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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 127 records · Page 7Linked to original sources

Role of hepatic lipase in intermediate-density lipoprotein and small, dense low-density lipoprotein formation in hemodialysis patients.

BACKGROUND: It has been reported that remnant lipoproteins and small, dense low-density lipoproteins (LDLs) are risk factors for cardiovascular disease. To determine whether these risk factors are present in hemodialysis (HD) patients who are suffering from a high incidence of atherosclerotic vascular disease, we measured concentrations of remnant lipoproteins and LDL particle diameter in HD patients and compared these with controls. We also measured lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) that play important roles in the generation of remnant lipoproteins and small, dense LDL, and we correlated these changes with plasma lipoprotein abnormalities in HD patients. METHODS: Lipoproteins were separated by ultracentrifugation. Apoprotein B in very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) fractions were measured by a sensitive enzyme-linked immunosorbent assay method. The average LDL particle diameter was measured by gradient gel electrophoresis. RESULTS: Plasma triglyceride, total cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations were comparable between HD patients and controls, whereas LDL cholesterol was significantly lower in HD patients. The average LDL particle diameter was not significantly different between HD patients and controls. LDL particle diameter was inversely related to plasma triglyceride concentrations in all of the subjects. VLDL triglyceride, VLDL cholesterol, and VLDL apoprotein B were comparable between HD patients and controls. IDL triglyceride, IDL cholesterol, and IDL apoprotein B concentrations were all significantly increased in HD patients compared with those in controls. LPL mass was not altered, but HTGL activity was significantly decreased in HD patients. The HTGL activity was inversely related to IDL concentrations. CONCLUSIONS: These results suggest that a prominent characteristic of lipoprotein abnormalities in HD patients is a marked increase in IDL particle number. In addition, small, dense LDL is not associated with uremic dyslipidemia. Because HTGLs promote the conversion from IDL to LDL and the generation of lipid-poor LDL, a decrease in HTGL activity may contribute to the accumulation of IDL particle and may prevent small, dense LDL formation in HD patients.

Case-Control Studies↗

Plasma exchange for acquired hemophilia: a case report.

A patient with acquired hemophilia complicated with chronic renal failure and lung tuberculosis was successfully treated by consecutive plasma exchange (PE). A 71-year-old man with serious bleeding tendency showed low coagulation factor levels and a high titer of factor VIII (FVIII) inhibitor, and he was diagnosed with acquired hemophilia. Because of the complication of active lung tuberculosis, instead of immunosuppressive therapy, he undertook a series of PE with fresh frozen plasma replacement for 3 months. After the start of PE, his bleeding symptoms and activated partial thromboplastin time (APTT) improved gradually according to the decrease in FVIII inhibitor levels. These results suggest that PE is an effective therapeutic tool for refractory acquired hemophilia.

Aged↗

The prepuce flap in the reconstruction of male anal stenosis.

Circumferential stenosis of the male anal canal was repaired using a subcutaneous prepuce flap. The stenosis was released to create a rhomboid defect. Then, to cover the defect a rectangular flap was designed on the hairless ventral side of the penis. The flap was raised over the Buck's fascia while preserving the subcutaneous vessels in the dartos fascia, which formed the pedicle of the flap. The flap was transposed to the defect by passing it through a tunnel in the perineum. The postoperative course was uneventful and the result was good. The flap had reliable vascularity, was very thin, and pliable so that it could adapt to the rhomboid defect in the anal canal.

Anus Diseases↗

Inhibitory effect of ferulic acid and isoferulic acid on the production of macrophage inflammatory protein-2 in response to respiratory syncytial virus infection in RAW264.7 cells.

We investigated the effect of ferulic acid (FA) and isoferulic acid (IFA), which are the main active components of the rhizoma of Cimicifuga heracleifolia (CH), an anti-inflammatory drug used frequently in Japanese traditional medicine, on the production of macrophage inflammatory protein-2 (MIR-2) in a murine macrophage cell line, RAW264.7, in response to respiratory syncytial virus (RSV) infection. Following the exposure of cells to RSV for 20h, the MIP-2 level in condition medium was increased to about 20 ng/ml, although this level in mock-infected cells was negligible. In the presence of either FA or IFA, RSV-infected cells reduced MIP-2 production in a dose-dependent manner. These data suggest that FA and IFA might be responsible, at least in part, for the anti-inflammatory drug effect of CH extract through the inhibition of MIP-2 production.

Animals↗

Resected peripheral small cell carcinoma of the lung: computed tomographic-histologic correlation.

In order to clarify the characteristic computed tomographic findings of peripheral small cell lung cancer, the authors investigated 12 patients with surgically resected and histologically proven peripheral small cell lung cancer. Conventional computed tomography was performed on all, and additional high-resolution computed tomographic images were obtained for nine patients. Marginal, internal, and surrounding features of the tumors were analyzed, and these findings were correlated with histologic findings. All 12 tumors appeared as homogenous masses, and eight had well-defined margins. Lobulation was found in seven, marginal ground-glass opacity in three, fine spiculation in two, and both ground-glass opacity and spiculation in one. Cut specimens showed whitish medullary masses without large areas of necrosis, and microscopic specimens showed small areas of necrosis in 11 patients. Marginal ground-glass opacities corresponded to focal edema and hemorrhage in two patients and to intraalveolar invasion in one. Fine spiculation corresponded to vascular/lymphatic invasion in one patient and to irregular intraalveolar spread in another. The authors concluded that a homogenous mass without necrosis is the most characteristic feature of peripheral small cell carcinoma on computed tomography.

Aged↗

Prognostic factors for short-term survival in patients with stage IV non-small cell lung cancer.

Prognostic factors which can forecast short-term survival in patients with stage IV non-small cell lung cancer have not been well evaluated. Characteristics of such factors may be different from those for overall survival, and would be an important eligibility criterion for clinical trials of chemotherapy. We retrospectively analyzed the data of 158 patients with stage IV non-small cell lung cancer whose performance status was 0, 1 or 2. Univariate and multivariate logistic regression models revealed demographic variables which significantly correlated with the survival at 8 or 12 weeks. The univariate model showed the following significant variables: T factor, N factor, number of organs with metastases, grade of performance status, weight loss within 6 months, evidence of metastasis either at bone or lymph node, and lactate dehydrogenase level. The subsequent multivariate model demonstrated that both grade of performance status under 2 and number of metastasized organs less than 3 are important factors for 8- or 12-week survival. The survival rate in patients meeting the two criteria (grade of performance status under 2 and number of metastasized organs less than 3) and in those meeting only one of them was 93% versus 80% at 8 weeks (P = 0.030) and 88% versus 62% at 12 weeks (P < 0.001), respectively. Grade of performance status and number of organs with metastases appear to be important prognostic factors for short-term survival in patients with stage IV non-small cell lung cancer.

Adult↗

Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart.

Endothelin (ET)-1 has a positive inotropic effect and induces hypertrophy in cardiomyocytes. We previously reported that the peptide level of ET-1 is increased in the failing heart of rats with chronic heart failure (CHF) and that treatment with an ETA-receptor antagonist greatly improves survival in rats with CHF. However, precise analysis for alteration of the myocardial ET system in the failing heart is not known. In this study, we used rats with CHF due to chronic myocardial infarction. Sham-operated rats served as a control. The results showed that the level of preproendothelin (preproET)-1 mRNA and the peptide level of ET-1 were markedly increased in the heart of rats with CHF, whereas the expression of endothelin-converting enzyme (ECE)-1 mRNA in the heart did not differ between CHF and control rats. The intensity of ET-1 staining (ET-1-like immunoreactivity) in cardiomyocytes was markedly stronger in rats with CHF than in control rats, and the fibrotic tissues of the infarcted area were not stained. The mRNA and protein levels of both ETA and ETB receptors in the heart were significantly higher in rats with CHF than in control rats. The present study suggests that the increase in ET-1 peptide level in the heart of the rats with CHF originated from upregulation of preproET-1 mRNA, which was not attendant with the alteration of ECE-1 mRNA expression, and that both the ETA- and ETB-receptor systems are greatly accelerated in the failing heart.

Animals↗

Effects of physiological or pathological pressure load in vivo on myocardial expression of ET-1 and receptors.

Endothelin (ET)-1 has potent positive inotropic and chronotropic activity in the heart and induces cardiac hypertrophy. The production of ET-1 in the heart is reported to be increased under some conditions. In normal circulation, the pressure load to the left ventricle (LV) is much greater than that to the right ventricle (RV). In this study, we investigated the gene expression of the myocardial ET-1 system (ET-1, ET(A) receptor, and ET(B) receptor) in the RV and LV of normal rats and also investigated these genes in hypertrophied RV due to pathological pulmonary hypertension (PH). Normal rats showed no differences between the RV and LV in the gene expression of either ET-1, ET(A) receptor, or ET(B) receptor in either the adult stage (11 wk old) or the neonatal stage (1 and 8 days old). On the other hand, the expression of both atrial natriuretic peptide (ANP) mRNA and B-type natriuretic peptide (BNP) mRNA was significantly greater in the LV than in the RV in adult rats. Gene expression of ET-1, ET(A) receptor, and ET(B) receptor in the RV was markedly higher in rats with monocrotaline-induced (pathological) PH than that in control rats. The expression of ANP mRNA and BNP mRNA in the RV was also markedly higher in the rats with PH. In conclusion, the data suggest that gene expression of the ET-1 system in the myocardium is not affected by physiological pressure load in either the adult stage or neonatal stage; however, it is enhanced by pathological pressure overload such as that in PH.

Animals↗

Improvement of myocardial fatty acid metabolism through L-carnitine administration to chronic hemodialysis patients.

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, (123)I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 +/- 6.5 micromol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 +/- 7.7 micromol/l, p < 0. 0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 +/- 0.19 vs. 1.52 +/- 0.24, p < 0.005), and the patients' washout rate (WOR) of BMIPP was lower (17.2 +/- 6.0 vs. 22.8 +/- 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 +/- 27.0 micromol/l (p < 0.0001). Although the H/M ratio did not change (1.89 +/- 0.20) with this treatment, their WOR increased to 21.9 +/- 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.

Carnitine↗

Association between plasma homocysteine concentration and carotid atherosclerosis in hemodialysis patients.

Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0+/-16.9 micromol/L, a significantly higher amount than that of healthy subjects (11.0+/-3.1 micromol/L, p<0.0001). The patients' carotid maximum IMT was 1.79+/-1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r = 0.417, p<0.0001), systolic blood pressure (r = 0.262, p = 0.0043), smoking (r = 0.177, p = 0.0076), duration of hemodialysis (r = 0.083, p = 0.0045), and tHcy (r = 0.195, p = 0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients.

Age Factors↗

Effects of PMA and transcription factors on ovine interferon-tau transactivation in various cell lines.

Interferon-tau (IFNtau) is produced by the trophectoderm of ruminant ungulates and its gene transactivation in vitro has so far been achieved only in human choriocarcinoma cells, JAR and JEG3. To examine if ovine IFNtau gene transactivation could be induced in cells other than JAR or JEG3 cells and its activation could be aided by the expression of a protooncogene(s), a transient transfection system was developed with the upstream region of ovine IFNtau gene that had been inserted into the chloramphenicol acetyltransferase (CAT) reporter plasmid (IFNtau-CAT). The effect of a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), on IFNtau-CAT transcriptional activity was examined in JEG3, human embryonic kidney (293), HeLa and Vero cells. Upon transfection and PMA treatment, ovine IFNtau gene was transactivated in two unrelated cell lines, JEG3 and 293 cells. Since IFNtau-CAT was not induced in HeLa or Vero cells, HeLa and JEG3 cells were further examined for their ability to support IFNtau-CAT transactivation in a co-transfection system. While the expression of c-myc, interferon regulatory factor 1 or 2 (IRF-1 or IRF-2) was not effective, CAT activity was strongly enhanced in both JEG3 and HeLa cells with the co-transfection of c-Jun or c-Jun plus c-Fos. These data suggest that ovine IFNtau gene transcription induced by PMA is not specific for trophoblast cells and a protooncogene, c-jun, is a downstream effector of PMA activated nuclear factors in its signal transduction cascade resulting in IFNtau gene transactivaion.

Animals↗

[A case of metachronous bilateral testicular tumors with burned-out histology in one side].

A 22-year-old man with a history of left radical orchiectomy due to a testicular tumor had bilateral pulmonary tumors. Transbronchial biopsy specimens revealed them to be germ cell tumors. The serum levels of AFP and hCG-beta were elevated. The right testis was free from a palpable mass but showed a small hyperechoic lesion on scrotal ultrasonography. We excised the echogenic focus, which was a whitish nodule under the tunica albuginea. By pathological findings it was diagnosed as a burned-out testicular tumor. This was a case with metachronous bilateral testicular tumors.

Adult↗

Three pollination guilds and variation in floral characteristics of Bornean gingers (Zingiberaceae and Costaceae).

The pollinators of 29 ginger species representing 11 genera in relation to certain floral morphological characteristics in a mixed-dipterocarp forest in Borneo were investigated. Among the 29 species studied, eight were pollinated by spiderhunters (Nectariniidae), 11 by medium-sized Amegilla bees (Anthophoridae), and ten by small halictid bees. These pollination guilds found in gingers in Sarawak are comparable to the pollination guilds of neotropical Zingiberales, i.e., hummingbird-, and euglossine-bee-pollinated guilds. Canonical discriminant analysis revealed that there were significant correlations between floral morphology and pollination guilds and suggests the importance of plant-pollinator interactions in the evolution of floral morphology. Most species in the three guilds were separated on the plot by the first and second canonical variables. Spiderhunter-pollinated flowers had longer floral tubes, while Amegilla-pollinated flowers had wider lips than the others, which function as a platform for the pollinators. Pistils and stamens of halictid-pollinated flowers were smaller than the others. The fact that gingers with diverse morphologies in a forest with high species diversity were grouped into only three pollination guilds and that the pollinators themselves showed low species diversity suggests that many species of rare understory plants have evolved without segregating pollinators in each pollination guild.

Journal Article↗

[A case of spontaneous pyeloduodenal fistula].

A 61-year-old woman visited our hospital complaining of right flank pain and fever. The radiograph demonstrated multiple renal calculi. Radio renography showed no uptake in the right kidney. Therefore, we diagnosed her with pyonephrosis, and recommended open nephrectomy. However, she selected the conservative treatment with extra corporeal shockwave lithotripsy (ESWL). In spite of disappearance of multiple calculi, pyuria continued for 3 months after ESWL. Retrograde pyelography showed a fistula from the right pelvis into the duodenum. The patient was successfully treated by nephrectomy and duodeno-fistelectomy.

Duodenal Diseases↗

Pharmacological analysis of etoposide in elderly patients with lung cancer.

To analyze the pharmacological characteristics of etoposide in elderly patients, we conducted a Phase I trial of a 14-day administration of oral etoposide on 12 chemotherapy-naive patients, ages 75 years or older, with lung cancer. The pharmacological profiles of etoposide in elderly patients were compared with those of younger patients in our previous studies (H. Minami et al., J. Clin. Oncol., 11: 1602-1608, 1993; H. Minami et al., J. Clin. Oncol., 13: 191-199, 1995; Y. Ando et al., Jpn. J. Cancer Res., 87: 200-205, 1996). The sigmoid Emax model and logistic regression model were used for pharmacodynamic analysis. The maximum tolerated dose for elderly patients was 75 mg/body/day. The apparent oral clearance in elderly patients was 37+/-10 (mean +/- SD) ml/min, which was not different from that in younger patients (44+/-12 ml/min). The area under the concentration-versus-time curve of etoposide over the treatment period (total AUC) that produced a 50% decrease in absolute neutrophil counts was significantly different between elderly and younger patients, 14.3+/-2.5 and 21.6+/-2.7 mg x min/ml, respectively (P = 0.048). The incidence of grade 3 or 4 neutropenia at total AUC of 30 mg x min/ml (corresponding to a plasma concentration of 1.5 microg/ml for 14 days) was 81% in elderly patients but only 48% in younger patients. Although there was no pharmacokinetic difference between elderly and younger patients, equivalent exposure to etoposide resulted in severer myelosuppression in elderly patients. These findings suggest that prolonged etoposide administration with plasma concentration maintained at 1-2 microg/ml may cause severe myelotoxicity in elderly patients.

Administration, Oral↗

Plant reproductive phenology over four years including an episode of general flowering in a lowland dipterocarp forest,Sarawak, Malaysia.

The first systematic observation of a general flowering, a phenomenon unique to lowland mixed-dipterocarp forests in Southeast Asia, is presented. During general flowering, which occurs at irregular intervals of 3-10 yr, nearly all dipterocarp species together with species of other families come heavily into flower. We monitored reproductive phenology of 576 individual plants representing 305 species in 56 families in Sarawak, Malaysia. Observations continued for 53 mo from August 1992 and covered one episode of a general flowering cycle. Among 527 effective reproductive events during 43 mo, 57% were concentrated in the general flowering period (GFP) of 10 mo in 1996. We classified 257 species into flowering types based on timing and frequency of flowering. The most abundant type was "general flowering" (35%), which flowered only during GFP. The others were "supra-annual" (19%), "annual" (13%), and "sub-annual" (5%) types. General flowering type and temporal aggregation in reproductive events were commonly found among species in various categories of taxonomic groups, life forms, pollination systems, and fruit types. Possible causes for general flowering, such as promotion of pollination brought about by interspecific synchronization and paucity of climatic cues suitable for flowering trigger, are proposed, in addition to the predator satiation hypothesis of Janzen (1974).

Journal Article↗

[Bacillus Calmette-Guerin intravesical instillation treatment for carcinoma in situ of the bladder. Gifu BCG Instillation Therapy Research Group].

We performed a retrospective long-term study to evaluate the efficacy of intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guerin (BCG) on carcinoma in situ (CIS) of the bladder. Between 1989 and 1998, 42 patients with CIS of bladder underwent intravesical instillation of BCG. In the follow-up period from 6 to 116 months (mean: 37.3 months), the efficacy rate of intravesical BCG instillation for CIS of the bladder was 81.0%. Two patients died from the bladder cancer. The non-recurrence rate in patients with grade 2 carcinoma (19 cases) was not significantly different from that in those with grade 3 carcinoma (23 cases). However, the recurrence rate in patients with secondary CIS (15 cases) was significantly higher than in those with primary CIS (27 cases). The recurrence of CIS was observed in 7 of 42 cases. In 6 of 7 patients, CIS recurred within one year after treatment. Total cystectomy was performed in 10 of 42 patients, and pathological findings of muscle layer invasion were detected in 8 patients. Although side effects occurred in 33 patients (77.5%), no clinically significant side effects were observed. Our results suggest that intravesical BCG therapy may be useful for the treatment of CIS of the bladder.

Adjuvants, Immunologic↗