Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 181 records · Page 10Linked to original sources

PubMed2000

Ghrelin-induced growth hormone secretion in humans.

Ghrelin is a novel growth hormone (GH) releaser acylated peptide that has recently been purified from stomach, and which potently binds to the GH secretagogue receptor. Ghrelin releases GH in vitro and in vivo in animal models, however its actions, potency and specificity in humans are unknown. In the present study, 12 healthy subjects were studied: 6 underwent four tests with ghrelin administered i.v. at the dose of 0 (placebo), 0.25, 0.5 and 1 microg/kg which corresponds to 0, 18, 37 and 75 microg total dose. A further 6 volunteers underwent two tests on different days with ghrelin at the dose of 3.3 or 6.6 microg/kg which corresponds to 250 microg and 500 microg total dose. Ghrelin-mediated GH secretion showed a dose-response curve, in which 1 microg/kg was the minimally effective dose in some individuals, but not as a group. On the contrary, the total doses of 250 microg and 500 microg elicited a powerful GH secretion, with a mean peak of 69.8+/-9.2 microg/l and 90.9+/-16.9 microg/l respectively, and areas under the curve of 4435+/-608 and 6125+/-1008 microg/l per 120 min respectively. All of them statistically significant vs placebo and vs the 1 microg/kg dose. Ghrelin administration also elicited a relevant dose-response mediated prolactin secretion suggesting no specificity of its actions. No relevant side effects were observed with ghrelin apart from a hyperhydrosis episode in two individuals tested with the higher ghrelin doses. In conclusion, ghrelin is a potent releaser of GH in normal individuals, with a dose-response pattern of operation. No saturating dose was observed.

Adult↗

PubMed2000

Sleep patterns and total mortality: a 12-year follow-up study in Japan.

A population-based cohort study was conducted to assess the relationship between total mortality and self-reported sleep patterns as regards not only to sleep duration but also subjective sleep quality. A total of 5,322 inhabitants in Gifu Prefecture, Japan, completed a self-administered questionnaire on health status and lifestyles including habitual sleep patterns, and were followed-up for an average of 11.9 years. Relative risks were computed by using Cox proportional hazards models. Both longer and shorter sleep, compared to 7-8 hour-sleep, was related to significantly increased risk of total mortality in males (relative risk [RR] for > or = 10 hours = 1.94, and RR for < 7 hour = 1.90), but not in females. Females complaining of poor awakening state experienced a higher mortality risk compared to those who woke up normally (RR: 1.97). Males who usually fell asleep easily showed a marginally lower mortality risk compared to those who fell asleep normally (RR: 0.70). Female users of sleeping pills were at an elevated risk (RR: 1.89). These findings were almost unchanged after adjustment for sleep duration and other confounders. Poor self-reported quality of sleep seemed to be associated with an increased risk of mortality independently of sleep duration.

Adult↗

PubMed2000

Causes of nocturnal urinary frequency and reasons for its increase with age in healthy older men.

PURPOSE: We investigate the causes of nocturnal urinary frequency and reasons for its increase with age. MATERIALS AND METHODS: All voided volumes and times were recorded for 3 days in 188 healthy older men without prostatic diseases during a mass screening program for prostatic diseases in Japan. Nocturnal urinary frequency for each night was defined as the frequency during sleep not counting the morning void. Relationships between nocturnal urinary frequency and functional bladder capacity, nocturnal bladder capacity, nocturnal urinary volume and sleep time were analyzed. Age related changes in functional and nocturnal bladder capacity, and nocturnal and diurnal urinary volume were evaluated. RESULTS: Multiple regression analysis demonstrated nocturnal bladder capacity and urinary volume to be significant independent determinants of nocturnal frequency. In age related analysis nocturnal bladder capacity and diurnal urinary volume decreased with age, while nocturnal urinary volume did not change. CONCLUSIONS: Nocturnal urinary volume and nocturnal bladder capacity were the significant determinants of nocturnal urinary frequency in healthy older men. The increase of nocturnal frequency with age was thought to be due to a decrease in nocturnal bladder capacity, since urinary volume did not change. In older men a decrease in water intake might influence age related changes in urinary volume.

Age Distribution↗

PubMed2000

[Clinical evaluation in oral lichen planus with chronic hepatitis C: the role of interferon treatment].

Hepatitis C virus (HCV) infection induces a variety of extrahepatic manifestations such as oral lichen planus (OLP). To clarify the role of HCV in the development of OLP, we investigated the occurrence of OLP in patients with chronic hepatitis C treated with interferon (IFN). Of 275 patients with chronic hepatitis C, 6 developed OLP during the IFN treatment. However, OLP developed in none of 230 patients with chronic hepatitis C who did not undergo the IFN therapy. The IFN treatment in chronic hepatitis C patients developed OLP significantly, as compared with the non-treated group (p < 0.05). 4 of 6 patients who developed OLP during the IFN treatment had a complete response with normalization of ALT levels and undetectable HCV RNA after the treatment. There were no significant correlations between the effect of the IFN treatment and outcome of OLP. Furthermore, 3 of the 6 patients developed OLP, when serum HCV RNA became negative. These results suggest that direct viral factors may not be important in the pathogenesis of OLP in patients with chronic hepatitis C. Immunological changes caused by IFN may play a role in the development of OLP associated with HCV infection.

Adolescent↗

PubMed2000

[Recent advances in colorectal cancer surgery].

Recent advances in colorectal cancer surgery have been made in improving the cure rate after surgery, the preservation of postoperative function, and the development of minimally invasive procedures. Indication for wide lymph node dissection in rectal cancer surgery is now limited to a smaller number of cases. Functional outcome is being improved thanks to the introduction of autonomic nerve preserving operations as well as the increasing number of sphincter preserving operations. Laparoscopic colectomy for cancer has been practiced for 7-8 years, and the advantages and disadvantages of this procedure are being clarified. Transanal endoscopic microsurgery (TEM) is a minimally invasive surgery for rectal tumors in early stages. The procedure is now overtaking the posterior surgical approach, which is used less and less in recent years. Future goals in colorectal cancer surgery are further improvements in the cure rate and the functional results. Minimally invasive surgery may become the established procedure after a careful assessment of its cure rate compared to the open surgical procedure.

Colorectal Neoplasms↗

PubMed2000

[Randomized comparative study of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) and UFT-tamoxifen regimens as adjuvant chemotherapy after surgery for breast cancer: Tochigi Prefectural Study Group for Post-Breast Cancer Adjuvant Chemotherapy].

This prospective randomized study aimed at establishing the optimal postoperative adjuvant chemotherapy regimen for premenopausal n+ breast cancer patients. The treatments were Regimen A, comprising 6 courses of CMF (cyclophosphamide, 100 mg/body on days 1-14; methotrexate, 40 mg/m2 on days 1 and 8; and 5-fluorouracil, 500 mg/m2 on days 1 and 8), and Regimen B, consisting of UFT (300 mg/day) and tamoxifen (30 mg/day) administered orally each day for 2 years. Telephone registration allocated the patients to the treatment groups by the minimization method in relation to the T category, number of n+ lesions and estrogen receptor status. Forty-five patients were registered, and 44 of them were eligible (22 cases each to Regimen A and Regimen B). The principal background factors showed no biases between the groups. The adverse reaction incidence was significantly higher with Regimen A (90.9% vs 22.7%). The 5-year survival rate was 89.8% with Regimen A and 100% with Regimen B, while the 5-year disease-free rates were 64.5% and 76.3%, showing no statistical significance. Regimen B showed a better QOL rating after 6 months of therapy in relation to nausea-vomiting and hair loss, and after 24 months in relation to appetite, sleep, performance status, happiness, anorexia and hair loss.

Adult↗

PubMed2000

[Intracameral and lenticular penetration of locally applied deuterium-labeled vitamin E in rats].

PURPOSE: To confirm the intraocular dynamics of 1% deuterium (D)-labeled alpha-tocopherol acetate (VEA) solution. METHODS: The concentrations of D3-VEA and D3-alpha-tocopherol (VE) derived from D3-VEA in the aqueous humor and lens were measured after instilling 1% D3-VEA continuously into the cul-de-sac of rat eyes for one and three weeks. D3-VEA and D3-VE concentrations were determined by gas chromatograph/mass spectrometry. RESULTS: D3-VEA and D3-VE concentrations in the aqueous humor after one and three weeks of continuous administration were 93.1 and 498.9, and 9.4 and 21.5 ng/ml, respectively. The concentrations in the lens were 15.0 and 6.1, and 9.8 and 4.8 ng/g, respectively. CONCLUSION: The penetration of VEA into the aqueous humor and lens by eyedrop application was confirmed.

Animals↗

PubMed2000

[Laparoscopic colectomy for colorectal carcinoma].

Laparoscopic-assisted colectomy is considered to be a less invasive technique, and patients experience less pain and more rapid postoperative recovery. This operation has been indicated for large sessile adenomas or for early invasive carcinomas in Japan. The indications for this procedure in more advanced colorectal carcinomas is controversial. However, based on our experience with 130 cases, laparoscopic-assisted colectomy can be as curative as open colectomy provided that the patients are properly selected. In this review, the technical difficulties of this procedure are also discussed.

Colectomy↗

PubMed2000

[Ultrasound in urodynamics].

Recent developments of ultrasound imaging have contributed much to the understanding of urodynamics in patients with lower urinary tract symptoms (LUTS). These include ultrasound estimated bladder weight (UEBW), transrectal power Doppler imaging of the prostate and transrectal ultrasonography during voiding (voiding TRUS). UEBW, which is obtained by measuring the thickness of the anterior bladder wall using a 7.5 MHz probe, represents well the degree of bladder hypertrophy caused by obstruction. This parameter is, accordingly, of clinical use in the evaluation of obstruction. The UEBW predicted the presence of obstruction as determined by pressure-flow study with a diagnostic accuracy of 73%. Transrectal power Doppler imaging of the prostate has made it easy to detect prostatic vessels and furthermore to obtain their resistive index (RI). Accumulating data suggest strongly that RI reflects the intraprostatic pressure. More interestingly, RI decreases significantly during voiding in normal subjects but not in patients with benign prostatic hyperplasia. Thus, this method is of particular use in monitoring noninvasively the dynamic change in intraprostatic pressure during voiding. Voiding TRUS makes it possible to monitor the movement of not only the posterior urethra but also the prostate during voiding. Based on our recent study, the anterior fibromuscular stroma (AFMS) seems to contract to open the urethra. Although the physiological function of the AFMS in the prostate remains unknown, AFMS may play a significant role in normal micturition. Due to its noninvasiveness and ease of application, ultrasound imaging would play a vital role in the diagnostic process for patients with LUTS in future.

Humans↗

PubMed1999

Ghrelin is a growth-hormone-releasing acylated peptide from stomach.

Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH). We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.

Acylation↗

PubMed1999

New hyperprolactinemia and anovulation model in common marmoset (Callithrix jacchus) and effect of cabergoline.

We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg(-1)) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg(-1)) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg(-1) or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg(-1) restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg(-1) resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.

Animals↗

PubMed1999

Gas chromatographic-mass spectrometric determination of 4-nonylphenols and 4-tert-octylphenol in biological samples.

A simple and rapid method is described for the GC-MS determination of 4-nonylphenols (NOs) and 4-tert-octylphenol (OC) in biological samples. The NOs and OC in the sample are extracted with acetonitrile and the lipid in the sample extract is eliminated by partitioning between hexane and acetonitrile. After Florisil PR column clean-up, the sample extract is analyzed by GC-MS in the selected ion monitoring (SIM) mode. Average recoveries in pale chub (fish) and corbicula (shellfish) are 86.0 and 93.4% for NOs, and 95.8 and 96.4% for OC, respectively, spiked at the levels of 1.0 microg of NOs and 0.1 microg of OC per 5 g of fish and shellfish samples. The detection limits are 20 ng/g for NOs and 2 ng/g for OC.

Animals↗

PubMed1999

Definitive but not primitive hematopoiesis is impaired in jumonji mutant mice.

A novel gene, jumonji was identified by a mouse gene trap strategy. The jumonji gene encodes a protein containing a putative DNA binding domain. The mice homozygous for jumonji gene with a BALB/cA genetic background show hypoplasia of the fetal liver and embryonic lethality, suggesting impaired hematopoiesis. In the peripheral blood of jumonji mutant embryos, the number of fetal liver-derived definitive erythrocytes, but not yolk sac-derived primitive erythrocytes, showed a marked reduction, suggesting that jumonji mutants die of anemia. The defects of definitive erythrocytes in jumonji mutants seemed to be caused by a decrease in the numbers of multiple hematopoietic progenitors including colony-forming unit-spleen (CFU-S) in the fetal liver. However, hematopoietic stem cells (HSCs) in the fetal liver of jumonji mutants could reconstitute the hematopoietic system of lethally irradiated recipients. In the fetal liver, the jumonji gene is expressed in fibroblastic cells and endothelial cells, but not in Lin-/c-Kit+/Sca-1(+) cells known to include HSCs. These results suggest that an environmental defect induce the impaired hematopoiesis in the fetal liver of jumonji mutant embryos.

Animals↗

PubMed1999

Nitric oxide synthase expression and nitric oxide production in human colon carcinoma tissue.

BACKGROUND AND OBJECTIVES: Nitric oxide (NO), the production of which is dependent on NO synthase (NOS), has been shown to contribute to various pathogeneses in cancer. The aim of this study was to determine whether inducible NO synthase (iNOS) is overexpressed in human colon carcinoma tissue, and whether NO is produced in tumor tissue. METHODS: We investigated iNOS mRNA expression in 24 human colon carcinoma tissue specimens by reverse transcription-polymerase chain reaction (RT-PCR). We then examined the expression of iNOS protein and nitrotyrosine, which indicates NO production in tissue, by immunohistochemistry. The possible immunosuppressive role of NO produced by colon carcinoma cells was analyzed in vitro. RESULTS: Semiquantitative RT-PCR analysis showed that iNOS mRNA expression in carcinoma tissues is elevated significantly compared to that in noncarcinoma tissue. Immunohistochemistry revealed that iNOS and nitrotyrosine are expressed strongly in carcinoma tissues. In vitro experiments showed that the supernatant from a culture of cytokine-treated colon carcinoma cells, which contained high levels of NO, significantly reduced the phytohemagglutinin (PHA)-stimulated, human lymphocyte proliferative response (60% of the control value). CONCLUSIONS: In human colon carcinoma tissue, iNOS mRNA, protein, and NO products are overexpressed and may contribute to tumor-related immunosuppression.

Adenocarcinoma↗

PubMed1999

A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR.

The pattern of X-chromosome inactivation in females is currently evaluated by assays of differential methylation in the genes between the active and the inactive X chromosomes, with methylation-sensitive enzymes. We report a new assay in the human androgen receptor (HUMARA) locus involving a methylation-specific polymerase chain reaction (M-PCR) technique, independent of the use of restriction enzymes. The assay involves the chemical modification of DNA with sodium bisulfite and subsequent PCR. By using the assay with specific primers for the methylated allele, we obtained an X-inactivation pattern based on the ratio of the maternal inactive X to the paternal inactive X. These patterns were consistent with those obtained by conventional PCR assay at the same locus in 48 female cases. We also obtained another X-inactivation pattern based on the ratio of the maternal active X to the paternal active X by using specific primers for the unmethylated allele. The latter pattern was complementary to the former pattern, and a combination of these patterns produced a reliable X-inactivation pattern. The assay revealed that 12 (11%) of the 105 normal females had non-random inactivation patterns (>80:20 or <20:80). Four patients with an X; autosome translocation showed extremely non-random patterns, and these results were consistent with those obtained by previous molecular/cytogenetic studies. We conclude that M-PCR provides an accurate assay for X-inactivation and that it can be performed on various DNA samples unsuitable for restriction digestion.

Cell Line, Transformed↗

PubMed1999

Treatment effects of bisphosphonates on ovariectomy-induced osteopenia in rats: comparison between clodronate and etidronate.

We studied the effects of clodronate and etidronate on bone loss induced by ovariectomy (OVX) in rats. Drug administration was initiated 8 weeks after the surgery and continued for 12 weeks (twice per week, s.c.). Lumbar (L4-L5) bone mineral density (BMD) and femoral BMD in the sham-operated group were increased to 113% and 114%, respectively, whereas those in OVX group were suppressed to 98.8% and 105%. Clodronate significantly restored the suppressed BMD over the entire dose range used (4-25 mg/kg). Etidronate restored BMD only at 4 mg/kg. In a histomorphometric analysis of lumbar vertebrae, both bisphosphonates depressed the amount of labeled surface, which was increased by OVX, to 11.9%-20.1% of the OVX group value for clodronate and to 0.23%-9.7% of the OVX group value for etidronate. The osteoid area was significantly increased by etidronate treatment over the entire dose range (OS/BS, 175%-295%). On the other hand, the osteoid area in the clodronate group did not increase at any dose tested (OS/BS, 38.1%-49.9%). Urinary excretion of deoxypyridinoline and plasma level of osteocalcin were elevated in the OVX group (162%-182% and 123%, respectively), suggesting that OVX enhanced bone turnover. Both bisphosphonates suppressed the bone turnover accelerated by OVX, and the data indicated that both bisphosphonates recovered BMD by means of inhibition of bone resorption. These data suggested that clodronate and etidronate reversed osteopenia induced by ovariectomy in rats. As judged from the dose response of BMD and histomorphometric findings, clodronate showed a wider safety margin than etidronate.

Amino Acids↗

PubMed1999

Expression of adrenomedullin in the endometrium of the human uterus.

OBJECTIVE: Our purpose was to determine whether adrenomedullin is present in the human uterus. METHODS: We obtained specimens from five patients with leiomyoma and four patients with endometrial adenocarcinoma who were undergoing abdominal hysterectomy. Tissue sections were stained with antibody against adrenomedullin using an avidin-biotin-peroxidase complex technique. Total RNA from normal and cancerous endometrium, myometrium, and leiomyoma was prepared and analyzed by northern blot methodology. RESULTS: Sections stained with an antibody to adrenomedullin showed prominent expression of adrenomedullin in the normal and cancerous endometrial epithelial cells. Northern blot analysis showed that normal and cancerous endometrium expressed the messenger RNA (mRNA) for adrenomedullin and that the size of the mRNA transcript was 1.6 kilobases (kb). No significant difference was observed between the abundance of mRNA in normal and cancerous endometrium. CONCLUSION: The findings in this study demonstrated that both adrenomedullin protein and mRNA are present in normal and carcinomatous endometrium of the human uterus.

Adrenomedullin↗

PubMed1999

Kinetic study of tumor blood flow in prostatic cancer using power Doppler imaging.

We examined the changes in tumor Doppler flow signals as well as prostatic volume in 11 cases of prostatic cancer, before and after castration, by using power Doppler imaging, and compared the changes in vascular resistance (RI) and prostatic volume (PV) in 11 cases. RI, except for one case, and PV decreased after castration in all cases without exception. In both, the manner of decrease showed an exponential curve. However, the reduction time of RI fell in an extremely narrow range compared with that of PV. Tumor vascular flow was influenced by castration, resulting in a decrease of RI. The dynamic change of vascular flow occurred earlier than that of PV. Analysis of changes in tumor blood flow signals could offer valuable information on early therapeutic effects in patients with prostatic cancer; however, it might not be a useful parameter for the prediction of prognosis.

Adenocarcinoma↗