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Biomedical subjects

N Kobayashi

Publications and source records attributed to N Kobayashi.

At least 217 records · Page 12Linked to original sources

In vitro metabolism of human and salmon calcitonins in rat liver and kidney evaluated by liquid chromatography-tandem mass spectrometry.

1. Using LC-MS and LC-MS/MS, an in vitro study was conducted on the metabolism of human calcitonin (hCT) and salmon calcitonin (sCT) in rat liver and kidney to determine the rates of metabolism and the positions of hydrolytic cleavage in both peptides. 2. In lysosomal fractions of rat liver and kidney, hCT was degraded 9-12 times faster than sCT. Many metabolites of hCT were produced in the lysosomal fractions, whereas the metabolites of sCT were scarcely found. 3. In the case of the cytosolic fractions, three positions of initial endoproteolytic cleavage were found in hCT, leading to the production of many peptide fragments via subsequent exoproteolytic metabolism. The initial cleavage position of sCT could not be identified precisely, but it was postulated that the rate-determining step in the metabolism of sCT is the endoproteolytic hydrolysis. 4. The studies using pure proteases and protease inhibitors indicated that the metabolism of calcitonins proceeds by initial endoproteolytic cleavage and subsequent exoproteolytic digestion, catalysed by an aspartate-protease in lysosomes and by a metalloprotease and cysteine-protease in combination in the cytosol. 5. The result suggested that the higher in vivo pharmacological activity of sCT compared with that of hCT may be due to a slower metabolism of the former.

Amino Acid Sequence↗

Analysis of histidine-dependent antitermination in Bacillus subtilis hut operon.

We have previously shown that a positive regulator, HutP, of Bacillus subtilis hut operon is a RNA binding protein. Here, we report precise binding site of HutP in cis-regulatory region on hut mRNA and the role of HutP in histidine-dependent antitermination of hut expression. Ethylnitrosourea modification interference assay showed that four binding sites of HutP were found in the cis-regulatory sequences and were located at the stem and the internal loop of an antiterminator structure. In vitro transcription assay indicated that HutP suppressed transcription termination in the presence of histidine. These results suggest that HutP function as an antiterminator in response to the presence of histidine.

Bacillus subtilis↗

Effects of angiotensin II type 1 receptor antagonist on nitric oxide synthase expression and myocardial remodeling in Goldblatt hypertensive rats.

We evaluated the effects of long-term treatment with TCV-116, an angiotensin II type 1 receptor antagonist, on endothelial-cell nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression in the left ventricle and its relation to myocardial remodeling in Goldblatt hypertensive rats. Two-kidney, one-clip Goldblatt hypertensive rats (RHR) were assigned either to a TCV-116 treatment group (RHR-TCV, n = 8, 3 mg/kg/day, subdepressor dose) or to a group without treatment (RHR-V, n = 7) after their kidneys had been clipped for 4 weeks. TCV-116 was administered to rats in the treatment group for 6 weeks, and age-matched sham-operated rats (ShC, n = 7) served as a control group. Blood pressure in RHR-V and RHR-TCV was similar and significantly higher than that in ShC. The eNOS mRNA and protein levels and NOS activity in the left ventricle was significantly decreased in RHR-V compared with ShC, and significantly increased in RHR-TCV compared with ShC and RHR-V. RHR-V demonstrated a significant increase in fibrosis factor (type I collagen) mRNA expression, perivascular fibrosis, and myocardial fibrosis. These parameters in the microvasculature were improved significantly by TCV-116. Subdepressor dose of TCV- 116 improved pathological myocardial changes in RHR, which may be due in part to an increased eNOS mRNA and protein expression and NOS activity in the left ventricle.

Angiotensin Receptor Antagonists↗

Null mutation of PCLN-1/Claudin-16 results in bovine chronic interstitial nephritis.

Inherited chronic renal diseases are associated with failures in glomerular filtration and tubular resorption. Such failures invariably result from defects in selective filtration and absorption in surface renal epithelium. Recently, we described an autosomal recessive chronic interstitial nephritis with diffuse zonal fibrosis (CINF) in cattle. Bovine CINF, characterized by increased blood urea nitrogen, creatinine, and urinary proteins, leads to lethality before puberty, usually within the first 6 months or year of life. Here, we demonstrate that the first four exons of PCLN-1/Claudin-16 (CL-16), which encodes a member of the claudin family of tight junction proteins, were deleted in CINF-affected cattle. CL-16 was expressed preferentially in kidneys of normal cattle, but transcripts were totally absent in affected offspring. This observation suggests that the lack of CL-16 protein contributes to the dysfunction of paracellular renal transport systems.

Amino Acid Sequence↗

Caspase-3 activation and apoptosis induction coupled with the retrograde transport of shiga toxin: inhibition by brefeldin A.

Caspase proteolytic activities, such as caspase-3, -2 and -6, of THP-1 human monocytic cells were markedly increased in a time- and dose-dependent manner by treatment with purified Shiga toxin 1 (Stx1) or Stx2. Caspase-3 activation was strictly correlated with internucleosomal DNA fragmentation and chromatin condensation of the cells. In addition, the specific caspase-3 inhibitor, Ac-DEVD-CHO, decreased the percentage of apoptotic cells. The purified B-subunit of Stx1 did not induce apoptosis in THP-1 cells. Caspase-3 activation, DNA fragmentation and chromatin condensation caused by Stx were completely blocked by pretreatment of cells with brefeldin A, an inhibitor of Golgi functions. The findings suggest that Stx1 as well as Stx2 activate caspase-3, which plays a critical role in apoptosis, and that the apoptotic signals rise after Stx is transported to the Golgi apparatus.

Apoptosis↗

Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease.

BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.

Adult↗

Pulmonary edema after cardioversion for paroxysmal atrial flutter: left ventricular diastolic dysfunction induced by direct current shock.

This report describes a patient with the pulmonary edema after cardioversion for paroxysmal atrial flutter without organic heart disease. A 68-year-old man was admitted to hospital for paroxysmal atrial flutter. Antiarrhythmic agents were not effective, and direct current cardioversion was performed on the 4th hospital day. Three hours after cardioversion, the patient complained of dyspnea, and a chest X-ray showed pulmonary edema. He responded to oxygen, intravenous furosemide and drip infusion of nitroglycerine. During tapering of the medication, his condition remained stable. The patient was discharged on the 7th day after admission. Echocardiographic findings indicated that transient left ventricular diastolic dysfunction due to direct current shock was the most likely cause of the lung edema.

Aged↗

The effect of oral clonidine premedication on lumbar cerebrospinal fluid pressure in humans.

Alpha-2 adrenergic agonists including clonidine decrease cerebral blood flow. The specific actions of clonidine on cerebrospinal fluid (CSF) pressure in humans remain to be elucidated. We evaluated the effect of oral clonidine premedication on lumbar CSF pressure in patients without intracranial disease. Seventy-four patients undergoing subarachnoidal block were divided randomly into either a clonidine or a control group. In the clonidine group, the patients were premedicated orally with 5 microg/kg clonidine 60 min before arrival in the operating room. Subarachnoidal puncture was performed via midline approach using a 23-gauge needle at the L2-3 or L3-4 intervertebral space with the patient in the lateral decubitus position. Before the injection of local anesthetic, lumbar CSF pressure was measured. Lumbar CSF pressure was 8.1+/-2.4 mmHg in the clonidine group, which was significantly lower than that in the control group (9.4+/-2.8 mmHg, p<0.05). The cerebral perfusion pressures were 76.2+/-12.5 mmHg in the clonidine group and 91.7+/- 15.4 mmHg in the control group (p<0.001). In the clonidine group, preanesthetic mean blood pressure had a significant correlation with lumbar CSF pressure (r=0.619, p=0.019). We conclude that Lumbar CSF pressure was attenuated by oral premedication with 5 microg/kg clonidine. Clonidine also contributed to a significant correlation between preanesthetic mean blood pressure and CSF pressure.

Administration, Oral↗

What determines the heart rate response to exercise in patients with atrial fibrillation?

We evaluated the factors that determine the heart rate response to exercise in 60 patients with atrial fibrillation (25 men and 35 women, with a mean age of 61+/-10 years) who underwent symptom limited cardiopulmonary exercise testing with blood sampling of atrial natriuretic peptide (ANP), 2-dimensional echocardiography and cardiac catheterization. Atrial muscles resected during the Maze operation were examined histologically in 12 patients. The heart rate response to exercise depended on the severity of the atrial organic injury, which was expressed as left atrial diameter, ANP secretion during the maximal exercise testing and the histological findings of atrial tissue. Conversely, we believe that the severity of the atrial injury can be predicted from the heart rate response to exercise in patients with atrial fibrillation.

Aged↗

Contrast-enhanced conventional CT in patients after surgery for malignant tumors: evaluation of the optimal method of the administration of the contrast medium.

Patients after ablative surgery for malignant tumors require computed tomography (CT) examination of a wide area on the head and neck to follow-up for recurrence and lymph metastasis. The aim of this study was to determine a more effective method for the infusion of the contrast medium into post-operative patients undergoing conventional CT, based on the relationship between the method of administering the contrast medium and the contrast-enhancing effect in the internal jugular vein. First eleven images were selected from the existing contrast-enhanced and plain CT images in a manner such that the CT values of the internal jugular vein were distributed evenly in a range of 50-180. Seven experienced observers evaluated the contrast-enhancing effect of each image set at a window value of 40 and window widths of 120, 200, and 280. Secondly, the CT values of the right internal jugular vein were measured in a total of 10 CT images from the thyroid to maxillary sinus level from each of 60 post-operative patients. The injection needles and contrast-enhancing techniques used in the 60 patients were drip infusion using an 18G injection needle in 20, drip infusion using a 21G injection needle with bolus intravenous injection immediately before scanning in 20, and drip infusion using a 23G injection needle with bolus intravenous injection immediately before scanning in 20. A CT value of 100 or above, preferably 120 or above, in the internal jugular vein was needed for the contrast-enhancing effect of a CT image to be judged as clinically significant. Our results found that, when a conventional CT was used in patients after surgery for malignant tumors, drip infusion using a 21G or 23G injection needle should be combined with bolus injections immediately before the beginning of scanning, and at the glottis or submandibular gland level during the scanning. A sufficient contrast-enhancing effect can also be obtained by drip infusion using an 18G injection needle without bolus injection.

Adult↗

[Ocular counter-rolling after prolonged alteration in the direction of gravity].

To investigate the dynamics of otolith and oculomotor function, we subjected volunteers to a lateral body tilt for a period of two hours and analyzed ocular counter-rolling. Six healthy adult volunteers were roll-tilted along the naso-occipital axis at a speed of 0 degree/sec. from the 0 degree earth vertical position to the 90 degrees lateral tilt position. After two hours, the volunteers were returned to the 0 degree earth vertical position. Ocular counter-rolling was recorded using an infrared CCD camera. The video recordings were made in the dark while the volunteers had their eyes open. Recordings were obtained (1) as the volunteers was moved from the 0 degree earth vertical position to the 90 degrees lateral position, (2) 5 minutes after reaching the lateral position, (3) during the roll-back from the 90 degrees lateral position to the 0 degree upright position, two hours after the lateral tilt loading, and (4) 5 minutes after reaching the final upright position. The occurrence of ocular counter-rolling between the 0 degree upright position and the 30 degrees tilt position was confirmed during both roll movements from 0 degree to 90 degrees and from 90 degrees to 0 degree. The counter-rolling was most noticeable between the 0 degree and the 30 degrees positions. No differences in ocular counter-rolling during the roll-tilt and the roll-back situations were observed. These results indicate that the two-hour lateral tilt position did not produce any functional changes in the hair cells and/or the otolith-oculomotor system. All of the subjects exhibited ocular counter-counter-rolling during the initial stage of their roll-back to a normal upright position. This phenomenon might result from the additional bending of the hairs by inertia during the initiation of the backward roll motion.

Adult↗

New P serotype of group A human rotavirus closely related to that of a porcine rotavirus.

The VP7 and VP4 genes of two human group A rotavirus strains Mc323 and Mc345 with unique serologic and genomic properties, and isolated in Chiang Mai, Thailand, in 1989 [Urasawa et al. (1992) Journal of Infectious Diseases 166:227-234] were further characterized. The nucleotide and deduced amino acid sequences of the VP7 genes allowed the classification of both strains as serotype G9. The VP4 genes of both strains are 2,359 nucleotides in length and encode a protein of 775 amino acids like in most human rotaviruses. A comparison of the VP4 amino acid sequence of strain Mc323 with those of strain Mc345 and 24 human and animal rotaviruses representing 20 distinct VP4 genotypes reported to date showed that VP4 of Mc323 and Mc345 belong to genotype 19 previously reported for porcine rotavirus [Burke et al. (1994) Journal of General Virology 75:2205-2212]. To investigate the serological type (P serotype) of these VP4s, six reassortant viruses each containing a distinct VP4 gene characteristic of human rotaviruses and the VP7 gene of porcine rotavirus strain Gottfried (G4) were prepared, and antisera to these reassortants produced in rabbits. In neutralization tests, the P serotype of Mc323 was clearly differentiated from the five major P serotypes reported previously for human rotaviruses, suggesting that Mc323 and Mc345 represent a new human rotavirus P serotype tentatively called P11.

Amino Acid Sequence↗

[Successful treatment using detachable coils for traumatic carotid cavernous fistula as a complication of transsphenoidal surgery for a pituitary adenoma: a case report].

We report a case of a patient with traumatic carotid cavernous fistula (CCF) caused by transnasal-transsphenoidal surgery, who was successfully treated using detachable coils. A 47-year-old man was admitted to our hospital because of severe headache. He was confirmed to have a nonfunctioning pituitary adenoma with presellar-type sphenoid sinus. Cerebral angiography initially disclosed no vascular lesions. A transnasal-transsphenoidal adenomectomy was performed. When the anterior wall of the sphenoid sinus was dissected with a chisel, the chisel deeply stuck into the posterolateral part of the sinus. Profuse arterial bleeding was observed through the sphenoid sinus. The bleeding was stopped easily by compression and packing with bone wax. The operation was continued, the sellar floor was opened widely and the tumor was removed subtotally. The medial wall of the cavernous sinus was intact. Histological examination revealed a pituitary adenoma. Immediately after surgery, the patient noticed a bruit. He developed chemosis and abducent palsy on the right side. Cerebral angiography displayed a high-flow CCF, which was attributed to the carotid artery injury caused by the transnasal-transsphenoidal surgery. The CCF disappeared after two-staged embolization using detachable coils, 1st transvenous and 2nd transarterial. Ten months later, cerebral angiography showed persistent occlusion of the fistula, and the patient experienced no tumor recurrence. It is suggested that drilling is a safer procedure than using a chisel for dissection of a sphenoid sinus with incomplete pneumatization. Endovascular treatment using detachable coils proved useful to manage the CCF, an unusual complication of transsphenoidal surgery.

Adenoma↗

[A clinical study on pulmonary tuberculosis in younger age groups].

In 1997, the number of newly registered patients with pulmonary tuberculosis increased, compared with that in 1996, in Japan. The majority of the increase were occupied by elder patients 70 years of age or higher. But in younger group less than 30 years old, a reduction in the incidence of tuberculosis had been slowed down, until 1996. The purpose of this report is to elucidate the characteristics of these younger patients. 139 cases younger than 30 years of age, who were hospitalized in the tuberculous ward of IMCJ from April 1995 to March 1998, were investigated, and were compared with the control group (557 cases), 30-79 years old who were hospitalized during the same period. In the younger group, the proportion of women cases, discovered by health examination, foreigners, and contact with TB patients in the past was significantly higher than in the control group. But there were no difference between the both groups, concerning the proportion of those spending irregular life or living alone. The proportion of sputa smear negative cases was significantly higher in the younger group than in the control. For early diagnosis of TB among younger group, the application of bronchofiberscopy and nucleic acid diagnostic method, are encouraged.

Adolescent↗

Granisetron/dexamethasone combination for the prevention of postoperative nausea and vomiting after thyroidectomy.

This study was undertaken to evaluate the efficacy of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) after thyroidectomy. In a prospective, randomized, double-blind study, 130 female patients received either granisetron 40 micrograms/kg or granisetron 40 micrograms/kg plus dexamethasone 8 mg intravenously immediately before the induction of anaesthesia (n = 65 in each group). A standard general anaesthetic technique was used. A complete response (no PONV, no rescue) during the first three hours after anaesthesia occurred in 85% of patients with granisetron alone and 98% with granisetron plus dexamethasone; the corresponding incidence for the period 3 to 24 hours after anaesthesia was 86% and 98% (P < 0.05; Fisher's exact probability test). No clinically serious adverse events were observed in any of the groups. In conclusion, prophylactic use of granisetron/dexamethasone combination is more effective than granisetron alone for preventing PONV in women undergoing thyroidectomy.

Adult↗

[Intracardiac floating thrombi in patients with acute pulmonary thromboembolism].

The mortality and morbidity associated with residual intracardiac floating thrombi in patients with acute pulmonary thromboembolism remain uncertain. Thirteen patients (2 men and 11 women, mean age 56 +/- 15 years) with pulmonary thromboembolism underwent echocardiography within 24 hours from onset of symptoms. Four patients (31%) had floating intracardiac thrombi in the right heart: 3 in the right atrium and one in the inferior vena cava. The time to evaluation by echocardiography was shorter than in the patients without thrombi. The thrombi disappeared shortly (3.2 +/- 2.4 hr) after thrombolysis without adverse effects in these patients. After thrombolysis, clinical symptoms improved and pressure gradient between the right ventricle and right atrium decreased significantly (p < 0.01) from baseline 47 +/- 6 to 26 +/- 5 mmHg. Major bleeding complications occurred in 3 (43%) of the patients who underwent thrombolysis. Right-side intracardiac floating thrombus was easily detectable by early echocardiography. Thrombolytic agents are likely to be effective in patients with intracardiac floating thrombi.

Acute Disease↗

[Depression of serum pyridoxal levels in theophylline-related seizures].

In order to study whether a theophylline-related seizure is caused by a decrease in serum vitamin B6, serum pyridoxal (PAL) levels were measured in children with bronchial asthma treated with theophylline. The serum PAL levels of asthmatic children (n = 31) treated with theophylline were significantly lower than those of control subjects (n = 21). Moreover, we evaluated PAL levels in four subjects within twenty-four hours after a seizure with or without fever. The level was low in three of the four. These results suggest that the decrease in PAL levels caused by theophylline may lower the seizure threshold.

Adolescent↗