Search PubMed⌕ Search

Biomedical subjects

M Emoto

Publications and source records attributed to M Emoto.

At least 109 records · Page 6Linked to original sources
PubMed1995

Diversity of V gamma gene segments rearranged to the J gamma 4 gene in mice.

Because there are limited numbers of V gamma gene segments and most V gamma rearrangements occur within clusters of the J gamma-C gamma genes in mice, gamma-chains display limited diversity compared with other TCR chains. In this study, we examined the nucleotide sequences of the V gamma-J gamma genes expressed in the gamma delta T cells appearing at the inflamed sites after Salmonella infection in DBA/2 mice. Most of the productive gamma gene rearrangements were V gamma 1-J gamma 4, whereas V gamma 2 and a unique V gamma, the 5' region of which was identical with sequences of the V gamma 2 gene, and the 3' region of which was identical with that of the V gamma 1 gene, were found to be rearranged to J gamma 4 gene, albeit at low frequency. Analysis of the ontogenic appearance of the rearrangements in the J gamma 4-C gamma 4 locus revealed that V gamma 2-J gamma 4 gene rearrangement was frequent in fetal thymocytes at the early stage of gestation. Most of the early fetal V gamma 2-J gamma 4 rearrangements exhibited the identical junction, a nonfunctional canonical sequence. The sequence analysis of the coding joint and the reciprocal recombination signal joint suggests that short homology-mediated direct recombination and chromosomal inversion mechanism are involved in fetal V gamma 2-J gamma 4 gene rearrangement. Taken together, our data suggest that the recombination of multiple V gamma segments with J gamma 4 can diversify the V gamma repertoire.

Amino Acid Sequence↗
PubMed1995

The role of gamma delta T cells in priming macrophages to produce tumor necrosis factor-alpha.

The secretion of tumor necrosis factor (TNF)-alpha from macrophages is regulated by both priming and triggering signals. We found that macrophages from mice lacking gamma delta T cells [T cell receptor (TCR) delta-/- mice], which lack the gene encoding the delta chain, produced only small amounts of TNF-alpha in response to lipopolysaccharide (LPS) and showed a reduced level of expression of CD14. Pre-incubation of macrophages from TCR delta-/- mice with gamma delta T cells from their TCR delta +/- littermates restored their capacity to produce TNF-alpha in response to LPS. The priming activity of gamma delta T cells was in part inhibited by neutralizing anti-interferon (IFN)-gamma monoclonal antibodies. Collectively, these results suggest that gamma delta T cells play a role in priming macrophages to a steady state of activation via IFN-gamma secretion, which allows them to produce TNF-alpha when exposed to LPS.

Animals↗
PubMed1995

Control of thymus-independent intestinal intraepithelial lymphocytes by beta 2-microglobulin.

Murine intestinal intraepithelial lymphocytes (i-IEL) comprise thymus-dependent cells such as T cell receptor (TcR) alpha/beta CD8 alpha/beta+ i-IEL, as well as thymus-independent ones such as TcR alpha/beta CD8 alpha/alpha+ and TcR gamma/delta CD8 alpha/alpha+ i-IEL. Whilst the development of the CD8 alpha/beta expressing i-IEL is strictly contingent on major histocompatibility complex (MHC) class I surface expression, that of CD8 alpha/alpha i-IEL appears largely MHC class I independent. We have used beta 2-microglobulin (beta 2m)-/- mutant mice lacking surface-expressed MHC class I and TcR alpha/beta CD8 alpha/beta+ i-IEL to analyze the potential impact of MHC class I on regional activation of thymus-independent i-IEL. To analyze the role of TcR gamma/delta i-IEL in regional cell interactions, these mice were treated with the anti-TcR gamma/delta mAb, GL3. Whilst numbers of TcR alpha/beta CD8 alpha/alpha i-IEL were markedly reduced in beta 2m-/- mice, those of TcR gamma/delta i-IEL were elevated. Administration of GL3 in vivo caused TcR down-modulation and functional inactivation of TcR gamma/delta i-IEL in beta 2m+/- mice. In contrast, TcR expression and functional activities of TcR gamma/delta i-IEL from beta 2m-/- mice were not impaired by GL3 treatment. The TcR alpha/beta CD8 beta- i-IEL from beta 2m-/- mice were expanded and functionally activated as a consequence of TcR gamma/delta engagement. The TcR gamma/delta i-IEL and TcR alpha/beta CD8 alpha/alpha+ i-IEL from athymic nu/nu mice which express MHC class I, but lack TcR alpha/beta CD8 alpha/beta+ i-IEL, responded to TcR gamma/delta engagement as those from the beta 2m+/- controls. In addition, the TcR gamma/delta i-IEL from TcR beta-/- and TCR beta+/- mutants were equally affected by GL3. We conclude that the absence of beta 2m renders TcR gamma/delta i-IEL resistant to TcR-mediated inactivation and promotes activation of TcR alpha/beta CD8 beta- i-IEL. The activation of TcR gamma/delta i-IEL seems to be directly controlled by beta 2m/MHC class I expression and independent from TcR alpha/beta CD8 beta+ i-IEL. Regulation of self-reactive thymus-independent i-IEL through beta 2m/ MHC class I may contribute to control of autoreactive immune responses in the intestine.

Animals↗
PubMed1995

Interleukin-4-producing CD4+ NK1.1+ TCR alpha/beta intermediate liver lymphocytes are down-regulated by Listeria monocytogenes.

Experimental infection of mice with the intracellular bacterium, Listeria monocytogenes, provides a paragon model for immune defence dominated by T helper type 1 (Th1) responses. Potent production of interleukin (IL)-12 by infected macrophages is considered the determining factor in Th1 cell development. In contrast, it is assumed that IL-4 producers remain virtually unstimulated in listeriosis. In the liver, the major target organ of listeriosis, an unusual T lymphocyte population exists with the intriguing phenotype CD4+ NK1.1+ TCR alpha/beta intermediate (TCR alpha/beta int). Here we show that IL-4-producing CD4+ NK1.1+ TCR alpha/beta int liver lymphocytes are down-regulated early in listeriosis. We assume that curtailment of IL-4-producing CD4+ NK1.1+ TCR alpha/beta int liver lymphocytes promotes unconstrained development of Th1 cells which are central to protection against intracellular bacteria.

Animals↗
PubMed1995

High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia.

We sought to determine whether artherosclerosis may be accelerated in uremic patients on maintenance hemodialysis and investigated the risk factors for carotid and femoral atherosclerosis in such patients. High-resolution B-mode ultrasonography was used to determine the intima-media thickness (IMT) of the carotid and femoral arteries in 199 hemodialysis patients and 81 age-matched healthy controls subjects. The IMT values of the carotid and femoral arteries in the hemodialysis patients were significantly higher than in age-matched control subjects in most age groups. The IMT values of the carotid or femoral artery were significantly correlated with age in both the hemodialysis patients and the control subjects. There was a significant relationship between the IMT values of the two arteries in the hemodialysis patients (r = 0.418, P = 0.0001) and in the control subjects (r = 0.321, P = 0.0037). Multiple regression analysis showed that age, cigarette smoking, and uremic state were independent risk factors for atherosclerosis of both arteries in the patients and the control subjects (R2 = 0.174, P < 0.0001; R2 = 0.205, P < 0.0001, respectively). In the hemodialysis patients, the independent risk factors associated with the extent of the IMT of the carotid artery were age, cigarette smoking, and serum phosphorus level (R2 = 0.230, P < 0.0001), while those associated with the extent of the IMT of the femoral artery were age, cigarette-smoking, and serum m-PTH level (R2 = 0.230, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

IL-4 producing CD4+ TCR alpha beta int liver lymphocytes: influence of thymus, beta 2-microglobulin and NK1.1 expression.

The present report describes developmental, phenotypic and functional features of unconventional CD4+ TCR alpha beta lymphocytes. In C57BL/6 mice, the majority of liver lymphocytes expressing intermediate intensity of TCR alpha beta (TCR alpha beta int) are CD4+ NK1.1+ and express a highly restricted TCR V beta repertoire, dominated by V beta 8 with some contribution by V beta 7 and V beta 2. Although these cells express the CD4 co-receptor, they are present in H2-1 A beta (A beta)-/- gene disruption mutants but are markedly reduced in beta 2-microglobulin (beta 2m)-/- mutant mice and hence are beta 2m dependent. Thymocytes expressing the CD4+ NK1.1+ TCR alpha beta phenotype are also beta 2m contingent, suggesting that these two T lymphocyte populations are related. The CD4+ NK1.1+ TCR alpha beta lymphocytes in liver and thymus share several markers such as LFA-1+, CD44+, CD5+, LECAM-1- and IL-2R alpha-. The CD4+ NK1.1+ TCR alpha beta int liver lymphocytes were not detected in athymic nu/nu mice. We conclude that beta 2m expression is crucial for development of the CD4+ NK1.1+ TCR alpha beta int liver lymphocytes and that thymus plays a major role. CD4+ TCR alpha beta int liver lymphocytes were also identified in NK1.1- mouse strains, there lacking the NK1.1 marker. We assume that the NK1.1 molecule is a characteristic marker of the CD4+ TCR alpha beta int liver lymphocytes in NK1.1+ mouse strains, although its expression is not obligatory for their development. The liver lymphocytes from beta 2m+/-, but not from beta 2m-/-, mice are potent IL-4 producers in response to CD3 or TCR alpha beta engagement and the IL-4 production by liver lymphocytes was markedly reduced by treatment with anti-NK1.1 mAb. We conclude that the CD4+ NK1.1+ TCR alpha beta int liver lymphocytes are capable of producing IL-4 in response to TCR stimulation.

Animals↗
PubMed1995

Impaired retinal artery blood flow in IDDM patients before clinical manifestations of diabetic retinopathy.

OBJECTIVE: To determine whether hemodynamic changes in retinal arteries precede clinical manifestations of diabetic retinopathy and to examine the effects of control of hyperglycemia on retinal artery blood flow. RESEARCH DESIGN AND METHODS: We assessed blood flow in bilateral central retinal arteries in 50 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 20 sex- and age-matched control subjects using duplex Doppler sonography. We determined the peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged velocity (TAV), resistance index (RI), and pulsatility index (PI). RESULTS: PSV, EDV, and TAV were significantly lower in IDDM patients than in control subjects (P < 0.05, P < 0.01, and P < 0.01, respectively). The RI was significantly higher in IDDM patients than in control subjects (P < 0.01) and was significantly correlated with plasma levels of glucose in IDDM patients (r = 0.0.310, P = 0.0248). Multiple regression analysis identified the plasma levels of glucose as a significant determination of RI in IDDM patients. After 14 days of intensive insulin therapy in 7 IDDM patients, the RI and plasma levels of glucose showed significant decreases (P = 0.018, P = 0.001, respectively). CONCLUSIONS: Our results showed that changes in retinal hemodynamics were present before the clinical detection of overt diabetic retinopathy and suggest that the presence of short-term hyperglycemia partly contributes to impaired retinal circulation.

Adolescent↗
PubMed1995

Conversion of Salmonella typhimurium to L-forms contributes to the maintenance of acquired immunity against murine typhoid.

Conversion of Salmonella typhimurium to L-forms, both in vitro and in vivo, resulted in the expression of proteins cross-reacting to the mycobacterial 65,000 MW heat-shock protein (hsp). Immunization of C3H/HeJ mice with a protective dose of stable L-form S. typhimurium induced gamma delta T cells in the liver, in accordance with the multiplication of L-form Salmonella in Kupffer cells. The number of gamma delta T cells decreased after the intracellular growth of L-form Salmonella plateaued. Persistance of the L-forms in Kupffer cells, however, allowed hepatic gamma delta T cells to increase within 48 hr of infection with virulent S. typhimurium. Thus, the intrahepatic colonization of L-form Salmonella seems to keep gamma delta T cells on standby, but the emergence of these T cells does not correlate with the expression of L-form hsp. In addition, Kupffer cells colonized by L-forms constitutively synthesized mRNA for interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). These results suggest that conversion of S. typhimurium to L-forms in phagocytic cells builds up and maintains acquired resistance, conferred by live-cell vaccines of S. typhimurium, against murine typhoid.

Animals↗
PubMed1995

Growth of parathyroid gland in uremic patients on maintenance hemodialysis.

High-resolution, real-time ultrasonography was performed in 245 uremic patients on maintenance hemodialysis and the growth of the enlarged parathyroid glands was compared with the clinical and biochemical signs during follow-up periods of 12 months. The total volume of the parathyroid glands was significantly correlated with the serum C-terminal parathyroid hormone (C-PTH; r = 0.379, p = 0.0001) and calcium levels (r = 0.252, p = 0.0224). After 12 months, the total volume of the enlarged parathyroid glands and serum C-PTH or calcium levels were correlated more closely than in the initial study (r = 0.615, p = 0.0001, and r = 0.489, p = 0.0002, respectively). Both the serum C-PTH levels and the total volume of the enlarged parathyroid glands increased significantly (p = 0.0001), while the ratio between the serum C-PTH levels and the volume of the parathyroid glands decreased significantly (p = 0.0001). There was no difference in the clinical and biochemical signs except for the serum aluminum levels between the patients with and without an increased gland volume. These results suggest that the growth of parathyroid glands may progress more rapidly than the increase in the serum PTH levels, independent of the serum calcium levels, in uremic patients on maintenance hemodialysis.

Adolescent↗
PubMed1995

Influence of serum phosphate on the efficacy of oral 1,25-dihydroxyvitamin D3 pulse therapy.

In patients with a moderate degree of renal insufficiency, restriction of dietary phosphate suppresses PTH secretion by increasing serum calcitriol. However, this may not operate in advanced renal failure. The present study was designed to evaluate the influence of serum phosphate levels on PTH secretion in oral 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] pulse therapy. 22 patients with secondary hyperparathyroidism [carboxy-terminal PTH (c-PTH) concentration: 19.5+/-13.9 ng/ml, mean +/-SD] received oral doses of 1,25(OH)2D3 (3.0-4.0 micrograms) twice a week, each at the end of hemodialysis, for 12 weeks. Doses of phosphate binders remained unchanged throughout this period. Patients were divided into two groups: group A (11 subjects) with mean serum phosphate levels of less than 6.0 mg/dl and group B (11 subjects) with levels of 6.0 mg/dl and above. There was no significant difference in the average corrected serum calcium levels. The reduction in serum intact PTH levels was greater in group A than in group B. A negative correlation (r = -0.48; p < 0.05) was observed between mean serum phosphate levels and the percent decrease in serum c-PTH levels. The findings of this study indicate an important role for dietary phosphate reduction in oral 1,25(OH)2D3 pulse therapy and suggest that serum phosphate reduction may play a part in suppressing PTH secretion through a mechanism independent of 1,25(OH)2D3 and plasma calcium levels.

Administration, Oral↗
PubMed1995

Reduction of intermediate density lipoprotein by pravastatin in hemo- and peritoneal dialysis patients.

Elevated plasma intermediate density lipoprotein (IDL) is one of the features of uremic dyslipidemia which is potentially atherogenic. We examined the effects of pravastatin, an HMG-CoA reductase inhibitor, on IDL levels as well as other lipoprotein parameters in 19 uremic patients treated with hemodialysis (HD, n = 11) or continuous ambulatory peritoneal dialysis (CAPD, n = 8). The patients were administered 5 mg/day pravastatin for the initial 4 weeks and 10 mg/day for the subsequent 12 weeks. In the analysis of the total subjects, IDL-cholesterol was reduced by 31% as well as low density lipoprotein (LDL)-cholesterol. Cholesterol in very low density lipoprotein (VLDL) also decreased whereas that in high density lipoprotein (HDL) did not. Significant decrease of serum triglycerides was due mainly to reduced IDL- and LDL-triglycerides. Apolipoprotein (apo) A-I did not change, whereas apo A-II, B, C-II, C-III, E, and B/A-I ratio were significantly lowered. Pravastatin did not affect measured activity of lecithin: cholesterol acyltransferase, post-heparin plasma lipoprotein lipase or hepatic triglyceride lipase. HD and CAPD patients responded almost equally to the treatment. IDL elevation was present independent of serum total cholesterol, and it was lowered by pravastatin even in non-hypercholesterolemic subjects. There was no critical adverse effect besides transient and asymptomatic increase of serum creatine kinase level. We conclude that pravastatin can be a safe and effective approach to the management of dyslipidemia in uremic patients who have an elevated level of IDL.

Apolipoproteins↗
PubMed1995

[The prevention of cancer chemotherapy-induced emesis with granisetron and clonazepam].

The antiemetic efficacy of a combination of granisetron and clonazepam was investigated in 39 gynecological cancer patients treated with cisplatin. Granisetron (3 mg/body/day) was administered by intravenous drip infusion before and 24 hours after anticancer drug administration, and clonazepam was taken orally twice a day. With a combination of granisetron and clonazepam, excellent efficacy was found in 87% (34/39) of the cases. Delayed emesis occurred in 38% (13/34), but the degree of nausea was mild. Clinically, antiemetic therapy with a combination of granisetron and clonazepam demonstrated superior antiemetic effects and seems to be useful for controlling nausea and vomiting associated with cancer chemotherapy.

Administration, Oral↗
PubMed1995

Functions of T-cell subsets and cytokines in mycobacterial infections.

Phagocytosed M. tuberculosis either multiply inside the endocytic compartment of mononuclear phagocytes or they are destroyed by the host cell. Due to this macrophage-shelter (ab)used by mycobacteria, tuberculosis is controlled by the cellular immune response. Protection against mycobacteria depends on alpha/beta T-cells expressing the CD4 or CD8 phenotype. T-cell-mediated immunity amplifies macrophage capacities to kill and digest the bacilli. Specific alpha/beta T-cells produce several cytokines that attract and activate macrophages and additional lymphocytes, such as: interferon-gamma (IFN-gamma) which has the capacity to activate several antimicrobial properties of macrophages; tumour necrosis factor-alpha (TNF-alpha) a key cytokine involved in granuloma formation; interleukins 2, 6 and 8 (IL-2; IL-6 and IL-8); and interleukin 12 (IL-12), a candidate cytokine for the induction of Th1 cells. Furthermore, CD4+ and CD8+ T-cells display cytotoxic activity, which permits them to control mycobacterial growth through destruction of the infected cells. Escaping bacteria are subsequently ingested and destroyed by surrounding macrophages activated by T-cells. There is evidence to associate gamma/delta T-cells with antimycobacterial immunity, such as their preferential accumulation in inflammatory lesions, in necrotic areas of tuberculous lymphadenitis, and potent in vitro stimulation by M. tuberculosis components. In addition, M. tuberculosis activated gamma/delta T-cells are cytolytic and secrete several cytokines. Hence, clinical tuberculosis is associated with T-cell reactivity which controls the local concentrations of tubercle bacilli. Taken together, the cellular response, cytokine regulation, and the definition of target molecules are important aspects for the understanding of pathological immune mechanisms in tuberculosis.

CD4-Positive T-Lymphocytes↗
PubMed1994

CS-045, a new oral antidiabetic agent, stimulates fructose-2,6-bisphosphate production in rat hepatocytes.

Fructose-2,6-bisphosphate is a potent activator of 6-phosphofructo-1-kinase, a key enzyme in glycolysis. We previously revealed that sulfonylureas stimulate fructose-2,6-bisphosphate production in the rat liver by activating 6-phosphofructo-2-kinase. In the present study, we show that CS-045, a new antidiabetic agent, activated 6-phosphofructo-2-kinase and raised fructose-2,6-bisphosphate levels in dispersed rat hepatocytes. This action was time- and dose-dependent. Ten micromolar CS-045 raised the fructose-2,6-bisphosphate content linearly to the submaximal level in 20 min. Dose dependency was observed in the range of 1-30 microM. Thirty micromolar CS-045 completely reversed the inhibitory effect of 0.1 nM glucagon on fructose-2,6-bisphosphate production. CS-045 activated 6-phosphofructo-2-kinase by decreasing the Km value for the substrate (fructose-6-phosphate) without affecting the Vmax. The combination of suboptimal doses of CS-045 and tolbutamide increased fructose-2,6-bisphosphate content more than that induced by each agent alone. These results indicate that CS-045 may reduce plasma glucose by facilitating glycolysis in the liver.

Animals↗
PubMed1994

Primary osteosarcoma of the uterus: report of a case with immunohistochemical analysis.

Primary osteosarcoma of the uterus is an extremely rare neoplasm, and its immunohistochemical characteristic is unknown. We report a case of osteosarcoma occurring primarily in the uterine corpus of a 67-year-old woman with lower abdominal pain. The excised tumor showed bony inconsistency and histologically displayed a "pure" osteosarcoma of the uterus. Immunocytochemically, the tumor cells were positive for vimentin but negative for epithelial markers. The patient died 4 months after surgery because of developed local recurrence and pulmonary metastases. In conclusion, uterine osteosarcoma differs from malignant mixed Müllerian tumor (MMMT) in biological behavior, macroscopic and histologic features, and immunohistochemical profile. Osteosarcoma shows more aggressive behavior than MMMT, and displays nonpolypoid feature in appearance and no evidence of epithelial differentiation.

Aged↗
PubMed1994

Sendai virus pneumonia: evidence for the early recruitment of gamma delta T cells during the disease course.

We previously reported that gamma delta T cells appeared and could play a protective role early in infections with intracellular bacteria such as Listeria monocytogenes, Mycobacterium bovis BCG, and Salmonella choleraesuis. To extend these findings to virus infection, we examined the developmental sequence of gamma delta T cells in bronchoalveolar lavage during the course of Sendai virus infection in C57BL/6 mice. To produce a natural but nonlethal infection course as far as possible, we used a sublethal dose of a wild-type virus which had not been subjected to serial passages in a chicken embryo, hence retaining full virulence for mice. Virus titers in lungs reached a peak on day 6 and then decreased to an undetectable level by day 10. This time course of virus reproduction was immediately and coincidentally followed by the developmental course of gamma delta T cells, in which the cell number peaked on day 7 and then decreased to a marginal level by day 10. On the other hand, the alpha beta T-cell number continued to increase until day 10 and remained at a high level thereafter. The early-appearing gamma delta T cells were CD4-, CD8-, IL-2R alpha- beta+, CD44+, Mel-14-, and LFA-1 alpha/beta+ in phenotype and used V gamma 1/2 and V gamma 4 and V delta 3, V delta 4, V delta 5, and V delta 6. The gamma delta T cells were responding to macrophages from infected mice when the cells were cultured in vitro. Furthermore, the expression of endogenous heat shock protein (hsp) was infection specific, and its level appeared to correlate with the gamma delta T-cell development. These results suggest that the early recruitment of gamma delta T cells, which proliferate in response to endogenous hsp+ cells, is also characteristic of this virus infection, although this view appears to be contradictory to earlier reports.

Animals↗
PubMed1994

A protective role of extrathymic alpha beta TcR cells in the liver in primary murine salmonellosis.

The liver comprises unique T cells differentiating extrathymically and expressing an intermediate intensity of alpha beta T-cell receptor (TcR) and a high intensity of leucocyte function antigen-1 (LFA-1). To elucidate the functional roles of the intermediate alpha beta TcR cells in host defence against bacterial infection, we examined the effects of depletion of the intermediate alpha beta TcR cells by in vivo administration of monoclonal antibodies (mAb) to intercellular adhesion molecule-1 (ICAM-1)/LFA-1 and alpha beta TcR on the bacterial growth in the liver after infection with Salmonella chorelaesuis in mice. Pretreatment with mAb to LFA-1 (200 micrograms/mouse) together with mAb to ICAM-1 (200 micrograms/mouse), which could preferentially deplete the intermediate alpha beta TcR cells and gamma delta TcR cells in the liver, resulted in a severely reduced ability to resolve acute phase of Salmonella infection in the liver. Pretreatment with a low dose of anti-alpha beta TcR mAb (60 micrograms/mouse), which depleted only bright alpha beta TcR cells, did not affect the bacterial growth in the liver at the early stage after Salmonella infection, while the depleting of both intermediate and bright alpha beta TcR cells by pretreatment with a high dose of anti-alpha beta TcR mAb (120 micrograms/mouse) allowed the bacteria to multiply exaggeratedly in the liver at this stage. These results suggest that intermediate alpha beta TcR cells may play an important role in protection at the early stage after Salmonella infection in liver and that the interaction of ICAM-1/LFA-1 is critically involved in protective roles of extrathymic T cells bearing intermediate alpha beta TcR in liver at the early stage after Salmonella infection.

Animals↗