Search PubMed⌕ Search

Biomedical subjects

S Ohkawa

Publications and source records attributed to S Ohkawa.

At least 37 records · Page 2Linked to original sources

[Sustained long-term complete remission in an elderly aplastic anemia patient after cessation of combined therapy consisting of granulocyte-colony stimulating factor and erythropoietin].

An 83-year-old woman received a diagnosis of moderate aplastic anemia in November 1990. Immunosuppressive therapy consisting of anti-lymphocyte globulin combined with high-dose corticosteroids was effective until pancytopenia developed in August 1993. The patient was hospitalized again and recurrence of aplastic anemia was diagnosed on the basis of hematologic findings, including RBC 129 x 10(4)/microliter, Hb 5.5 g/dl, Ret 23,200/microliter, WBC 2,200/microliter with 27% neutrophils, platelets 2.2 x 10(4)/microliter, and hypoplastic bone marrow. Recombinant human granulocyte-colony stimulating factor (G-CSF) of 125 micrograms/day combined with recombinant human erythropoietin (EPO) of 6,000 U/day were started in November 1993. The doses of G-CSF and EPO were increased to 250 micrograms/day and 12,000 U/day, respectively. We stopped combination therapy in March 1995, after trilineage hematopoietic cell recovery had been achieved. Complete recovery in peripheral blood was sustained for more than 2 years despite the termination of G-CSF and EPO therapy. Combination therapy with G-CSF and EPO may be safe and effective for elderly patients with aplastic anemia when the choice of therapy is limited.

Aged↗

[Clinicopathologic study of calcified aortic valve stenosis in the aged, and evaluation of the indications for percutaneous aortic balloon valvuloplasty].

OBJECTIVES: We performed clinicopathologic study of 56 aged patients with calcified aortic valve stenosis and investigated the indications for percutaneous aortic balloon valvuloplasty. METHODS: The patients were 24 men and 32 women with a mean age of 81.9 years, who were classified into the following 3 types by etiology: 33 patients (58.9%) had senile aortic stenosis, 10 patients (17.9%) had bicuspid aortic stenosis, and 13 patients (23.2%) had rheumatic aortic stenosis. The sites of calcification were divided into the following 3 categories: cusp bases (base type), free edges (edge type), and both bases and edges (mixed type). RESULTS: Among the 33 patients with senile aortic stenosis, 10 (30.3%) had calcification of base type, 2 (6.1%) of edge type and 21 (63.6%) of mixed type. Among the 10 patients with bicuspid aortic stenosis, one (10%) had calcification of base type and 9 (90%) of mixed type. Among the 13 patients with rheumatic aortic stenosis, 3 (23.1%) had calcification of edge type and 10 (76.9%) of mixed type. In addition, 2 or 3 commissures were fused in patients with rheumatic aortic stenosis. The cusps of the aortic valves in the bicuspid type were the most severely thickened among the 3 groups. Soft X-ray imaging showed the aortic valves of rheumatic aortic stenosis were the most severely calcified (calcification score: 2.4), followed by those of bicuspid aortic stenosis (1.9) and senile aortic stenosis (1.6). CONCLUSIONS: Percutaneous aortic balloon valvuloplasty is most suitable in patients with calcified senile aortic stenosis because of the milder calcification, compared with those of the other 2 types.

Aged↗

Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis.

BACKGROUND: Many studies have demonstrated in animal experiments that persistent inflammation may accelerate the development of carcinoma. In this article, the question of whether the persistent elevation of serum alanine aminotransferase (ALT) levels (which represents the inflammatory necrosis of hepatocytes) correlates with the development of hepatocellular carcinoma (HCC) was studied in patients with early stage hepatitis C virus (HCV)-associated cirrhosis. METHODS: Sixty-nine consecutive patients with biopsy proven HCV-associated cirrhosis (mostly Child's Stage A) who had been followed for >5 years for the development of HCC were studied. They were subdivided into 3 groups according to their serum ALT levels: Group A was comprised of 28 patients whose annual average serum ALT level was persistently high (>/= 80 IU) (high ALT group), Group B was comprised of 28 patients whose annual average serum ALT level was persistently low (< 80 IU) (low ALT group), and Group C was comprised of 13 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for > 5 years. RESULTS: In the high ALT group HCC developed in 71.4% of patients compared with 25.0% in the low ALT group over the observation period (P < 0.005). The 5-year rate of incidence of HCC in the high ALT group was as high as 53.6% compared with only 7.1% in the low ALT group (P < 0.001). The expected interval between the diagnosis of cirrhosis and the development of HCC was 6.0 +/- 0.7 years (mean +/- standard error) in the high ALT group and 12.7 +/- 1.2 years in the low ALT group (P < 0.001). CONCLUSIONS: The results of the current study demonstrated that the development of HCC was more rapid in the high ALT group with HCV-associated cirrhosis.

Aged↗

Study of the relationship between sticky human serum IgA1 and its O-glycan glycoform.

The high-affinity IgA1 toward jacalin was mostly composed of aggregated IgA1 and abundantly contained the asialo disaccharide, Galbeta1,3GalNAc, in the O-linked oligosaccharide in the hinge region [Journal of Biochemistry 120, 92-97 (1996)]. Meanwhile, the removal of sialic acid from IgA1 accelerated the aggregation of the IgA1 molecule [J. Am. Soc. Nephrol. 9, 2048-2054 (1998)]. In order to examine the nature of such a sticky IgA1, affinity chromatography using asialo-IgA1 (deSIgA1)-Sepharose was carried out. Seventeen percent of normal human serum IgA1, 27% of asialo-IgA1 (IgA1-S), and 48% of asialo-, agalacto-IgA1 (IgA1-SG) were bound to the column. Removal of the N-acetylgalactosamine residue from IgA1-SG resulted in a decreasing affinity toward deSIgA1-Sepharose. Thus, the binding ability toward the column was the highest for the IgA1-SG among the deglycosylated IgA1s. On the other hand, heat treatment of IgA1 accelerated the aggregation but decreased its binding ability toward the column. Such heat denaturation probably destroys the structure of the binding site. Since the enzymatic removal of the N-glycan sugar chains did not induce the aggregation and exhibited no effect on the binding, the incomplete O-linked sugar chain on the hinge portion should be directly related to the sticky characteristics of the IgA1 molecule. The binding was non-covalent and not strong because the asialo-, agalacto-hinge glycopeptide was eluted slightly slower than the native one from the column and the bound IgA1 was dissociated in the presence of 1 M NaCl.

Chromatography, Affinity↗

Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa.

The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.

Animals↗

Altered abdominal fat distribution and its association with the serum lipid profile in non-diabetic haemodialysis patients.

BACKGROUND: Disturbances of lipid and carbohydrate metabolism may be associated with the distribution of abdominal adiposity. However, little is known about the alteration of abdominal adiposity and its association with the serum lipid profile in haemodialysis patients. METHODS: We evaluated the distribution of abdominal adiposity by using computed tomography and examined its relationship with the serum lipid profile in 92 non-diabetic haemodialysis patients and 80 control subjects with normal renal function. Since the mean body mass index (BMI) and total body fat mass were significantly lower in the haemodialysis patients than in the control subjects, the subcutaneous abdominal fat area and the visceral fat area were standardized by body mass index and compared between the haemodialysis patients and the control subjects. RESULTS: Mean subcutaneous fat area/body mass index (SFA/BMI) was significantly lower, and mean visceral fat area/body mass index (VFA/BMI) was significantly higher in the haemodialysis patients (SFA/BMI, 2.40+/-0.12; VFA/BMI, 2.28+/-0.15) than in the control subjects (SFA/BMI, 3.75+/-0.21, P<0.01; VFA/BMI, 1.65+/-0.15, P<0.01). Consequently, visceral fat area/ subcutaneous fat area ratio was significantly higher in the haemodialysis patients (1.05+/-0.07) than in the control subjects (0.46+/-0.04, P<0.01). A scattered plot of visceral fat area relative to BMI revealed that visceral fat area was higher in the haemodialysis patients than in the control subjects at any BMI level. A simple regression analysis showed that BMI, total body fat mass, subcutaneous fat area and visceral fat area were all associated with serum triglycerides and the atherogenic index, (total cholesterol-HDL cholesterol)/HDL cholesterol. Furthermore, a multiple regression analysis indicated that the visceral fat area was the best predictor for either the atherogenic index or triglycerides among these fat components. CONCLUSIONS: These data indicate that haemodialysis patients exhibited a visceral fat accumulation irrespective of BMI, and this shift of abdominal adiposity might be associated with disturbance of the serum lipid profile in non-diabetic haemodialysis patients.

Abdomen↗

[Influence of dexamethasone on the clinical course of bacterial meningitis in children. Especially on secondary fever. Experiences in 27 institutions].

Of pediatric patients with purulent meningitis seen at the institutions listed in the title page of this paper between 1986 and 1994, 93 patients treated with antibiotics and dexamethasone (DXM) were compared with 91 patients treated with antibiotics alone. The patients receiving antibiotics with dexamethasone achieved overall improvement in inflammatory symptoms and signs and cerebrospinal fluid findings and became afebrile significantly earlier than those receiving antibiotics alone. However, some of the patients became febrile again. The secondary fever rate for the DXM group was much higher than that for the antibiotic alone group (p < 0.0001). In most of the rebounded cases, the body temperature rose above 38 degrees C and remained elevated for 2-4 days. Cerebrospinal fluid (CSF) was cultured daily in 54 and 32 patients receiving antibiotics with and without DXM, respectively. Although this study was not a controlled study in a strict sense, these patients compared. In both groups, the CSF became mostly culture-negative within 48 hours. In a few patients receiving DXM, however, it became culture-negative after 72 hours or longer. DXM caused an adverse effect in a patient with meningitis caused by Streptococcus pneumoniae. The adverse effect was mild gastrointestinal bleeding, which recovered spontaneously. From the findings described above, the use of DXM combined with antibiotic therapy was considered to accelerate the relief from fever and improvement of inflammatory symptoms and signs and CSF findings. The body temperature rose again in more than half of the patients receiving DXM, but fell to normal spontaneously without treatment. The elevation doubtlessly could not be distinguished from recurrence of the meningitis itself or complications. It seems to be likely that no treatment but careful observation is required even if the fever recurs as far as the CSF findings showed favorable progress with excelluent general conditions. When DXM is given, it is essential that CSF tests and culture are repeated during the early stages and the progress is monitored carefully.

Anti-Bacterial Agents↗

Implications of marked fatty infiltration around and in the atrophic atrioventricular node in elderly patients with permanent pacemaker implantation for symptomatic sick sinus syndrome.

The present study undertook an extensive analysis of the histopathological findings of the atrioventricular conduction system in 14 elderly patients treated with permanent pacemakers for sick sinus syndrome (SSS). Special attention was given to the lowest Wenckebach block points of atrioventricular conduction during rapid atrial pacing, and ventricular rate or duration of ventricular pause during chronic atrial fibrillation. An electrophysiological study (EPS) was conducted under sinus rhythm in 13 patients and under junctional escape rhythm in 1 patient. Three of the 14 cases showed a lower Wenckebach block point of 130 beats/min or less. Two of these 3 cases showed excessive fatty infiltration around the atrionodal junction area and into the atrophic atrioventricular node (AVN) itself. Of the 6 patients who had chronic atrial fibrillation after pacemaker implantation, 2 cases showed a slow ventricular response of less than 60 beats/min and/or a long ventricular pause of 3.3 s. One of the 2 cases showed a lower Wenckebach block point of 130 beats/min at the time of EPS. The other, who later progressed to idiopathic atriomegaly, also showed marked fatty infiltration around the AVN. This fatty lesion was closely associated with diffuse disruption of the muscular fibers connecting the atrophic AVN with the atrium. In addition, most of the remaining cases also had an atrophic AVN. In conclusion, a sparse or absent atrionodal connection and an atrophic AVN due to excessive fatty infiltration in the atrionodal transitional area should be investigated in atrioventricular conduction disturbances in the elderly with SSS.

Aged↗

Torsades de pointes in a case of hypertrophic cardiomyopathy with special reference to the pathologic findings of the heart including the conduction system.

A clinicopathologic study was performed in a 77-year-old female with hypertrophic cardiomyopathy who had experienced recurrent syncopal attacks due to Torsades de Pointes (TdP) following QT prolongation and atrioventricular block. She died suddenly two years later while eating dinner. Pathologic findings of the heart showed a dilated and hypertrophied left ventricle. The heart weighed 550 g. There were two foci of localized endocardial fibroelastosis (EFE) beneath the aortic valve, one with a size of 3.5 x 3.5 cm, and the other (2 x 1 cm) located on the upper ventricular septum. Histologic findings showed hypertrophy and disarray in the left ventricular myocardium. The conduction system using serial sectioning revealed remarkable bilateral bundle branch fibrosis and hypertrophied Purkinje fibers in the left bundle branch adjacent to the EFE on the ventricular septum. These findings were thought to be related to the occurrence of TdP.

Aged↗

Extensive involvement of the myocardium and the cardiac conduction system in a case of Wegener's granulomatosis.

A 61-year-old female who had shown Raynaud's phenomenon and articular swelling for 10 years, was admitted to hospital because of fever of unknown origin (FUO) and dry cough. She was diagnosed by skin biopsy to have a collagen disease or overlap syndrome. Anemia developed rapidly and FUO persisted, but blood culture was negative. Although indomethacin and prednisolone were administered for the progression of clinical signs and symptoms, severe dyspnea developed, resulting in bradycardia, followed by recurrent episodes of ventricular tachycardia. In spite of extensive treatment for her arrhythmia she died on the 9th hospital day. An autopsy revealed generalized Wegener's granulomatosis with extensive cardiac involvement. Necrotizing angitis and severe granulomatous inflammatory foci affected characteristically the common bundle of His and right bundle branch in addition to the ordinary myocardium.

Electrocardiography↗

[An autopsy case of elderly idiopathic enlargement of the right atrium].

We report an autopsy case of an 88-year-old man with idiopathic enlargement of the right atrium which is considered to be the oldest case reported. The patient was given a diagnosis of atrial fibrillation at the age of 75 years, when he developed congestive heart failure. Bradycardia associated with partial atrial standstill was detected and, the patient underwent implantation of a pacemaker at age 77. An echocardiogram revealed marked enlargement of the right atrium and moderate enlargement of the left atrium. Thus, idiopathic enlargement of the right atrium was diagnosed. He had recurrent congestive heart failure before admission to our hospital because of malnutrition and anemia. Although he was treated with high calorie intravenous infusion and blood transfusion, he died of pneumonia and heart failure. Postmortem examination revealed that the heart weighed 430 g, and there was marked dilatation of the right atrium which had an extremely thin wall. The annular circumference of the tricuspid valve was markedly dilated, 170 mm, resulting in tricuspid regurgitation. The left atrium was moderately dilated and the right and left ventricles were slightly dilated. Histologically, the free wall of the right atrium was totally replaced by fibrous tissue and atrioventricular valves did not reveal any rheumatic changes. These pathological findings were compatible with idiopathic enlargement of the right atrium. There has been no previous case report of idiopathic enlargement of the right atrium in a patient aged 80 years of age or over.

Aged↗

[Usefulness and safety of intravenous thrombolytic therapy for elderly patients with acute myocardial infarction: relationship with cardiac rupture].

The usefulness and safety of intravenous thrombolytic therapy were investigated in 298 patients older than 65 years (145 males, 153 females, mean age 78 years) with acute myocardial infarction from 1984 to 1993. These patients were divided into 2 groups of 88 patients younger than 74 years (Group A) and 210 patients older than 75 years (Group B). Seventy patients received thrombolytic therapy with urokinase (UK) or tissue-plasminogen activator [t-PA (UK96 X 10(4)U: 57 patients, t-PA 30-40 X 10(4)U/kg: 12, UK + t-PA: 1)] within 6 hours after the onset of acute myocardial infarction (Group TL). Two hundred twenty-eight patients received conventional therapy (Group C). There were no differences in the frequencies of the site of myocardial infarction, Killip class, admission within 6 hours after the onset of acute myocardial infarction or thrombolytic therapy between the 2 age groups. In-hospital mortality was significantly higher in Group B than in Group A (43% vs 24%, p < 0.01). In Groups A and B, in-hospital mortality was 20% lower in Group TL compared with Group C (20% vs 25% in Group A, 36% vs 45% in Group B). In Group B, the mortality from pump failure including shock and congestive heart failure was half in Group TL compared with Group C (13% vs 30%). Cardiac rupture was found in 11 patients of Group TL and 7 patients of Group C. Therefore, the mortality from cardiac rupture was fivefold higher in Group TL compared with Group C (8% vs. 1.6% in Group A, 20% vs 3.6% in Group B). Of 11 patients with cardiac rupture in Group TL, 8 patients suffered rupture in the early phase within 12 hours after the onset of acute myocardial infarction and the tear was present near the center of infarcted area in all 7 autopsy cases. The case of recanalization of the infarct-related coronary artery in Group TL revealed moderate to massive hemorrhagic infarction at autopsy. This indicates that the mechanisms involved in cardiac rupture are different in thrombolytic therapy and conventional therapy. Intravenous thrombolytic therapy is effective for the reduction of mortality from pump failure in elderly patients with acute myocardial infarction older than 75 years. However, it must be evaluated as one of the risk factors of cardiac rupture in elderly patients.

Age Factors↗

7-Arylidenenaltrexones as selective delta1 opioid receptor antagonists.

A series of 7-arylidinenaltrexones (2a-m) related to the prototypical delta1-selective antagonist, 7-benzylidenenaltrexone 1 (BNTX), have been synthesized in an effort to develop more selective ligands. Testing in smooth muscle preparations revealed that members of the series exhibited varying degrees of selectively for delta receptors, with the o-methoxy (2e) and o-chloro (2j) congeners being most potent and most selective (Ke approximately 0.8 nm). Evaluation of 1, 2e, and 2f sc in mice using the tail-flick procedure indicated that they are selective delta1 opioid receptor antagonists in the lower dose range. At high doses these ligands, including BNTX, exhibited decreased delta1 selectivity due to increases in the ED50 ratios of [D-Ser2,Leu5]enkephalin-Thr6 and morphine. It is concluded that 2e and 2f possess in vivo selectivity similar to that of BNTX, but are less potent as delta1 antagonists.

Animals↗

The contribution of nitric oxide to renal vascular wall thickening in rats with L-NAME-induced hypertension.

We investigated the mechanisms of renal vascular wall thickening in a rat model of N-nitro L-arginine methyl ester (L-NAME)-induced hypertension. To separate the effects of L-NAME-induced hypertension from other effects of nitric oxide (NO) inhibition, we created two models of L-NAME-induced hypertension: both had the same blood pressure level but NO inhibition was moderate in one group (group M) and severe in the other (group S). Urinary excretion of nitrates and nitrites was lower in group S than in group M. Wall thickening and lipid deposition in renal vessels were significantly greater in group S than in groups M. Simple and multiple regression analyses indicated that renal vascular wall thickening was more strongly correlated with lipid deposition than with blood pressure. The number of vessels positive for staining with Sudan black B was negatively correlated with urinary NO excretion. Expression of fibronectin and transforming growth factor-beta was greater in the Sudan black B-positive than in the Sudan black B-negative vessels, suggesting that extracellular matrix production was increased in vessels with lipid deposition. Lipid deposition and increased production of extracellular matrix may contribute to renal vascular wall thickening in L-NAME-induced hypertension. Some mechanisms independent of hypertension play important roles in vascular wall thickening induced by NO inhibition.

Actins↗