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Biomedical subjects

H Ikegami

Publications and source records attributed to H Ikegami.

At least 181 records · Page 10Linked to original sources
PubMed1994

Chemical modification of natural human tumor necrosis factor-alpha with polyethylene glycol increases its anti-tumor potency.

Natural human tumor necrosis factor-alpha (TNF-alpha) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG-modified TNF-alpha depended on the reaction time as well as the initial molar ratio of PEG to TNF-alpha. The specific activity of modified TNF-alpha was gradually reduced with increase in the degree of PEG-modification, but the plasma half-life of TNF-alpha was increased by up to 40-fold. Modified TNF-alpha showed approximately 100 times greater anti-tumor potency than unmodified TNF-alpha. Covalent attachment of PEG to TNF-alpha thus increased the bioavailability of TNF-alpha, and may facilitate its potential therapeutic use.

Animals↗
PubMed1994

Responses of sweating and body temperature to sinusoidal exercise.

This study determined the phase response and amplitude response (delta) of esophageal temperature (T(es)), mean skin temperature (Tsk), and forearm sweating rate (Msw) to sinusoidal work. Six healthy male subjects exercised on a cycle ergometer with a constant load (approximately 35% maximal O2 uptake) for a 30-min period; for the next 40 min they exercised with a sinusoidal load at 25 degrees C at 35% relative humidity. The sinusoidal load varied between approximately 10 and 60% maximal O2 uptake, and three different time periods (1.3, 4, and 8 min) were selected. Each subject performed three experiments that differed only in the timing of sinusoidal work. During the 4- and 8-min periods, T(es), Tsk, and Msw changed almost sinusoidally. The phase of Msw change significantly preceded those of T(es) and Tsk changes (P < 0.05). During the 1.3-min period, the level of T(es) and Tsk remained almost constant (delta T(es) 0.01 +/- 0.00 degrees C, delta Tsk 0.03 +/- 0.01 degrees C), whereas Msw showed a clear sinusoidal pattern. We conclude that the sweating response during sinusoidal work depends on both thermal and nonthermal factors, the latter being emotional, mental, or sensory stimulation. The contribution of the nonthermal factors to the general sweating response during exercise can be separated from that of the thermal factors by using sinusoidal work during a short period (e.g., 1.3 min).

Adult↗
PubMed1994

Monosynaptic and disynaptic connections in the utriculo-ocular reflex arc of the cat.

1. Connections from the utricular (UT) nerve to motoneurons and interneurons in the ipsilateral abducens (AB) nucleus were studied in anesthetized and decerebrated cats. Bipolar electrodes were fixed on the left UT nerve under visual observation. The other branches of the vestibular nerve and the facial nerve were transected in the left inner ear. 2. Stimulation of the UT nerve evoked a small positive-negative (P/N) deflection and a negative (N1) potential in the vestibular nuclei, with mean latencies of 0.56 and 0.84 ms, respectively. In the AB nucleus a small P/N deflection with a mean latency of 0.72 ms was recorded, which was considered as a incoming volley of the UT nerve. 3. Excitatory postsynaptic potentials (EPSPs) were recorded from AB motoneurons with short latencies after UT nerve stimulation. They were classified into two types, M and D. M-type EPSPs, which followed repetitive high-frequency stimuli and were recorded from the majority of AB motoneurons, had latencies ranging from 0.9 to 1.2 ms. Double shocks to the UT nerve evoked EPSPs that had the same latency. It was suggested that the AB motoneurons had monosynaptic connections with the UT nerve. D-type EPSPs, which were recorded from most of the AB motoneurons, had slightly longer latencies ranging from 1.2 to 1.8 ms. They showed temporal facilitation when double shocks were provided to the UT nerve. They did not follow repetitive high-frequency stimuli (< or = 2.5-ms interval). It was suggested that D-type EPSPs were di-synaptically evoked via secondary vestibular neurons. Interneurons in the AB nucleus had the same characteristics as AB motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Abducens Nerve↗
PubMed1994

Identification of estrogen receptor in human adipose tissue and adipocytes.

Estrogen has various effects on adipose tissue. Although the presence of estrogen receptor (ER) has been demonstrated in rat adipose tissue and adipocytes, ER has not been identified in human adipose tissue. In this study, we demonstrated the existence of ER protein and ER messenger RNA (mRNA) in human sc adipose tissue and adipocytes. The cytosol fraction of human adipose tissue was partially purified by ammonium sulfate precipitation, and the presence of ER protein was analyzed by [3H]estradiol (E2) binding assay and Western blot analysis. [3H]E2 binding assay showed a low specific binding due to high nonspecific binding, and the dissociation constant (Kd) and maximal binding sites could not be obtained by Scatchard analysis. Western blots, however, showed the presence of ER protein in both the partially purified cytosol and nuclear fractions of human adipose tissue. The mol wt of ER in both fractions was approximately 66,000. Furthermore, Northern blot analysis of total RNA samples isolated from human adipose tissue showed the expression of ER mRNA at 6.2 kilobase in size. ER mRNA was also identified in isolated human adipocytes by the reverse transcription and polymerase chain reaction. These results indicated that both ER protein and ER mRNA are expressed in human adipocytes, suggesting that the effect of estrogen on human adipose tissues might involve a direct action.

Adipocytes↗
PubMed1994

[Effects of pravastatin administration for 12 months on serum lipid levels in aged patients with hypercholesterolemia].

To evaluate long-term efficacy of pravastatin, we administered this HMG-CoA reductase inhibitor at a mean dose of 9.9 mg/day to 208 aged patients with serum levels of total cholesterol (TC) over 220 mg/dl (mean +/- SD aged of 70 +/- 7 years; 62 males and 146 females) for 12 months. The mean serum value of TC significantly decreased from the basal level of 265 mg/dl to 216 mg/dl in the 3rd month, and this decrease was maintained throughout the observation period. Similar change was observed in the serum level of low density lipoprotein-cholesterol (LDL-C). Although the mean serum level of high density lipoprotein-cholesterol (HLC-C) in all patients did not change significantly, the HDL-C level in 34 patients with a HDL-C level below 40 mg/dl significantly increased from the 3rd month. The mean serum level of triglyceride (TG) in all patients significantly decreased from the 3rd month, and this decrease in the TG was more prominent in 101 aged patients with TG levels higher than 150 mg/dl. In 168 aged patients on 10 mg/day of pravastatin throughout the period, there were significant negative correlations between the ratio of the decrease in TC in basal serum and each of the basal serum TC levels (r = -0.345, p < 0.001) and age of the subjects (r = -0.208, p = 0.007). These results indicate that long-term administration of pravastatin is effective treatment for lipid metabolism even in aged patients.

Aged↗
PubMed1994

Long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensives: a multicenter prospective study.

The effects of long-term monotherapy with terazosin, an alpha-1 blocker, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 53 hypertensive patients: 19 with normal glucose tolerance (NGT) and 34 with impaired glucose tolerance (IGT). The plasma glucose, serum lipids, fructosamine, and glycosylated hemoglobin A1c (HbA1c) levels were determined before and during long-term (6 months) therapy with terazosin. A 75-g oral glucose tolerance test was performed before and during long-term terazosin therapy. Significant falls in both systolic and diastolic blood pressure in both patient groups were maintained during the long-term therapy with terazosin. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and diabetes mellitus did not develop in any patient with NGT during the study. There was no significant change in the insulinogenic index (delta IRI/delta BS at 30 minutes after glucose load) in either patient group. In patients with IGT, glucose intolerance was slightly improved with significant reductions in HbA1c and fructosamine during terazosin therapy. Serum total cholesterol (TC) and triglyceride levels were significantly decreased in patients with IGT. In addition, TC and low density lipoprotein (LDL) cholesterol were significantly decreased in patients with hypercholesterolemia (TC > 220 mg/dL). These results suggest that long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensive patients and terazosin seems to be an antihypertensive agent with beneficial effects for hypertensive patients with either dyslipidemia or impaired glucose metabolism.

Adrenergic alpha-Antagonists↗
PubMed1994

Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer. Japanese Lung Cancer Chemotherapy Group in Japanese Clinical Oncology Group.

A recent approach in the treatment of limited-stage small cell lung cancer (LDSCLC) has involved a combined modality of chemotherapy and chest irradiation. In using the modality, the study of scheduling methods for combining chemotherapy and radiotherapy should lead to other trials of combined modalities against LDSCLC since it is the most basic issue to be evaluated. We have thus conducted a multicenter phase II trial of concurrent cisplatin-etoposide (PVP) chemotherapy and radiotherapy for LDSCLC to determine the effects of the concurrent administration of a PVP regimen and chest irradiation on response rate, relapse, survival and treatment toxicity. The chemotherapy regimen consisted of a four-week cycle: cisplatin (80 mg/m2, given intravenously on day 1) and etoposide (100 mg/m2, given intravenously on days 1-3). This cycle was given four to six times within six months. Chest irradiation to the primary tumors at both the hili and the mediastinum was administered in standard fractions on days 2-12 in the first cycle of chemotherapy and on days 29-47 in the second cycle, with a total dose of 40-50 Gy. Prophylactic cranial irradiation was performed among complete remission (CR) or good partial remission (PR) patients after completion of the concurrent therapy. A total of 66 patients were entered into the trial and 59 were evaluated. The concurrent therapy induced an overall response rate of 94.9% in 59 patients: 24 patients, 40.7% CR, 32 patients, 54.2% PR. The median response duration was 8.7 months, and the median survival time for all eligible patients was 14.8 months. The percentage of patients with two-year survival periods was 20. A local relapse within the irradiated area was seen in only 22% of relapse patients. Brain metastases occurred in 24% of patients. Four of 32 patients treated with prophylactic cranial irradiation had brain metastases. Toxic effects, chiefly grades 3 and 4 leukopenia, as established by the World Health Organization, were detected in all treated patients. Other toxicities, including radiation-induced esophagitis and pneumonitis, were deemed almost acceptable. We concluded concurrent treatment of a PVP regimen with chest irradiation to be a feasible and beneficial therapy with an efficacy compatible to that of other published reports. The outcome of this protocol warrants further investigation to determine the optimal type of schedule for concurrent chemoradiotherapy against LDSCLC.

Adult↗
PubMed1994

[Decreased theophylline clearance in children with acute asthma with concurrent febrile respiratory infection].

Elevated serum levels of theophylline, a first-line anti-asthma drug, are sometimes associated with febrile respiratory infection (FRI). Although it seems to be wellknown, conflicting reports still appear in journals. We studied retrospectively theophylline clearance (th-cl) in 74 episodes of acute asthma (44 with and 30 without FRI, in patients aged 12-mos.-13-yrs.) and tried to reveal the effect of fever or pathogens on th-cl. Th-cl was estimated by a single sample technique during intravenous drip infusion of aminophylline. The results were as follows: 1) Forty four episodes with FRI included 20 viral, 10 bacterial and 2 Mycoplasma pneumoniae infections (Table 2). 2) Th-cl in 44 episodes with FRI was significantly lower than in 30 without FRI (p < 0.001). 3) Decreased tendency of th-cl in episodes with viral infection was observed, but statistically it was not significant (p < 0.1). However, the differences of th-cl among 9 pair-cases with and without viral infection were quite clear (p < 0.01). 4) Th-cl in episodes with 10 bacterial and 2 Mycoplasma infections was reduced significantly (p < 0.01). 5) There was no difference in th-cl between episodes with viral, and bacterial or Mycoplasma infections (p < 0.1). As a result, it is suggested that fever, regardless of its origin, may decrease th-cl in acute asthma with FRI.

Acute Disease↗
PubMed1994

[Enzyme-linked immunosorbent assay for the quantification of Cry j I and Cry j II].

Enzyme-linked immunosorbent assays (ELISA) were developed to specifically quantify the two major allergens from Japanese cedar pollen, Cry j I and Cry j II. Polystyrene microplates coated with antibodies specific for Cry j I or Cry j II were incubated with an allergen and then with biotinylated anti-Cry j I or Cry j II antibody. The bound allergen-biotin Ab complexes were detected with HRPO-conjugated streptavidin and an enzyme substrate. The working ranges of Cry j I ELISA and Cry j II ELISA were 0.3-20 ng/ml and 0.6-20 ng/ml, respectively. Intra- and inter-assay coefficients of variation for reproducibility were 1.5-10.3% and 0.9-12.9%. These ELISA systems showed no cross-reactivity between Cry j I and Cry j II and showed little cross-reactivity with pollen allergens of plants botanically related to the Japanese cedar. Using the Cry j I ELISA and the Cry j II ELISA, it was possible to quantify Cry j I and Cry j II easily and accurately. These ELISA systems will be useful in various fields, especially for the analysis and standardization of the allergens necessary for diagnosis and treatment of Japanese cedar pollinosis.

Allergens↗
PubMed1993

Cellular mechanism of glyburide-induced insulin gene expression in isolated rat islets.

The cellular mechanism for the effects of glyburide on the synthesis and release of insulin and insulin gene expression in isolated islets was investigated. On incubation for 1 h, glyburide increased insulin release without affecting either the insulin content or the PPI mRNA level. H-7, an inhibitor of PKC, inhibited the glyburide-induced insulin release, while H-8, an inhibitor of cyclic nucleotide-dependent protein kinases, did not affect the glyburide-induced insulin release. On incubation for 20 h, glyburide increased insulin release and the PPI mRNA level, without affecting the insulin content. H-7 inhibited glyburide-induced insulin release and increased the PPI mRNA level. H-8 significantly inhibited both the glyburide-induced increase in insulin release and increase in PPI mRNA level. In conclusion, glyburide stimulated insulin release via a PKC-mediated pathway and increased the PPI mRNA level via cyclic nucleotide-dependent protein kinase(s).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Autocrine growth mechanism by transforming growth factor (TGF)-beta 1 and TGF-beta 1-receptor regulation by epidermal growth factor in a human endometrial cancer cell line IK-90.

Transforming growth factor-beta 1 (TGF-beta 1) enhanced cell proliferation in a concentration-dependent manner in a human endometrial cancer cell line, IK-90. Scatchard analysis of TGF-beta 1 receptor in IK-90 cells, using 125I-TGF-beta 1 as a ligand, revealed the presence of a class of high-affinity TGF-beta 1 receptors (2,000 sites per cell, KD = 74pM). Moreover, IK-90 cells produced and secreted TGF-beta 1: TGF-beta 1 messenger RNA was detected at 2.5 and 4.0 kb by Northern-blot analysis using 32P-labeled TGF-beta 1 cDNA as a probe, and TGF-beta 1 activity in conditioned medium by the inhibition of 3H-thymidine uptake into CCl 64 mink lung epithelial cells. We investigated the regulation of TGF-beta 1 receptor by 4 kinds of growth factor: epidermal growth factor (EGF) but not TGF-beta 1, insulin or insulin-like growth factor-1 increased the level of TGF-beta 1 binding sites in a concentration- and time-dependent manner. These findings suggest that TGF-beta 1 may be a potential autocrine growth factor in a human endometrial cancer cell line IK-90 and that this autocrine mechanism may be affected by EGF.

Adult↗
PubMed1993

MHC-linked diabetogenic gene of the NOD mouse: molecular mapping of the 3' boundary of the diabetogenic region.

To localize and characterize the MHC-linked diabetogenic gene of the NOD mouse, we studied the class III region of the MHC in the NOD mouse and related strains. Hsp70, Bat5, Tnfa and Tnfb loci were studied by microsatellite polymorphism analysis and/or restriction mapping. The CTS mouse had the same allele as the NOD mouse at the Hsp70 locus, but different alleles at the Bat5, Tnfa and Tnfb loci from those of the NOD mouse. Our previous studies indicated that in the CTS mouse, class II MHC was the same as that of the NOD mouse, but that class I MHC was different at both K and D loci, and that CTS MHC was diabetogenic in the presence of NOD background genes. These data map major genetic susceptibility to type 1 diabetes to the segment flanked by class I K and class III Bat5 loci. Moreover, since the diabetogenic effect of the CTS MHC is weaker than that of the NOD MHC, these data suggest the presence of a second MHC-linked gene or gene complexes that modulate susceptibility to type 1 diabetes outside this segment.

Animals↗
PubMed1993

A comparison of sweating responses during exercise and recovery in terms of sweating rate and body temperature.

Based on the hypothesis that the relation between sweating rate and body temperature should be different during exercise and rest after exercise, we compared the sweating response during exercise and recovery at a similar body temperature. Healthy male subjects performed submaximal exercise (Experiment 1) and maximal exercise (Experiment 2) in a room at 27 degrees C and 35% relative humidity. During exercise and recovery of 20 min after exercise, esophageal temperature (Tes), mean skin temperature, mean body temperature (Tb), chest sweating rate (msw), and the frequency of sweat expulsion (Fsw) were measured. In both experiments, msw and Fsw were clearly higher during exercise than recovery at a similar body temperature (Tes, Tb). msw was similar during exercise and recovery, or a little less during the former, at a similar Fsw. It is concluded that the sweating rate during exercise is greater than that during recovery at the same body temperature, due to greater central sudomotor activity during exercise. The difference between the two values is thought to be related to non-thermal factors and the rate of change in mean skin temperature.

Adult↗
PubMed1993

Ovariectomy increases the level of estrogen receptor mRNA and estrogen receptor binding sites in female rat adipose tissue.

The roles of estrogen in the changes in estrogen receptor (ER) mRNA and ER binding sites in rat adipose tissue were studied in female rats. To elucidate the mechanism(s) behind ovariectomy (OVX)-induced obesity, the levels of ER mRNA and ER binding sites in adipose tissue were analyzed three weeks after OVX using Northern blot analysis of ER mRNA and the [3H]E2 binding assay, respectively. OVX induced an increase in body weight, and replacement of estradiol (E2) prevented that increase. Significant increases in the amounts of ER mRNA and in [3H]E2-specific binding were observed after OVX, and E2 replacement reduced both of those increases. These results suggest that E2 may regulate rat obesity directly through ER in adipose tissues.

Adipose Tissue↗
PubMed1993

A microsatellite polymorphism in the human insulin receptor gene: a highly informative marker for linkage analysis.

To study genetic susceptibility to non-insulin dependent diabetes mellitus (NIDDM), association of insulin receptor gene, a candidate gene for NIDDM, with NIDDM was studied. A microsatellite polymorphism located in intron 2 of the human insulin receptor gene was detected by the polymerase chain reaction and used as a genetic marker. Eight different alleles were observed, indicating highly polymorphic nature of this marker. Although no association of this marker with NIDDM was observed in Japanese subjects, this marker will be useful for linkage studies of insulin receptor gene and genes located close to this gene on chromosome 19.

Alleles↗
PubMed1993

Suppression of murine IgE responses with ovalbumin-pullulan conjugates: comparison of the suppressive effect of different conjugation methods and different molecular weights of pullulan.

Ovalbumin (OVA)-pullulan conjugates were made using four different conjugation methods and eight different molecular weights of pullulan ranging from 4,200 to 600,000. Pretreatment of mice by the administration of conjugates made by using cyanulic chloride or cyanogen bromide and pullulan of molecular weight 40,000 or more, anti-OVA IgE antibody response was suppressed completely and anti-OVA IgM and IgG antibody response was enhanced. In contrast, by the administration of conjugates made by using an oxidation or thiol activation method, only partial suppression of anti-OVA IgE antibody response was achieved and no enhancement of anti-OVA IgM and IgG antibody production was observed.

Animals↗
PubMed1993

Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.

Angiotensin II↗