an OGTT, IVGTT, and GST were studied. RESULTS: Early-phase insulin responses to OGTT and IVGTT were decreased in subjects with IGT to levels comparable with those in NIDDM patients, whereas the response to GST was preserved in the subjects with IGT compared with NIDDM patients. The insulinogenic index of OGTT correlated well (r = 0.78) with early-phase insulin response to IVGTT, suggesting that the insulinogenic index in OGTT is related to the early-phase insulin response to IVGTT in nonobese subjects. CONCLUSIONS: Impaired early-phase insulin response to glucose was associated with mild glucose intolerance, suggesting the importance of impaired insulin secretion in the development of glucose intolerance in nonobese subjects.

Blood Glucose

[A case of late-onset Pick's disease with polyuria].

A 72-year-old male was admitted to our hospital with a 2-year history of polyuria, prosopagnosia and aphasia. He showed characteristic clinical features of Pick's disease such as stereotyped verbal output and behavior and personality changes. CT and MRI scans showed marked atrophy in the bilateral anterior temporal lobes mild atrophy of the bilateral frontal lobes. SPECT scans revealed perfusion abnormalities in corresponding areas. A 6-hour-water deprivation test resulted in decrease in the urine volume and in concentration of the urine, suggesting abnormality of his secondary drinking behavior. Polyposia resulting in polyuria as a clinical manifestation may be due to stereotypic behavior which is often seen in Pick's disease.

Aged

[A case of hyperinsulinemia due to hypersecretion of incretin].

A 65-year-old male presented with postprandial hypoglycemic episodes. He had normal glucose tolerance, but plasma glucose reached a hypoglycemic level of 31 mg/dl at 120 min during 75 g oral glucose tolerance test. He had markedly increased insulin response to oral glucose but not to intravenous glucose, intravenous arginine or intravenous glucagon. Hyperresponse of insulin after oral but not intravenous glucose suggested the possible involvement of insulinotropic hormonal factor in the gut (incretin) in hyperinsulinemia of this patient. Therefore we evaluated the secretory response of glucagon like peptide-1 (GLP-1), a most likely candidate for incretin, to oral and intravenous glucose administration. Plasma GLP-1 response to oral glucose was almost five times greater than that of normal subjects. On the other hand, there was no significant response in plasma GLP-1 after intravenous glucose. These results suggest that hypersecretion of GLP-1 may be responsible for the hyperinsulinemia after oral glucose in this patient.

Aged

[Dysuria in male elderly outpatients evaluated by a questionnaire survey].

We surveyed complaints of dysuria in male elderly outpatients by questionnaire survey. Seven hundred and twenty outpatients (39 aged 30-39, 63 aged 40-49, 170 aged 50-59, 229 aged 60-69, and 219 aged 70 or more) visiting our outpatient internal medicine clinics were asked by a questionnaire about the subjective symptoms of dysuria, including frequencies of nocturia, prolongation of the start of urination, straining at urination, and residual urine, graded as asymptomatic, mild, moderate and severe. The subjects were divided into three groups as to the dysuria; normal group without symptoms or one mild symptom, borderline group with two or more mild symptoms, and dysuria group with one moderate or severe symptom or more. The rates of the patients in the dysuria group were increased with age, being 15%, 16%, 21%, 31% and 53%, respectively, in the above-mentioned age groups. This finding emphasized the importance of questions about dysuria in elderly patients also in internal medicine outpatient clinics, and of differential diagnosis for the causal factor(s) for dysuria in elderly patients including benign prostate hypertrophy.

Adult

[Drug compliance in the elderly].

In order to clarify the characteristics of elderly patients concerning their attitudes toward taking prescribed medicine, self-reported compliance with prescriptions was compared among different age groups. We performed a survey in 626 outpatients and their attending physicians in 4 of our affiliated hospitals, and analyzed self-reported compliance by the patients to the prescription and their answers to questions related to drug-taking along with the diagnoses and prescriptions reported by the physician. The number of prescribed medicine was 2.3 tablets on the average for patients younger than 40, while 5.1 tablets were prescribed for patients over 70. However, self-reported compliance was best in patients over 70 than in other age groups. Compliance was good in 76% of patients who answered that the amount of medicine was appropriate, while good compliance was lower in those who thought the prescription excessive (67%). Likewise, compliance of patients who had concerns with drug side effects or who were not feeling well under medication was lower than that of patients who felt well under medication. Prescriptions for after lunch were most liable to be forgotten than those for other times of the day. Moreover, a high percentage of elderly patients attended more than 2 departments or medical facilities, and one third of those patients did not inform the physician of the fact suggesting that they were at higher risks of overdosing and unexpected drug interaction. Furthermore, the percentage of patients who did not receive explanation from physicians was higher in the elderly thus demonstrating that elderly patients have quite different characteristics in attitude with regard to medicine from younger age group patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Clinical characteristic of elderly patients with insulin-dependent diabetes mellitus].

The number of elderly patients with insulin-dependent diabetes mellitus (IDDM) is increasing because of the prolongation of life due to the improvement of diabetic control. For better management of elderly patients with IDDM, we investigated the clinical and genetic characteristic of older patients with IDDM in comparison with younger patients. The subjects studied consisted of 19 patients with IDDM treated at the Department of Geriatric Medicine, Osaka University Hospital. Among the 19 subjects, 7 patients (37%) were more than 50 years old, including 3 patients (16%) more than 65 years old. The clinical and genetic characteristics of these 7 patients (older patients group) were compared with those of 12 patients (younger patient group) whose age was less than 50 years old. The age at onset of IDDM was significantly higher in older patient group (46 +/- 13 years old; mean +/- SD) than in younger patient group (34 +/- 6 years old). There was no significant difference in the duration of IDDM between older and younger patients (13 +/- 6 and 12 +/- 8 years, respectively). There were no significant differences in daily insulin dose, glycemic control (fasting plasma glucose and HbA1c levels) and glycemic stability as measured by the standard deviation of 10 measured fasting plasma glucose levels between the two groups. The frequency of diabetic retinopathy and neuropathy in the older patients was slightly, but not significantly, higher than that in younger patients. The frequency of diabetic nephropathy was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.

Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.

Adult

Effects of nocturnal hyperprolactinemia on ovarian luteal function and galactorrhea.

To determine the effects of nocturnal hyperprolactinemia on luteal function and galactorrhea we studied six diurnal normoprolactinemic women with regular menstrual cycles. The diurnal serum levels of prolactin (PRL), luteinizing hormone (LH) and progesterone (Prog) and the nocturnal PRL levels at 1 h intervals were determined throughout the first menstrual cycle. Four of the women were nocturnally normoprolactinemic and two showed nocturnal hyperprolactinemia and low luteal progesterone values. In the second menstrual cycle, they were given metoclopramide (10 mg) at midnight before sleep every day, and their serum levels of PRL, LH and Prog were determined by the same protocol as in the first cycle. During treatment with metoclopramide, all the women showed nocturnal hyperprolactinemia, but their diurnal PRL levels remained within the normal range. Low luteal Prog values were observed in all of them and the peak LH levels decreased in all four nocturnally normoprolactinemic women. They had galactorrhea but neither of the nocturnally hyperprolactinemic women had galactorrhea. These results suggest that nocturnal hyperprolactinemia is a cause of luteal insufficiency and galactorrhea.

Adult

Placebo-controlled double-blind comparative study on the preventive efficacy of mesna against ifosfamide-induced urinary disorders.

In order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P = 0.0003 for micturition pain; P = 0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P = 0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of "useful" was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P = near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study.

Adult

Urinary C-peptide as an index of unstable glycemic control in insulin-dependent diabetes mellitus (IDDM)

In order to investigate whether urinary C-peptide (UCP) excretion can be a useful index of insulin-dependent diabetes mellitus (IDDM) with unstable glycemic control, UCP was measured in nine IDDM patients with unstable glycemic control, nine IDDM patients with stable glycemic control, and 12 non-insulin-dependent diabetic (NIDDM) patients treated with insulin. The UCPs in overnight urine (U1) and fasting single void urine (U2) in IDDM patients with unstable glycemic control were significantly lower than those in IDDM patients with stable glycemic control (U1: 0.03 +/- 0.03 vs 0.24 +/- 0.20 nmol/mmol-Creatinine, U2: 0.02 +/- 0.01 vs 0.20 +/- 0.20 nmol/mmol-Cr, mean +/- SD, both P less than 0.01). The UCPs in U1 and U2 in both groups of IDDM were significantly lower than those in NIDDM (U1: 0.97 +/- 0.52, U2: 0.73 +/- 0.41 nmol/mmol-Cr, both P less than 0.01). The UCPs in U1 and U2 significantly correlated with incremental C-peptide response to intravenous glucagon injection and with glycemic stability assessed by the standard deviation of 10 previous fasting plasma glucose levels. These results suggest that UCP reflects their residual insulin secretory capacity and that UCP can be a useful index which distinguishes patients with unstable IDDM from those with stable diabetes mellitus.

Adult

Renal handling of glycated albumin in non-insulin-dependent diabetes mellitus with nephropathy.

Renal handling of glycated albumin in diabetic nephropathy was examined by studies on renal selectivity for glycated albumin in 23 normal controls and 52 patients with non-insulin-dependent diabetes mellitus (NIDDM) with various degrees of nephropathy. The serum and urinary levels of glycated albumin were measured by enzyme-immunoassay with monoclonal antibody to glucitol-lysine residues in human glycated albumin. The diabetic patients were divided into 3 groups according to the albumin index (AI): patients with normoalbuminuria [AI less than or equal to 30 mg/g creatinine(Cr)], with microalbuminuria (30 less than AI less than or equal to 270 mg/g Cr), and with macroalbuminuria (AI greater than 270 mg/g Cr). The renal selectivity for glycated albumin was calculated from the ratio of the urinary to serum level of glycated albumin. In the controls, the renal selectivity was as high as 4.40 +/- 0.48, and significantly higher than those in patients with normo- (2.87 +/- 0.29), micro- (1.72 +/- 0.20) and macroalbuminuria (1.26 +/- 0.23). The renal selectivity was inversely correlated with the AI in diabetic patients (r = -0.58, P less than 0.01). These data indicate that glycated albumin was selectively excreted in the urine and that the renal selectivity in diabetic patients gradually decreased to a value of 1 with increase in albuminuria. When the patients with normoalbuminuria were divided into two subgroups with high and low albumin excretion, the renal selectivities for glycated albumin in both subgroups were still significantly lower than that in controls. These results suggested that early diabetic nephropathy which cannot be detected clinically by albuminuria can be diagnosed by measurement of renal selectivity for glycated albumin.

Aged

Epidermal growth factor attenuates cell proliferation by down-regulating the transforming growth factor-beta receptor in the osteoblastic cell line MC3T3-E1.

We investigated the role of transforming growth factor beta 1 (TGF-beta 1) in growth regulation of the murine osteoblastic cell line, MC3T3-E1. We detected TGF-beta activity in the conditioned medium of MC3T3-E1 cells and its activity was increased by acid treatment of the bioassay system using CC1 64 cells. Northern blot analysis revealed the expression of TGF-beta 1 precursor messenger ribonucleic acid (mRNA). MC3T3-E1 cells possessed a single class of high affinity TGF-beta 1 receptor (2.8 x 10(4) sites per cell, Kd = 196 pM). Cross-linking studies revealed three specific TGF-beta receptors with molecular masses of 65, 95 and 280 kDa. Both TGF-beta and epidermal growth factor (EGF) stimulated [3H]-thymidine incorporation into cells. EGF decreased the number of TGF-beta receptor dose-dependently, and pretreatment of cells with 10 nM EGF attenuated cell growth by TGF-beta. All these data suggested that TGF-beta might be an autocrine growth factor in murine osteoblastic MC3T3-E1 cells and that EGF might modulate the growth of cells by down-regulating the TGF-beta receptor level.

Animals