Biomedical subjects

T Koike

Publications and source records attributed to T Koike.

At least 91 records · Page 5Linked to original sources

PubMed2001

Measurement of stapes mobility in guinea pigs and rabbits.

In tympanoplasty, it is essential to know the condition of the stapes. However, it has been difficult to evaluate stapes mobility in routine measurement. With the eye on improving future clinical practice, in this study we developed a new, easy system of measuring stapes mobility quantitatively and, as a first step, applied it to measurement of the relationship between the load and displacement of the stapes in guinea pigs and rabbits. The stapes displacement increased linearly with an increase in load in the small displacement region, and increased nonlinearly in the large displacement region. The slope of the regression line of this stiffness curve in the small displacement region was used as an index of the stapes mobility. The values in the guinea pigs and rabbits were 16+/-7 N/m and 115+/-25 N/m, respectively. A significant difference between the two species was observed.

Animals↗

PubMed2001

Genetics of antiphospholipid syndrome.

The mechanisms of thrombosis in antiphospholipid syndrome (APS) are highly heterogeneous and multifactorial, and some genetic factors may be involved in its pathophysiology. The genetic variants of representative antigen, beta 2-glycoprotein I (beta 2GPI), have been known, and valine/leucine247 polymorphism is a genetic risk for having anti beta 2GPI antibodies and APS. Congenital beta 2GPI deficiency did not correlate with thrombophilia, thus its responsible gene (beta 2GPI-Sapporo) was not a risk for thrombosis. Many other thrombosis-related genetic factors have been investigated in APS, but no additional risk for thrombosis has been indicated in patients with antiphospholipid antibodies.

Antibodies, Antiphospholipid↗

PubMed2001

Anti-phosphatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages.

OBJECTIVE: To determine whether the presence of anti-phosphatidylserine/ prothrombin antibodies (anti-PS/PT) can be a major factor in otherwise unexplained recurrent miscarriages. PATIENTS AND METHODS: Eighty-one consecutive patients with history of 2 or more recurrent miscarriages were studied. Patients with history of overt thrombotic events were not included. Patients were examined for plausible causes of miscarriages, and titer of IgG, IgM and IgA anti-PS/PT were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-five patients had one or more plausible causes of recurrent miscarriages, including 12 positive for well-established anti-phospholipid antibodies, such as anti-beta2-glycoprotein I. None of the patients included in this study was found to be positive for anti-PS/PT. CONCLUSION: Detection of anti-PS/PT in addition to other anti-phospholipid antibodies does not seem to aid in the evaluation of patients with unexplained recurrent miscarriages.

Abortion, Habitual↗

PubMed2001

Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins.

1. The mechanism of Na(+) channel block by three macrocyclic polyamine derivatives and two spider toxins was studied with voltage clamp and internal perfusion method in squid axons. 2. All these chemicals specifically block Na(+) channels in the open state only from the internal surface, and do not affect K(+) channels. 3. The blocking effect is enhanced as the depolarizing pulse becomes larger. Blocked channels are unable to shift to the inactivated state. 4. In the case of cyclam and guanidyl-side armed cyclam (G-cyclam), quick release of these chemicals from the binding sites is proven by the increase in the tail current and prolongation of the time course of the off gating current. On the other hand, in the presence of N-4 and the spider toxins, their detachment was delayed significantly. 5. Molecular requirements for the block of Na(+) channels by these molecules are the presence of positive charge and hydrophobicity.

Algorithms↗

PubMed2001

A possible role for lamivudine as prophylaxis against hepatitis B reactivation in carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Hepatitis B virus (HBV) reactivation, a well-known complication in immunosuppressed patients, can give rise to acute hepatitis and even fatal fulminant hepatitis. Three Japanese males with non-Hodgkin's lymphoma (NHL) who were carriers of HBV received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). To prevent HBV reactivation, all received oral lamivudine (150 mg/day), a nucleoside analogue, at the start of chemotherapy. All were treated at full-dose intensity, including corticosteroids, without modification of treatment regimens. All three patients completed the total course of chemotherapy and PBSCT, with no signs of HBV reactivation. Peripheral blood stem cell (PBSC) harvests and hematological recoveries after transplantation were not affected by lamivudine, which was continued for at least 16 weeks after transplantation. HBV-DNA and DNA polymerase levels remained negative/normal after discontinuation of lamivudine. Lamivudine effectively inhibits HBV replication and has few serious adverse effects, particularly those related to hematopoiesis. Thus, prophylactic use of lamivudine from initiation of chemotherapy deserves consideration in the treatment of HBV carriers who require immunosuppressive chemotherapy, and may prevent HBV reactivation.

Adult↗

PubMed2001

Successful non-myeloablative stem cell transplantation for a heavily transfused woman with severe aplastic anemia complicated by heart failure.

A 30-year-old Japanese woman weighing 35 kg with severe hemochromatosis due to multiple transfusions was referred to our clinic for treatment of severe aplastic anemia (SAA). The patient had heart failure with an ejection fraction of 36% requiring diuretics and a severe liver dysfunction with an indocyanine green clearance rate of 18%, as well as other transfusion-related complications such as chronic hepatitis due to hepatitis C virus and diabetes mellitus. She was treated with a non-myeloablative preparative regimen that included fludarabine monophosphate (Flu, 120 mg/m(2)), cyclophosphamide (CY, 1200 mg/m(2)) and antithymocyte globulin (ATG, 15 mg/kg) followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-matched sister. The regimen was well tolerated, and engraftment rapidly occurred without any therapy-related complications. Chimerism analysis on day 14 after transplant showed reconstitution with 100% donor cells. She no longer needed transfusion after day 23 and has been well in 90% Karnofsky status at 4 months post transplant. The clinical course of this patient indicates that this preparative regimen enables SAA patients with severe organ failure to safely undergo allogeneic stem cell transplantation.

Adult↗

PubMed2001

Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome.

Mannose-binding lectin (MBL) is a key element of the innate immunity, with a structure similar to complement C1q. Serum MBL levels are greatly affected by the polymorphisms of the MBL gene. In particular, codon 54 mutation of the MBL gene results in a significant reduction of serum MBL. To determine whether polymorphism of the MBL gene is associated with occurrence of systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjögren's syndrome in the Japanese population, we analyzed the MBL gene polymophisms of these patients and controls, by polymerase chain reaction-restriction fragment length polymorphism methods. We found that patients studied had a significantly higher frequency of having homozygous codon 54 mutation compared to controls. In particular, patients with SLE or Sjögren's syndrome showed higher probabilities of being homozygous for this mutation. Among subjects with the same genotype, SLE patients tended to have higher serum MBL concentration than controls. Analysis of the promotor region suggested that SLE patients heterozygous for the codon 54 mutation have a higher probability of having a low producing haplotype for the gene without the codon 54 mutation. We conclude that persons homozygous for codon 54 mutation of the MBL gene may be prone to occurrence of autoimmune disorders including SLE, in the Japanese. MBL may have protective effects on occurrence and progression of SLE.

Arthritis, Rheumatoid↗

PubMed2001

Increased gastric acid secretion after Helicobacter pylori eradication may be a factor for developing reflux oesophagitis.

BACKGROUND: The role of acid secretion in reflux oesophagitis which may develop after H. pylori eradication is not well known. AIM: To investigate the participation of altered gastric acid secretion and the presence of hiatal hernia in the development of reflux oesophagitis after eradication therapy for H. pylori. SUBJECTS AND METHODS: A total of 105 patients with H. pylori infection, but without reflux oesophagitis at the time of eradication therapy, were followed prospectively for 7 months after the clearance of this microorganism. Gastric acid secretion was assessed by endoscopic gastrin test, and the presence of hiatal hernia by endoscopy. RESULTS: Reflux oesophagitis developed in 11 out of 105 (10.5%) patients when examined at 7 months after the eradication therapy. The incidence was correlated significantly with the increase in gastric acid secretion after the eradication of H. pylori, and was significantly higher in the patients with hiatal hernia (20%) than in those without it (0%). CONCLUSIONS: Increased acid secretion after H. pylori eradication is an important risk factor of reflux oesophagitis, especially in patients with hiatal hernia.

Adult↗

PubMed2001

Detection of 'antiphospholipid' antibodies: a single chromogenic assay of thrombin generation sensitively detects lupus anticoagulants, anticardiolipin antibodies, plus antibodies binding beta(2)-glycoprotein I and prothrombin.

The diagnosis of the antiphospholipid syndrome (APS) requires both a typical clinical event plus a persistently positive test in an assay for either anticardiolipin (aCL) antibodies or a lupus anticoagulant (LA). Enzyme linked immunosorbent assays (ELISA) specific for autoantibodies against beta(2)-glycoprotein I (beta(2)GPI) or prothrombin are also used, but none of the tests are adequately sensitive or specific. A chromogenic assay was developed that measures the effect of test antibody or plasma samples on in vitro thrombin formation. It is able to detect both LA and beta(2)GPI-dependent aCL antibodies and may have greater specificity for APS than currently available tests. Using this method various monoclonal antibodies (MoAbs) were examined, from mice immunized with beta(2)GPI, mice with a spontaneous animal model of APS, and from three humans with APS. Plasma and affinity purified antibodies from patients with APS and control groups were also examined. Thrombin inhibition was more sensitive to perturbation by MoAbs than a combination of tests for LA (P < 0.05) and at lower antibody concentrations (12.5 microg/ml versus 100 microg/ml). There was a significant correlation between inhibition of thrombin generation and the level of MoAb reactivity to beta(2)GPI (r = 0.90; P < 0.001) but not to CL (r = 0.06; P = 0.76). Plasma and affinity purified antibodies from patients with APS also inhibited thrombin generation, and significantly more so than patients with aPL from causes other than APS. APS patient samples showed thrombin inhibition in the presence of anti-beta(2)GPI or antiprothrombin antibodies. All MoAbs binding beta(2)GPI showed inhibition of thrombin generation, while MoAbs binding domain I of beta(2)GPI had more LA effect.

Animals↗

PubMed2001

Interleukin-6 (IL-6) producing phaeochromocytoma: direct IL-6 suppression by non-steroidal anti-inflammatory drugs.

A 35-year-old Japanese woman presented with a phaeochromocytoma and demonstrated marked inflammatory reactions and pyrexia as a result of excessive production of interleukin-6 (IL-6) by the tumour. Serum IL-6 level was 262 ng/l (normal; < 4.0 ng/l). Fever and inflammatory markers were largely overcome by the administration of the nonsteroidal anti-inflammatory drug, naproxen, and all symptoms disappeared soon after the tumour was excised. Immunohistochemical study revealed positive staining using an antihuman IL-6 antibody and Northern analysis showed increased IL-6 mRNA levels in the tumour. Cultured tumour cells showed IL-6 protein synthesis, and nonsteroidal anti-inflammatory drugs such as naproxen and indomethacin directly inhibited IL-6 release. These results indicate that the effects of naproxen in vivo were due, at least in part, to direct suppression of IL-6 secretion from the tumour.

Adrenal Gland Neoplasms↗

PubMed2001

Rapid induction and Ca(2+) influx-mediated suppression of vitamin D3 up-regulated protein 1 (VDUP1) mRNA in cerebellar granule neurons undergoing apoptosis.

Cerebellar granule neurons (CGNs) grown under depolarizing conditions with high K(+) (HK; 30 mM) undergo apoptosis following replacement of HK by physiological K(+) (5.4 mM). Differential display analysis identified eight genes up-regulated in this paradigm of apoptosis. Vitamin D3 up-regulated protein 1 (VDUP1) mRNA was markedly up-regulated as early as 2 h following HK withdrawal. VDUP1 mRNA was up-regulated in other paradigms of neuronal apoptosis as well both in vitro and in vivo. HK effectively suppressed the up-regulation of VDUP1 mRNA in CGNs undergoing apoptosis via Ca(2+) influx through voltage-dependent L-type Ca(2+) channels, which did not require de novo protein synthesis. The up-regulation occurred in parallel with that of the c-jun transcript and c-jun protein phosphorylation. Moreover, SB203580, p38 mitogen-activated protein kinase inhibitor, suppressed up-regulation of both c-jun and VDUP1 mRNAs, and c-jun phosphorylation in CGNs undergoing apoptosis. IGF-1, one of the neuroprotective agents for CGNs, also inhibited VDUP1 mRNA up-regulation through a phosphoinositide 3 kinase-dependent pathway. These results suggest that the VDUP1 gene is a novel member of early response genes in neuronal apoptosis whose expression is directly regulated by Ca(2+) influx and coordinately regulated with the transcription factor c-jun in CGNs.

Animals↗

PubMed2001

Tissue distribution of NS-49, a phenethylamine class alpha 1A-adrenoceptor agonist, in pigmented rats.

After a single oral administration of 1 mg/kg of 14C-NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, CAS 137431-04-0), the radioactivity distribution in tissues of male pigmented rats was studied and compared with that in male albino rats. One eye of each pigmented rat was divided into melanin-containing structures (uvea, pigmented epithelium and sclera) and others without melanin (cornea and lens), and the radioactivity concentration in each ocular tissue was measured. In all the pigmented rat body tissues tested, maximum radioactivity concentrations (Cmax) were reached within 4 h after administration. At 1 h, the kidney showed the highest concentration (11 times the plasma concentration), followed by the urethra, liver, urinary bladder and lung. Concentrations in the other tissues were similar to or less than the plasma concentration. The radioactivity concentrations in most tissues decreased rapidly, being less than 10% of the Cmax 24 h after administration. These characteristics of the 14C-NS-49 tissue distribution in the pigmented and albino rats did not differ. In the eye, however, the radioactivity concentration decreased more slowly in the pigmented than in the albino rats. Most of the radioactivity in the eyes of the pigmented rats was present in melanin-containing structures indicating that NS-49 binds to ocular melanin. The radioactivity concentration in the melanin-containing structures reached a maximum 4 h after administration, then decreased as did that for the whole eye with a t1/2, beta of 66.8 h.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2001

Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy.

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.

Aged↗

PubMed2001

Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station.

BACKGROUND: The number of N2 stations (single vs multiple N2 stations) is an important prognostic factor in patients with completely resected stage IIIA-N2 non-small cell lung cancer. However, the significance of both the N2 station(s) actually involved and the primary tumor location remains unclear. METHODS: The database was built with the use of a questionnaire survey on the survival of patients with pathologic stage IIIA-N2 non-small cell lung cancer completely resected between January 1992 and December 1993. The survey was performed by the Japan Clinical Oncology Group as of July 1999. The data include information on the survival and N2 stations of 402 patients. RESULTS: A frequently metastasized single N2 station was the lower pretracheal station in primary tumors in the right upper lobe, the subaortic station in the left upper lobe, and the subcarinal station in the right middle or lower lobe and the left lower lobe. In multiple N2 stations, the frequency of metastasis of the N2 station observed in a single N2 station was as high as 72% to 89%, and one or two other frequently metastasized stations were added to each group. Regarding the survival of patients with a primary tumor in each lobe except for the left lower lobe, a single N2 station resulted in a significantly better survival than did multiple N2 stations. Furthermore, the overall survivals classified according to each primary site showed a significant difference among the four primary sites (P =.04). CONCLUSIONS: The primary tumors in each lobe showed a prevalence of N2 station(s). The number of N2 stations is a good prognosticator except in patients with a primary tumor in the left lower lobe. In addition, the site of a primary tumor itself is also considered to influence the survival of the patients.

Adult↗

PubMed2001

Leaf morphology and photosynthetic adjustments among deciduous broad-leaved trees within the vertical canopy profile.

Photosynthetic acclimation of deciduous broad-leaved tree species was studied along a vertical gradient within the canopy of a multi-species deciduous forest in northern Japan. We investigated variations in (1) local light regime and CO2 concentration ([CO2]), and (2) morphological (area, thickness and area per mass), biochemical (nitrogen and chlorophyll concentrations) and physiological (light-saturated photosynthetic rate) attributes of leaves of seven major species on three occasions (June, August and October). We studied early successional species, alder (Alnus hirsuta (Spach) Rupr.) and birch (Betula platyphylla var. japonica (Miq.) Hara); gap phase species, walnut (Juglans ailanthifolia Carrière) and ash (Fraxinus mandshurica var. japonica Rupr.); mid-successional species, basswood (Tilia japonica (Miq.) Simonk.) and elm (Ulmus davidiana var. japonica (Rehd.) Nakai); and the late-successional species, maple (Acer mono Bunge). All but maple initiated leaf unfolding from the lower part of the crown. The [CO2] within the vertical profile ranged from 320-350 ppm in the upper canopy to 405-560 ppm near the ground. The lowest and highest ambient [CO2] occurred during the day and during the night, respectively. This trend was observed consistently during the summer, but not when trees were leafless. Chlorophyll concentration was positively related to maximum photosynthetic rate within, but not among, species. Leaf senescence started from the inner part of the crown in alder and birch, but started either in the outer or top portion of the canopy of ash, basswood and maple. Chlorophyll (Chl) to nitrogen ratio in leaves increased with decreasing photon flux density. However, Chl b concentration in all species remained stable until the beginning of leaf senescence. Maximum photosynthetic rates observed in sun leaves of early successional species, gap phase or mid-successional species, and late successional species were 12.5-14.8 micromol m(-2) s(-1), 4.1-7.8 micromol m(-2) s(-1) and 3.1 micromol m(-2) s(-1), respectively.

Carbon Dioxide↗

PubMed2001

Growth and annual ring structure of Larix sibirica grown at different carbon dioxide concentrations and nutrient supply rates.

We compared effects of ambient (360 vpm) and elevated (720 vpm) carbon dioxide concentration ([CO2]) and high and low nutrient supply rates on stem growth, annual ring structure and tracheid anatomy of Siberian larch (Larix sibirica Ledeb.) seedlings over two growing seasons. Elevated [CO2] had no significant effect on either stem height or diameter growth; however, both stem height and diameter growth were enhanced by the high nutrient supply rate, and these increases were stimulated by elevated [CO2]. Elevated [CO2] tended to increase the width of the annual xylem ring, the number of cells in a radial file spanning the ring, and tracheid lumen diameter, whereas it tended to reduce cell wall thickness, although there were no statistically significant CO2 effects on tracheid anatomy. Changes in tracheid cell morphology seemed to be dependent on changes in shoot elongation rates.

Carbon Dioxide↗

PubMed2001

Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion.

BACKGROUND: Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly. AIMS: We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects. SUBJECTS: A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis. METHODS: The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test. RESULTS: H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis. CONCLUSION: In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.

Adolescent↗

PubMed2001

Insulin response patterns contribute to different perinatal risks in gestational diabetes.

The aim of this study was to evaluate the insulin dynamics of patients with gestational diabetes mellitus (GDM) and to compare perinatal outcomes according to the insulin response patterns. Twenty-two out of 925 consecutive women examined were diagnosed as having GDM. One hundred and ten women who experienced a normal pregnancy were used as controls. Plasma glucose levels and insulin responses were evaluated by a 2-hour 75-gram oral glucose tolerance test (OGTT). Immunoreactive insulin (IRI), the area under the curve (AUC) of glucose (AUCg) and insulin (AUCi), and the insulinogenic index (II = DeltaIRI 30 min/DeltaBS 30 min) were measured. The GDM patients were divided into three subgroups, consisting of hyper-, normo- and hypoinsulinemic groups, according to the mean +/- 2 SD of the AUCi obtained from the controls. Clinical and laboratory findings were compared among the GDM subgroups and controls. The GDM patients showed impaired insulin secretion to glucose stimuli, with low plasma insulin levels (at 30 min) and reduced insulin/glucose ratios (at 30 and 60 min) early in the 75-gram OGTT. The II and AUCi/AUCg values of GDM patients were reduced as compared with those of controls. These reduced insulin responses were remarkable in hypo- and normoinsulinemic GDM patients, but were not detected in hyperinsulinemic GDM patients. The number of babies large for their gestational age in normo- and hypoinsulinemic GDM patients was significantly higher than that in hyperinsulinemic GDM patients or controls. Hyperinsulinemic GDM patients had a high frequency of pregnancy-induced hypertension (40%). The body mass index prior to pregnancy of hyperinsulinemic GDM patients was significantly higher than that of normoinsulinemic GDM patients or controls. It was demonstrated that not only insulin secretion, but also perinatal clinical characteristics, differed among the GDM subgroups. The heterogeneity of the disease was thus confirmed.

Adult↗