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Biomedical subjects

Y Kajimoto

Publications and source records attributed to Y Kajimoto.

At least 19 recordsLinked to original sources

Mental fatigue-induced decrease in levels of several plasma amino acids.

To investigate the relation between plasma amino acid levels and mental fatigue, we measured the plasma concentrations of 20 amino acids in 9 healthy volunteers before and after a fatigue-inducing mental task session for 8 hr. As fatigue-inducing mental tasks, the subjects performed an advanced trail making test, a Japanese KANA pick up test, and a mirror drawing test. As a control, 8-hr relaxation session was performed in the same subjects at an interval of 4 weeks. Immediately after the fatigue session, the plasma levels of branched-chain amino acids, tyrosine, cysteine, methionine, lysine, and arginine were below those after a relaxation session. The values for other blood parameters including total protein, albumin, glucose, and total cholesterol did not show any differences between the 2 sessions. These results indicate that mental fatigue may be characterized by a decrease in the plasma level of these amino acids.

Adult↗

Effect of corosolic acid on postchallenge plasma glucose levels.

Corosolic acid (CRA) is a substance extracted from Lagerstroemia speciosa L. and has been reported to have biological activities in in vitro and experimental animal studies. In this study, 31 subjects were orally administered 10mg CRA or a placebo, on different occasions, in a capsule 5min before the 75-g oral glucose tolerance test (OGTT) in a double-blind and cross-over design. Nineteen subjects had diabetes, seven had impaired glucose tolerance, one had impaired fasting glucose, and four had normal glucose tolerance according to the 1998 WHO criteria. There were no significant differences in plasma glucose levels before and 30min after the administration. CRA treatment subjects showed lower glucose levels from 60min until 120min and reached statistical significance at 90min. In this study, we have shown for the first time that CRA has a lowering effect on postchallenge plasma glucose levels in vivo in humans.

Blood Glucose↗

Ectopically expressed PDX-1 in liver initiates endocrine and exocrine pancreas differentiation but causes dysmorphogenesis.

To date, the potency of pancreatic and duodenal homeobox gene 1 (PDX-1) in inducing differentiation into insulin-producing cells has been demonstrated in some cells and tissues. In order to carry out efficient screening of somatic tissues and cells that can transdifferentiate into beta-cell-like cells in response to PDX-1, we generated CAG-CAT-PDX1 transgenic mice carrying a transgene cassette composed of the chicken beta-actin gene (CAG) promoter and a floxed stuffer DNA sequence (CAT) linked to PDX-1 cDNA. When the mice were crossed with Alb-Cre mice, which express the Cre recombinase driven by the rat albumin gene promoter, PDX-1 was expressed in more than 50% of hepatocytes and cholangiocytes. The PDX-1 (+) livers expressed a variety of endocrine hormone genes such as insulin, glucagon, somatostatin, and pancreatic polypeptide. In addition, they expressed exocrine genes such as elastase-1 and chymotrypsinogen 1B. However, the mice exhibited marked jaundice due to conjugated hyperbilirubinemia, and the liver tissue displayed abnormal lobe structures and multiple cystic lesions. Thus, the in vivo ectopic expression of PDX-1 in albumin-producing cells was able to initiate but not complete the differentiation of liver cells into pancreatic cells. The conditional PDX-1 transgenic mouse system developed in this study appeared to be useful for efficient screening of PDX-1 responsive somatic tissues and cells.

Animals↗

Association of (-)786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance.

AIMS/HYPOTHESIS: Endothelial derived nitric oxide synthase ( eNOS) gene polymorphisms affect eNOS activity and are associated with abnormal vasomotility and impaired local blood flow. A decrease in local blood flow has been reported to cause insulin resistance. The aim of this study was to examine a possible association of two eNOS polymorphisms, Glu298Asp (G894T) in exon 7 and (-)786T-C mutation with insulin resistance. METHODS: Genotypes of both Glu298Asp and (-)786T-C mutation were examined by the PCR-RFLP method. Plasma nitrate and nitrite concentrations were also measured. RESULTS: The allele frequencies of both polymorphisms showed no considerable differences in 233 non-diabetic subjects and 301 patients with Type II (non-insulin-dependent) diabetes mellitus. Non-diabetic subjects with the (-)786C allele had (p<0.05) higher fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the (-)786T/ (-)786T genotype. Diabetic subjects with (-)786C allele showed higher HbA(1c) than those with the (-)786T/(-)786T genotype. A euglycaemic hyperinsulinemic clamp study done on 71 of the 301 patients showed a lower glucose infusion rate in diabetic patients with the (-)786C allele than those without it. In diabetic patients with the (-)786C allele, plasma nitrate and nitrite concentrations were lower than in subjects without it (p=0.026). No differences were observed between mutant carriers of Glu298Asp and non-carriers among both non-diabetic subjects and Type II diabetic patients. CONCLUSIONS/INTERPRETATION: The (-)786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients.

Adult↗

A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with Type II diabetes.

AIMS/HYPOTHESIS: This study aimed to evaluate the effect of a phosphodiesterase inhibitor, cilostazol, on the prevention of silent brain infarction in diabetic patients without symptoms of vascular events. METHODS: A total of 89 subjects were allocated at random to the cilostazol group ( n = 43) or the control group ( n = 46). RESULTS: After the study period (3.2 +/- 0.5 years), carotid intima-media thickness (IMT) (means +/- SD) had increased ( p < 0.01) by 0.18 +/- 0.19 mm in the control group. In the cilostazol group, intima-media thickness showed almost no change (-0.00 +/- 0.16 mm). In the control group, 2 out of 46 subjects showed symptomatic brain infarctions and 10 out of 34 subjects without infarct-like region assessed by standard brain MRI examination showed silent brain infarctions after the observation period. On the other hand, no subjects in the cilostazol group showed silent brain infarction or strokes during the study period. Both at the beginning and end of the study period, the number of infarct-like regions positively correlated with IMT ( r = 0.335, p < 0.001 or r = 0.347, p < 0.001 respectively). The progression of infarct-like regions was directly related to the increase in IMT during the study period ( r = 0.299, p = 0.004). CONCLUSION/INTERPRETATION: These data demonstrated that cilostazol could prevent the onset of silent brain infarction in Japanese subjects with Type II (non-insulin-dependent) diabetes mellitus. Also, an increase in intima-media thickness of the carotid artery wall could be able to predict the onset of silent brain infarction.

Aged↗

Size-related and size-unrelated functional heterogeneity among pancreatic islets.

Functional heterogeneity of pancreatic islets was systematically analyzed for the first time using freshly isolated single rat pancreatic islets. First, 60 islets were sequentially exposed to 3, 9.4, 15.6, and 24.1 mM glucose for 30 min each in incubation experiments: 36 (60%) responded in a concentration-dependent and 19 (32%) in an all-or-none manner, and 5 (8%) islets did not respond to high glucose. As a group, the larger the islet, the higher the beta cell glucose sensitivity. However, glucose-stimulated elevation of [Ca2+]i in the beta cell. insulin/glucagon ratio in the islet, and expression of glucose transporter 2, glucokinase, and pancreatic duodenal homeobox factor-1 in the beta cell were not significantly related to islet size. Second, 50 islets were stimulated with 16.7 mM glucose in perifusion. A biphasic insulin release was found in 39 (78%), and no or little first phase response in 11 (22%) islets, irrespective of the islet size. Nevertheless, when the response was plotted as a group, it was clearly biphasic. Islet size, insulin content and the amount of insulin release were positively correlated with each other. In conclusion, there are size-related and size-unrelated functional diversity among pancreatic islets. The reason for such heterogeneity remained to be determined.

Animals↗

Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes mellitus and normoalbuminuria.

To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy, simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing the highest with the lowest quartile of diabetic duration, the relative risk for retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and 64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds ratio of diabetic duration and nocturnal HR to the existence of retinopathy was 1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy.

Albuminuria↗

Development and clinical application of near-infrared surgical microscope: preliminary report.

Visualization of near-infrared fluorescence through a surgical microscope can provide intraoperative information about deep-seated tissues. We studied the possibility of taking a near-infrared image through a surgical microscope after intravenous injection of indocyanine green (ICG). The surgical microscopes we used were Zeiss models OPMI MD and OPMI CS-NC. We used a halogen lamp as a light source, a band pass filter of 760 - 810 nm as an excitation filter, a laser light of 800 nm as an external light source, and a band pass filter of 820 - 920 nm as a barrier filter. Near-infrared fluorescence of vessels on the brain surface and of the dural sinus was visualized through the dura mater after intravenous injection of 25 mg ICG using a Hitachi KP-160 camera. Near-infrared fluorescence of vessels on the brain surface was observed through the dura mater. Venous images were clearer than were arterial ones. The dural sinus and the bridging veins were also clearly visualized. These results suggest that a clinical application of near-infrared fluorescence microscopy is possible. However, a stronger fluorescence emitted from ICG will be necessary for such a microscope to have practical use.

Coloring Agents↗

A missense mutation of Pax4 gene (R121W) is associated with type 2 diabetes in Japanese.

Pax4 is one of the transcription factors that play an important role in the differentiation of islet beta-cells. We scanned the Pax4 gene in 200 unrelated Japanese type 2 diabetic patients and found a missense mutation (R121W) in 6 heterozygous patients and 1 homozygous patient (mutant allele frequency 2.0%). The mutation was not found in 161 nondiabetic subjects. The R121W mutation was located in the paired domain and was thought to affect its transcription activity through lack of DNA binding. Six of seven patients had family history of diabetes or impaired glucose tolerance, and four of seven had transient insulin therapy at the onset. One of them, a homozygous carrier, had relatively early onset diabetes and slowly fell into an insulin-dependent state without an autoimmune-mediated process. This is the first report of a Pax4 gene mutation that exhibits loss of function and seems to be associated with type 2 diabetes. This work provides significant implications for the Pax4 gene as one of the predisposing genes for type 2 diabetes in the Japanese.

Adult↗

[Extracranial carotid artery bypass using artificial vessels--4 case reports].

We successfully completed extracranial carotid artery reconstruction in four cases (case 1: arteriosclerotic occlusion of the left common carotid artery between the origin at the aorta to just below the cervical bifurcation, case 2-4: combined removal of the carotid artery with malignant cervical tumor) using various types of synthetic vessels, e.g. 1) Double Velour Dacron, or 2) Expanded polytetrafluoroethylene. In case 2, Xenon CT under balloon occlusion was useful for revealing the indication for carotid artery reconstruction. Recent progress in the development of materials for use in synthetic vessels has remarkably improved the long-term patency of synthetic vessels, especially in medium to large size ones (larger than 6 mm in diameter). Synthetic vessels have the following advantages: 1. No need to harvest autogenous vessels, 2. An external shunt is available for patients with poor ischemic tolerance to temporary occlusion of the carotid artery, 3. A vessel of the most suitable size can be selected, 4. No risk of tumor invasion, 5. Easy suturing because the orifice of a synthetic vessel does not collapse. We report the usefulness, the indication for, and the surgical procedures of extracranial carotid artery bypass using synthetic vessels.

Blood Vessel Prosthesis↗

Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes.

The intima-media thickness of the carotid artery has been established as a surrogate of definite atherosclerosis in subjects with high risk of vascular events. This study was done to evaluate the effectiveness of long-term antiplatelet therapy in attenuating progression of the intima-media thickness of the carotid artery of subjects with type 2 diabetes. Subjects who had an intima-media thickness over the threshold of the normal subjects but showed no symptoms of vascular events were randomly divided into groups given antiplatelet drugs [ticlopidine (n = 34) or a small dose of aspirin (n = 40)] or no drugs (n = 74). For the follow-up period (3.0+/-0.06 years), the subjects not given antiplatelet drugs showed a significantly higher progression of intima-media thickness (0.067+/-0.009 mm/year) than those given ticlopidine (0.034+/-0.013 mm/year) or aspirin (0.033+/-0.010 mm/year). Stepwise multivariant regression analysis showed that long-term administration of ticlopidine or aspirin significantly reduced the progression of intima-media thickness of diabetic subjects by 0.041 mm/year or 0.032 mm/ year, respectively. These data indicated that despite differences of their pharmacological mechanisms, antiplatelet drugs could attenuate the progression of intima-media thickness of the carotid artery wall of asymptomatic type 2 diabetics who had early-stage carotid atherosclerosis.

Aged↗

Important role of the hepatic vagus nerve in glucose uptake and production by the liver.

We examined the role of the hepatic vagus nerve in hepatic and peripheral glucose metabolism. To assess endogenous glucose production (EGP), hepatic uptake of first-pass glucose infused intraportally (HGU), and the metabolic clearance rate of glucose (MCR), rats were subjected to hepatic vagotomy (HV, n = 7) or sham operation (SH, n = 8), after 10 days, they were then subjected to a euglycemic-hyperinsulinemic clamp together with a portal glucose load in the 24-hour fasting state. Metabolic parameters were determined by the dual-tracer method using stable isotopes. During the experiment, [6,6-2H2]glucose was continuously infused into the peripheral vein. To maintain euglycemia (4.5 mmol/L), insulin (54 pmol x kg(-1) x min(-1)) and glucose were infused peripherally after the 90-minute tracer equilibration and 30-minute basal periods, and glucose containing 5% enriched [U-13C]glucose was infused intraportally (50 micromol x kg(-1) x min(-1)) for 120 minutes (clamp period). EGP was significantly higher in HV rats versus SH rats during the basal period (64.3 +/- 7.6 v 43.6 +/- 5.3 micromol x kg(-1) x min(-1), P < .005)) and was comparable to EGP in SH rats during the clamp period (9.3 +/- 21.5 v 1.1 +/- 11.7 micromol x kg(-1) x min(-1)). HGU was reduced in HV rats compared with SH rats during portal glucose infusion (5.9 +/- 2.4 v 10.1 +/- 3.2 micromol x kg(-1) x min(-1)). The MCR in HV rats was significantly higher than in SH rats in the basal period (11.0 +/- 2.0 v 7.9 +/- 0.8 mL x kg(-1) x min(-1), P < .01)) and was comparable to the MCR in SH rats during the clamp period (41.9 +/- 10.0 and 36.6 +/- 5.7 mL x kg(-1) x min(-1)). We conclude that innervation of the hepatic vagus nerve is important for the regulation of hepatic glucose production in the postabsorptive state and HGU in the postprandial state.

Animals↗

Evaluation of gut motility in type II diabetes by the radiopaque marker method.

BACKGROUND: The clinical usefulness of the radiopaque marker method for detecting diabetic gastrointestinal motility disturbances, was evaluated by examining 21 type II diabetes subjects who did not have any neuropathic symptoms. METHODS: After administration of a Sitzmark capsule, markers were located using plain abdominal radiographs, and the transit time of the markers through seven areas of digestive tract was calculated by Arhan's methods. The plasma concentration of acetaminophen at 45 min after oral administration was measured to evaluate gastric emptying time. The coefficient of variation of R-R intervals on the electrocardiograms (CV(R-R)) was measured to evaluate parasympathetic autonomic function. RESULTS: In the diabetics, the average (+/- SD) transit time through upper digestive tracts was slightly but not significantly elongated compared with control subjects (14.4 +/- 8.3 vs 9.9 +/- 6.1 h). Significant elongation was observed in transit time through the lower digestive tracts or the whole gut (44.6 +/- 20.9 and 57.9 +/- 22.3 h, respectively) compared with control subjects (23.3 +/- 8.5 and 33.2 +/- 11.0 h). The transit time of the markers from stomach to small intestine was highly correlated (r = 0.693) with plasma concentration of acetaminophen. The transit time through either the whole colon (r = 0.564) or the whole gut (r = 0.630) was highly correlated with CV(R-R). CONCLUSIONS: These findings suggest that the radiopaque marker method is a useful tool for detecting the sections of the digestive tract responsible for gut motility disturbances. In type II diabetics with no neuropathic symptoms, the lower digestive tracts may deteriorate prior to the impairment of upper digestive tracts.

Acetaminophen↗

Isolated dilation of the trigono-inferior horn--four case reports.

Four patients presented with isolated dilation of the trigono-inferior horn associated with either mass lesion at the trigone of the lateral ventricle or with shunt over-drainage. We investigated clinical symptoms, course, and neuroradiological findings of these cases. The pressure of the isolated ventricle was measured or estimated at surgery in all cases. The common symptoms were recent memory disturbance and contralateral homonymous hemianopia. Contralateral hemiparesis was observed occasionally. Rapid deterioration of the isolation caused uncal herniation in one case. Comma-shaped dilation of the inferior horn was observed in all cases. Midline shift was not conspicuous except in one case. Intraventricular pressure at surgery was 18 cmH2O, 35 cmH2O, 3 cmH2O, and within normal range. These cases had very similar clinical symptoms and neuroradiological findings. The pathophysiology of isolation suggested three types of isolation (high-, normal-, and low-pressure isolation), depending on the pressure of the isolated ventricle. The isolation of trigono-inferior horn is an important clinical entity as it may cause uncal herniation in patients with high-pressure lesions.

Aged↗

Intraventricular aneurysms--three case reports.

Three rare cases of purely intraventricular aneurysms are described, including a unique aneurysm in the fourth ventricle. A 30-year-old female, a 47-year-old male, and an 11-year-old girl presented with disturbance of consciousness due to massive intraventricular hemorrhage. Digital subtraction angiography revealed an idiopathic peripheral aneurysm in the fourth ventricle in the first patient, and aneurysms in the lateral ventricle associated with moyamoya disease in the latter two patients. The former two aneurysms were treated surgically and histologically confirmed to be pseudoaneurysms. The latter aneurysm disappeared spontaneously within 2 months after onset. The aneurysm in the lateral ventricle was resected via a parietal corticotomy with stereotactic insertion of an 8-Fr silicone tube to guide the approach route. This method was very useful because computerized neuronavigation was not available. The aneurysm in the fourth ventricle was resected via a midline suboccipital approach with C-1 laminectomy. Conservative treatment is usually recommended initially for patients with intraventricular aneurysm because spontaneous cure often occurs. We recommend direct surgery if the size of the aneurysm remains unchanged, because the risk of surgery has decreased recently owing to new techniques for neuronavigation.

Adult↗

Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease.

OBJECTIVE: To examine carotid intima-media thickness (IMT), predictors of its progression, and its relationship with incident coronary heart disease (CHD) in type 2 diabetic Japanese patients. RESEARCH DESIGN AND METHODS: Carotid IMT of 287 subjects with type 2 diabetes (mean age 61.6 years) without CHD or cerebrovascular disease was examined at baseline and after a mean follow-up of 3.1 years. RESULTS: The annual progression of IMT (means +/- SEM) was 0.04+/-0.004 mm/year. Stepwise multivariate analysis demonstrated that independent risk factors for progress of IMT were the initial IMT (P<0.001), the average HbA1c level (P<0.001), and age (P = 0.001). Both the initial IMT (odds ratio [OR] 4.9, 95% CI 1.7-14.1) and a low average HDL cholesterol (OR 0.2, 0.1-0.8) were identified as predictors of incident nonfatal CHD (angina pectoris or nonfatal myocardial infarction; 3-year incidence 10.1%) after adjusting for age, sex, average HbA1c, and other risk factors. CONCLUSIONS: The predictors of the progression of carotid IMT in Japanese type 2 diabetic subjects were its baseline thickness and the average HbA1c during the follow-up. Baseline carotid IMT and low HDL cholesterol predicted the incidence of nonfatal CHD.

Asian People↗

Feasibility of high-dose chemotherapy without stem cell support as a first-line treatment for non-Hodgkin's aggressive lymphoma: a pilot study.

A regimen which incorporates cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) is the standard treatment for patients with non-Hodgkin's lymphoma (NHL), but it has not been effective in patients with aggressive NHL who are at high risk. The aim of the present trial was to investigate the feasibility of high-dose chemotherapy (HDC) without stem cell support as a first-line treatment. The primary endpoint was a complete remission rate. The second endpoint was survival. Fourteen patients with aggressive NHL entered the study and were treated according to the K93 protocol (3 cycles of CHOP, high-dose etoposide and ifosfamide, and high-dose methotrexate) Eleven patients (79%) achieved complete remission (CR) and two (14%) achieved partial remission (PR). Overall survival (OS) after five years was 79%. The actuarial five year disease free survival (DFS) for the eleven cases of CR was 75%. During chemotherapy, grade IV hematologic toxicity was observed in all patients and grade IV non-hematologic toxicity in only one patient, who experienced oral ulcers. Peripheral blood stem cell (PBSC) apheresis was performed in eight cases. One harvesting was enough to provide an adequate number of CD34+ cells for the subsequent PBSC transplantation (PBSCT). In conclusion our study confirmed the efficacy of the K93 protocol in obtaining a good response (CR + PR) rate and a very good DFS rate in most cases of aggressive NHL, with acceptable toxicity. This regimen may improve the outcome in cases of aggressive NHL without stem cell support. It seems worthwhile to conduct a randomized controlled study comparing the K93 protocol with the standard CHOP regimen.

Adult↗