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Biomedical subjects

Y Sakuma

Publications and source records attributed to Y Sakuma.

At least 19 recordsLinked to original sources
PubMed2006

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer.

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.

Adult↗
PubMed2005

Retroperitoneoscopic living donor nephrectomy: a safe and minimally invasive procedure for the donor.

A living kidney donor surgery must be safe and minimally invasive. In addition the removed kidney must be in good condition. Retroperitoneoscopic nephrectomy has the advantage that it does not risk intra-abdominal organ injuries and provides direct access to the renal artery/vein despite the small working space. An abdominal wall-lifting method combined with the pneumoretroperitoneum provides sufficient space to use a hand skillfully in retroperitoneoscopic surgery. Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy with the abdominal wall-lifting method yielded safer and easier operations as well as shorter warm ischemia (mean: 3 minutes; 7 seconds) and operative times (mean: 3 hours; 28 minutes) in the current 10 cases. The procedure is a useful alternative to procure a kidney graft.

Adult↗
PubMed2005

Initial functional status predicts infections during steroid therapy for renal diseases.

BACKGROUND AND AIM: Corticosteroid therapy is an effective way of treatment for many renal diseases, however, it is sometimes associated with infections. Our aim is to identify useful predictive markers of infection during steroid therapy. METHODS: We examined 121 patients (M/F = 71/50, mean age 43.8, range 15 - 82 years) who were treated with corticosteroids (IgA nephropathy in 51, minimal-change disease in 17, membranous nephropathy in 16 rapidly progressive glomerulonephritis (RPGN) in 13, lupus nephritis in 12 and other disorders in 12). Karnofsky's performance score (KPS) was employed to assess the physical functional status at the time of diagnosis. Infections were defined as conditions that required more than 1-week care, and those that caused the patient's death. RESULTS: Nineteen patients (15.7%) had infections during treatment. A logistic multivariate analysis showed significant correlations between infection and the use of immunosuppressive agents (relative risk RR = 7.7, p = 0.0265), ages of 52.9 years or more (RR = 13.5, p = 0.0026), initial number of lymphocytes (Lym) less than 1.250/microl (RR = 14.2, p = 0.0011), and KPS less than 77.4 (RR = 12.1, p = 0.0020). All correlations with infection were independent of all the other variables listed above. CONCLUSION: KPS, along with age, Lym and the use of immunosuppressive agents, are useful for the prediction of infectious complications during steroid therapy.

Activities of Daily Living↗
PubMed2004

Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 19 patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received two cycles of chemotherapy. Cycles were repeated every 4 weeks. The starting doses (dose level 1) were docetaxel 60 mg m(-2), cisplatin 70 mg m(-2), and 5-day continuous infusion of 5-FU 600 mg m(-2) day(-1). Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose to the primary tumour site and neck lymph nodes was between 63.0 and 74.0 Gy. At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was docetaxel 60 mg m(-2), cisplatin 60 mg m(-2) and 5-FU 600 mg m(-2) day(-1). The main toxicities were mucositis (grade 3 and 4, 79%), leukocytopenia (grade 3 and 4, 53%), neutropenia (grade 3 and 4, 42%), anaemia (grade 3, 16%), liver dysfunction (grade 3, 11%) and renal dysfunction (grade 2, 11%). The overall response rate was 100%, including 84% complete responses (CRs). This concurrent chemoradiotherapy with TPF was safe and well tolerated. The high CR rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients.

Aged↗
PubMed2004

Sex and region-specific regulation of oestrogen receptor beta in the rat hypothalamus.

Sexual dimorphism in the expression of oestrogen receptor (ER)beta mRNA and protein was characterized in the rostral forebrain of the rat and its dependence on the neonatal endocrine environment was revealed. We present novel data demonstrating, in gonadectomized adult rats, that the amount of oestrogen caused a significant reduction in the number of ERbeta messages and protein in the ventromedial nucleus in both sexes, but no such effects were detected in the preoptic area or the amygdala. In gonadectomized females, more so than in males, the ventromedial nucleus of the adult rat contained a significantly larger number of ERbeta-positive neurones both in terms of ERbeta mRNA and protein. In the juvenile rat on day 14, sex difference in ERbeta expression was already observed in the ventromedial nucleus. Treatment of neonatal females with oestrogen from days 1-10 or neonatal orchidectomy of males reversed the sex difference in the ventromedial nucleus when observed on day 14, showing that the neonatal presence of oestrogen had caused irreversible masculinization of this structure. Our results suggest that sex-specific expression of ERbeta is patterned by perinatal hormone exposure: down-regulation of ERbeta caused by oestrogen in a region-specific manner.

Age Factors↗
PubMed2004

Close relationship of plasminogen activator inhibitor-1 4G/5G polymorphism and progression of IgA nephropathy.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) 4G/4G genotype influences the development of diabetic nephropathy and lupus nephritis. However, the association of the PAI-1 4G/4G genotype and IgA nephropathy (IgAN) has not been investigated. SUBJECTS AND METHODS: The PAI-1 and ACE polymorphisms were examined in 270 healthy volunteers and 202 biopsy-proven IgAN patients, including 117 untreated IgAN patients who had an annual health check, allowing an estimation of the time of onset of overt proteinuria and/or hematuria. The relationship between the gene polymorphisms and the pathogenesis of IgAN were examined in 202 IgAN patients and the relationship between the gene polymorphisms clinical and pathohistological findings were examined in 117 untreated IgAN patients cross-sectionally at the time of renal biopsy. RESULTS: 202 IgAN patients and 117 untreated IgAN patients did not have different frequencies in PAI-1 4G/5G (4G/4G : 4G/5 : 5G/5G = 82 : 90: 30, 45 : 55 : 17) and ACE I/D (DD : ID : II = 41 : 82 : 79, 21 : 54 : 42) gene polymorphisms compared with 270 healthy volunteers (4G/4G : 4G/5 : 5G/5G = 99 : 124 : 47, DD : ID : II = 53 : 106 : 111). However, IgAN with 4G/4G had significantly more advanced histological changes than IgAN with 4G/5G or 5G/5G both in glomerular and tubulointerstitial findings (p < 0.0005). The disease duration in IgAN with 4G/4G was shorter than in IgAN with 4G/5G + 5G/5G (6.22 +/- 6.38 and 8.80 +/- 9.79 years, respectively, p < 0.05). Creatinine clearance (Ccr) in IgAN with 4G/4G was significantly lower than IgAN with 4G/5G or 5G/5G (72.3 +/- 26.5 and 82.4 +/- 22.8 ml/min, respectively, p < 0.05). The mean urinary protein excretion in IgAN with 4G/4G was significantly more than in IgAN with 4G/5G or 5G/5G (1.10 +/- 1.48 and 0.70 +/- 1.01 g/day, respectively, p < 0.05). There was no difference between IgAN with the DD ACE genotype and IgAN with ID + II genotypes in either the clinical or histopathological findings. CONCLUSION: PAI-1 polymorphism is not associated with genesis of IgA nephropathy, but may be a risk factor for the progression of IgA nephropathy in Japanese.

Adolescent↗
PubMed2003

Possible involvement of preoptic estrogen receptor beta positive cells in luteinizing hormone surge in the rat.

The anteroventral periventricular nucleus (AVPV) of the preoptic area has been implicated in the induction of spontaneous ovulation. In the AVPV, we found a striking sex difference in the distribution of estrogen receptor (ER) positive cells. In females, a significantly larger number of ER mRNA-positive cells were visualized than in males using in situ hybridization in the most medial part of the AVPV next to the ependymal lining of the third ventricle. In males, the labeled cells were dispersed into more lateral region. Immunohistochemistry revealed a similar sexual dimorphism in the ER protein. The dimorphism persisted from Day 7 to Day 60. Orchidectomy of male neonates or estrogen treatment of female pups had reversed the brain phenotype when examined on Day 14. No gross sex difference was detected in the pattern of ER expression in the medial preoptic nucleus and the bed nucleus of the stria terminals. Estrogen receptor immunoreactive cells co-localization in 83% of ER mRNA positive cells in the AVPV of adult females. Infusion of an ER antisense oligonucleotide into the third ventricle resulted in a significantly longer period of successive vaginal estrus and 50% reduction in the number of ER-immunoreactive cells in the AVPV. These findings suggest an important role of ER AVPV in the female-typical estrogen-dependent induction of the luteinizing hormone surge.

Animals↗
PubMed2003

Oestrogen-induced vigorous mounting in female rats carrying hypothalamic knife cuts.

In ovariectomized Wistar rats, 1- or 2-mm wide knife cuts were placed in a coronal plane from the surface of the cortex to the floor of the cranial cavity to interrupt posterior efferents of the ventromedial nucleus of the hypothalamus (VMN). Sham-operated females had the same knife lowered to a depth of 7 mm. Ovariectomized nonoperated females were also used. After recovery, all rats received a single injection of 2 microg oestradiol benzoate, and were tested 48 h later for male and female sexual behaviour and partner preference. When placed with highly receptive stimulus females, the rats with the 2-mm cut showed a significantly higher incidence of mounting with ejaculatory thrusts than any other groups. When placed with stud males, 1-mm cut, as well as sham-operated females, had increased lordosis quotients. Similarly, both 1-mm and 2-mm cuts and sham operation enhanced the incidence of ear wiggling. Despite the display of a transsexual behaviour (i.e. vigorous mounting), all females with the cut showed heterosexual partner preference. Thus, the cut in the present study removed the inhibitory neural effect on mounting, which presumably descends from the VMN. In the absence of this inhibition, minute amounts of oestrogen sufficed to induce vigorous mounting. Sham operation in the present study appeared to interfere with certain inhibitory neural circuitry for lordosis.

Animals↗
PubMed2003

Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas.

BACKGROUND: Gastric mucosa associated lymphoid tissue (MALT) lymphomas are clinically subdivided into Helicobacter pylori dependent and independent, according to H. pylori infection and the therapeutic course. In previous reports it has been suggested that H. pylori independent cases develop from H. pylori dependent cases, and sometimes transform into high grade diffuse large B cell lymphomas (DLBCLs). METHODS: To better understand the pathogenesis of H. pylori dependent and independent MALT lymphomas, we analysed the methylation profiles of eight independent CpG islands, including p15, p16, p73, hMLH1, death associated protein kinase, MINT1, MINT2, and MINT31 in H. pylori dependent and independent MALT lymphomas, DLBCLs, and H. pylori associated chronic gastritis. RESULTS: We first confirmed that H. pylori independent cases had a high incidence of t(11;18)(q21;q21) (4/8 cases) and aberrant BCL10 expression (7/8 cases) compared with H. pylori dependent cases and gastric DLBCLs. In the methylation pattern study, all 13 H. pylori dependent MALT lymphomas had more than four methylated loci while H. pylori independent cases had less than two. According to the previous criterion, all H. pylori dependent MALT lymphomas (13/13, 100%) and five of 10 (50%) DLBCLs were classified as CpG island methylator phenotype positive (CIMP+). In contrast, all H. pylori independent MALT lymphomas were CIMP-. CONCLUSION: The distinct methylation pattern together with lack of chromosomal translocation in H. pylori dependent MALT lymphomas suggest that H. pylori dependent and independent MALT lymphomas have a different pathogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Insulin resistance highly associates with hypertension in IgA nephropathy.

BACKGROUND: Insulin resistance has been reported to induce hypertension. Previous studies described that there was no relationship between insulin resistance and hypertension in patients with chronic renal diseases with mild to moderate renal dysfunction. The aim of the present study is to clarify the relationship between insulin resistance and blood pressure, renal function, histopathological changes and other characteristics in IgA nephropathy (IgAN). METHODS: Eighty-eight IgAN patients were included in this cross-sectional study. Hypertension was diagnosed according to the WHO/ISH criteria. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). RESULTS: Male gender, age, body mass index, serum creatinine, urinary protein excretion, triglycerides and HOMA-IR were positively correlated with hypertension. C(Cr), serum albumin and HDL cholesterol were negatively correlated with blood pressure by Spearman's simple correlation test. By logistic multivariate analysis, C(Cr), insulin resistance, age and male gender were significantly correlated with hypertension, independently of all other variables. CONCLUSIONS: Insulin resistance is not directly related to renal dysfunction, but is also independently associated with hypertension in IgAN. Since hypertension is considered as a risk factor for renal disease progression, insulin resistance may be an indirect deteriorating factor for IgAN. To identify and improve insulin resistance may be another therapeutic target in the clinical management of IgAN.

Adult↗
PubMed2002

Spatio-temporal expression of gonadotropin-releasing hormone receptor subtypes in gonadotropes, somatotropes and lactotropes in the cichlid fish.

The description of two or more forms of gonadotropin-releasing hormone (GnRH) in most vertebrates suggests multiple roles for this family of peptide hormones. In order to verify these functions, we analysed the anatomical location, time of initial expression and ontogenic changes in three distinct GnRH receptors (GnRH-Rs) in developing and sexually mature tilapia, using antisera raised against the extracellular loop three of the receptor, which is a determinant in ligand-selectivity and receptor coupling to signalling pathways. In all age groups, including males and females, using in situ hybridization and double-label immunological methods, GnRH-R type IA was colocalized in cells containing luteinizing hormone (LH) beta-subunit in the pituitary. GnRH-R type IB was visualized in prolactin cells and LH cells. The type III GnRH-R was expressed in growth hormone cells. On day 8 after fertilization, GnRH-R type III was first seen in growth hormone cells and, subsequently, on day 15, GnRH-Rs type IA and type IB were first seen in LH and prolactin cells, respectively. On day 25, the receptor occupied area per pituitary and the staining intensity of GnRH-R type IA increased significantly, consistent with the hypothesis that differentiation of GnRH neurones and their inputs to the pituitary coincide precisely with gonadal sex differentiation and steroidogenesis in tilapia. The differential distribution of GnRH-Rs in the pituitary provides the first clear evidence that the three native GnRH variants in tilapia have cognate receptors, each capable of regulating different pituitary endocrine cells.

Animals↗
PubMed2002

Access-control and interlock-signal systems for the LHD experimental hall.

An access-control system has been developed and installed at the National Institute for Fusion Science. The system uses an interlock-signal system and a group-access-control system to safeguard the operation of the large helical device. In this paper, the access-control system is described along with its features, advantages and disadvantages, and benefits.

Environmental Exposure↗
PubMed2001

Green fluorescent protein-transgenic rat: a tool for organ transplantation research.

The purpose of this study is to evaluate green fluorescent protein (GFP) transgenic rats for use as a tool for organ transplantation research. The GFP gene construct was designed to express ubiquitously. By flow cytometry, the cells obtained from the bone marrow, spleen, and peripheral blood of the GFP transgenic rats consisted of 77, 91, and 75% GFP-positive cells, respectively. To examine cell migration of GFP-positive cells after organ transplantation, pancreas graft with or without spleen transplantation, heart graft with or without lung transplantation, auxiliary liver and small bowel transplantation were also performed from GFP transgenic rat to LEW (RT1(1)) rats under a 2-week course of 0.64 mg/kg tacrolimus administration. GFP-positive donor cells were detected in the fully allogenic LEW rats after organ transplantation. These results showed that GFP transgenic rat is a useful tool for organ transplantation research such as cell migration study after organ transplantation without donor cell staining.

Animals↗
PubMed2001

Sex differences in the brain of goldfish: gonadotropin-releasing hormone and vasotocinergic neurons.

The differences between male and female behaviors are reflected in sexual dimorphism of brain structures and are found throughout the nervous system in a variety of vertebrates. The present study examined neurons immunolabeled for gonadotropin-releasing hormone and arginine vasotocin in the brain of the goldfish Carassius auratus to determine if these neurons are sexually dimorphic. There was no sex difference or influence of sex steroids on the neuronal volume and optical density of staining of arginine vasotocin neurons. Similarly, gonadotropin-releasing hormone neurons of the terminal nerve and midbrain tegmentum did not differ between sexually mature males, females and maturing females replaced with sex steroids with respect to distribution, numbers, optical density of staining, or gross morphology. In maturing females, testosterone specifically recruited additional preoptic gonadotropin-releasing hormone neurons to equal those in sexually mature individuals. Since estrogen had no effect, the influence of testosterone on gonadotropin-releasing hormone neuronal numbers appears to be independent of aromatization. Specifically, the preoptic gonadotropin-releasing hormone neuronal size was significantly larger in sexually mature males than females. 11-Ketotestosterone-replacement to ovariectomized maturing females induced male-typical secondary characters and male-type courtship behavior but did not masculinize the preoptic gonadotropin-releasing hormone neuronal size. Our results show that the sexually dimorphic preoptic gonadotropin-releasing hormone neuronal size is determined by factors (genetic) other than gonadal steroids. Further, we propose the hypothesis that phenotypic and behavioral sex differences need not be accompanied by structural differences in gonadotropin-releasing hormone and arginine vasotocin in the brain.

Animals↗
PubMed2001

High-dose tacrolimus and lengthy survival of the combined rat pancreas/spleen graft in a high-responder combination.

Pancreas grafts do not survive for lengthy periods, especially in a high-responder rat combination. Recent data indicated that a combined spleen/pancreas graft protects against acute graft rejection and induces donor-specific tolerance. In this study, we performed a combination spleen/pancreas transplantation using high-dose tacrolimus in a high-responder rat combination of DA (RT1a) to LEW (RT1) and induced permanent survival in the few recipient rats. In these recipients, there was no difference in the mixed lymphocyte reaction (MLR) of the recipients when compared with that of the naive LEW splenic cells, but MLR inhibition by the serum from the recipients was significantly decreased. We also performed immunoblotting and detected a protein that has an affinity for the anti-DA class antibody. This protein may be an anti-idiotypic antibody and contribute to donor- and tissue-specific tolerance.

Animals↗