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Biomedical subjects

M Shindo

Publications and source records attributed to M Shindo.

At least 73 records · Page 4Linked to original sources

Long-term follow-up of hepatitis G virus/GB virus C replication in liver during and after interferon therapy in patients coinfected with hepatitis C and G viruses.

We investigated changes in the titers of positive and negative strands of hepatitis G virus (HGV) RNA and hepatitis C virus (HCV) RNA in serum and liver during and 1 to 3 years after interferon therapy in patients with chronic hepatitis C coinfected with HGV/ GBV-C. Eight (6%) of 134 patients with chronic hepatitis C treated with interferon were positive for HGV RNA and were examined retrospectively. Titers of positive and negative strands of HGV RNA and HCV RNA were determined by strand-specific reverse transcriptase-polymerase chain reaction. Before therapy, HGV RNA titers in liver were lower than those in serum (P = 0.0169), while HCV RNA titers in liver were significantly higher than those in serum (P = 0.0074). No negative strands of HGV RNA were detected in serum, liver, or peripheral blood mononuclear cells in any patients. With interferon therapy, 5 of the 8 patients lost HCV RNA from serum and liver, with sustained normal liver biochemical values and significant histological improvement. HGV RNA disappeared transiently from serum and liver at the end of therapy in 5 patients, but reappeared again after therapy in 4 of them. Two of the 8 patients naturally lost HGV RNA after completion of therapy. These findings suggest that: (1) HGV/GBV-C does not appear to replicate in liver, serum, or peripheral blood mononuclear cells, (2) detection of HGV RNA in liver and peripheral blood mononuclear cells may be a mere reflection of serum HGV RNA, and (3) the long-term clinical outcome of chronic HGV/GBV-C infection appeared to be benign.

Antiviral Agents↗

Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects.

The concentration of high-density lipoprotein cholesterol (HDL-C) is inversely correlated with the risk of coronary heart disease. The effects of low-intensity aerobic training on serum HDL-C and other lipoprotein concentrations were examined in healthy elderly subjects. The subjects were randomly assigned to two groups matched for sex, age, height, and weight. The training group (n = 20, 10 men and 10 women aged 67 +/- 4 years) participated in a supervised physical exercise regimen using a bicycle ergometer at an intensity of 50% estimated maximal oxygen consumption (VO2max) for 60 minutes two to four times per week for 5 months. In contrast, the control group (n = 20, 10 men and 10 women aged 68 +/- 4 years) did not perform any particular physical training. The training protocol resulted in significant increases in the VO2max (P < .05), HDL-C, HDL2-C, and HDL2-C/HDL3-C ratio (P < .01). The change in HDL2-C (r = .57, P < .01) and HDL2-C/HDL3-C (r = .63, P < .01) was positively associated with an increase in the total exercise duration per week. In addition, the total weekly exercise duration also showed a significant positive relationship with HDL-C (r = .75, P < .01), HDL2-C (r = .81, P < .01), and HDL2-C/HDL3-C (r = .71, P < .01) after the training period. The changes in body weight and the VO2max were not significantly correlated with any lipid parameters. Low-intensity aerobic training may improve the profile of HDL-C and its subfractions in healthy elderly subjects. Also, the total exercise duration may be an important factor for improving HDL-C and HDL2-C in elderly subjects.

Aged↗

Decreased skeletal muscle capillary density is related to higher serum levels of low-density lipoprotein cholesterol and apolipoprotein B in men.

The relationships between skeletal muscle morphology, particularly muscle fiber capillary density, and serum lipid profiles were evaluated in 25 non-obese men aged 18 to 36 years (body mass index [BMI], 22.7 +/- 2.5 kg/m2; body fat, 13.6% +/- 4.0%, maximal oxygen uptake [VO2max], 46.2 < or = 6.3 mL/kg/min). Skeletal muscle samples were taken from the vastus lateralis using the needle-biopsy method. The fiber types (I, IIa, and IIx) and their percent distribution, the indices of capillary density, and the diffusion index expressed as the cross-sectional area occupied by one capillary were determined. Blood samples were drawn from the antecubital vein after a 12-hour fast. Based on Pearson's correlation analysis, the number of capillaries around type IIx fiber correlated inversely with the serum level of low-density lipoprotein cholesterol ([LDL-C] r = -.50, P < .05). The number of capillaries per fiber (cap/fiber ratio), number of capillaries per area (cap/mm2), and capillaries around each fiber type correlated inversely with the serum level of apolipoprotein B ([apo B] r = -.40 to -.54, P < .05 to .01). Further, the diffusion index for each fiber type correlated positively with LDL-C and apo B (r = .42 to .50, P < .05 to .01). Among 14 subjects in whom high-density lipoprotein cholesterol (HDL-C) subfractions were analyzed, a positive correlation was found between cap/mm2 and HDL2-C (r = .64, P < .05). Partial correlation analysis showed that these correlations either remain or improve after adjusting for age, VO2max, and body fatness. These results indicate that skeletal muscle capillary density and diffusion capacity are related to lipid and apolipoprotein concentrations for both type I and type II fibers.

Adipose Tissue↗

Management of facial nerve paralysis.

Facial paralysis is a dreaded complication of parotid surgery. It can lead to a variety of troubling symptoms in the patient, such as ocular problems and nasal obstruction. It can also have a significant emotional impact on the patient because of facial disfigurement and difficulties with communication, eating, and drinking. Successful outcome for patients inflicted with facial paralysis depends on proper selection of the appropriate rehabilitation technique. This article discusses the acute and late management of facial paralysis resulting from parotid surgery.

Facial Paralysis↗

Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow.

To elucidate the mechanisms by which haemopoietic progenitor cells lodge in the bone marrow, we examined the secretion of chemoattractants for haemopoietic progenitor cells by bone marrow and lung endothelial cells. The bone marrow endothelial cells, but not lung endothelial cells, secreted chemoattractants for the haemopoietic progenitor cell line, FDCP-2, and normal haemopoietic progenitor cells. Checkerboard analysis demonstrated that the conditioned medium of the bone marrow endothelial cells had chemotactic activity and random motility-stimulating activity. The bone marrow endothelial cells expressed stromal-cell-derived factor-1 (SDF-1) mRNA and produced SDF-1 protein, whereas the lung endothelial cells did not. Adhesion of FDCP-2 cells to the bone marrow endothelial cells was partially inhibited by anti-SDF-1 antibody. These findings suggest that the chemoattractants for haemopoietic progenitor cells including SDF-1 and random motility-stimulating factor(s) selectively secreted by the bone marrow endothelial cells may contribute to the homing of haemopoietic progenitor cells to bone marrow.

Animals↗

The clinical significance of core promoter and precore mutations during the natural course and interferon therapy in patients with chronic hepatitis B.

OBJECTIVE: We aimed to determine the clinical significance of mutations in core promoter and precore regions in chronic hepatitis B. We investigated changes in these mutations during the natural course and interferon therapy in patients with chronic hepatitis B. METHODS: A total of 93 patients with hepatitis B virus surface antigen were divided into four groups according to hepatitis B e antigen (HBeAg)/anti-HBe status and serum aminotransferase levels. Group I (n = 16) comprised HBeAg-positive patients with normal aminotransferase levels, group II (n = 31) HBeAg-positive patients with elevated aminotransferase levels, group III (n = 30) anti-HBe-positive patients with normal aminotransferase levels, and group IV (n = 16) anti-HBe-positive patients with elevated aminotransferase levels. All patients of group II and seven of group IV were treated with interferon. Three serial serum samples per untreated patient and eight samples per treated patient were tested for HBV DNA levels and core promoter and precore mutations by polymerase chain reaction combined with restriction fragment length polymorphism, and some were cloned and sequenced. RESULTS: Core promoter mutation was found in 38% of group I, 74% of group II, 97% of group III, and 100% of group IV. Precore mutation was found in 6% of group I, 90% of group II, and 100% of groups III and IV. The HBV DNA levels were significantly higher in groups I, II, IV, and III, in that order. Serial determination of these two mutations and viral levels showed that the core promoter mutation appeared to occur first, followed by a completion of the precore mutation along with a decrease in viral levels in patients who seroconverted to anti-HBe after interferon therapy. Interferon therapy suppressed both precore wild- and mutated-type viral levels equally. However, it did not induce any specific mutations. CONCLUSIONS: Core promoter mutation appeared to develop or complete first, followed by completion of the precore mutation, and the virus with these two mutations seemed to be the form to persist in the natural course of chronic hepatitis B. The clinical significance of these mutations appeared to be profoundly associated with the viral levels.

Adolescent↗

Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma.

BACKGROUND: A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma. METHODS: Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. Another group of eight asthmatic children served as control subjects. Aerobic capacity and the degree of EIB were assessed by both cycle ergometer and swimming ergometer before and after swimming training. RESULTS: The mean (SD) aerobic capacity at LT increased by 0.26 (0.11) kp after training when assessed with the swimming ergometer and by 10.6 (4.5) W when assessed with the cycle ergometer, and these changes were significantly different from the control group. The mean (SD) maximum % fall in forced expiratory volume in one second (FEV1) to an exercise challenge (cycle ergometer) set at 175% of LT decreased from 38.7 (15.4)% before training to 17.9 (17.6)% after training, but with no significant difference from the control group. There was, however, no difference in histamine responsiveness when compared before and after the training period. CONCLUSION: A six week swimming training programme has a beneficial effect on aerobic capacity but not on histamine responsiveness in children with asthma.

Asthma↗

Influence of mild exercise at the lactate threshold on glucose effectiveness.

The effect of a single bout of mild exercise on glucose effectiveness (S(G)) and insulin sensitivity (S(I)) was studied in six young male subjects by using a minimal model. An intravenous glucose tolerance test was performed under two conditions as follows: 1) 25 min after a bout of exercise on a cycle ergometer at the lactate threshold level for 60 min (Ex) and 2) without any prior exercise (Con). Leg blood flow (LBF) was also measured by strain-gauge plethysmography simultaneously with blood sampling. S(I) did not significantly change after exercise (18.1 +/- 1.5 vs. 17.7 +/- 1.9 x 10-(5) min/pM), whereas S(G) significantly increased (0.016 +/- 0.002 vs. 0.025 +/- 0.002 min(-1), P < 0.01). The increased blood flow after exercise remained high during the time period for measurement of the glucose disappearance constant and may be a determinant of S(G). The incremental lactate area under the curve until insulin loading was also significantly higher in Ex than in Con (2.6 +/- 0.9 vs. -3.5 +/- 1.5 mM/min, P < 0.05). These results suggest that increased S(G) after mild exercise may be due, at least in part, to increased LBF and lactate production under a hyperglycemic state.

Adult↗

[The effects of low intensity aerobic training on the physiological indexes and the quality of life in middle-aged white collar workers].

The effects of short-term low intensity aerobic training on the physiological indexes and the Quality of Life were examined in 43 middle-aged White Collar Workers. Training was carried out for 205 +/- 117 minutes/week, at least 2-3 times/week for 2 months on a cycle ergometer or walking with intensity level set at the 50% VO2max. Following this training protocol, thirty-six men (exercise group) completed the 2-month training program and 7 men dropped out (the dropout group). In the exercise group, both the VO2max (l/min) and VO2max/wt increased significantly (VO2max (l/min): P < 0.05. VO2max/wt: P < 0.01), whereas the weight, body mass index, %fat, fat (kg) and the waist hip ratio (WHR) decreased significantly (WHR: P < 0.05, others: P < 0.01) after 2 months. In addition, the DBP and serum TC, LDL-c/HDL-c decreased significantly (LDL-c/HDL-c: P < 0.01, others: P < 0.05) whereas the HDL-c increased significantly (P < 0.05). A modified Croog questionnaire was used to assess the subject's Quality of Life. The questionnaire consisted of 59 questions and the overall assessment was based on eight components. Regarding the Quality of Life, physical symptoms, work performance and satisfaction, total Quality of Life all improved significantly (physical symptoms, P < 0.05; others: P < 0.01) and social participation also tended to improve (P < 0.08). There was a significantly negative correlation between the initial Quality of Life and the changes in the Quality of Life (6 of the 8 components). In the all subjects, there was a significantly positive correlation between the changes in physical symptoms and the changes in VO2max/wt (r = 0.36, P < 0.05). In the dropout group, the FBS increased significantly (P < 0.05) but no other variables regarding the Quality of Life significantly changed after 2 months. In conclusion the above results suggest that short-term low intensity aerobic training in the present study can help improve the physiological indexes, VO2max and Quality of Life in middle-aged White Collar Workers and the observed improvement in the Quality of Life was also found to be greater in the subjects with a low Quality of Life than in those with a high Quality of Life.

Adult↗

Deep infection and fracture healing in immediate and delayed locked intramedullary nailing for open femoral fractures.

Fifty-nine patients with 61 open femoral fractures were treated with immediate locked intramedullary (IM) nailing (group 1; n=15), delayed IM nailing following nonoperative treatment (group 2; n=42), and delayed IM nailing following external fixation (group 3; n=7). Sixteen fractures were Gustilo type I, 28 were type II, 7 were type IIIA, 6 were type IIIB, and 4 were type IIIC open fractures. Four (6.6%) deep infections occurred. Significant differences existed in the deep infection rate (DIR) between types I and II and all type III fractures (2.3% for types I and II versus 17.6% for type III). The deep infection rate did not differ significantly among the nailing groups (13.3%, 2.6%, and 15.3% for groups 1, 2, and 3, respectively), nor did the deep infection rate correlate with the degree of fracture comminution, the existence of polytrauma or polyskeletal trauma, or preexistence of superficial or pin-site infections. Seven (11.7%) of these fractures resulted in nonunion, excluding one secondary amputation; the nonunion rate correlated with fracture location. There were no significant differences in the mean fracture healing times between any of the nailing groups. These results suggest that IM nailing for the treatment of type III open femoral fractures should be considered carefully, regardless of whether it is performed immediately or delayed.

Adolescent↗

A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy.

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.

ABO Blood-Group System↗

CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase.

CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and is expressed on T, B, and NK cells. The signal via CD27 plays pivotal roles in T-T and T-B cell interactions. Here we demonstrate that overexpression of CD27 activates NF-kappaB and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that the C-terminal PIQEDYR motif was indispensable for both NF-kappaB and SAPK/JNK activation and was also required for the interaction with TNF receptor-associated factor (TRAF) 2 and TRAF5, both of which have been implicated in NF-kappaB activation by members of the TNF-R superfamily. Co-transfection of a dominant negative TRAF2 or TRAF5 blocked NF-kappaB and SAPK/JNK activation induced by CD27. Recently, a TRAF2-interacting kinase has been identified, termed NF-kappaB-inducing kinase (NIK). A kinase-inactive mutant NIK blocked CD27-, TRAF2-, and TRAF5-mediated NF-kappaB and SAPK/JNK activation. These results indicate that TRAF2 and TRAF5 are involved in NF-kappaB and SAPK/JNK activation by CD27, and NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-kappaB and SAPK/JNK activation.

Calcium-Calmodulin-Dependent Protein Kinases↗

Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1.

NF-kappaB is activated by various stimuli including inflammatory cytokines and stresses. A key step in the activation of NF-kappaB is the phosphorylation of its inhibitors, IkappaBs, by an IkappaB kinase (IKK) complex. Recently, two closely related kinases, designated IKKalpha and IKKbeta, have been identified to be the components of the IKK complex that phosphorylate critical serine residues of IkappaBs for degradation. A previously identified NF-kappaB-inducing kinase (NIK), which mediates NF-kappaB activation by TNFalpha and IL-1, has been demonstrated to activate IKKalpha. Previous studies showed that mitogen-activated protein kinase/ERK kinase kinase-1 (MEKK1), which constitutes the c-Jun N-terminal kinase/stress-activated protein kinase pathway, also activates NF-kappaB by an undefined mechanism. Here, we show that overexpression of MEKK1 preferentially stimulates the kinase activity of IKKbeta, which resulted in phosphorylation of IkappaBs. Moreover, a catalytically inactive mutant of IKKbeta blocked the MEKK1-induced NF-kappaB activation. By contrast, overexpression of NIK stimulates kinase activities of both IKKalpha and IKKbeta comparably, suggesting a qualitative difference between NIK- and MEKK1-mediated NF-kappaB activation pathways. Collectively, these results indicate that NIK and MEKK1 independently activate the IKK complex and that the kinase activities of IKKalpha and IKKbeta are differentially regulated by two upstream kinases, NIK and MEKK1, which are responsive to distinct stimuli.

Amino Acid Sequence↗

Serial changes of sensory nerve conduction velocity and minimal F-wave latency in streptozotocin-induced diabetic rats.

We studied the serial changes of sensory nerve conduction velocity (SNCV) in the caudal nerve of streptozotocin (STZ)-induced diabetic rats using a new technical method. Minimal F-wave latency was also studied by stimulating the tibial nerve. The SNCV in the diabetic rats was slower than that in the normal rats 2 weeks after STZ injection, and minimal F-wave latency was prolonged compared to normal rats 4 weeks after STZ injection. Treatment of the diabetic rats with insulin for 14 days inhibited SNCV slowing and minimal F-wave latency prolongation. This new method to measure SNCV is useful for various studies, and improvement of diabetic neuropathy with insulin treatment is indicated by recovery from SNCV slowing and minimal F-wave latency prolongation.

Animals↗

cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2.

Chromosomal segregation during mitosis as well as meiosis is considered to be regulated by multiple kinases, but the precise mechanism remains largely unknown. A mutation in Drosophila, designated aurora, was identified as a responsible gene for a chromosomal segregation defect and encodes a putative serine-threonine kinase. Here we have identified mammalian aurora homologues, designated aurora-related kinase (ARK) 1 and ARK2. Kinase domains of murine ARK1 and ARK2 showed 61 and 62% identity, respectively, to that of aurora at the amino acid levels, respectively. Cell cycle analysis revealed that the expression of ARK1 was correlated with G2/M phase, while ARK2 was expressed during S and G2/M phases. Immunofluorescence analysis demonstrated that ARK2 was mainly localized to the midbody, while ARK1 has been reported to be localized to the spindle pole during mitosis. Collectively, these results suggest that these two kinases may have distinct roles with different expression timing and subcellular localization during the cell cycle progression. Interspecific backcross mapping revealed that Ark1 is located in a distal region of mouse chromosome 2, while Ark2 is located in a central region of mouse chromosome 11.

3T3 Cells↗

Inhibitory projections from pronator teres to biceps brachii motoneurones in human.

Neural projections from the pronator teres (PT) muscle to biceps brachii (BB) motoneurones were studied in three healthy human subjects using a post-stimulus time histogram method. In 25 BB motor units, electrical stimulation to the PT nerve with intramuscular needle electrodes induced inhibition in nine units (36%), whereas facilitation was produced in 18 units (72%) by stimulation to the median nerve trunk with surface electrodes at the distal end of the intermuscular septum of the arm or in the cubital fossa. Six motor units (24%) received both inhibition (PT nerve stimulation) and facilitation (median nerve trunk stimulation). In the six, the latency of the inhibition was, on average, 1.2 ms longer than that of the facilitation. The stimulation site for the inhibition was, on average, 4.8 cm distal to that for the facilitation. The inhibition was evoked with an intensity well below the motor threshold. These findings suggest that BB motoneurones receive oligosynaptic inhibition of group I afferents from PT in human.

Adult↗

Intravenous glucose tolerance test-derived glucose effectiveness in strength-trained humans.

The effect of long-term strenuous resistance training on glucose effectiveness (SG) was examined by comparing 11 strength-trained and 20 sedentary males by a minimal model approach. Lean body mass (LBM) was measured by hydrostatic weighing. The LBM in strength-trained subjects (65.7 +/- 3.1 kg) was significantly larger than in sedentary subjects (56.6 +/- 1.2 kg, P < .01). The glucose disappearance constant ([KG] 3.07% +/- 0.45% min(-1)) and insulin sensitivity ([SI] 17.5 +/- 2.0 x 10(-5) x min(-1) x pmol/L(-1)) in strength-trained subjects were significantly higher than in sedentary subjects (2.06% +/- 0.14% x min(-1) and 10.3 +/- 1.2 x 10(-5) x min(-1) x pmol/L(-1), P < .05). SG in strength-trained subjects (0.024 +/- 0.003 min(-1)) was significantly higher than in sedentary subjects (0.018 +/- 0.001 min(-1), P < .05). These results thus suggest that the improved glucose tolerance in strength-trained subjects was due to increased SG and SI.

Adult↗