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Biomedical subjects

H Nakamoto

Publications and source records attributed to H Nakamoto.

At least 19 recordsLinked to original sources
PubMed2007

The small heat shock proteins and their clients.

Small heat shock proteins are ubiquitous proteins found throughout all kingdoms. One of the most notable features is their large oligomeric structures with conserved structural organization. It is well documented that small heat shock proteins can capture unfolding proteins to form stable complexes and prevent their irreversible aggregation. In addition, small heat shock proteins coaggregate with aggregation-prone proteins for subsequent, efficient disaggregation of the protein aggregates. The release of substrate proteins from the transient reservoirs, i.e. complexes and aggregates with small heat shock proteins, and their refolding require cooperation with ATP-dependent chaperone systems. The amphitropic small heat shock proteins were shown to associate with membranes, although they do not contain transmembrane domains or signal sequences. Recent studies indicate that small heat shock proteins play an important role in membrane quality control and thereby potentially contribute to the maintenance of membrane integrity especially under stress conditions.

Animals↗
PubMed2005

Proinsulin C-peptide activates vagus efferent output in rats.

The aim of this study was to examine the effect of proinsulin C-peptide on the autonomic nervous systems in rats. Intravenous administration of C-peptide gradually increased electrophysiological activity of the vagus nerves into the stomach and pancreas for at least 90 min. It also slightly increased gastric acid secretion that was suppressed by the treatment with atropine. Intraperitoneal injection of C-peptide did not affect the basal and stress-induced norepinephrine (NE) turnover rate, a biochemical index of sympathetic nerve activity. These results indicate that C-peptide increases parasympathetic nerve activity without affecting sympathetic nerve activity. This could explain, at least in part, the ameliorating effects of C-peptide on impaired cardiac autonomic nerve functions in patients with type 1 diabetes.

Animals↗
PubMed2002

Self-measured systolic blood pressure in the morning is a strong indicator of decline of renal function in hypertensive patients with non-diabetic chronic renal insufficiency.

While blood pressure is a recognized major determinant of renal function deterioration, the role of self blood pressure measurement (BPM) in predicting the loss of renal function in hypertensive patients with chronic renal insufficiency (CRI) has not been adequately addressed. One hundred and thirteen patients (F/M: 46/67; 56 +/- 1 years) with CRI (mean serum creatinine: 1.87 +/- 0.08; range: 1.4 to 3.5 mg/dl; average urinary protein excretion: 1.2 +/- 0.2 g/24 hrs.) were followed for 3 years. The record of renal biopsy revealed that 74 patients had IgA nephropathy, 16 had chronic glomerulonephritis, and 6 had membranous nephropathy, while 17, unbiopsied patients had underlying renal disease of unknown origin. Self BPM were made at regular intervals throughout the course of the study. All recorded blood pressures were included in a stepwise multiple regression analysis in which the decline in GFR per year was the dependent variable. Patients were primarily treated with a combination of amlodipine (5 to 20 mg daily), a calcium antagonist, and benazepril (2.5 to 5 mg daily), an ACE inhibitor in an effort to reduce their blood pressure at the office to < 130/85 mmHg. The simple correlation between blood pressures (i.e., office, home morning and home evening) and the decline in GFR were all statistically significant. The correlation coefficients of determination for this model were as follows: r = 0.64 for home morning SBP; 0.43 for office SBP; 0.39 for office DBP; and 0.38 for home morning DBP. The level of urinary protein excretion did not correlate with the decline in GFR. These data suggest that self BPM improves prognostic ability in hypertensive patients with CRI.

Adult↗
PubMed2001

A novel heat shock protein plays an important role in thermal stress management in cyanobacteria.

A novel heat shock gene, orf7.5, which encodes a putative acidic polypeptide of 63 amino acids, was cloned from the cyanobacterium Synechococcus sp. PCC 7942. Northern blot analysis revealed the presence of 400- and 330-base orf7.5 mRNAs, which were barely detectable in the cells grown at 30 degrees C but increased transiently in response to heat shock at 40 or 45 degrees C. Primer extension analysis showed that the two mRNAs have different 5'-ends. Chloramphenicol enhanced the accumulation of the orf7.5 mRNA, whereas it inhibited the increase in the amount of the groESL mRNA. To reveal the role of the orf7.5 gene in thermal stress management, we constructed a stable mutant in which a gene conferring resistance to an antibiotic was inserted into the coding region of the orf7.5 gene. The interruption led to a marked inhibition of growth at 45 degrees C and a decrease in the basal and acquired thermo-tolerances at 50 degrees C in the transformants, indicating that the gene plays a role in thermal stress management. The orf7.5 mutant could be complemented with a return to the wild type phenotype by a DNA fragment containing orf7.5 but not by mutated orf7.5s, in which a nonsense mutation was generated by introducing a frameshift or a point mutation within the orf7.5-coding region. Thus, thermo-tolerance requires an appropriate translation product, not simply a transcript. Accumulation of the groESL transcript in the orf7.5 mutant was strongly reduced, suggesting that the orf7.5 gene product controls the expression of the groESL operon.

Amino Acid Sequence↗
PubMed2001

Antithrombotic effects of a synthetic inhibitor of activated factor X, JTV-803, in animals.

JTV-803, 4-[(2-amidino-1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl]-1-(4-pyridinyl)piperidine-4-carboxylic acid monomethanesulfonate trihydrate, at > or = 0.1 mg/kg/h inhibited the increase in plasma thrombin-antithrombin III complex in response to continuous infusion of thromboplastin in rats. JTV-803 inhibited thrombus formation in an arteriovenous shunt model by intravenous infusion at > or = 0.3 mg/kg/h and prolonged the occlusion time of photochemically induced arterial thrombus in the middle cerebral artery at >1.5 mg/kg/0.5 h. Activated partial thromboplastin time was prolonged at 10 mg/kg/h. Intravenous administration of JTV-803 prolonged bleeding time at 30 mg/kg/h, a dose 10-100 times higher than the dose that inhibited thrombus formation. Compared with thrombin inhibitor, JTV-803 had less of an effect on the bleeding time. In the arteriovenous shunt model in cynomolgus monkey, JTV-803 prolonged the occlusion time when administered by continuous infusion at 0.3 mg/kg/h or orally at 10 mg/kg. These results suggest that the human factor Xa inhibitor JTV-803 is an orally active anticoagulant that does not affect bleeding time and is useful for the prevention of thrombus.

Animals↗
PubMed2001

Ruptured dissecting aneurysm in bilateral iliac arteries caused by Ehlers-Danlos syndrome type IV: report of a case.

Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue characterized by hyperextensible skin, hypermobile joints, and abnormalities of the cardiovascular system. Ten types and several subtypes of EDS have so far been recognized based on genetic, clinical, and biochemical characteristics. The spectrum of the disorder varies from mild to life-threatening vascular complications. EDS type IV is a particularly dangerous form with a lethal spontaneous rupture of the major arteries and aneurysmal formation. We present herein a case of a ruptured dissecting aneurysm in the bilateral iliac arteries caused by EDS type IV. A previously healthy 33-year-old man without any physical features of this connective tissue disorder experienced a metachronous vascular rupture two times. Successful synthetic bypass grafting was performed with great difficulty. The diagnosis of EDS type IV was made afterwards based on an electrophoresis analysis of a skin biopsy specimen which revealed a lack of type III collagen. Surgical intervention in cases of arterial complications in EDS type IV patients have been reported to be both difficult and frequently unsuccessful. The early clinical recognition of this syndrome is therefore of great importance due to the hazards of such surgical therapies.

Adult↗
PubMed2001

Regular exercise improves cognitive function and decreases oxidative damage in rat brain.

The biochemical mechanisms by which regular exercise significantly benefits health and well being, including improved cognitive function, are not well understood. Four-week-old (young) and 14-month-old (middle aged) Wistar rats were randomly assigned to young control and young exercised, middle-aged control and middle-aged exercised groups. Exercise groups were exposed to a swimming regime of 1 h a day, 5 days a week for 9 weeks. The passive avoidance test showed that middle-aged exercised rats had significantly (P<0.05) better short- (24 h) and long-term (72 h) memory than aged-matched control rats. Conditioned pole-jumping avoidance learning was improved markedly in both age groups by exercise. Brain thiobarbituric acid-reactive substances and 8-hydroxy-2'deoxyguanosine content in the DNA did not change significantly, while the protein carbonyl levels decreased significantly (P<0.05) in both exercised groups. This decrease was accompanied by an increase in the chymotrypsin-like activity of proteasome complex in the exercised groups, whereas trypsin-like activity did not differ significantly between all groups. The DT-diaphorase activity increased significantly (P<0.05) in the brain of young exercised animals. These data show that swimming training improves some cognitive functions in rats, with parallel attenuation of the accumulation of oxidatively damaged proteins.

Age Factors↗
PubMed2001

In vivo visualization of angiotensin II- and tubuloglomerular feedback-mediated renal vasoconstriction.

BACKGROUND: A noninvasive technique to monitor renal microcirculation would be a useful tool for investigation of renal disease and the effects of drugs on the renal system. We have developed a novel, less invasive technique to visualize renal microcirculation in vivo using an intravital tapered-tip (1 mm phi) lens-probe (pencil lens-probe) videomicroscopy, which only requires insertion of the probe into superficial renal cortex in situ. METHODS: To assess validity of this technique, the effects of angiotensin II (Ang II) and intrarenal sodium chloride loading (activator of tubuloglomerular mechanism) were examined. The renal microvasculature was successfully visualized and monitored. RESULTS: Administration of Ang II (1, 3, 10 and 30 ng/kg/min) produced a dose-dependent constriction of afferent and efferent arterioles in similar degrees; at 30 ng/kg/min, Ang II elicited 52 +/- 3 (N = 9) and 53 +/- 3% decreases in diameter (N = 9), respectively. The Ang II-induced arteriolar constriction was completely prevented by losartan, an Ang II type 1 (AT1) antagonist. The intrarenal hypertonic saline administration elicited transient increments (from 98 +/- 8 to 122 +/- 7 mL/min, N = 6, P < 0.05), followed by a marked reduction in renal blood flow (RBF; 78 +/- 7 mL/min, P < 0.05). This response was accompanied by prominent constriction of afferent (from 15.0 +/- 1.1 to 8.5 +/- 1.1 microm, N = 6, P < 0.05), but not efferent (from 14.3 +/- 1.2 to 13.8 +/- 1.0 microm, N = 3) arterioles. Furthermore, this response was completely inhibited by furosemide, a tubuloglomerular feedback inhibitor. CONCLUSION: : The intravital pencil lens-probe videomicroscopy can be a powerful tool for in vivo observation of renal microcirculation, with intact renal microvascular responses to two important renal homeostatic mechanisms, angiotensin II and tubuloglomerular feedback.

Adult↗
PubMed2001

Improved outcome prediction for patients with multiple organ failure undergoing continuous hemodiafiltration.

A number of patients with multiple organ failure (MOF) regardless of accompanying acute renal failure have been treated with continuous hemodiafiltration (CHDF). However, despite its high cost, the costs/benefits of CHDF for MOF patients still need to be evaluated. Although many scoring systems were established to predict the outcome of MOF, their predictive powers were not estimated in MOF patients undergoing CHDF. Therefore, using 52 Japanese patients with MOF treated with CHDF for more than 1 week, we estimated the predictive powers of multiple organ dysfunction (MOD) scores and acute physiology and chronic health evaluation (APACHE) III scores, retrospectively. The patients were divided into 2 groups according to outcome at Day 28 after the initiation of CHDF. In both scoring systems, the median values at Day 0 were not significantly different between the survival (n = 19) and the nonsurvival (n = 33) groups. In contrast, at Day 3, the median values of MOD scores was 4 (0-14) in the survival group and 9 (1-12) in the nonsurvival group (p = 0.0035). The median value of APACHE III scores were 37 (19-97) and 87 (16-150) at Day 3, respectively (p < 0.0001). In the survival group, APACHE III scores significantly decreased from the median value of 64 (32-89) to 37 (p = 0.0269), and in the nonsurvival group, it increased significantly from the median value of 70 (29-103) to 87 (p = 0.0116). In contrast, no significant changes were observed in the MOD scores. In conclusion, the MOD score and the APACHE III score systems had less power to predict the outcome of MOF patients undergoing CHDF at Day 0. However, rescoring at Day 3 of each index was much more powerful to accurately predict the outcome of such patients.

APACHE↗
PubMed2001

Successful use of thoracoscopic pericardiectomy in elderly patients with massive pericardial effusion caused by uremic pericarditis.

We report the use of thoracoscopic pericardiectomy to treat two elderly patients with massive pericardial effusion caused by uremic pericarditis. A 79-year-old man, admitted to our hospital complaining of dyspnea, was diagnosed with end-stage renal failure and began maintenance hemodialysis. Although intensive hemodialysis was performed, the patient could not remain on hemodialysis because of severe hypotension during the procedure. Echocardiography revealed massive pericardial effusion and severe hypokinesis of the left ventricular wall. Pericardiocentesis was performed first, without success, followed by thoracoscopic pericardiectomy under general anesthesia. One month after the pericardiectomy, episodes of hypotension during hemodialysis improved, and dyspnea diminished. Echocardiography showed no pericardial effusion and improvement of left ventricular wall motion. Pericarditis is a fatal complication in patients with end-stage renal failure and patients on maintenance hemodialysis. The second patient received the same procedure with a similar improvement of clinical symptoms. These cases suggest that thoracoscopic pericardiectomy is a safe and effective treatment of pericardial effusion caused by uremic pericarditis in elderly patients on hemodialysis.

Aged↗
PubMed2001

Stenosis differentially affects subendocardial and subepicardial arterioles in vivo.

The presence of a coronary stenosis results primarily in subendocardial ischemia. Apart from the decrease in coronary perfusion pressure, a stenosis also decreases coronary flow pulsations. Applying a coronary perfusion system, we compared the autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12) arterioles (<120 microm) after stepwise decreases in coronary arterial pressure from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were performed with and without stenosis on the perfusion line. Maximal arteriolar diameter during the cardiac cycle was determined and normalized to its value at 100 mmHg. The initial decrease in diameter during reductions in pressure was significantly larger at the subendocardium. Diameters of subendocardial and subepicardial arterioles were similar 10--15 s after the decrease in pressure without stenosis. However, stenosis decreased the dilatory response of the subendocardial arterioles significantly. This decreased dilatory response was also evidenced by a lower coronary inflow at similar average pressure in the presence of a stenosis. Inhibition of nitric oxide production with N(G)-monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude that the decrease in pressure caused by a stenosis in vivo results in a larger decrease in diameter of the subendocardial arterioles than in the subepicardial arterioles, and furthermore stenosis selectively decreases the dilatory response of subendocardial arterioles. These two findings expand our understanding of subendocardial vulnerability to ischemia.

Animals↗
PubMed2001

Newly developed immobilized polymyxin B fibers improve the survival of patients with sepsis.

BACKGROUND: Sepsis and septic shock are still major causes of morbidity and mortality in spite of the availability of powerful and broadly active antibiotics. METHODS: A prospective, open and randomized trial of the effect of immobilized polymyxin fibers (PMX-F) on the survival of patients with sepsis throughout a follow-up period of 28 days or until discharge, if earlier, was carried out. Ninety-eight patients were included who met at least 4 of the criteria for systemic inflammatory response syndrome due to infection. The patients were classified into three groups based on their Acute Physiology and Chronic Health Evaluation (APACHE) II score. RESULTS: The overall survival rate was significantly improved by using PMX-F compared to the control group (41 vs. 11%) (p = 0.002). In patients with an APACHE II score less than 20, treatment with PMX-F was shown to improve outcome (65 vs. 19%) (p = 0.01). In cases of more severe sepsis with an APACHE II score of 20-29, PMX-F still maintained efficacy in improving outcome (40 vs. 11%) (p = 0.04). However, PMX-F treatment did not improve the survival rate in patients with an APACHE II score of greater than 30 (survival rate 7 vs. 0%) (p = 0.59). CONCLUSION: From these results, it is concluded that treatment with PMX-F in patients with sepsis is effective and prolongs the survival rate when applied at an early stage of sepsis. However, in severe sepsis, this therapy does not improve the survival rate.

APACHE↗
PubMed2001

Comparison of the effects of an ACE inhibitor and alphabeta blocker on the progression of renal failure with left ventricular hypertrophy: preliminary report.

The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and alphabeta blocker in combination with a calcium antagonist on the progression of renal function and left ventricular hypertrophy (LVH) in patients with chronic renal insufficiency and hypertension. The 65 subjects in this study were recruited from a cohort of 316 patients. The main criteria for inclusion were echocardiographic diagnosis of LVH (posterior wall thickness >12 mm) and serum creatinine of more than 1.5 mg/dl. Antihypertensive treatments were switched to the combination of amlodipine at a dose of 5 mg and benazepril at a dose of 2.5 mg daily or the combination of amlodipine at a dose of 5 mg and arotinolol at a dose of 20 mg daily at random irrespective of whether or not patients had been previously treated. The follow-up period was 2 years. Systolic and diastolic blood pressure were significantly reduced from 150/90 +/- 15/11 mmHg to 130/75 +/- 11/9 mmHg (ACE) and the levels of serum creatinine were increased significantly from 1.8 +/- 0.3 to 2.0 +/- 0.4 mg/dl (ACE). In the alphabeta-blocker group, these two values were similar and no significant changes were found. PWT was decreased from 14.2 +/- 0.6 to 12.9 +/- 0.3 cm in alphabeta blocker but was not significantly decreased in the ACE inhibitor group. In conclusion, combination therapy with a calcium antagonist and abeta blocker might be effective treatment for hypertensive patients with chronic renal insufficiency and left ventricular hypertrophy.

Adrenergic alpha-Antagonists↗
PubMed2001

[A case of myeloma kidney complicated by extramedullary plasmacytoma with massive bleeding].

A 76-year-old woman, who had received hemodialysis due to chronic renal failure of unknown cause for two months, was admitted to our hospital. She was suffering from severe pain in the left thigh, rapidly progressive anemia and thrombocytopenia after receiving a contusion on her left thigh. Soon after admission, the patient died of shock. Autopsy revealed multiple myeloma(lamda type) with extramedullary plasmacytoma and systemic amyloidosis. In the kidney, there were typical tubular casts with multinucleated giant cells and interstitial fibrosis. More specific findings included an extramedullary plasmacytoma in the left iliopsoas muscle surrounded by a huge hematoma. Internal hemorrhage resulting from indirect contusion at this site was likely to have caused her shock. Since typical clinical findings of multiple myeloma, such as serum M protein and hypercalcemia, were not found in this case, it was difficult to make a diagnosis of multiple myeloma. In case of multiple myeloma, micro- or macroscopic extramedullary tumor formation is not rare, but there has been no report of a case with macroscopic tumor formed in skeletal muscle, exhibiting massive hemorrhage. We report here a case of multiple myeloma with an unusual clinical course.

Aged↗
PubMed2001

Heme oxygenase-1 regulates vascular tone of the peritoneum undergoing peritoneal dialysis.

The present study investigated the role of heme oxygenase-1 (HO-1) in regulating the vascular tone of the peritoneum undergoing peritoneal dialysis. First, we used reverse-transcriptase polymerase chain reaction (RT-PCR) to measure changes in the expression of HO-1 mRNA in the peritoneum of dehydrated Wistar Kyoto (WKY) rats. Second, we used a charge-coupled-device (CCD) camera to measure changes in the diameter and blood flow in the small artery of the peritoneum after intravenous administration of saline, hemin (4-12 mumol/kg), and tin-protoporphyrin (4-12 mumol/kg) in dehydrated WKY rats. In non dehydrated rats (control), no expression of HO-1 mRNA in the peritoneum was seen. In dehydrated and 10% glucose-treated dehydrated rats, HO-1 expression was significantly enhanced as compared with the control rats. Intravenous administration of saline induced no significant changes in the diameter of the small artery in dehydrated WKY rats. Intravenous administration of hemin induced a significant increase in the diameter of the small artery in dehydrated WKY rats. Intravenous administration of tin-protoporphyrin induced a significant reduction in the diameter of the small artery in dehydrated WKY rats. Our results suggest that 10% glucose injection into the peritoneal cavity induces overexpression of HO-1 in the peritoneum of dehydrated rats. In addition, HO-1 regulates peritoneal function by the regulation of vascular tone in the peritoneum.

Animals↗
PubMed2001

Renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum.

The present study was carried out to investigate changes in the expression of aquaporins (AQPs) in the peritoneum. The effects of the renin-angiotensin system on the expression of AQPs with and without angiotensin converting enzyme inhibitor (ACEI) or angiotensin II type 1a receptor blocker (ARB) were then examined. We divided 20 male Wistar Kyoto (WKY) rats into four groups, dialyzed with these solutions: saline; 10% glucose (TZ); 10% glucose plus benazepril (ACEI: 4 mg/kg daily); and 10% glucose plus valsartan (ARB: 10 mg/kg daily). The ACEI and ARB were administered into the peritoneum for 7 days. Expression of AQP-1-AQP-4 mRNA was studied by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR). Ultrafiltration volume (UFV) and peritoneal function were measured by peritoneal equilibration test (PET). In the TZ group, expression of AQP-1 and AQP-4 was enhanced in parallel with an increment in UFV. Expression of AQP-1 and AQP-4 was also observed in the mesothelium by immunofluorescence microscopy. On the other hand, in ACEI- and ARB-treated rats, expression of AQP-1 and AQP-4 was significantly suppressed, accompanied by loss of UFV. Our results suggest that the renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum. Administration of ACEI or ARB in patients undergoing continuous ambulatory peritoneal dialysis should be carried out with caution.

Angiotensin II↗
PubMed2001

Low serum albumin in elderly continuous ambulatory peritoneal dialysis patients is attributable to high permeability of peritoneum.

Our study was carried out to investigate changes in nutrition and individual peritoneal membrane transport characteristics in elderly patients on continuous ambulatory peritoneal dialysis (CAPD), expressed as the personal dialysis capacity (PDC). We performed 376 PDC tests in 229 non diabetic patients who were undergoing CAPD from May 1995 to May 1999 in a multicenter study in Japan. We divided the patients into three groups: elderly (age > or = 65 years, n = 56), middle-aged (age 50-65 years, n = 150), and young (age < 50, n = 170). No significant differences were seen in duration of CAPD and incidence of peritonitis between the groups. We then compared the peritoneal function calculated by PDC test in the groups. Serum levels of albumin in elderly patients were significantly lower than those in middle-aged and young patients (elderly: 3.2 +/- 0.1; middle-aged: 3.4 +/- 0.1, p = 0.0447 vs elderly; young: 3.4 +/- 0.1, p = 0.0272 vs elderly). Plasma protein loss from the peritoneum in elderly patients was significantly higher than in middle-aged and young patients (elderly: 0.11 +/- 0.01; middle-aged: 0.09 +/- 0.01, p = 0.0136 vs elderly; young: 0.09 +/- 0.01, p = 0.0161 vs elderly). No significant differences in ultrafiltration volume and water permeability were seen between the groups. Peritoneal area in the elderly group was significantly higher than in the middle-aged and young groups. Peritoneal creatinine clearance (CCr) and Kt/V in elderly patients were significantly higher than in middle-aged and young patients. However, no significant difference in protein nitrogen appearance (PNA) or protein catabolic rate (PCR) was seen between the groups. Urea and creatinine generation rates in elderly patients were significantly lower than in the middle-aged and young patients. These data show that elderly patients receiving CAPD are well maintained from the perspective of urea and water metabolism, indicating that CAPD therapy for the elderly is more acceptable than expected. However, caution should be exercised, owing to the lower serum albumin seen in elderly patients.

Adult↗