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Biomedical subjects

S Nozaki

Publications and source records attributed to S Nozaki.

At least 19 recordsLinked to original sources

Mental fatigue-induced decrease in levels of several plasma amino acids.

To investigate the relation between plasma amino acid levels and mental fatigue, we measured the plasma concentrations of 20 amino acids in 9 healthy volunteers before and after a fatigue-inducing mental task session for 8 hr. As fatigue-inducing mental tasks, the subjects performed an advanced trail making test, a Japanese KANA pick up test, and a mirror drawing test. As a control, 8-hr relaxation session was performed in the same subjects at an interval of 4 weeks. Immediately after the fatigue session, the plasma levels of branched-chain amino acids, tyrosine, cysteine, methionine, lysine, and arginine were below those after a relaxation session. The values for other blood parameters including total protein, albumin, glucose, and total cholesterol did not show any differences between the 2 sessions. These results indicate that mental fatigue may be characterized by a decrease in the plasma level of these amino acids.

Adult↗

Recurrent multinodular neurilemmoma of the female upper lip.

Neurilemmoma is the most commonly encountered nerve sheath tumour of the oral cavity. It generally appears as a single encapsulated nodule. The tongue is involved most frequently and the lip rarely. The tumour is usually uninodular. Multinodular neurilemmoma of the upper lip is very rare and has been reported in only one patient. This is the first reported case of multinodular neurilemmoma in the upper lip of a female.

Child↗

Natural killer-like T-cell lymphoma in a calf.

A case of natural killer (NK)-like T-cell lymphoma in a 9-month-old female Holstein calf is described. The liver, spleen and lymph nodes were affected with lymphoma. The neoplastic cells showed not only epitheliotropism in the biliary epithelium and hepatic cords but also preferential homing to follicular centres of the lymph nodes. In the cytoplasm, there were eosinophilic granules of various sizes, which were positive with phosphotungstic acid haematoxylin and naphthol AS-D chloroacetate esterase. Erythrophagia by lymphoma cells was rarely detected. Immunohistochemically, the neoplastic cells expressed surface CD3, surface CD5 and CD57, and perforin expression was present in the cytoplasmic granules. The lymphoma described resembled feline NK-like T-cell lymphoma in epitheliotropism in the liver and phagocytic activity but differed in respect of follicular involvement and marked variation in granule size.

Animals↗

Reduced adhesion of monocyte-derived macrophages from CD36-deficient patients to type I collagen.

CD36 is an 88-kDa glycoprotein expressed on platelets and monocyte/macrophages (Mphi). CD36 is a multifunctional receptor for collagen, thrombospondin, oxidized low density lipoproteins (LDL), and long-chain fatty acids. The present study was performed to investigate whether CD36 can function as an adhesion molecule which is involved in mediating human macrophages (Mphi) adhesion to type I collagen in vitro. The Mphi of human CD36-deficient as well as normal control subjects were isolated and cultured on the multi-well plates coated with type I collagen, a natural ligand for CD36. Up to 2 h of incubation, the Mphi from CD36-deficient patients showed almost a approximately 55% decrease in adhesion to type I collagen in comparison to those from controls (P < 0.01). However, there was no significant difference in the adhesion thereafter. Furthermore, the addition of antibody against CD36 into the media of control Mphi significantly inhibited the adhesion by approximately 50% (P < 0.05). The addition of oxidized LDL (OxLDL) did not alter adhesion of Mphi from both CD36-deficient and controls. These data suggest that CD36 is involved in the adhesion of Mphi to type I collagen, especially in the early stage of adhesion.

Antibodies, Monoclonal↗

Repression of GADD153/CHOP by NF-kappaB: a possible cellular defense against endoplasmic reticulum stress-induced cell death.

Exposure of mammalian cells to ultraviolet light, nutrient deprived culture media, hypoxia, environmental toxicants such as methyl mercury, methyl methanesulfonate, crocodilite asbestos or the agents that disrupt the function of endoplasmic reticulum (ER) leads to activation of the pro-apoptotic transcription factor GADD153/CHOP. Paradoxically, several of these agents also induce the anti-apoptotic transcription factor NF-kappaB. In this report, we demonstrate that NF-kappaB inhibits GADD153 activation in breast cancer cells exposed to nutrient deprived media, tunicamycin (which blocks protein folding in ER) or calcium ionopore (which depletes calcium stores in ER). Basal and calcium ionopore-induced GADD153 expression was more pronounced in fibroblasts obtained from mouse embryos lacking in p65 subunit of NF-kappaB compared to fibroblasts from wild type littermate embryos. Moreover, p65-/- fibroblasts were killed more efficiently by calcium ionopore and tunicamycin but not hydrogen peroxide compared to wild type fibroblasts. We also show that parthenolide, a NF-kappaB inhibitor, sensitizes breast cancer cells to tunicamycin. Transient transfection assay revealed that the p65 subunit but not the p50 subunit of NF-kappaB represses GADD153 promoter activity. These results establish a correlation between repression of pro-apoptotic genes by NF-kappaB and increased cell survival during ER stress as well as identify a distinct NF-kappaB regulated cell survival pathway.

Animals↗

The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors.

Numerous chemotherapeutic agents have been shown to have an inhibitory effect on endothelial cell proliferation and migration, and tubule formation. In this study, we examined the antiangiogenic activity of docetaxel. Docetaxel inhibited endothelial cell proliferation and tubule formation in vitro in a dose-dependent fashion. Docetaxel treatment also inhibited angiogenesis in an in vivo Matrigel plug assay. The endothelial stimulating factors, vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor are able to protect endothelial cells from the antiangiogenic properties of docetaxel. This protective effect can be overcome by a recombinant humanized monoclonal antibody directed against VEGF in both in vitro and in vivo models. Similarly, combination of docetaxel with the antiangiogenic agent 2-methoxyestradiol also overcomes the protective effect of VEGF in both in vitro and in vivo models. These data suggest that microenvironmental factors (e.g., local release of VEGF and basic fibroblast growth factor) could play a role in decreasing the antiangiogenic effects of docetaxel, whereas agents such as 2- methoxyestradiol and recombinant humanized monoclonal antibody directed against VEGF may reverse this protective effect.

2-Methoxyestradiol↗

CD36 deficiency associated with insulin resistance.

No major genes responsible for insulin resistance have yet been identified. CD36 is a multifunctional receptor, which plays a part in mediating intracellular signalling as well as in taking up biologically active substances such as long-chain fatty acids. We looked for insulin resistance in genetic CD36 deficiency, which is common in Asian and African populations. The euglycaemic hyperinsulinaemic clamp technique showed insulin resistance in the five CD36-deficient people tested. We conclude that CD36 could be responsible for insulin resistance.

CD36 Antigens↗

Coagulation and fibrinolysis disorder in muscular dystrophy.

To investigate whether there are any basic abnormalities of coagulation and fibrinolysis in muscular dystrophy, we measured serum levels of the MM isozyme of creatine kinase (CK-MM), fibrin and fibrinogen degradation products (FDP), plasma levels of fibrinogen, antithrombin (AT), and D-dimer in 36 patients with Duchenne muscular dystrophy (DMD), 11 with Becker muscular dystrophy (BMD), 5 with Fukuyama congenital muscular dystrophy (FCMD), 5 with myotonic dystrophy (MyD), and 5 with spinal muscular atrophy (SMA) type 2. FDP levels were elevated in the patients with DMD, BMD, and FCMD (1.0 to 84.9 microg/ml), but not in the patients with MyD and SMA type 2. In DMD, BMD, and FCMD, FDP levels significantly correlated with CK-MM, but not with age, fibrinogen, AT, D-dimer, and type of dystrophy (multiple regression analysis; r(2) = 0.814, P < 0.0001). These findings suggested that enhanced coagulation and fibrinolysis are associated with muscle degeneration in patients with DMD, BMD, and FCMD.

Adolescent↗

Smoking behavior and related factors among Japanese nursing students: a cohort study.

BACKGROUND: Although there have been several surveys on smoking behavior among Japanese nursing students, most have been cross-sectional studies. No longitudinal studies, such as a prospective cohort study, have ever been carried out. We therefore conducted a cohort study on, and analyzed smoking behavior and related factors among, Japanese nursing students. METHODS: A survey on smoking behavior using a confidential questionnaire was conducted on nursing students at two vocational schools of nursing and two nursing colleges/universities located in the Tokyo metropolitan area. Another survey was subsequently conducted in the same manner among the same subjects 1 year later. The surveys were conducted between 1997 and 1999. RESULTS: Over the 1-year period, the prevalence of smoking among nursing students increased by 10% for students at the vocational schools of nursing (n = 224) and by 3% for students at the nursing colleges/universities (n = 222). The average score for nicotine dependence for students who were daily smokers at both time points rose from 3.6 to 4.4 (P < 0.05). Two factors found to significantly predict smoking behavior were having friends who smoke and living alone. CONCLUSION: Smoking prevalence is increasing among Japanese nursing students. Smoking prevention and cessation interventions should be instituted in all nursing training programs.

Adult↗

Analyses of genetic abnormalities in type I CD36 deficiency in Japan: identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man.

To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 839-841, and 5 bp, AAAAC, were inserted at the same position (839-841del-->insAAAAC). Mutation 839-841del-->insAAAAC led to a frameshift and appearance of a premature stop codon; it was also accompanied with a marked reduction in the amount of CD36 mRNA. The other was a 12-bp deletion at nt 1438-1449 (1438-1449del) accompanied with or without skipping of exon 9 (nt 959-1028). Mutation 1438-1449del led to an inframe 4-amino-acid deletion, whereas exon 9 skipping led to a frameshift and the appearance of a premature stop codon. Expression assay revealed that both 1438-1449del and exon 9 skipping directly caused impairment of the surface expression of CD36. A survey of the five known mutations including 839-841del-->insAAAAC and 1438-1449del in type I CD36-deficient subjects demonstrated that the five mutations covered more than 90% of genetic defects among them and that the substitution of T for C at nt 478 (478C-->T) was the most common mutation with more than 50% frequency. However, none of the four subjects that possessed isoantibodies against CD36 had 478C-->T, suggesting that 478C-->T prevents the production of isoantibodies against CD36.

Alleles↗

Urinary bile alcohol profiles in healthy and cholestatic children.

BACKGROUND: Bile alcohols are normal constituents of urine. METHODS: To better understand bile alcohol profile in childhood, urinary specimens from 41 healthy children and 10 children with cholestasis, and 3 healthy adults, were analyzed by GLC and GC-MS. RESULTS: Five bile alcohols, 27-nor-5beta-cholestane-3alpha,7alpha,12alpha,24S,25R-pentol, 5beta-cholestane-3alpha,7alpha,12alpha,24S, 25-pentol, 5beta-cholestane-3alpha,7alpha,12alpha,24S,26-pentol, 5beta-cholestane-3alpha,7alpha, 12alpha,25,26-pentol, and 5beta-cholestane-3alpha,7alpha,12alpha,26,27-pentol were identified in all specimens. C(26)-Pentol was the most abundant constituent, constituting 29.5 to 65% of bile alcohols. Among healthy children (n=41), no significant relationship was seen between proportions of the C(26)-pentol and age, but older children (n=15, 6 to 14 years) showed a significantly greater mean percentage of the C(26)-pentol than young children (n=26, 0 to 5 years; 58.1+/-4.23% vs. 46.0+/-9.24%, p<0.001). In children with cholestatic liver diseases, the percentage of C(26)-pentol in urinary bile alcohols was significantly lower than age-matched controls. CONCLUSIONS: There is an increased composition of C(26)-pentol in older children and relatively decreased composition of C(26)-pentol in children with cholestatic liver diseases.

Adolescent↗

Localization of CD36 and scavenger receptor class A in human coronary arteries--a possible difference in the contribution of both receptors to plaque formation.

CD36 and scavenger receptor class A types I and II (SR-AI/II) are major receptors for oxidized low density lipoproteins (OxLDL) expressed on macrophages. To elucidate the role of these two macrophage scavenger receptors in the development of coronary atherosclerosis, we examined the localization of CD36 and SR-AI/II in human coronary atherosclerotic lesions. Serial cryostat sections of 49 coronary arteries obtained from 43 autopsied cases were examined immunohistochemically. Regarding the relationship between the severity of atherosclerosis and immunoreactivities to CD36, there was almost no immunoreactivity to CD36 in regions with diffuse intimal thickening, while the expression of CD36 was accelerated in parallel with the progression of atherosclerosis. In contrast, SR-AI/II was expressed persistently from regions with diffuse intimal thickening to atherosclerotic plaques. We also clarified the differential distribution of CD36 and SR-AI/II in atheromatous plaques. Close to the luminal surface of the intima, macrophages were relatively small in size, contained lesser lipids, and expressed SR-AI/II more abundantly than CD36. In contrast, macrophages in the core region were larger in size, contained more lipids, were strongly positive for CD36 and showed a weaker immunoreactivity to SR-AI/II than those in the luminal surface of the intima. In conclusion, the expression of CD36 and SR-AI/II on macrophages may be regulated differently in the process of coronary atherogenesis.

Adolescent↗

Ultrasonic tissue characterization can predict beta-blocker efficacy in dilated cardiomyopathy.

The aim was to determine if the combination of cyclic variation of myocardial integrated backscatter (variation IB) and left ventricular mass measurements can predict the efficacy of beta-blocker treatment in dilated cardiomyopathy. In 32 patients, left ventricular mass and variation IB were measured at baseline and during 6 microg/kg/min dobutamine infusion before the initiation of beta-blocker therapy. Variation IB was measured at left and right ventricular halves in the ventricular septum. The baseline left ventricular mass index and transseptal variation IB gradient during dobutamine were significantly greater in the effective group (1.16 +/- 0.18 g/mL and 1.8 +/- 0.6 dB) than in the ineffective group (0.94 +/- 0.28 g/mL, p = 0.032 and 0.4 +/- 0.6 dB, p < 0.005). When both baseline left ventricular mass index > or = 1.05 g/mL and transseptal variation IB gradient during dobutamine > or = 1.5 dB were defined as predictive criteria for the effective group, the sensitivity was 78% and the specificity was 86%. Analysis of transseptal variation IB during dobutamine may provide useful information predicting the efficacy of beta-blocker therapy in dilated cardiomyopathy.

3-Iodobenzylguanidine↗

Ultrasonographic assessment of coronary flow reserve and abdominal fat in obesity.

Recent technological advances in transthoracic Doppler echocardiography (TTDE) have provided noninvasive measurement of coronary flow velocity reserve (CFVR). We aimed to quantitate a correlation between endothelial dysfunction and fat distribution. In 36 patients with obesity, 16 with noninsulin-dependent diabetes mellitus (DM) and 12 healthy volunteers, coronary flow velocity was measured at the distal site of the left anterior descending branch. CFVR was defined as the ratio of hyperemic (IV infusion of 0.15 mg/kg/min adenosine) to basal peak diastolic flow velocity. Abdominal wall fat index (AWFI) was estimated by ultrasonography. Insulin resistance was quantified by the euglycemic hyperinsulinemic clump method. AWFI was significantly related to CFVR (r = -0.46, p = 0.011) and insulin resistance (r = -0.71, p < 0.0001). CFVR could be noninvasively evaluated using TTDE. Coronary endothelial dysfunction indicated as CFVR, body fat distribution and insulin resistance was quantitatively correlated in obesity.

Abdomen↗

Effect of cibenzoline, a class ia antiarrhythmic agent, on left ventricular diastolic function in hypertrophic cardiomyopathy.

We aimed to investigate whether the improvement of left ventricular (LV) diastolic function by cibenzoline, a class Ia antiarrhythmic drug, in hypertrophic obstructive cardiomyopathy (HOCM) is due to LV afterload reduction or a primary lusitropic effect on LV. Twenty-three patients with hypertrophic cardiomyopathy (11; HOCM, 12; non-obstructive HCM; HNCM) were examined. Pulsed-wave Doppler, color M-mode and tissue Doppler echocardiography were performed before and 90 minutes after oral administration of cibenzoline (300 mg), and were compared with a treatment of bisoprolol (5 mg/day, 10 days). Early (E) and late diastolic LV inflow velocity, E flow propagation velocity (FPV) and early diastolic mitral annulus velocity (Ea) were measured. E/FPV and E/Ea were calculated as indices of LV filling pressure. LV outflow pressure gradients estimated using continuous-wave Doppler in HOCM markedly decreased after cibenzoline (83 +/- 42 to 40 +/- 33 mmHg, p < 0.005) and bisoprolol (44 +/- 40 mmHg, p < 0.005). Following cibenzoline, E/FPV and E/Ea were significantly decreased in both HOCM (1.75 +/- 0.53 to 1.32 +/- 0.28, p < 0.05, 18.9 +/- 6.2 to 14.8 +/- 5.0, p < 0.05, respectively) and HNCM (1.75 +/- 0.58 to 1.41 +/- 0.73, p< 0.05, 13.0 +/- 4.3 to 9.7 +/- 3.6, p< 0.01, respectively). Those in HNCM did not change by bisoprolol. Cibenzoline improved LV diastolic function in HCM, whereas bisoprolol did not affect it. Thus, the primary lusitropic effect of cibenzoline rather than LV after load reduction might have contributed to the improvement of diastolic function in HOCM.

Administration, Oral↗

Occurrence of coring in insulin vials and possibility of rubber piece contamination by self-injection.

Coring is reported to occur because rubber pieces are shaved off from a rubber stopper when a needle is inserted into the rubber stopper of transfusion liquid formulation. We verified whether coring really occurs in insulin vials of self-injecting patients. We collected insulin cartridges from 30 hospitalized patients and used the primary injection (trial injection), the secondary injection and the cartridge remaining preparation as samples. We observed the rubber pieces using a microscope and measured the shape, number of pieces. The occurrence rate of coring was 73% for the primary injection, 47% for the secondary injection and 97% for the cartridge remaining preparation. The rubber pieces in the primary injection and the secondary injection which went through the needle are mostly in aggregate shape and the rubber pieces in the cartridge remaining preparation which did not go through the needle are mostly in needle-like shape. A number of small rubber pieces are found in both the primary injection and the secondary injection, indicating a high possibility that rubber pieces may be injected under subcutaneous tissue. The coring is considered to occur because needles are repeatedly inserted and rotated at the same spot. It is required to improve the structure to mount a needle to the pen-type injector in future. Coring is a very serious problem from the medical and pharmaceutical points of view. Further study should be made on the implication to latex allergy and lipodystrophy.

Adult↗

Fenestrated epithelium of the pelvic recess wall on the lateral parenchymal tissue in the dog kidney.

The epithelium of the pelvic recess separating the urine and the lateral parenchym of the dog kidney was examined by scanning and transmission electron microscopy (SEM and TEM) to try and identify the epithelial structures permitting filtration of urine substances. In cross sections through of the renal hilus, recesses were found in the pelvic space extending along the internal surface of the lateral parenchym. Light microscopy (LM) showed the external wall of the recess facing the parenchymal tissue to be a thin squamous epithelium underlined with a layer of smooth muscle cells. The cytoplasm of epithelial cells observed by TEM was extremely thin in comparison to the epithelia on other parts of the pelvic wall. Their peripheral cytoplasm usually demonstrated interdigitations or showed overlapping of cytoplasm of neighboring cells in two or three laminae. Distinct junctional structures were observed but no distension of the intercellular space was seen. The lumenal cell surface was relatively smooth, but the peripheral cytoplasm was equipped with either angular or stumped processes and deep cavae. In addition to a small number of cell organellae, numerous vesicles and vacuoles of varying sizes were conspicuously observed. The vacuoles contained flucculent materials and were fenestrated by pores closed by a diaphragm at fused potions of their limiting membrane with the adluminal and abluminal plasma membrane. The openings of the vacuoles were also seen at the basal cytoplasm. Similar fenestrations also occurred between the neighboring vacuoles in chains or conglomerations. Attenuated epithelial cytoplasm in close association with urinary tubules was also fenestrated by uniformly sized pores closed by thin diaphragm with punctuate central thickening. The fenestrations through the cytoplasm and between the chained vacuoles may thus be structures which have yet to be previously identified, and this finding seems to indicate that the filtration of urine substances occurs across the epithelial lining of the pelvic wall. Layers of thin smooth muscle cells with mutual connections are seen to underline the epithelium. The innermost muscle cells penetrated the basal lamina and thus come in contact with epithelial cells. However, their significance could not be clearly determined.

Animals↗

[Carvedilol effectiveness for left ventricular-insufficient patients with Duchenne muscular dystrophy].

To evaluate the efficacy of carvedilol for left ventricular dysfunction in Duchenne muscular dystrophy (DMD), we enrolled 8 patients with DMD who had elevated plasma atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP), and a low ejection fraction (EF < 40%) in echocardiography. Written informed consent was obtained from all of them. Four agreed to be treated with oral carvedilol 0.3125-1.25 mg/day (10.1-40.3 micrograms/kg/day) for 6 months (treated group). The others served as the controls (untreated group). In both groups, we evaluated clinical symptoms, plasma ANP, BNP and EF before, 3 and 6 months after the trial, and iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging at 6 month interval. Parameters in the treated and untreated groups before respectively were ANP, 83.8 +/- 17.5 and 89.5 +/- 44.4 pg/ml (mean +/- SEM); BNP, 169.0 +/- 46.2 and 186.3 +/- 61.8 pg/ml; EF, 24.0 +/- 2.2 and 16.5 +/- 1.9%; Heart/Mediastrinum ratio of the 123I-MIBG delayed image, 1.65 +/- 0.08 and 1.6 +/- 0.10; and Washout rate, 46.5 +/- 8.6 and 41.4 +/- 7.8. These values did not change significantly before and 6 months after for either group. Clinical symptoms also did not change in either group. Carvedilol therapy did not change the left ventricular dysfunction in DMD.

Adolescent↗