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Biomedical subjects

H Ikegami

Publications and source records attributed to H Ikegami.

At least 109 records · Page 6Linked to original sources
PubMed1997

Prognostic factors and prognostic staging system for small cell lung cancer.

This study was performed to assess the prognostic factors and the predictors of long-term (3-year) survival in patients with small cell carcinoma of the lung, accrued in one randomized trial, and to define patient subgroups showing significantly different survivals using recursive partitioning and amalgamation analysis. A total of 300 patients with small cell carcinoma of the lung were entered into a randomized study comparing cyclophosphamide, adriamycin and vincristine (CAV), cisplatin and etoposide (PE) and alternating treatments of CAV and PE. Of these, 286 patients were analysed for the present study of prognostic factors. Multivariate analysis showed that poor performance status (2-3) (P = 0.0001), extensive disease (P = 0.0015) and abnormally elevated serum lactate dehydrogenase (P = 0.0001) and alkaline phosphatase (P = 0.0013) were independently adverse pretreatment prognostic factors. Of limited disease patients, performance status (P = 0.029) and white blood cell count (P = 0.044) had a significant influence on the probability of 3-year disease-free survival. Using recursive partitioning and amalgamation analysis, three classes of similar prognosis were identified: the most favorable class was defined by knowledge of lactate dehydrogenase (normal), performance status (0-1) and serum sodium levels (normal) with median survival time of 16.0 months, and the class with the poorest prognosis was defined by knowledge of lactate dehydrogenase (elevated) and performance status (2-3) (median survival time 6.6 months). The intermediate class had a median survival time of 9.4 months. In conclusion, this subclassification system will be used for the design, implementation and interpretation of clinical studies as well as decision-making in individual patients.

Adult↗
PubMed1997

Insulin-dependent diabetes mellitus associated with autoimmune thyroiditis and rheumatoid arthritis.

A case associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), and autoimmune thyroid disease (AITD) was reported. A high titer of anti-glutamic acid decarboxylase antibody (GAD) and a positive islet cell antigen were observed. The patient's human leukocyte antibody (HLA) haplotype was a homozygote of DQA1*0301, DQB1*0401, and DRB1*0405. Because this haplotype was in linkage disequilibrium with DPB1*0501, an allele associated with AITD in Japanese patients, the patient was homozygous for alleles susceptible to IDDM, RA, and AITD. A specific HLA haplotype susceptible to several autoimmune disease may result in the development of IDDM, RA, and AITD.

Alleles↗
PubMed1997

Exercise-induced changes in beta-adrenergic-receptor mRNA level measured by competitive RT-PCR.

Competitive reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to clarify whether dynamic exercise-induced increases in beta-adrenergic-receptor (beta-AR) number in human lymphocytes are accompanied by increases in the beta-AR mRNA level. Sixteen healthy subjects performed cycle ergometry until exhaustion. Before and immediately after exercise, peripheral blood was drawn from a forearm vein for preparation of lymphocytes. Both the beta-AR mRNA level and the beta-AR number were significantly increased by exercise. The changes in beta-AR mRNA level and beta-AR number were significantly correlated (r = 0.63, P < 0.01). This finding suggests that a rapid increase in beta-AR mRNA level might be an early adaptive response of the sympathetic nervous system to dynamic exercise. In vitro incubation of lymphocytes with epinephrine had no effect on beta-AR mRNA levels, nor did adenosine 3',5'-cyclic monophosphate, protein kinase C, or intracellular Ca2+ increase the beta-AR mRNA level in vitro. Therefore, it appears that other mechanisms underlie the exercise-induced elevation of beta-AR mRNA levels in human lymphocytes.

Adult↗
PubMed1997

Sacculocollic reflex arcs in cats.

Neuronal connections and pathways underlying sacculocollic reflexes were studied by intracellular recordings from neck extensor and flexor motoneurons in decerebrate cat. Bipolar electrodes were placed within the left saccular nerve, whereas other branches of the vestibular nerve were removed in the inner ear. To prevent spread of stimulus current to other branches of the vestibular nerve, the saccular nerve and the electrodes were covered with warm semisolid paraffin-Vaseline mixture. Saccular nerve stimulation evoked disynaptic (1.8-3.0 ms) excitatory postsynaptic potentials (EPSPs) in ipsilateral neck extensor motoneurons and di- or trisynaptic (1.8-4.0 ms) EPSPs in contralateral neck extensor motoneurons, and di- and trisynaptic (1.7-3.6 ms) inhibitory postsynaptic potentials (IPSPs) in ipsilateral neck flexor motoneurons and trisynaptic (2.7-4.0 ms) IPSPs in contralateral neck flexor motoneurons. Ipsilateral inputs were about twice as strong as contralateral ones to both extensor and flexor motoneurons. To determine the pathways mediating this connectivity, the lateral part of the spinal cord containing the ipsilateral lateral vestibulospinal tract (i-LVST) or the central part of the spinal cord containing the medial vestibulospinal tracts (MVSTs) and possibly reticulospinal fibers (RSTs) were transected at the caudal end of the C1 segment. Subsequent renewed intracellular recordings following sacculus nerve stimulation indicated that the pathway from the saccular nerve to the ipsilateral neck extensor motoneurons projects though the i-LVST, whereas the pathways to the contralateral neck extensors and to the bilateral neck flexor motoneurons descend in the MVSTs/RSTs. Our data show that sacculo-neck reflex connections display a qualitatively bilaterally symmetrical innervation pattern with excitatory connections to both neck extensor motoneuron pools, and inhibitory connections to both neck flexor motoneuron pools. This bilateral organization contrasts with the unilateral innervation scheme of the utriculus system. These results suggest a different symmetry plane along which sacculus postural reflexes are organized, thus supplementing the reference planes of the utriculus system and allowing the gravistatic system to represent all three translational spatial degrees of freedom. We furthermore suggest that the sacculocollic reflex plays an important role in maintaining the relative position of the head and the body against the vertical linear acceleration of gravity.

Afferent Pathways↗
PubMed1997

Asp905Tyr polymorphism of protein phosphatase 1 G subunit gene in hypertension.

A possible pathogenic polymorphism in the gene for the G subunit of the glycogen-associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be associated with insulin resistance and hypersecretion of insulin in the white population. Since marked heterogeneity has been reported in the association of mutations of candidate genes with essential hypertension between Japanese and other ethnic groups, we investigated the association of Asp905Tyr with essential hypertension in Japanese subjects. The frequency of the Tyr allele in Japanese control subjects (0.70) was much higher than that in the Danish population (0.10, P<1x10(-8)), indicating that the Tyr allele, previously reported as a rare variant in white subjects, is a common allele in our population. The genotype distribution in Japanese hypertensive patients (n=109; Asp/Asp=0.09, Asp/Tyr=0.39, Tyr/Tyr=0.52) was not significantly different (chi2=0.7, df=2, P>.6) from that in normotensive control subjects (n=148; Asp/Asp=0.12, Asp/Tyr=0.36, Tyr/Tyr=0.52). Among subjects with different PP1 G subunit genotypes, there was no difference in blood pressure, serum cholesterol, plasma glucose and insulin levels, and glucose disposal rate estimated by the euglycemic hyperinsulinemic clamp test. These data indicate that the Asp905Tyr polymorphism of the PP1 G subunit is not associated with essential hypertension, nor with insulin resistance and/or hyperinsulinemia in Japanese patients with essential hypertension, suggesting that the polymorphism plays little if any role in susceptibility to insulin resistance or hypertension.

Aged↗
PubMed1997

Norepinephrine stimulates mitogen-activated protein kinase activity in GT1-1 gonadotropin-releasing hormone neuronal cell lines.

The GT1-1 GnRH neuronal cell lines exhibit highly differentiated properties of GnRH neurons. We have used GT1-1 cells to study the roles of norepinephrine (NE), membrane depolarization, calcium influx, and phorbol esters in the regulation of mitogen-activated protein (MAP) kinase. NE, which is known to stimulate the release of GnRH, induced MAP kinase activity, the tyrosine phosphorylation of MAP kinase, and MAP kinase kinase activity. Forskolin led to activation of MAP kinase comparable with that induced by NE, and a selective inhibitor of cAMP-dependent protein kinase, H8, attenuated the NE-induced activation of MAP kinase. On the other hand, elimination of extracellular calcium by EGTA completely blocked NE-induced tyrosine phosphorylation of MAP kinase, and a selective inhibitor of calcium/calmodulin-dependent protein kinase, KN-62, attenuated the NE-induced activation of MAP kinase. Furthermore, depolarization of GT1-1 cells with 75 mM KCl, 10 microM BayK 8644, or 1 microM calcium ionophore (A23187) induced rapid tyrosine phosphorylation of MAP kinase. The omission of calcium from the extracellular medium completely abolished these effects of tyrosine phosphorylation of MAP kinase. Phorbol 12-myristate 13-acetate (PMA) also induced MAP kinase activity, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the activation of MAP kinase by NE. In addition, although phosphorylation of Raf-1 kinase was stimulated by PMA, this phosphorylation was not induced by either NE or A23187. These results demonstrate that NE activates MAP kinase directly in GT1-1 cells, and that the effect of NE is mediated by increase in the cAMP level and by calcium influx, but not by PMA-sensitive protein kinase C or Raf-1 kinase.

Animals↗
PubMed1997

Role of mitogen-activated protein kinase pathway in prostaglandin F2alpha-induced rat puerperal uterine contraction.

In this study, prostaglandin (PG) F2alpha was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2alpha stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2alpha induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase 1 (betaARK1), which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP kinase. Ritodrine (1 microM), which is known to relax uterine muscle contraction, attenuated PGF2alpha-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2alpha-induced calcium mobilization, this inhibitor partially inhibited PGF2alpha-induced uterine contraction. These results provide evidence that PGF2alpha stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gbetagamma protein, suggesting that this new pathway may play an important role in the biological action of PGF2alpha on these cells.

Animals↗
PubMed1997

[Glucose tolerance and insulin resistance in the elderly].

Glucose tolerance is reported to be impaired in the elderly, and this is said to be mainly due to a decrease in insulin sensitivity (insulin resistance). Insulin resistance is known to be associated with atherosclerosis and coronary artery disease. To clarify whether or not age-dependent changes in glucose tolerance and insulin sensitivity are risk factors for coronary artery disease, as they are in the case of the insulin resistance syndrome, we studied age-dependent changes in glucose tolerance, insulin sensitivity, blood pressure, and serum lipids in a large number of subjects who underwent annual health check-ups, and then studied the relationships between coronary artery disease and aging, insulin sensitivity, and other risk factors in subjects who underwent coronary angiography. Aging was associated with an increased prevalence of noninsulin-dependent diabetes mellitus and impaired glucose tolerance; even in subjects with normal glucose tolerance, plasma glucose levels during an oral glucose tolerance test were significantly higher in the elderly. Insulin sensitivity, as assessed by the ratio of the sum of the plasma glucose divided by the sum of the serum insulin during the test (sigma PG/sigma IRI), was significantly lower in subjects over 60 years old than in younger subjects. Age-dependent impairment of insulin sensitivity and glucose tolerance was associated with increased blood pressure and serum cholesterol levels, but not with changes in boy mass index or serum triglyceride levels. As an independent variable, aging, but not insulin sensitivity, was related to the severity of coronary artery disease. These data suggest that aging is associated with glucose intolerance, insulin resistance, and an increased risk of coronary artery disease, but that the effect of aging on coronary artery disease cannot be explained by insulin resistance alone. Other factors, such as glucose intolerance and increased blood pressure, in addition to insulin resistance, appear to be responsible of the increased risk for coronary artery disease in the elderly.

Aged↗
PubMed1997

[Insulin, as a regulating factor of blood pressure].

In patients with hypertension, insulin resistance and hyperinsulinemia are more prevalent than in normal individuals. Furthermore, the prevalence of hypertension in diabetic patients is higher than in nondiabetic individuals. Insulin resistance has been implicated in the common mechanisms underlying diabetes, hypertension, hyperlipidemia and obesity. A number of mechanisms have been proposed to account for the elevation of BP secondary to hyperinsulinemia, such as 1) increased tubular reabsorption of sodium ions, 2) increased intracellular sodium and calcium ions, 3) increased sympathetic nervous activity, and 4) proliferation of vascular smooth muscle cells. Moreover, hypertension was reported to be a possible cause of insulin resistance. The detailed mechanism of insulin leading hypertension are still under investigation.

Animals↗
PubMed1997

Effects of football training on ventilatory and gas exchange kinetics to sinusoidal work load.

The purpose of this study was to evaluate the effects of football training on maximal oxygen uptake (VO2max), ventilatory threshold (VT) and kinetics of ventilation and gas exchange variables to sinusoidal work load. The sinusoidal work load during cycling exercise was varied from 30 watts to 60% of VO2max (60% VO2max) with a period of 2 min. O2 uptake (VO2), CO2 output (VCO2), minute ventilation (VE) and heart rate (HR) were measured on a breath-by-breath basis using a computer system. Training periods were continued for 9 months. Six males who had no football experience were performed in which VO2max, VT, and the kinetics of each variable were measured for 3-month intervals (PRE, TR.3, TR.6, and TR.9). They usually underwent football training, such as sprint and strength training for 2-3 hours day-1, 6 days week-1. Mean VO2max was significantly increased at TR.3 and TR.6. VT was also significantly increased during the training period. The amplitude of VO2, VCO2, VE, and HR responses during sinusoidal exercise unchanged during the training period. Phase shifts to work load in VO2 and HR responses did not significantly change during the 9 months, but the phase shift in VCO2 and VE responses significantly continued increasing as the training intervals progressed. These results suggest that football training does not significantly affect the development of the kinetics of VO2 and HR during submaximal exercise, but that it dramatically increases VO2max and VT values.

Anaerobic Threshold↗
PubMed1996

The role of mitogen-activated protein kinase in oxytocin-induced contraction of uterine smooth muscle in pregnant rat.

Oxytocin causes the rapid tyrosine phosphorylation of mitogen-activated protein (MAP) kinase in both human and rat puerperal uterine myometrial cultured cells. The potential role of the MAP kinase pathway in oxytocin action was investigated with the specific MAP kinase kinase (MEK) inhibitor, PD98059. Oxytocin stimulation of the tyrosine phosphorylation of MAP kinase in both human and rat cultured puerperal uterine cells was abolished by pretreatment of the cells with MEK inhibitor in a dose-dependent manner. Although MEK inhibitor had no effect on oxytocin-induced intracellular Ca2+ mobilization in either pregnant human or pregnant rat uterine cells, it partly inhibited oxytocin-induced pregnant rat uterine contraction in a dose-dependent manner. These results suggest that MAP kinase pathway may have some important roles in oxytocin-induced uterine contraction.

Animals↗
PubMed1996

Dose escalation study of carboplatin with fixed-dose etoposide plus granulocyte-colony stimulating factor in patients with small cell lung carcinoma. A study of the Lung Cancer Study Group of West Japan.

BACKGROUND: We performed a Phase I-II trial to determine the maximum tolerated dose of carboplatin (CBDCA) with a fixed dose of VP-16 and granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC) patients. METHODS: Treatment consisted of a starting dose of CBDCA, 400 mg/m2 (i.v., Day 1); VP-16, 100 mg/m2 (i.v., Days 1-3), and G-CSF, 2 micrograms/kg (s.c., Days 4-17) every 4 weeks for four cycles. The dose of CBDCA was escalated in increments of 50 mg/m2 until Grade IV toxicity on the World Health Organization scale developed in two-thirds or more of the patients. RESULTS: Seventy-five previously untreated patients with pathology confirmed SCLC were entered into the trial. Seventy-one patients were eligible and 70 patients were evaluated for response. Forty-five patients had limited disease (LD) and 26 had extensive disease (ED). The response rate of the 70 patients who could be evaluated was 81%, with 23% attaining a complete response (CR) and 58% attaining a partial response (PR). The response rate was 80% in LD patients (CR, 23%; PR, 57%) and 85% in ED patients (CR, 23%; PR, 62%). The major dose-limiting toxicity was thrombocytopenia. Nephrotoxicity, neurotoxicity, and ototoxicity were uncommon. The doses of CBDCA that resulted in unacceptable thrombocytopenia were 700 mg/m2 in patients younger than 70 years and 500 mg/m2 in patients older than 70 years. Overall median survival time (MST) was 9 months. MST of LD patients and ED patients were 11 months and 7 months, respectively. The dose-limiting toxicity of CBDCA with a fixed dose of VP-16 and using G-CSF as bone marrow rescue was age-related thrombocytopenia. The maximum tolerated dose of CBDCA was 650 mg/m2 if patients were younger than 70 years and 450 mg/m2 if they were 70 years or older. CONCLUSIONS: When we retrospectively compared our results with those using standard chemotherapy regimens, we saw no therapeutic benefit from increasing planned doses of CBDCA up to 700 mg/m2 in combination with G-CSF in patients with SCLC.

Aged↗
PubMed1996

Properties of utricular nerve-activated vestibulospinal neurons in cats.

The axonal pathway, conduction velocities, and locations of the cell bodies of utricular nerve-activated vestibulospinal neurons were studied in decerebrated or anesthetized cats using the collision test of orthodromic and antidromic spikes. For orthodromic stimulation, bipolar tungsten electrodes were placed on the utricular nerve and the other vestibular nerve branches were transected. Monopolar tungsten electrodes were positioned on both sides of the upper cervical segments (C2-4), caudal end of the cervical enlargement (C7-T1), and from the lower thoracic to the upper lumbar segments (T12-L3) and were used for antidromic stimulation of the spinal cord. Another monopolar electrode was also placed in the oculomotor nucleus to study whether utricular nerve-activated vestibulospinal neurons have ascending branches to the oculomotor nucleus. Of the 173 vestibular neurons orthodromically activated by the stimulation of the utricular nerve, 46 were second-order vestibulospinal neurons and 5 were third-order neurons. The majority of the utricular nerve-activated vestibulospinal neurons were located in the rostral part of the descending vestibular nucleus and the caudal part of the ventral lateral nucleus. Seventy-three percent of the utricular nerve-activated vestibulospinal neurons descended through the ipsilateral lateral vestibulospinal tract. Approximately 80% of these neurons reached the cervico-thoracic junction, but a few reached the upper lumbar spinal cord. Twenty-seven percent of the utricular nerve-activated vestibulospinal neurons descended through the medial vestibulospinal tract or the contralateral vestibulospinal tracts. Those axons terminated mainly in the upper cervical segments. Almost none of the utricular nerve-activated vestibular neurons had ascending branches to the oculomotor nucleus.

Afferent Pathways↗