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Biomedical subjects

T Kitamura

Publications and source records attributed to T Kitamura.

At least 37 records · Page 2Linked to original sources
PubMed2003

Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein-kinase-dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats.

AIMS/HYPOTHESIS: Recent studies have suggested that proinsulin C-peptide improves vascular functions, possibly through nitric oxide (NO) production. To clarify the molecular mechanisms of vascular NO production induced by C-peptide, we examined the effects of C-peptide on NO production and NO synthase expression in rat aortic endothelial cells in connection with mitogen-activated protein kinase (MAPK) activation. METHODS: Aortic endothelial cells were isolated from female Wistar rats, cultured to confluence, and serum-starved for 24 h before treatment with C-peptide. Nitric oxide production was measured by the DAF-2 fluorescence dye method and relative amounts of endothelial nitric oxide synthase (eNOS) protein and its mRNA were semi-quantified by western blot and RT-PCR analyses respectively. Activation of MAPK was estimated by western blot detection of activity-related phosphorylation and in vitro kinase assay. RESULTS: Stimulation of cells with C-peptide for 3 h doubled NO production, which was suppressed by the NO synthase inhibitor, N(G)-nitro- L-arginine methyl ester (L-NAME). Stimulation also increased mRNA and protein contents of eNOS in a manner sensitive to the transcription inhibitor actinomycin D. It did not affect inducible NO synthase mRNA. C-peptide also induced rapid phosphorylation and activation of extracellular signal-regulated kinase (ERK, also known as p44/42MAPK), but not of p38MAPK. In cells pretreated with the ERK inhibitor PD98059 the C-peptide-elicited increase of NO production and eNOS was abrogated in a dose-dependent manner; suppression of ERK phosphorylation induced by C-peptide also occurred. CONCLUSIONS/INTERPRETATION: Our results show that C-peptide increases NO production by increasing eNOS protein contents through ERK-dependent up-regulation of eNOS gene transcription. This could explain some actions of C-peptide on the vasculature, indicating a pivotal role for C-peptide in vascular homeostasis.

Animals↗
PubMed2003

Unambiguous identification of JC polyomavirus strains transmitted from parents to children.

JC polyomavirus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically, then persisting in renal tissue. It has been proposed that JCV is transmitted mainly from parents to children through long-term cohabitation. The objective of this study was to further elucidate the mode of JCV transmission. In 5 families, we selected parent/child pairs between whom JCV was probably transmitted (judged on the basis of the identity of a 610-bp JCV DNA sequence between the parent and child). We established 5 to 9 complete JCV DNA clones from the urine of each parent or child. The complete sequences of these clones were determined and compared in each family. Nucleotide substitutions were detected in 4 parents and 1 child, and sequence rearrangements (deletions or duplications) were found in 2 parents and 2 children. Phylogenetic comparison of the detected sequences indicated that the diversity of JCV DNA sequences was generated in each family (i.e. not caused by multiple infection). We found that in 4 of the 5 families, a sequence detected in the parent was completely identical to one in the child. These findings provided further support for the proposed mode of JCV transmission, i.e. parent-to-child transmission during cohabitation.

Adult↗
PubMed2003

Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications.

Atherosclerotic vascular diseases are frequently associated with diabetes mellitus. There has been increasing evidence showing that the atherosclerotic diseases in diabetic patients are distinct from diabetic microvascular complications as to their pathophysiology and epidemiology. However, we have no information on the prevalence of asymptomatic atherosclerosis in diabetic patients before the onset of microvascular diseases. In the present investigation, we aimed to evaluate risk factors for the atherosclerosis in type 2 diabetic patients without the microvascular diseases. For this purpose, we evaluated atherosclerotic change of carotid arteries in 125 Japanese type 2 diabetic patients who had neither atherosclerotic vascular diseases nor diabetic microvascular complications. When atherosclerotic change was defined as the mean intima-media thickness (IMT) of >/= 1.1 mm and/or the presence of plaque lesion, 50% of patients had atherosclerosis of the carotid arteries. Risk factors for the carotid atherosclerosis were age, low-density lipoprotein (LDL)-cholesterol, hypertension, and diabetes treatment. Age and LDL-cholesterol were associated with mean IMT. Age, diabetes treatment, LDL-cholesterol, and hypertension were positively associated with plaque lesion, while high-density lipoprotein (HDL)-cholesterol was negatively associated with it. Fasting plasma glucose, glycosylated hemoglobin (HbA(1c)), and known diabetes duration remained unassociated with any parameters of asymptomatic atherosclerosis of the carotid arteries. These results indicate that glycemic control is unrelated with asymptomatic atherosclerosis in type 2 diabetic patients without diabetic microvascular complications. Conventional risk factors and diabetes treatment are independently associated with atherosclerosis of the carotid arteries in these patients.

Aged↗
PubMed2003

Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor epsilon 1 subunit.

Neurogenesis continues throughout adulthood in the dentate gyrus in mice, and is regulated by environmental, endocrine, and pharmacological stimuli. Although running wheel exercises have been reported to enhance neurogenesis, details of molecule mechanisms of the enhancement are not well understood. We report here that the hippocampal neurogenesis is enhanced when wild-type mice are raised in cages with running wheels for 3 weeks, but the wheel exercise does not enhance the neurogenesis in mice lacking the NMDA receptor epsilon1 subunit. Brain-derived neurotrophic factor (BDNF) has been reported to affect neuronal cell proliferation and survival. We examined the BDNF levels in the hippocampi of wild-type and epsilon1 knockout mice, and found that the BDNF level was increased through wheel exercises in the wild-type but not in the knockout mice. The enhancement of neurogenesis by the wheel exercise was also found to be reversible: when the exercise-stimulated wild-type mice were returned to the environment without running wheels for 3 weeks, the neurogenesis was the same as that in the mice which had never experienced the exercise. These results suggest that the wheel exercise may activate NMDA receptors in the hippocampus, which in turn may enhance BDNF production and neurogenesis.

Animals↗
PubMed2003

Anthropogenic radionuclides in the Japan Sea: their distributions and transport processes.

The anthropogenic radionuclides, (90)Sr, (137)Cs and (239+240)Pu, were measured in the water column of the Japan Sea/East Sea during 1997-2000. The vertical profiles of radionuclide concentrations showed: exponential decrease with depth for (90)Sr and (137)Cs, and surface minimum/subsurface maximum for (239+240)Pu. These results do not differ substantially from results reported previously. The area-averaged concentrations of radionuclides in the Japan Sea are higher than those found in the Northwest Pacific Ocean below surface layer showing the accumulation of the radionuclides in the deep waters in the Japan Sea. Concerning spatial distributions, the area of high (137)Cs inventory extends from the Japan Basin into the Yamato Basin. It is suggested that wintertime convection of water, occurring mainly in the Japan Basin, causes the radionuclides to sink. The nuclides then advect into the Yamato Basin after detouring around the Yamato Rise.

Environmental Monitoring↗
PubMed2003

Compression and stretching of the brachial plexus in thoracic outlet syndrome: correlation between neuroradiographic findings and symptoms and signs produced by provocation manoeuvres.

In order to investigate the mechanism of nerve irritation in thoracic outlet syndrome (TOS), we studied 150 patients who presented with symptoms of neurologic TOS between 1985 and 1999. They first performed various provocative physical manoeuvres and then underwent injection of contrast medium into the supraclavicular part of the brachial plexus. Several of the provocative manoeuvres were then repeated and radiographs were again obtained. Based on the neuroradiographs, we identified three subsets of patients; those with only compression (type 1 TOS, n=27, 18%), those with combined compression and stretching (type 2 TOS, n=111, 74%), and those with only stretching (type 3 TOS, n=12, 8%). We were able to correlate the neuroradiological subsets with symptoms elicited by pre-radiographic provocative manoeuvres; in 92 patients (61%) these were elicited by traction manoeuvres. We conclude that stretching is an important factor of nerve irritation in TOS.

Adolescent↗
PubMed2003

Time to recurrence after recovery from major depressive episodes and its predictors.

BACKGROUND: Depression is a remitting but recurring disease. However, there is a paucity of prospectively recorded data on the course of depression after recovery. METHOD: A multi-centre prospective serial follow-up study of an inception cohort of hitherto untreated unipolar major depression (N = 95) for 6 years. We report the time to recurrence after recovery from the index depressive episode and their predictors. RESULTS: The cumulative probability of remaining well without subthreshold symptoms was 57% (95% CI, 46 to 68%) at 1 year, 47% (95% CI, 36 to 58%) at 2 years and 35% (95% CI, 23 to 47%) at 5 years. The same without full relapse was 79% (95% CI, 70 to 88%) at 1 year, 70% (95% CI, 60 to 80%) at 2 years and 58% (95% CI, 46 to 70%) at 5 years. The median duration of well-interval from the end of the index episode to the beginning of the subthreshold episode was 19-0 months (95% CI, 2-4 to 35-7), and that to the end of the full episode was over 6 years. Residual symptoms at time of recovery predicted earlier recurrence. CONCLUSIONS: The median length of the well-interval was much longer than previously reported in studies employing similar definitions but dealing with a more severe spectrum of patients. However, the sobering fact remains that less than half of the patients can expect to remain virtually symptom-free for 2 years or more after recovery from the depressive episode.

Adolescent↗
PubMed2003

Engineered IGF-I expression induces glandular enlargement in the murine prostate.

IGF-I has been implicated as a factor that may predispose one to prostate cancer and to benign prostatic hypertrophy (BPH). We established murine IGF-I transgenic mice under the control of rat probasin promoter and analysed the histology of the murine IGF-I-overexpressing prostate. Immunohistochemically, IGF-I was expressed in prostatic epithelial cells or basement membranes of the ventral, dorsal and lateral lobes in a line of IGF-I transgenic mice, but not in their control littermates. The anterior lobe did not express IGF-I. IGF-binding protein-3 (IGFBP-3), inhibitory to the mitogenic action of IGF-I, was detected in epithelial cells of prostatic ventral lobes, but not in those of the dorsal, lateral or anterior lobes of IGF-I transgenic mice. In controls, IGFBP-3 was not detected in epithelial cells of any prostatic lobe. Macroscopic prostatic size and the appearance of IGF-I transgenic mice were comparable with those of their control littermates of the same age. With a computed morphometric analysis, epithelial glands and intraglandular lumens in the prostatic lobes except the ventral lobe were smaller at 17 Months of age than at 14 Months both in IGF-I transgenic mice and controls. Glands and intraglandular lumens in the ventral prostatic lobes of IGF-I transgenic mice expressing more IGF-I protein in the prostate than controls were dense and enlarged similar to cysts compared with those of non-transgenic littermates without showing epithelial growth. Glands and lumens in the dorsal and lateral lobes of the IGF-I transgenic mice were also larger than controls at 14 and/or 17 Months of age. Glands in the anterior prostatic lobe of the IGF-I transgenic mice were not morphologically or morphometrically different from those of non-transgenic littermates. In conclusion, IGF-I transgenic mice under the control of rat probasin promoter showed more dense and enlarged epithelial glands in their prostatic ventral, dorsal and lateral lobes.

Aging↗
PubMed2002

Asian domains of four major genotypes of JC virus, Af2, B1-b, CY and SC.

JC virus (JCV) strains worldwide can be classified into various genotypes based on DNA sequence variations. To define the domains of the four major JCV genotypes in Asia, we collected urine samples at six unstudied sites: three in southeastern Asia, two in the central highlands and one in central Asia. DNA was extracted from urine samples, and used to amplify a 610-bp region of the viral genome. For each geographical site, we determined 16 to 31 sequences, from which a phylogenetic tree was constructed to unambiguously classify detected JCV isolates into distinct genotypes. From JCV genotype profiles at the sites studied here and elsewhere, the following conclusions were drawn. Although Af2 is the major genotype in Africa, this genotype also occurs in western and central Asia. B1-b mainly occurs in western and central Asia, including the central highlands. CY occurs in northeastern Asia with the southern boundary between China and southeast Asian countries. Although SC predominates in southeastern Asia, it also occurs in northern and central Asia at lower frequencies. In addition, a few minor JCV genotypes (B1-a, B2 and B3) occur at many sites. We discuss here the anthropological and medical significance of the present findings.

Adult↗
PubMed2002

Circadian rhythm of blood pressure is transformed from a dipper to a non-dipper pattern in shift workers with hypertension.

Shift workers make great use of health care services because they are associated with increased cardiovascular morbidity and mortality. Whether the circadian rhythm of blood pressure rapidly adapts to shift work is controversial. It is unknown if shift work has adverse effects on blood pressure in patients with hypertension. To evaluate the effects of shift work, we examined 12 male shift workers with untreated hypertension aged 53.6 +/- 2.5 years. Twenty-four hour ambulatory blood pressure monitoring was performed three times as follows: the last day of a 4-day period of day shifts (09.00 to 21.00), the first day of a 4-day period of night shifts (21.00 to 09.00), and the fourth day of night shifts (21.00 to 09.00). Blood pressure at night-time dropped significantly in the day-shift workers, showing a dipper pattern. Average differences in blood pressure in the sleep-wake cycle were decreased by 8.5% at the beginning of night shift work showing a non-dipper pattern. After 4 days the pattern was completely reversed to a dipper pattern. The results indicate that the circadian blood pressure pattern is changed from a dipper to a non-dipper pattern on the first day of the night shift and reverses to a dipper pattern within a few days. We suggest that night shift work may have unfavourable effects on blood pressure in patients with hypertension.

Blood Pressure↗
PubMed2002

Personality, social support, coping and emotional distress after repeated spontaneous abortions.

Systematic investigations on the emotional impacts of repeated spontaneous abortions have been few. We mounted a prospective study of a cohort of couples who had experienced two consecutive first trimester spontaneous abortions and for whom no clearly identifiable causes were found. The present report is based on the first part of the study and examines: (1) emotional distress reported by the miscarrying women at six months (median, range 1-12 months) after two abortions; and (2) psychosocial predictors influencing such distress. The mean score of the women on the Symptom Checklist 90-Revised--one of the most popular self-report scales for psychopathology--was 0.38, whereas that for the general population is reported to be 0.26 (the higher the score, the more psychopathology). Fourteen percent of the cohort scored above the cutoff point for mental disorders screening. Factors examined and found non-influential upon the level of emotional distress include: the maternal age; whether the last pregnancy was planned and wished for or not; and coping styles of the women after the abortions. Control by the husbands over the marital relationship and neurotic personality traits of the women increased the emotional distress, whereas the social support the women perceive decreased it. These findings suggest that martial and social support are important in determining the level of psychiatric morbidity after repeated abortions.

Abortion, Spontaneous↗
PubMed2001

Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord.

Recent studies have demonstrated that neural stem cells and other progenitors are present in the adult CNS. Details of their properties, however, remain poorly understood. Here we examined the properties and control mechanisms of neural progenitors in the adult rat spinal cord at the molecular level. Adult and embryonic progenitors commonly expressed various homeodomain-type (Pax6, Pax7, Nkx2.2, and Prox1) and basic helix-loop-helix (bHLH)-type (Ngn2, Mash1, NeuroD1, and Olig2) transcriptional regulatory factors in vitro. Unlike their embryonic counterparts, however, adult progenitors could not generate specific neurons that expressed markers appropriate for spinal motoneurons or interneurons, including Islet1, Lim1, Lim3, and HB9. Cells expressing the homeodomain factors Pax6, Pax7, and Nkx2.2 also emerged in vivo in response to injury and were distributed in unique patterns in the lesioned spinal cord. However, neither the expression of the neurogenic bHLH factors including Ngn2, Mash1, and NeuroD1 nor subsequent generation of new neurons could be detected in injured tissue. Our results suggest that signaling through the cell-surface receptor Notch is involved in this restriction. The expression of Notch1 in vivo was enhanced in response to injury. Furthermore, activation of Notch signaling in vitro inhibited differentiation of adult progenitors, whereas attenuation of Notch signals and forced expression of Ngn2 significantly enhanced neurogenesis. These results suggest that both the intrinsic properties of adult progenitors and local environmental signals, including Notch signaling, account for the limited regenerative potential of the adult spinal cord.

Animals↗
PubMed2001

Differential expression of estrogen receptor beta (ERbeta) and its C-terminal truncated splice variant ERbetacx as prognostic predictors in human prostatic cancer.

Estrogens have been widely used for the treatment of advanced prostatic adenocarcinoma. However, their direct effect to prostatic cancer cells via estrogen receptors remains unclear. We investigated expression of ERalpha, wild-type ERbeta (wtERbeta), and a C-terminal truncated splice variant of ERbeta (ERbetacx) in 50 benign and 100 malignant human prostatic tissue samples by immunohistochemistry. While strong immunostaining of ERalpha was consistently identified in the stromal compartment, wtERbeta was expressed in epithelial cells in both the benign and malignant foci. However, wtERbeta expression was significantly lower in the cancers than in the benign epithelium and inversely correlated with Gleason tumor grade (P < 0.0001 and P = 0.0099, respectively). In contrast, ERbetacx was significantly more expressed in the high-grade cancers (83%) compared with the low-grade tumors (22%) and the benign sites (11%) (P < 0.0001, both). Cancer-specific survival of patients with lower wtERbeta expression was significantly worse than those with higher expression of wtERbeta (P = 0.0018). Conversely, higher ERbetacx expression significantly correlated with poor cancer-specific survival (P = 0.0058). These results suggest that differential expressions of wtERbeta and ERbetacx may be prognostic predictors for prostatic cancer.

Adenocarcinoma↗
PubMed2001

SF20/IL-25, a novel bone marrow stroma-derived growth factor that binds to mouse thymic shared antigen-1 and supports lymphoid cell proliferation.

Using a forward genetic approach and phenotype-based complementation screening to search for factors that stimulate cell proliferation, we have isolated a novel secreted bone marrow stroma-derived growth factor, which we termed SF20/IL-25. This protein signals cells to proliferate via its receptor, which we have identified as mouse thymic shared Ag-1 (TSA-1). Enforced expression of TSA-1 in IL-3-dependent Ba/F3 cells that do not express endogenous TSA-1 rendered cells to proliferate in a dose-dependent manner when stimulated with SF20/IL-25. FDCP2, a factor-dependent hemopoietic cell line that expresses endogenous TSA-1, could also be stimulated to proliferate with SF20/IL-25. Binding of SF20 to TSA-1 was blocked by anti-TSA-1 Ab and SF20-induced proliferation of TSA-1-expressing cells was inhibited by anti-TSA-1. In vitro assay revealed that SF20/IL-25 has no detectable myelopoietic activity but supports proliferation of cells in the lymphoid lineage.

Amino Acid Sequence↗