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Biomedical subjects

M Totsuka

Publications and source records attributed to M Totsuka.

At least 19 recordsLinked to original sources

An unusual staining of the tooth roots: a case report with histological and micro-analytical studies.

The discoloration of tooth roots is rare. We report here a 22-year-old Japanese woman with blackish-brown staining of the roots of the upper and lower third molars. Staining was found in the dentin and cementum. Electron probe X-ray microanalysis showed no significant difference in the composing elements between the stained tooth root and control tooth. Fluorescent bands coincided with staining in the dentin of the root and cementum along the incremental lines under confocal laser-scanning microscope.

Adult↗

Histological and analytical studies of a tooth in a patient with cleidocranial dysostosis.

A histopathological and analytical study of a permanent tooth from a patient with cleidocranial dysostosis (CCD) was performed. The patient was a 47-year-old woman, who had 10 erupted permanent teeth and 2 partially erupted and 19 completely impacted teeth, including supernumerary teeth. The erupted right upper premolar was extracted and observed using a light microscope and an electron probe X-ray microanalyzer (EPMA). Findings showed enamel hypoplasia, predominantly irregular globular dentin and Tomes' granular layer, and a complete lack of cellular cementum in the ground section. The incremental von Ebner and counter Owen lines were obscure. Comparative quantitative analysis using the EPMA showed that the quantities of calcium and phosphate were lower in the enamel and dentin than those of the control sample.

Bicuspid↗

[The effect of celiprolol hydrochloride for lipid metabolism--especially for the low density lipoprotein particle size].

Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.

Aged↗

Effect of temocapril hydrochloride on serum lipid levels in patients with hypertensive type 2 diabetes mellitus.

The effect of angiotensin converting enzyme inhibitor, temocapril hydrochloride on the serum lipoproteins, and especially on the size of low density lipoproteins (LDL) of hypertensive diabetic patients, were studied. Temocapril hydrochloride (5 mg/day) was administered to 32 hypertensive type 2 diabetes patients for 16 weeks. During treatment, systolic and diastolic blood pressures decreased significantly from 162/95 mmHg to 138/76 mmHg at 16 weeks (p<0.001), and serum levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) showed significant reduction, but those of HbA1c, triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) showed no significant changes. LDL particle size evaluated by polyacrylamide gel disc electrophoresis was normalized from small size. It is concluded that temocapril hydrochloride favorably affects the serum lipoprotein metabolism of hypertensive type 2 dependent diabetes mellitus patients.

Antihypertensive Agents↗

[A case of IgA2-lambda type M-protein that IgA concentration differs from the values of M-protein by serum protein electrophoresis].

We report an IgA-lambda type M-protein in which the IgA concentration differed from the values of M-protein by serum protein electrophoresis found in a 53-year-old man with multiple myeloma. The M-protein value as determined by serum protein electrophoresis was 6,170 mg/dl. However, the serum IgA concentration was 3,052 mg/dl by turbidimetric immunoassay. Immuno-fixation electrophoresis using IgA subclass antisera revealed that this M-protein was the IgA2-lambda type. Western blotting analysis showed that the IgA2 molecules were composed of two approximately 68 kDa alpha 2 chains and two 28 kDa lambda chains. In addition the free lambda chain band was detected at the position of 28 kDa without 2-mercaptoethanol(2-ME) even though the patient IgA was purified. Since it is known that IgA2m(1) allotype easily release light chains from the IgA molecules in SDS-PAGE without 2-ME, we speculated that in this patient the IgA was the IgA2m(1) allotype. After peripheral blood stem cell transplantation(PBSCT), immunofixation electrophoresis of the patient serum revealed not only the bands of IgA2-lambda type M-protein, but also three bands of IgG1-kappa type M-protein in the gamma region.

Blood Protein Electrophoresis↗

Primary response of naive CD4(+) T cells to amino acid-substituted analogs of an antigenic peptide can show distinct activation patterns: Th1- and Th2-type cytokine secretion, and helper activity for antibody production without apparent cytokine secretion.

Naive CD4(+) T cells differentiate into two types of helper T cells showing an interferon-gamma-predominant (Th1) or an interleukin-4-predominant (Th2) cytokine secretion profile after repeated antigenic stimulation. Their differentiation can be influenced by slight differences in the interaction between the T cell receptor (TCR) and its ligand at the time of primary activation. However, the primary response of freshly isolated naive CD4(+) T cells to altered TCR ligands is still unclear. Here, we investigated the primary response of splenic naive CD4(+) T cells derived from transgenic mice expressing TCR specific for residues 323-339 of ovalbumin (OVA323-339) bound to I-A(d) molecules. Naive CD4(+) T cells secreted either Th1- or Th2-type cytokines immediately after stimulation with OVA323-339 or its single amino acid-substituted analogs. Helper activity for antibody secretion by co-cultured resting B cells was also found in the primary response, accompanied by either low-level Th2-type cytokine secretion or no apparent cytokine secretion. Our results clearly indicate that dichotomy of the Th1/Th2 cytokine secretion profile can be elicited upon primary activation of naive CD4(+) T cells. We also demonstrate that the helper activity of naive CD4(+) T cells for antibody production does not correspond to the amounts of the relevant cytokines secreted.

Amino Acid Sequence↗

Down-regulation of antigen-specific antibody production by TCR antagonist peptides in vivo.

The efficacy of TCR antagonist peptides in inhibition of antigen-specific antibody production and T cell responses in vivo was evaluated. Among amino acid-substituted analogs of a peptide corresponding to residues 119 - 133 of bovine beta-lactoglobulin (p119 - 133), pR124Q and pD129S, prepared by substitution of Gln and Ser for Arg(124) and Asp(129), respectively, have been shown to display TCR antagonist activity for three out of four distinct p119 - 133-specific T cell clones and for polyclonal T cells derived from p119 - 133-immunized C57BL / 6 mice. Both pD129S and pR124Q inhibited in vivo priming and subsequent activation of T cells by p119 - 133 when co-injected with p119 - 133 into mice, as shown by the decreased proliferation of T cells in response to p119-133 in vitro. pD129S significantly inhibited production of anti-p119 - 113 antibodies of IgG1, IgG2b and IgE isotype in vivo when co-injected into mice together with p119 - 133 at the time of the first immunization. However, pR124Q was totally ineffective in inhibition of the antibody responses. Anti-p119 - 133 antibodies from p119 - 133-immunized mice could bind to pR124Q but not to pD129S, suggesting that the difference in cross-reactivity is responsible for the different effect of these two peptides on specific antibody production. Our findings demonstrate that a single TCR antagonist peptide can inhibit antigen-specific polyclonal antibody production when this antagonist peptide does not cross-react with the antibody elicited in response to an antigenic peptide.

Animals↗

Enhancement of preheparin serum lipoprotein lipase mass by bezafibrate administration.

To clarify the clinical implication of preheparin serum lipoprotein lipase mass (preheparin LpL mass), we studied the relationships between preheparin LpL mass and serum lipids, including midband lipoproteins, which migrate between very low density lipoproteins and low density lipoproteins on polyacrylamide gel disc electrophoresis, in hyperlipidemias. And we also studied the changes of preheparin LpL mass in hypertriglyceridemic patients during bezafibrate administration, which is known to enhance LpL activity in postheparin plasma. Preheparin LpL mass correlated positively with high-density lipoprotein-cholesterol (HDL-C) (r=0.418, P<0.01) and negatively with triglyceride (TG) (r=-0.256, P<0.01), but did not correlate with total cholesterol (TC) in 64 hyperlipidemic (type IIa, IIb and IV) patients. The midband lipoproteins were observed in 80% of hypertriglyceridemic patients (32/40). Preheparin LpL mass in midband lipoprotein-positive subjects was lower significantly than that in midband-negative subjects. When bezafibrate (400 mg/day) was administrated to 40 hypertriglyceridemic patients for 4 months, TG level significantly decreased (-49+/-7%, P<0.01), TC levels decreased (-11+/-4%, not significant), and HDL-C levels increased (+27+/-4%, P<0.01). The midband lipoproteins disappeared in 95% of patients. Preheparin LpL mass significantly increased (+25+/-6%, P<0. 0005). In nine patients who stopped bezafibrate, TG levels significantly increased (+49+/-7%, P<0.01) and HDL-C levels decreased (-27+/-4%, P<0.01). Preheparin LPL mass significantly decreased (-25+/-6%, P<0.0005). These results suggested that bezafibrate administration enhanced preheparin LpL mass. And it might be implicated that enhanced LpL production by bezafibrate could reflect an increase of preheparin LpL mass.

Bezafibrate↗

Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertension.

OBJECTIVE: Intravascular ultrasound has the unique ability to provide cross-sectional images of the arterial wall. This study examined intravascular ultrasound (IVUS) images of the proximal pulmonary arteries in primary pulmonary hypertension (PPH). METHODOLOGY: Study 1: Specimens from four patients who had died of PPH (in vitro PPH group) were compared with those of three patients who had died of subarachnoid haemorrhage but had no evidence of cardiopulmonary disease (in vitro control group). Three-centimetre segments of the following levels were examined by IVUS: pulmonary trunk, eight secondary branch arteries of the upper, middle, and lower lobes of both lungs, and the thoracic descending aorta. Study 2: Four patients with PPH (in vivo PPH group) and five patients without pulmonary hypertension and no evidence of cardiopulmonary disease (in vivo control group) were examined. The IVUS images of the apical segmental artery of the right upper lobe and the descending branch of the right pulmonary artery were studied. RESULTS: Echographic examination of formalin-fixed preparations of secondary branch sections of the pulmonary artery failed to show a clear three-layer structure in the in vitro control group (24 preparations), but a distinct three-layer structure and increased vessel wall thickness were observed in the in vitro PPH group (32 preparations). Similar findings were obtained in the in vivo study. The mean echo density of the proximal pulmonary arterial wall correlated well with the mean pulmonary arterial pressure (mPA) in the in vitro PPH, and also correlated with the mPA in the in vivo study (r = 0.960, P < 0.0001). The echo intensity of secondary branch sections of the pulmonary artery was higher in the in vitro PPH group than in the in vitro control group (180.5 +/- 27.0 vs 132.5 +/- 26.7 counts, P < 0.001); similar results were obtained in the in vivo study (144.7 +/- 23.4 vs 85.0 +/- 14.3 counts, P < 0.01). CONCLUSIONS: These results suggest that the histological changes detected in the pulmonary artery walls in the PPH group were responsible for the increased echo intensity.

Adult↗

Dietary nucleotides can up-regulate antigen-specific Th1 immune responses and suppress antigen-specific IgE responses in mice.

BACKGROUND: It has been reported that dietary nucleotides enhance T helper cell activities. In this study, we have determined the effects of dietary nucleotides on antigen-specific Th1 and Th2 responses and IgE responses. METHODS: Ovalbumin (OVA)-specific T cell receptor (TCR) transgenic (OVA-TCR Tg) mice, 3 weeks old, were fed a nucleotide-free diet (NT(-) diet) or the NT(-) diet supplemented with dietary nucleotides (NT(+) diet) for 4 weeks. Cytokine production by spleen cells and macrophages obtained from these mice was measured in vitro. BALB/c mice, 3 weeks old, immunized intraperitoneally with OVA adsorbed onto alum, were fed the NT(-) diet or the NT(+) diet for 4 weeks. Serum levels of antigen-specific antibodies in the BALB/c mice were determined by ELISA. RESULTS: The level of production of antigen-specific interferon-gamma by spleen cells was significantly higher in the OVA-TCR Tg mice fed the NT(+) diet than in the control mice. The levels of secretion of bioactive IL-12 by spleen cells and peritoneal macrophages were also significantly increased in the NT(+) diet group. The serum OVA-specific IgE level was significantly decreased in BALB/c mice fed the NT(+) diet compared with those fed the NT(-) diet. CONCLUSION: These results show that dietary nucleotides up-regulate the antigen-specific Th1 immune response through the enhancement of IL-12 production and suppress the antigen-specific IgE response.

Adjuvants, Immunologic↗

Dietary nucleotides increase the proportion of a TCR gammadelta+ subset of intraepithelial lymphocytes (IEL) and IL-7 production by intestinal epithelial cells (IEC); implications for modification of cellular and molecular cross-talk between IEL and IEC by dietary nucleotides.

We have investigated the effects of dietary nucleotides on intraepithelial lymphocytes (IEL) and intestinal epithelial cells (IEC) in weanling mice. The proportion of T-cell receptor (TCR) gammadelta+ IEL in BALB/c mice fed a diet supplemented with nucleotides (NT(+) diet) was significantly higher than that in mice fed the nucleotide-free diet, while the proportion of TCR alphabeta+ IEL in NT(+) diet-fed mice was significantly decreased. The change of the TCR alphabeta+/TCR gammadelta+ ratio was mainly observed in a CD8 alphaalpha+ subset of IEL. IEC from NT(+) diet-fed mice produced a higher level of IL-7, which is important in the development of TCR gammadelta+ IEL, than those from control diet-fed mice. The expression levels of IL-7 and IL-2 receptors on IEL were not different between the two dietary groups. Our findings suggest that the increased population of a TCR gammadelta+ IEL subset by feeding nucleotides may be caused by the increased production of IL-7 by IEC.

Animals↗

Accelerated secretion of mutant beta-lactoglobulin in Saccharomyces cerevisiae resulting from a single amino acid substitution.

Transformed yeasts producing a mutant form of bovine beta-lactoglobulin (beta-LG), W19Y, in which Trp(19) was replaced with Tyr, were shown to secrete 6 times more than those producing wild type beta-LG. Northern blot analysis suggested that the enhanced level of secretion was not the result of upregulated transcription of W19Y. The ratio of the amount of W19Y secreted into the supernatant to the amount of W19Y remaining inside the cells was much larger than that in the case of wild type beta-LG as shown by immunoblot analysis. A pulse/chase experiment revealed that the speed of secretion of W19Y was significantly accelerated, compared to wild type beta-LG. These results indicated that W19Y was more efficiently and rapidly transported in the course of secretion than wild type beta-LG. Our previous study showed that the DeltaG of unfolding of W19Y in water is 6.9 kcal/mol smaller than that of wild type beta-LG. Furthermore, immunoblot analysis of intracellular beta-LG under non-reducing conditions indicated that W19Y as well as wild type beta-LG maintained a specific folded structure inside the yeast cells, whereas other non-secretable mutant beta-LGs with Phe or Ala at position 19 (W19F and W19A, respectively) did not. These data suggest that low molecular stability and the maintenance of a specific folded structure inside the yeast cells are prerequisites for efficient and rapid secretion. W19Y was more efficiently secreted than wild type beta-LG also in transformed ern1 mutant yeast cells expressing only a basal level of BiP which is considered to function in quality control in the endoplasmic reticulum (ER) by playing an important role in determining the secretion efficiency of secretory proteins. Thus, the reason for the enhanced secretion of W19Y is considered to be that the improved folding ability of W19Y can allow the half-life of the W19Y-BiP complex to become shorter than that of the wild type beta-LG-BiP complex, leading to faster translocation of W19Y into transport vesicles, or that W19Y can fold in a BiP-independent manner in the ER of the yeast cells. Our findings demonstrate that the amount of protein secreted can be improved by alteration of a single amino acid residue crucial for its structure.

Amino Acids↗

Autocrine B-cell stimulation by interleukin-2 during a cognate interaction with T-cells.

Interleukin-2 (IL-2) secretion as well as expression of IL-2 receptor has been demonstrated for B-cells in response to several activating stimuli. However, the exact role of B-cell-derived IL-2 in the T-cell-dependent antibody response remains to be determined. Here, we have examined the autocrine regulatory roles of IL-2 secreted from B-cells. Splenic resting B-cells were stimulated with a fixed pre-activated Th1 clone, G1.19, in the presence of a single amino acid-substituted peptide (pD129A; Ala-129 substituted for Asp-129), an analog of the original ligand (p119-133, derived from bovine beta-lactoglobulin) recognized by G1.19 cells. pD129A allowed a cognate interaction between B-cells and fixed pre-activated G1.19 T-cells, but pD129A had no agonistic activity against G1.19 T-cells. Thus, the level of expression of B-cell-activating molecules on T-cells remained unchanged after stimulation with pD129A. Regardless of the lack of ability to induce IL-2 secretion in the case of T-cells, pD129A significantly enhanced antibody secretion from B-cells, and this was partially blocked by anti-IL-2 antibody. Furthermore, IL-2 secretion from B-cells was modestly upregulated in response to added pD129A. Taken together, these data suggest that helper signals from interacting cognate T-cells induce IL-2 secretion by B-cells, which can enhance antibody secretion in an autocrine manner.

Animals↗

The effect of insulin sensitizer, troglitazone, on lipoprotein lipase mass in preheparin serum.

Lipoprotein lipase mass exists in preheparin serum, even though the activity is scarcely found. The implication of this is unclear. We studied the effect of an insulin sensitizer, troglitazone, on this preheparin serum lipoprotein lipase mass (preheparin LPL mass) in non-insulin-dependent diabetes mellitus (NIDDM) patients as well as on serum lipid levels and low density lipoproteins (LDL) particle size. Thirty-one NIDDM patients with poor control were administered troglitazone 400 mg/day. Hemoglobin A1c had significantly decreased (13%, P < 0.001) 2 months later. Preheparin LPL mass had gradually increased and a 69% increase (P<0.01) was observed 4 months later. Triglyceride significantly decreased (23%, P < 0.01) and high density lipoprotein-cholesterol increased (10%, P < 0.01), whereas total cholesterol and LDL levels did not change 4 months later. The size of LDL increased significantly (P < 0.01). These results were consistent with the idea that preheparin LPL mass might be relating to the insulin sensitivity enhanced by troglitazone, as well as LDL particle size.

Adult↗

Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

Adult↗

Supernumerary teeth with eumorphism in the lower incisor region: a report of five cases and a review of the literature.

Five cases of supernumerary teeth with eumorphism in the lower incisor region of the permanent dentition are reported. The patients were two males and three females. One (a 31-year-old woman) of them had bilateral supernumerary teeth. The review of the English language literature yielded only one such bilateral supernumerary teeth in the lower incisor region of the permanent dentition was reported.

Adolescent↗

Selective induction of CD8+ T cell functions by single substituted analogs of an antigenic peptide: distinct signals for IL-10 production.

The CD8+ T cell clone 5F1 produces interleukin 10 (IL-10) and interferon gamma(IFN-gamma) in response to stimulation with a peptide corresponding to region 142-149 of bovine alpha(s1)-casein (p142-149). Ninety analog peptides derived from p142-149 with single amino acid substitutions of putative T cell receptor contact residues were prepared to examine whether production of IL-10 and IFN-gamma by 5F1 can be altered by stimulation with these peptides. We found that some peptides triggered only IL-10 production whereas others induced production of IFN-gamma alone or both of these cytokines. Peptides inducing IFN-gamma production triggered both cytotoxicity and a proliferative response, whereas peptides inducing production of IL-10 but not IFN-gamma triggered neither of these responses. Our results clearly demonstrate that the signaling pathway required for IL-10 production in CD8+ T cells differs from that required for IFN-gamma production. The distinct cellular signals for IL-10 production appear to be independent of those for cytotoxicity and the proliferative response of CD8+ T cells.

Animals↗