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Biomedical subjects

K Shikata

Publications and source records attributed to K Shikata.

At least 19 recordsLinked to original sources
PubMed2006

Decreasing incidence of lacunar vs other types of cerebral infarction in a Japanese population.

BACKGROUND: There is scant information on secular trends in the incidence and survival of ischemic stroke subtypes. METHODS: The authors established three cohorts of Hisayama residents age > or =40 years in 1961 (1,618 subjects), 1974 (2,038 subjects), and 1988 (2,637 subjects). They followed up with each cohort for 12 years, comparing the incidence and survival rate of ischemic stroke subtypes. Morphologic examinations by autopsy or brain imaging was performed on most of the ischemic stroke cases in all cohorts. RESULTS: The age-standardized incidence of lacunar infarction significantly declined by 59% for men and by 28% for women from the first to the second cohort. It continued to decline by 41% for men, but the decline decelerated for women between the second and third cohort. The age-standardized incidence of atherothrombotic infarction tended to decline from the first to the second cohort, whereas it was sustained between the second and third cohort for both sexes. The age-standardized incidence of cardioembolic infarction was unchanged throughout the cohorts. In these cohorts, mean blood pressure levels among hypertensive subjects and the prevalence of current smoker decreased with time, though the prevalence of hypertension remained stable. The 5-year survival rate after lacunar infarction significantly improved among the cohorts, but those of atherothrombotic and cardioembolic infarction did not. CONCLUSIONS: These data suggest that, in the Japanese population, the incidence of lacunar infarction steadily declined for the last 40 years. The improvement of hypertension control and decreasing prevalence of smoking might be responsible for this trend.

Adult↗
PubMed2005

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats.

AIMS/HYPOTHESIS: Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats. METHODS: STZ-induced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks. To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-kappaB) activity. RESULTS: Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-beta1), type IV collagen protein production and NF-kappaB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment. CONCLUSIONS/INTERPRETATION: Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-kappaB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.

Albuminuria↗
PubMed2003

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education.

OBJECTIVE: To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: In total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months. RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and all other variables including DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at significant levels. CONCLUSION: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.

Adipose Tissue↗
PubMed2002

Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men.

OBJECTIVE: To investigate whether the changes in IGF-I concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: One-hundred and twelve Japanese overweight men aged 30-59 y (body mass index (BMI) 28.4+/-2.5 kg/m(2)) and 33 normal-weight men aged 30-39 y (BMI 22.1+/-1.5 kg/m(2)) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8+/-2.8) were further enrolled into a 1 y exercise program. MEASUREMENTS: Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-I at baseline and after 1 y. RESULTS: In 112 overweight subjects at baseline, insulin (10.5+/-5.0 microU/ml) and leptin (6.4+/-3.7 ng/ml) significantly correlated with both V (r=0.260, P=0.0073; r=0.410, P<0.0001) and S areas (r=0.377, P<0.0001; r=0.613, P<0.0001), respectively. IGF-I (156.8+/-48.7 microU/ml) significantly and negatively correlated with V area (r=-0.242, P=0.0125) and age (r=-0.192, P=0.0480). In normal-weight men aged 30-39 y (n=33) and age-matched subjects (n=30) selected from the 112 overweight men, the serum IGF-I further tightly correlated with V area (r=-0.467, P<0.0001). Visceral fat area and age were independently related to serum IGF-I levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224+/-2781 to 7898+/-4141 steps/day) and reduction of BMI (28.8+/-2.8 to 27.7+/-2.9). deltaIGF-I significantly correlated with deltaV area (r=-0.432, P=0.0009) but not with DeltaS area or deltaBMI. CONCLUSION: The present study indicated a negative correlation between IGF-I levels and visceral fat at baseline as well as an association between the reduction in visceral fat and increase in IGF-I levels after an exercise intervention.

Adipose Tissue↗
PubMed2002

Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis.

Leucocytes infiltrate into renal tissue and are involved in the pathogenesis of crescentic glomerulonephritis. The initial event in the process of leucocyte infiltration is characterized by selectin-mediated leucocyte rolling on endothelial surface. Role of selectins in pathogenesis of glomerulonephritis has still been controversial. Sulphated glycolipids and sulphated polysaccharides interfere with the binding of P- and L-selectin with carbohydrate ligands on endothelial cells or on leucocytes. Here we evaluated the role of selectins and the preventive effects of sulphated colominic acid (SCA), a synthetic sulphated polysaccharide, on experimental crescentic glomerulonephritis in Wistar-Kyoto (WKY) rats. Crescentic glomerulonephritis was induced by injection of nephrotoxic serum (NTS) in WKY rats. Rats subsequently received intraperitoneal injection of saline, neutralizing or non-neutralizing monoclonal antibody (mAb) to rat P-selectin and L-selectin, SCA (5 or 10mg/kg/day) or nonsulphated colominic acid (CA) (10mg/kg/day) for 2 weeks. Localization of P-, E-selectin, ligands for L-selectin and intraglomerular leucocytes was examined by immunohistochemistry. Gene expression of platelet-derived growth factor (PDGF) B chain in glomeruli was quantified using real-time RT-PCR. P-selectin was highly expressed on glomerular endothelial cells after injection of NTS, whereas E-selectin and L-selectin ligands were not detected. Anti-P-selectin mAb, but not anti-L-selectin mAb, significantly reduced glomerular infiltration of macrophages, crescent formation, and proteinuria. SCA also reduced proteinuria, macrophage infiltration, and crescent formation in a dose-dependent manner. Furthermore, SCA suppressed gene expression of PDGF B chain in glomeruli. Our results indicate that P-selectin partially mediates glomerular infiltration of macrophage in experimental crescentic glomerulonephritis. Moreover, SCA may inhibit intraglomerular infiltration of macrophages by interfering with P-selectin-dependent adhesion pathway, and progression of experimental crescentic glomerulonephritis.

Animals↗
PubMed2001

Role of galactosylation in the renal pathogenicity of murine immunoglobulin G3 monoclonal cryoglobulins.

Cryoglobulin activity associated with murine immunoglobulin G3 (IgG3) has been shown to play a significant role in the development of murine lupuslike glomerulonephritis. A fraction, but not all, IgG3 monoclonal antibodies are capable of inducing a severe acute lupuslike glomerulonephritis as a result of direct localization of IgG3 cryoglobulins, suggesting the importance of qualitative features of cryoglobulins in their nephritogenic activities. Here a remarkable difference is shown in the renal pathogenicity of 2 murine IgG3 monoclonal cryoglobulins, identical in the amino acid sequences of their heavy and light chains but different in galactosylation patterns of oligosaccharide side chains because of their synthesis in different myeloma cells. The antibody lacking the capacity to induce severe glomerulonephritis displayed an increased proportion of galactosylated heavy chains. Changes in conformation, as revealed by gel filtration analysis, reduced cryoglobulin activity, and accelerated clearance could account for the lack of the renal pathogenicity of the more galactosylated variant. This observation provides a direct demonstration for the role of IgG galactosylation in the pathogenic potential of cryoglobulins. (Blood. 2001;97:3537-3543)

Animals↗
PubMed2001

Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys.

Collectrin, a novel homolog of angiotensin-converting enzyme-related carboxypeptidase (ACE2), was identified during polymerase chain reaction-based cDNA subtraction and up-regulated in 5/6 ablated kidneys at hypertrophic phase. Collectrin, with 222 amino acids, has an apparent signal peptide and a transmembrane domain; the sequence is conserved in mouse, rat, and human and shares 81.9% identity. Human collectrin has 47.8% identity with non-catalytic extracellular, transmembrane, and cytosolic domains of ACE2; however, unlike ACE and ACE2, collectrin lacks active dipeptidyl carboxypeptidase catalytic domains. The collectrin mRNA transcripts are expressed exclusively in the kidney. In situ hybridization reveals its mRNA expression in renal collecting ducts, and immunohistochemistry shows that it is localized to the luminal surface and cytoplasm of collecting ducts. Immunoprecipitation studies, using [35S]methionine-labeled renal cortical and inner medullar collecting duct cells, i.e. M-1 and mIMCD-3, indicate that the protein size is approximately 32 kDa. During the development of mouse kidney, mRNA signal is detectable at day 13 of gestation, and the protein product is observed in the ureteric bud branches. Its expression is progressively increased during later stages of the gestation extending into the neonatal periods and then is decreased in adult life. Up-regulated expression of collectrin in the hypertrophic kidneys after renal ablation and restricted spatio-temporal expression during development indicates a possible role(s)in the process of progressive renal failure and renal organogenesis.

Amino Acid Sequence↗
PubMed2001

Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes.

Glomerular hyperfiltration plays a pathogenic role in the early stages of diabetic nephropathy. Experimental studies in laboratory animals suggest that nitric oxide (NO) might be involved in the pathogenesis of glomerular hyperfiltration. We performed a cross-sectional study to determine the relationship between diabetic glomerular hyperfiltration and the NO system. Normoalbuminuric (n=41), microalbuminuric (n=25), and macroalbuminuric (n=16) patients with type 2 diabetes were recruited in this study and compared with age-matched 84 non-diabetic control subjects. Creatinine clearance and urinary NO(2)(-)/NO(3)(-) excretion (urinary NOx) were measured, and the expression of endothelial cell nitric oxide synthase (ecNOS) was evaluated in human renal tissues. Glomerular hyperfiltration was present in 19 (37.5%) and nine (36.6%) of normoalbuminuric and microalbuminuric type 2 diabetic patients, respectively. The urinary NOx was significantly higher in normoalbuminuric patients compared with normal subjects. Creatinine clearance correlated significantly with urinary NOx in normoalbuminuric and microalbuminuric patients. Immunohistochemical staining intensities for ecNOS were significantly increased in glomerular endothelial cells of microalbuminuric type 2 diabetic patients as compared with the control subjects. These results suggest that NO may contribute to the pathogenesis of glomerular hyperfiltration in Japanese type 2 diabetic patients.

Adult↗
PubMed2001

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis.

BACKGROUND: To elucidate the molecular mechanism of diabetic nephropathy, a high-density DNA filter array was employed to survey the gene expression profile of streptozotocin-induced diabetic CD-1 (ICR) mouse kidneys. METHODS: Ten-week-old CD-1 male mice were divided into four groups: (1) control, (2) unilaterally nephrectomized (UX) mice, (3) streptozotocin (STZ)-induced diabetic (STZ) mice, and (4) STZ mice with unilateral renal ablation (STZ-UX). Pathological changes were examined at 24 weeks after the induction. The gene expression profile was compared between the control and STZ mice by a Gene Discovery Array (GDA). RESULTS: The glomeruli in UX mouse kidney showed prominent glomerular hypertrophy, while the accumulation of mesangial matrix was minimal. Both STZ and STZ + UX mice had significant glomerular hypertrophy and glomerulosclerosis, and the lesions were not enhanced by renal ablation. By comparison between control and STZ mice, 16 clones that increased in expression with the induction of diabetes and 65 clones that decreased in diabetic kidneys were identified. The 37 known genes were related to glucose and lipid metabolism, ion transport, transcription factors, signaling molecules, and extracellular matrix-related molecules. The genes known to be involved in cell differentiation and organogenesis in various tissues (that is, Unc-18 homolog, POU domain transcription factor 2, lunatic fringe gene homolog, fibrous sheath component 1, Sox-17, fibulin 2, and MRJ) were found to be differentially expressed in the early phase of diabetic kidneys. CONCLUSIONS: Hyperglycemia is a major determinant of glomerulosclerosis in STZ-induced diabetic CD-1 mice, and the altered gene expression in the early phase of diabetic kidney may be critical for the development of diabetic nephropathy.

Animals↗
PubMed2001

The human homologue of fission Yeast cdc27, p66, is a component of active human DNA polymerase delta.

An essential eukaryotic DNA polymerase, DNA polymerase delta (pol delta), synthesizes DNA processively in the presence of proliferating cell nuclear antigen (PCNA). Recently, a 66 kDa polypeptide (p66) that displays significant homology within its PCNA binding domain to that of fission yeast cdc27 was identified as a component of mouse and calf thymus pol delta. Our studies show that p66 interacts tightly with other subunits of pol delta during size fractionation of human cell extracts, and co-immunoprecipitates with these subunits along with PCNA-dependent polymerase activity. Active human pol delta could be reconstituted by co-expressing p125, p50, and p66 recombinant baculoviruses, but not by co-expressing p125 and p50 alone. Interaction studies demonstrated that p66 stabilizes the association between p125 and p50. Pull-down assays with PCNA-linked beads demonstrated that p66 increases the overall affinity of pol delta for PCNA. These results indicate that p66 is a functionally important subunit of human pol delta that stabilizes the pol delta complex and increases the affinity of pol delta for PCNA.

Animals↗
PubMed2001

The effect of antimicrobial periodontal treatment on circulating tumor necrosis factor-alpha and glycated hemoglobin level in patients with type 2 diabetes.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may play an important role in insulin resistance. In this study, we hypothesized that TNF-alpha produced due to periodontal inflammation synergistically affects insulin resistance as well as TNF-alpha produced from adipose tissues in insulin-resistant type 2 diabetes patients. Therefore, to understand the effects of antimicrobial periodontal therapy on serum TNF-alpha concentration and subsequent metabolic control of diabetes, we examined the periodontal and diabetic status on 13 type-2 diabetes patients. METHODS: These patients were treated with local minocycline administration in every periodontal pocket around all existing teeth once a week for a month. Before and after treatment, the number of total bacteria in the periodontal pockets and circulating TNF-alpha concentration were measured and the HbA1c value was assessed. RESULTS: Antimicrobial therapy significantly reduced the number of microorganisms in periodontal pockets (P <0.01). After treatment, the circulating TNF-alpha level was significantly reduced (P <0.015). The HbA1c value was also reduced significantly (P <0.007). In addition, the 6 patients who were not receiving insulin therapy demonstrated decreased fasting insulin levels (P <0.03), and HOMA-R (P <0.03) indices. The average reductions in circulating TNF-alpha concentration and HbA1c value were 0.49 pg/ml and 0.8%, respectively. CONCLUSION: The results indicate that anti-infectious treatment is effective in improving metabolic control in diabetics, possibly through reduced serum TNF-alpha and improved insulin resistance.

Adult↗
PubMed2000

Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold.

Prescription of aerobic exercise for Type 2 diabetes mellitus (Type 2 DM) in clinical practice is frequently based on exercise intensity at maximum heart rate (60<HR(max)<79%), heart rate reserve (50<HR(reserve)<74%), and rating of perceived exertion (12<RPE<13). We examined these parameters in Japanese males with Type 2 DM at ventilatory threshold (VT) to investigate the exercise capacity of Type 2 DM patients and re-evaluate the exercise prescription. Fifty-six Japanese Type 2 DM males without autonomic neuropathy [age, 53.5+/-7.7 years; body mass index (BMI), 23.7+/-3.6 kg/m(2)] were enrolled and compared with 56 age- and BMI-matched healthy Japanese males. VT was determined breath by breath during exercise test using a ramp protocol and rates of oxygen consumption (VO(2)), work rate (WR), HR, DeltaHR, %HR(max), %HR(reserve), and RPE were measured at VT. Type 2 DM patients had significantly lower VO(2) (3.6+/-0.4 metabolic equivalents (METs)) and WR (62+/-14 W) than controls (VO(2), 3.9+/-0.6 METs; WR, 74+/-13 W). %HR(reserve), (32.6+/-7.7%) was also significantly lower compared with controls (37.6+/-8.3%), while %HR(max), was not different. RPE was also similar in diabetics (12.4+/-1.5) and controls (12.9+/-1.2), however, it was significantly lower in diabetic patients aged 60-69 years (11.8+/-2.0) and those with distal symmetric sensory neuropathy (12.2+/-1.0). Our results indicate reduced exercise capacity in Japanese Type 2 DM males and the exercise intensity of 60%HR(max), 30%HR(reserve), and RPE 12 is recommended in elderly diabetics and those with diabetic sensory neuropathy.

Blood Pressure↗
PubMed2000

Clinical evaluation of muscle strength in 20-79-years-old obese Japanese.

It is well known that obesity is closely related to non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and cardiovascular disease, and the insulin resistance associated with obesity is supposed to play a central role for the development of these diseases. Thus, effective prevention and treatment of obesity need to be explored. In 357 obese (body mass index > or =26.4) subjects, aged 20-79 years, grip and leg strength were determined and compared with age- and sex-matched 1683 nonobese control subjects. Age-dependent alteration of body composition, evaluated by waist-hip ratio and the relative fat mass volume, was also compared. Finally, the relationship between the number of risk factors related to atherosclerosis and muscle strength was evaluated. Grip and leg strength in obese subjects were obviously stronger than controls under the age of 60 in both sexes. However, in the subjects over 60 years old, muscle strength was similar between obese subjects and controls. Weight bearing index (WBI) (leg strength (kg)/body weight (kg)) in obese subjects was remarkably lower than that in controls in all generations. In obese subjects, the waist-hip ratio and relative percentage of fat increased with aging, and obese subjects with multiple risk factors had higher waist-hip ratio and a tendency for lower muscle strength. Reduced WBI was considered to be a fundamental feature of obese subjects, and obese subjects increased fat composition with aging, which may be linked with low muscle strength. Thus, we need to design the most effective protocols to maximize and maintain quantitative and qualitative properties of muscle.

Adult↗
PubMed2000

Familial interstitial nephritis with progressive renal failure.

We describe a 53-year-old woman with chronic interstitial nephritis and asymptomatic impairment of renal function. Seven members of her family were suffering from renal failure and underwent hemodialysis. At the time of their hospital admissions, they had shown evidence of end-stage renal failure at 40 to 50 years of age. Lack of proteinuria, hematuria, hypertension, hyperuricemia, hearing loss, and visual impairment were present before the deterioration of the renal function. Renal biopsy of the presented case indicated chronic interstitial nephritis without glomerular basement membrane abnormalities. Progressive decline of renal function and the inheritance pattern of autosomal dominance in this family suggested the diagnosis of familial interstitial nephritis.

Female↗