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Biomedical subjects

S Kihara

Publications and source records attributed to S Kihara.

At least 19 recordsLinked to original sources
PubMed1997

Characteristics of coronary artery disease and lipoprotein abnormalities in patients with heterozygous familial hypercholesterolemia associated with diabetes mellitus or impaired glucose tolerance.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of serum low density lipoprotein (LDL) cholesterol and premature coronary atherosclerosis. In order to elucidate the influence of abnormal glucose metabolism on the development of coronary artery disease (CAD) in FH patients, we examined the prevalence of CAD and characteristics of lipoprotein abnormalities in patients with heterozygous FH who were accompanied by diabetes mellitus (DM) or impaired glucose tolerance (IGT). The subjects of the present study were 150 patients with heterozygous FH, all over 40 years of age. Oral glucose tolerance tests demonstrated that 15 patients had DM and 27 had IGT. The combination of DM or IGT with FH was associated with a further increase in the prevalence of CAD (DM:IGT:normal glucose tolerance (N), 87:59:43%). Furthermore, the prevalence of the stenoses in the distal coronary arteries was significantly higher in the DM group than in the N group, while there was no significant difference in the prevalence of proximal and middle lesions. Serum triglyceride levels were significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM versus N group; P < 0.01, IGT versus N group), while total cholesterol levels were not significantly different. When lipoproteins were analyzed by polyacrylamide gel electrophoresis, the frequency of midband appearance, which implies an increase in remnant lipoproteins, was significantly higher in the DM and IGT groups than in the N group (DM:IGT:N, 87:72:29%, P < 0.01, DM versus N group; P < 0.01, IGT versus N group). Ultracentrifugation analysis of lipoproteins revealed that intermediate density lipoprotein cholesterol was increased in DM and IGT groups compared with the N group. These data suggest that abnormal glucose metabolism may accelerate the development of CAD in FH patients due to an increase in atherogenic remnant lipoproteins in addition to high concentration of LDL. Special attention should be paid in the treatment of FH patients with impaired glucose metabolism, to avoid the advancement of coronary atherosclerosis.

Adult↗
PubMed1997

Interferon alpha induces disorder of lipid metabolism by lowering postheparin lipases and cholesteryl ester transfer protein activities in patients with chronic hepatitis C.

The effect of recombinant interferon alpha 2a (rIFN-alpha2a) on serum lipoprotein metabolism was assessed in 39 patients with chronic viral hepatitis C. rIFN-alpha2a was administered intramuscularly at a dose of 9 x 10(6) U/d for 2 weeks and then for 3 times a week over 6 months. The serum cholesterol concentration significantly decreased one week after rIFN-alpha2a administration. Approximately 67% of this decrease was attributed to the reduction of high-density lipoprotein (HDL)-cholesterol; a decrease in HDL2-cholesterol was more evident. By contrast, serum triglyceride levels, largely derived from very-low density lipoprotein (VLDL), significantly increased following rIFN-alpha2a treatment. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in the postheparin plasma were reduced by 75.7% and by 79.4%, respectively, and decreases in plasma cholesteryl ester transfer protein (CETP) activity and its protein mass were also observed. However, prothrombin time was ameliorated by rIFN-alpha2a, suggesting that the decrease in LPL, HTGL, and CETP activities may not be due to a reduction in protein synthesis by the liver. Simple correlation analysis demonstrated that the changes in LPL activity before and after 2 weeks of treatment with rIFN-alpha2a showed a significant negative correlation with changes in serum triglyceride and VLDL-triglyceride and a positive correlation with changes in HDL-cholesterol and HDL2-cholesterol. These results suggest a major contribution of reduced LPL activity with regard to the lipoprotein disorders. In conclusion, rIFN-alpha2a treatment on patients with chronic hepatitis C causes marked changes in serum lipoprotein metabolism associated with decreases in LPL, HTGL, and CETP activities.

Adult↗
PubMed1997

Increased serum remnant lipoproteins in patients with apolipoprotein E7 (apo E Suita).

Apolipoprotein (apo) E7 was originally identified by Yamamura et al. in subjects with atherosclerotic cardiovascular diseases (J. Clin. Invest. 1984;74:1229). However, the lipoprotein abnormalities associated with apo E7 phenotype have not been elucidated. In the current study, to clarify the physiological roles of apo E7, lipoprotein abnormalities were studied in 12 apo E7 heterozygotes. A total of seven subjects were hyperlipidemic and five subjects were normolipidemic. The apo E phenotype was apo E7/3 in 11 subjects and apo E7/4 in one subject. Polymerase chain reaction revealed that all of the subjects with apo E7 phenotype had the same mutation as that of apo E(Suita) as reported previously (J. Biochem. 1989;105:249). All the hyperlipidemic subjects were over 40 years of age and two of them also had and severe coronary heart disease. Ultracentrifugal analysis revealed that the cholesterol level both in very low density lipoprotein and in intermediate density lipoprotein (IDL) was substantially higher in hyperlipidemic apo E7 heterozygotes, compared with control subjects and that the IDL cholesterol was also increased even in normolipidemic apo E7 heterozygotes. Polyacrylamide gel electrophoresis of lipoproteins showed a midband, which implies the increase of remnant lipoproteins, in 11 subjects out of 12, irrespective of the presence or absence of hyperlipoproteinemia. In two cases, a broad beta pattern was observed similar to that seen in type III hyperlipoproteinemia. Dietary therapy was dramatically effective for the treatment of hyperlipidemia in patients with apo E7. These findings confirm that apo E is crucial for remnant lipoprotein metabolism and that apo E7 is related to the increase in serum remnant lipoproteins, which leads to hyperlipoproteinemia in association with obesity, aging and impaired glucose metabolism.

Adult↗
PubMed1997

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia.

OBJECTIVES: Hyper-low-density lipoprotein (LDL)-cholesterolaemia is a potent risk factor for coronary atherosclerosis. We have recently demonstrated that a cluster of risk factors including insulin resistance, glucose intolerance, hypertriglyceridaemia, and hypertension based on intra-abdominal visceral fat accumulation are closely related to coronary artery disease. In the current study, we evaluated the relationship between visceral fat accumulation and the severity and distribution of coronary atherosclerosis in familial hypercholesterolaemia (FH). DESIGN: The effect of visceral fat accumulation on coronary lesions and risk factors in patients with FH was investigated. SUBJECTS: Thirty-one male patients with heterozygous FH who underwent coronary angiography. MEASUREMENTS: Abdominal fat distribution was estimated by a cross-sectional computed tomographic scan at the umbilical level. Plasma lipid, glucose and insulin concentrations and blood pressure were measured. A 75 g oral glucose tolerance test was also performed. RESULTS: The patients were divided into two groups according to the degree of visceral fat accumulation. Fifteen patients had high visceral fat accumulation (High VF group) and 16 patients had normal visceral fat accumulation (Normal VF group). Body mass index (BMI) and subcutaneous fat area were significantly higher in the high VF group. Baseline serum triglyceride was significantly higher and baseline low-density lipoprotein (LDL)-cholesterol and reduction of LDL-cholesterol during treatment were significantly lower in High VF group. Fasting plasma glucose and insulin concentrations, and systolic and diastolic pressures were significantly higher in the High VF group. Significant correlations were found between visceral fat area and the sum of the glucose and insulin concentration during an oral glucose tolerance test. Visceral fat area was significantly correlated with the severity of coronary stenosis index. Distal coronary lesions were significantly more frequent in the High VF group. Moreover, the correlation between the visceral fat area and coronary stenosis index was found to be independent of age, BMI, and subcutaneous fat area by multiple regression analysis. CONCLUSIONS: Visceral fat accumulation is a potent cardiovascular risk factor in heterozygous FH.

Abdomen↗
PubMed1997

Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects.

OBJECTIVES: It is well known that obstructive sleep apnoea-(OSA) is frequently associated with obesity. In the current study, we investigated the correlation between abdominal visceral fat accumulation and the presence of OSA in obese subjects. SUBJECTS: A consecutive series of 37 patients (17 men and 20 women) with primary obesity who were admitted to the Second Department of Internal Medicine. Osaka University Hospital, were investigated Patients with OSA were designated as those whose apnoea index (number of apnoea h-1 of sleep) was more than 5. MAIN OUTCOME MEASURES: The distribution of body fat was determined using computed tomographic sections. The upper airway dimensions were evaluated with indices obtained by cephalometry in both inspiratory and expiratory phases. RESULTS: Visceral adipose tissue (AT) area which was measured at the level of the umbilicus, and its ratio to total AT area were both significantly greater in OSA patients as compared with those in non-OSA patients. All subjects whose visceral AT area measured more than 220 cm2 manifested OSA. These two parameters also closely correlated with an increase in apnoea index. A multiple linear regression analysis revealed that the visceral AT area significantly correlated to apnoea index when age, AT mass and lean body mass were taken into account. The fluctuations of the upper airway were significantly greater in the large visceral fat group than in the small visceral fat group. CONCLUSIONS: These results suggest that visceral fat accumulation is an important risk indicator for OSA in obese subjects.

Adipose Tissue↗
PubMed1997

"Best" PEEP during one-lung ventilation.

Eight patients were studied under general anaesthesia for elective pulmonary lobectomy to see if intrinsic positive end-expired pressure (PEEPi) would appear or increase in the dependent lung during one-lung ventilation (OLV) or if application of external PEEP equal to individually measured PEEPi would produce better arterial oxygenation, haemodynamic state and oxygen delivery than either zero PEEP (ZEEP) or an external PEEP 5 cm H2O greater than PEEPi. Patients were non-obese, without obstructive airways disease, aged 53-76 yr and ASA < III. They received standardized anaesthesia with fentanyl, 50% nitrous oxide in oxygen and isoflurane; monitoring included radial and fibreoptic pulmonary arterial catheters and intermittent positive pressure ventilation with a tidal volume of 8 ml kg-1, 16 bpm, and an I:E ratio of 1:2. PEEPi was measured during two-lung ventilation (TLV) and OLV, using rapid airway occlusion at end-expiration. There was no PEEPi during TLV, but 2-6 mm Hg of PEEPi appeared during OLV. Applying external PEEP equal to individually measured PEEPi reduced venous admixture and increased PaO2 without a decrease in cardiac index (thus increasing oxygen delivery) compared with ZEEP, but the improvement in pulmonary gas exchange was lost and an additional penalty of reduced cardiac output was imposed when external PEEP was increased to 5 mm Hg above PEEPi.

Aged↗
PubMed1997

Severe hemolysis due to artificial chordae displacement.

Hemolytic anemia is a well-recognized complication of mechanical heart valve prosthesis but, as yet, has not been reported after mitral valve repair with chordal replacement. We report a case of severe hemolytic anemia after mitral valve repair with chordal replacement and Carpentier-Edwards annuloplasty ring insertion. Progressive prolapse of the anterior leaflet due to the artificial chordae being too long caused recurrent regurgitation which was responsible for the hemolysis. The patient also had idiopathic thrombocytopenic purpura, but successful second mitral valve repair was performed after high-dose gamma-globulin therapy.

Anemia, Hemolytic↗
PubMed1996

A comparative study of apoptosis and cell proliferation in infantile and adult fibrosarcomas.

The infantile fibrosarcoma, a rare tumor phenotypically similar to the adult fibrosarcoma, frequently has a benign course marked by spontaneous regression. Because biologic mechanisms responsible for this regression remain unexplained, an investigation of the role of apoptotic cell death is warranted. The rate of apoptotic cell death has been compared in five cases each of infantile and adult fibrosarcoma by quantitative estimation of in situ DNA double strand breaks. Although positively stained apoptotic cells are evident in all 10 cases, the apoptotic index is significantly higher in infantile cases (mean 6.6% +/- 0.80) compared to adult cases (mean 0.5% +/- 0.08). The proliferative (MIB-1) index of each specimen has been calculated by immunostaining for cell cycle phase-dependent Ki-67 antigen with MIB-1 antibody. Infantile cases have a significantly lower proliferative (MIB-1) index (mean 0.4 +/- 0.15) than adult counterparts (mean 15.9 +/- 3.76). The relatively benign course of the infantile fibrosarcoma may be due to two factors--a significantly lower proliferative (MIB-1) index coupled with enhanced apoptosis.

Adult↗
PubMed1996

[A case report on graft replacement of ruptured aneurysm of the arch and the descending thoracic aorta associated with dense pulmonary adhesion].

A 73-year-old patient had been followed for aortic arch aneurysm of 54 mm in diameter. He was hospitalized complaining of chest and back pain. A chest CT scan showed ruptured aortic arch aneurysm extending to mid-descending thoracic aorta, and an emergent operation was decided. The trachea was intubated with a univent tube providing a movable blocker (System Corporation) which was directed to the left bronchus for differential lung ventilation. The descending thoracic aorta was exposed through the left 4th intercostal thoracotomy just at the site intending to anastomose a prosthetic graft because of dense pulmonary adhesion. The ascending and arch aorta was approached via median sternotomy. Under deep hypothermia and retrograde cerebral perfusion, total arch and descending aortic replacement was performed using an arch graft providing four branch grafts for neck vessels reconstruction and pump perfusion. The patient showed moderate pulmonary bleeding during and after cardiopulmonary bypass, but improved gradually. He was weaned from the respirator on the 13th post-operative day. During extensive thoracic aortic surgery using left thoracotomy combined with median sternotomy, left lung deflation using a univent tracheal tube with a blocker, and circulatory arrest during distal aortic anastomosis, are useful in preventing lethal pulmonary bleeding caused by lung injury under the fully heparinized condition. However, in cases associated with dense pulmonary adhesion, it is important to dissect carefully just a small area necessary to anastomose a graft, and to take elaborate assistant measures.

Aged↗
PubMed1995

Detection of DNA strand breaks associated with apoptosis in human brain tumors.

Apoptosis occurs spontaneously in a wide variety of neoplasms. However, it is difficult to detect apoptotic cells in routine histological sections because the cells undergoing apoptosis die singly and are then rapidly phagocytosed. Since DNA fragmentation is an important hallmark of apoptosis, visualization of DNA strand breaks in tissue sections provides the means for readily identifying apoptotic cells in situ. We have applied an in situ DNA strand break staining procedure for the quantitative estimation of apoptotic cells in surgical specimens of 62 different brain tumours. Positively stained apoptotic cells were observed in 25 (40.3%) cases and their percentage (apoptotic index) ranged from 0.1 to 8.9. Both fragmented and condensed nuclei of apoptotic cells and apoptotic bodies were stained. In addition, we assessed the proliferative activity of each specimen by immunostaining with the MIB-1 antibody (MIB-1 index) which detects the cell cycle phase-dependent Ki-67 antigen. Brain tumours with higher MIB-1 indices showed a tendency to higher apoptotic indices. The results of this study indicate that apoptosis occurs spontaneously in various brain tumours.

Apoptosis↗
PubMed1995

Enhancement of pressor response to intravenous phenylephrine following oral clonidine medication in awake and anaesthetized patients.

Clonidine, an alpha 2-adrenergic agonist, augments the pressor response to intravenous ephedrine. If this effect is partly due to clonidine-induced potentiation of alpha 1-adrenoceptor-mediated vasoconstriction, it is also assumed that clonidine would enhance the pressor effect of phenylephrine as an alpha 1-adrenergic agonist. The authors studied haemodynamic responses to intravenous phenylephrine in 80 patients who received either preanaesthetic medication with clonidine approximately 5 micrograms.kg-1 po (clonidine group, n = 40), or no medication (control group, n = 40). Each group was further divided into either awake subjects (n = 20) or subjects anaesthetized with enflurane and nitrous oxide in oxygen (n = 20). Haemodynamic measurements were made at one-minute intervals for ten minutes after phenylephrine 2 micrograms.kg-1 iv was injected as a bolus. The magnitudes of maximal mean blood pressure increases in the clonidine group (26 +/- 7% (mean +/- SD) for awake and 32 +/- 15% for anaesthetized subjects) were greater (P < 0.05) than in the control group (13 +/- 7% for awake and 18 +/- 7% for anaesthetized subjects). However, there was no difference in the pressor effect of phenylephrine between awake and anaesthetized patients in both groups. Oral clonidine preanaesthetic medication, 5 micrograms.kg-1, augments the pressor responses to phenylephrine 2 micrograms.kg-1 iv in awake and anaesthetized patients. These results suggest that the enhancement of the pressor responses to phenylephrine following oral clonidine may be due to clonidine-induced potentiation of alpha 1-adrenoceptor-mediated vasoconstriction. This implies that restoration of blood pressure can be achieved effectively by phenylephrine in hypotensive patients with clonidine premedication.

Administration, Oral↗
PubMed1995

Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase.

Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state accompanied by a longevity syndrome. However, we reported the cases of markedly hyperalphalipoproteinemic subjects with juvenile corneal opacification. The patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities, and one of them has recently been identified to be homozygous for a missense mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP) gene. In the current study, to elucidate the clinical significance of and atherogenicity in marked HALP, we determined the incidence of atherosclerotic cardiovascular disease (ACD) in patients with marked HALP and characterized the lipoprotein abnormalities in those who had ACD, focusing especially on CETP and HTGL. The subjects were 201 patients (111 males and 90 females) with marked HALP ( > or = 2.58 mmol/L [100 mg/dL]), 67% of whom were demonstrated to have the CETP gene mutations in the intron 14 splice donor site or in exon 15. Their mean age was 54 +/- 15 years. Plasma levels of total cholesterol, HDL cholesterol, and triglyceride in all subjects were 6.28 +/- 1.78, 3.15 +/- 0.90, and 1.08 +/- 0.53 mmol/L, respectively. Ten of the male patients (9.0%) and two of the female patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris, and peripheral vascular diseases. Ten patients with HALP who had ACD were identified to be heterozygotes for CETP deficiency. To further clarify the characteristics of marked HALP in patients with ACD, we compared the plasma lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP deficiency who were with and without ACD.

Adult↗
PubMed1995

Increased proportion of plasma apoB-48 to apoB-100 in non-insulin-dependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver.

To assess the alteration of apolipoprotein (apo) B mRNA editing in non-insulin-dependent diabetes mellitus (NIDDM), we measured plasma apoB-100 and apoB-48 levels and apoB mRNA editing efficiency in the liver and intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in this study. Ventromedial hypothalamus (VMH)-lesioned control rats were used as hyperinsulinemic models. VMH-lesioned GK rats (GK+VMH) were treated as an insulin-exhausted NIDDM model. Plasma cholesterol and triglyceride levels were increased in GK rats. Very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol concentrations were significantly higher in GK rats than in controls. The increase of VLDL-triglyceride was most marked in GK+VMH rats. Plasma apoB-48 levels, quantified by immunoblot, were increased in GK rats. However, apoB-100 levels were minimally elevated in GK rats. Therefore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. ApoB mRNA editing was analyzed by reverse transcriptase-polymerase chain reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly increased in the liver from GK rats compared with controls. Although the development of the VMH lesion increased plasma apoB-48 levels, it had no effect on the proportion of apoB-48-type to apoB-100-type cDNA in the liver from both GK and control littermates. ApoB mRNA in the intestine was almost totally edited (approximately 95%). Intestinal apoB-48/apoB-100 cDNA ratio showed no significant difference among the four groups. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the increase of plasma apoB-48 levels.

Animals↗
PubMed1995

[Comparison of airway complications on tracheal extubation in deeply sevoflurane anesthetized versus awake children].

We investigated the incidence of respiratory complications and oxygen saturation level during emergence from sevoflurane anesthesia in children whose tracheas were extubated while they were anesthetized or after they became awake. Thirty children, aged 1-10 years, were studied. Anesthesia was induced with sevoflurane or thiopental and maintained with nitrous oxide, oxygen and sevoflurane. After nitrous oxide was discontinued at the end of surgery, the patients were randomly assigned to two groups: deeply anesthetized extubation group (anesthetized group) and awake extubation group (awake group). In anesthetized group, the patients were extubated while they were administered 1.5% or higher sevoflurane in 100% oxygen. In awake group, extubation was performed while the patients were awake. The incidence of respiratory complications such as apnea, laryngospasm, bronchospasm and arrythmias was not significantly different between the two groups. There was a significantly higher incidence of the airway obstruction but less incidence of cough and breath-holding in anesthetized group. Oxygen saturation level before and after tracheal extubation was not different between the two groups. In conclusion, with proper attention to airway obstruction, it may be possible to extubate while children are deeply anesthetized with sevoflurane.

Anesthesia, Inhalation↗
PubMed1994

Visualization of DNA double strand breaks in the gerbil hippocampal CA1 following transient ischemia.

To clarify the relationship between delayed neuronal death and apoptosis, we made an attempt to detect DNA strand breaks in the gerbil hippocampal CA1 pyramidal neurons following transient ischemia by an in situ DNA double strand breaks staining. The condensed nuclei of neurons in CA1 were occasionally seen and positively stained 3 days after ischemia. The degenerating dark neurons with condensed nuclei in CA1 markedly increased in number and were clearly stained for DNA strand breaks 5 days after ischemia, whereas normal-looking nuclei remained unstained. No neurons were stained in other hippocampal subfields and dentate gyrus. The present study strongly indicates that the CA1 pyramidal neurons die through an apoptotic process.

Animals↗
PubMed1994

Structure of the mouse cholesterol 7 alpha-hydroxylase gene.

Three overlapping cholesterol 7 alpha-hydroxylasecDNAs were cloned from total mouse liver RNA by a combination of the polymerase chain reaction and mouse liver cDNA library screening. One of the cDNA clones was used to screen a mouse genomic library; three genomic clones were isolated and one of them was fully characterized. The mouse cholesterol 7 alpha-hydroxylase gene spans approximately 10 kb. The gene contains six exons including a 1509-bp open reading frame encoding 503 amino acid residues. The predicted amino acid sequence of mouse cholesterol 7 alpha-hydroxylase showed 93 and 82% identity to the rat and human enzymes, respectively. The transcription initiation site is mapped to 64 bases 5' of the translation initiation codon. Several transcription factor binding sequences are identified in the 5' flanking region of the mouse cholesterol 7 alpha-hydroxylase gene.

Amino Acid Sequence↗
PubMed1994

Age-related decrease in toe-thumb temperature difference with lumbar epidural anaesthesia.

With lumbar epidural anaesthesia, big toe skin temperature increases and is associated with a compensatory decrease of thumb temperature. The purpose of the present study was to examine whether thumb-big toe temperature differences were affected by age. Following the attachment of temperature probes at the digital pad of the right big toe and the right thumb, lumbar epidural anaesthesia at L2/3 was performed in 54 patients with 10 ml lidocaine 1.5%. Big toe and thumb skin temperatures were measured continuously and recorded every minute. Fifteen minutes after epidural injection, the toe temperature increased 6.3 +/- 2.1 degrees C (delta F) from the control value, 29.4 +/- 2.2 degrees C, and the thumb temperature decreased -1.5 +/- 1.0 degrees C (delta H) from the control value, 31.6 +/- 2.8 degrees C. Regression coefficient between delta T15 (toe-thumb skin temperature 15 min after epidural injection) and age was: Y = -0.7X + 8.95 (r = 0.35, P < 0.01; Y = delta T15, X = age). The ratio of delta H to delta F and age was expressed as: Y = 0.51X - 46.57 (r = 0.41, P < 0.01: Y = delta H/delta F, X = age). It is concluded that, in lumbar epidural anaesthesia, the decrease of the thumb skin temperature is reduced with aging.

Adult↗