Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 793 records · Page 44Linked to original sources

PubMed1998

Prevalence and characterization of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) directed against HMG1 and HMG2 in ulcerative colitis (UC).

In a previous study, we reported that the high mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 were novel target antigens of P-ANCA. In this study, we determined the immunodiagnostic value of anti-HMG1/HMG2 antibodies in patients with UC. Sixty sera from patients with UC were tested for reactivity with HMG1 and HMG2 by means of ELISA. Anti-HMG1 antibody was detected in 32% of patients (40% of P-ANCA+ patients). Anti-HMG2 antibody was detected in 33% (40% of P-ANCA+ patients). Thirty-five percent of sera were positive for antibody to either HMG1 or HMG2 (43% of P-ANCA+ patients). P-ANCA+ patients expressed anti-HMG1/HMG2 antibodies with significantly greater frequency compared with P-ANCA- patients. Furthermore, the anti-HMG1/HMG2 antibodies were significantly related to disease activity in UC. Sixteen of the 18 UC patients, who had high titres of anti-HMG1 or -HMG2 antibody during the active phase, showed lower titres in the inactive phase. Anti-HMG1/HMG2 antibodies appear to be useful as a marker for disease activity in UC.

Adolescent↗

PubMed1998

Region-specific expression of murine Hox genes implies the Hox code-mediated patterning of the digestive tract.

BACKGROUND: Hox genes encode transcription factors which are involved in the establishment of regional identities along the anteroposterior (AP) body axis. To elucidate the AP patterning of the digestive tract, we have systematically examined the expression patterns of Hox genes belonging to paralogue groups 6, 7, 8 and 9 by whole-mount in situ hybridization and by section in situ hybridization analyses. RESULTS: The expression patterns of these genes showed co-linearity along the wall of the digestive tract, thereby yielding the Hox code of the gut. The expression boundaries of the Hox genes at later stages (12.5 d.p.c.) corresponded to the morphological boundaries of individual gut subdomains. CONCLUSIONS: The visceral mesoderm-restricted expression suggested that the Hox code primarily functions in the mesenchymal specification which eventually leads to the regional differentiation of gut subdomains as the result of epithelial-mesenchymal interactions. Overlapping expression patterns were found among the paralogous Hox genes, indicating that the paralogues may have redundant functions in the specification of the gut.

Animals↗

PubMed1998

Flavonoids and lignans from Virola surinamensis twigs and their in vitro activity against Trypanosoma cruzi.

Dichloromethane extracts from twigs of Virola surinamensis (Myristicaceae) showed in vitro trypanosomicidal activity against trypomastigote form of Trypanosoma cruzi. The extract, fractionated by preparative circular chromatography and preparative high-performance liquid chromatography yielded two steroids, two lignans, five flavonoids, and one polyketide. Among the isolated compounds, the lignans presented the highest trypanosomicidal activity.

Animals↗

PubMed1998

Clinical experience of endovascular laser intervention in cardiovascular disease.

OBJECTIVE: The authors studies laser angioplasty for patients with obstructive arterial diseases since the 1980s. SUMMARY BACKGROUND DATA: Usefulness of laser angioplasty for endovascular surgery was recognized especially for patients having short segments of severe atherosclerotic changes in vessels. METHODS: The authors retrospectively reviewed clinical experience of angioplasty by argon laser for 113 patients (103 peripheral, 10 coronary artery). Using an argon laser optimal conditions were (a) 6W in output and 3 sec in irradiation time or (b) metal tip temperature of 200 degrees C and 5 sec of ablation time for the peripheral artery. On the other hand, 4-5 W in output and 2 sec in irradiation time were optimal conditions for the same procedure on the coronary artery. RESULTS: The initial success rate of laser angioplasty for the peripheral artery was 92% in the stenotic lesions and 73% in the occlusive lesions. However, cumulative patency rate was 85% in the stenotic lesions and 74% in the occlusive lesions in the long-term follow-up study of 106 months among the patients with clinical success. On the basis of the excellent results in the peripheral arterial diseases, coronary laser angioplasty and coronary artery bypass grafting was intraoperatively performed in 10 patients with anginal attack. Patency rate was 90% in this series. CONCLUSIONS: Laser angioplasty for endovascular surgery was a useful procedure for patients with stenotic and occlusive changes of the peripheral and coronary arteries. Consequently, this method should be recommended especially for high-risk patients with atherosclerosis.

Adult↗

PubMed1998

Cyclophosphamide, adriamycin, 5-fluorouracil and high-dose toremifene for patients with advanced/recurrent breast cancer. The Japan Toremifene Cooperative Study Group.

BACKGROUND: Multi-combination chemotherapy consisting of anthracyclines has been effective but has not invariably prolonged the survival period in advanced/recurrent breast cancer. The possibility has been discussed that chemoendocrine therapy combined with endocrine agents is more effective. METHODS: In order to evaluate the toxicity and efficacy of a new endocrine therapy for advanced/recurrent breast cancer, we ran a pilot study during the period from July 1994 to July 1996. RESULTS: Twenty-two patients with advanced/recurrent breast cancer were treated with chemoendocrine therapy consisting of cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m2) i.v. and 5-fluorouracil (500 mg/body) i.v. on day 1 (repeated every 3 weeks for 9 weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20 evaluable patients, two showed complete response (10%), eight partial response (40%), six no change (30%) and four progressive disease (20%). The overall response rate was 50%, and the median duration of response was 69.5 days (28-133+ days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity and hematological toxicity, but these were clinically well tolerated. No serious cardiac, liver or renal symptom was seen. CONCLUSIONS: Based on these results, we consider the addition of high-dose toremifene to the CAF therapy to be useful in the treatment of advanced and recurrent breast cancer.

Adult↗

PubMed1998

Glycolaldehyde-modified low density lipoprotein leads macrophages to foam cells via the macrophage scavenger receptor.

It was shown that proteins modified with advanced glycation end products (AGE) are effectively endocytosed by macrophages or macrophage-derived cells in vitro, and immunohistochemical studies involving anti-AGE antibodies demonstrated the accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE-modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL was modified with glycolaldehyde, a highly reactive intermediate of the Maillard reaction. Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was characterized by increases in negative charge, fluorescence intensity, and reactivity to anti-AGE antibodies, properties highly similar to those of AGE-proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages showed that GA-LDL was specifically recognized and endocytosed, followed by lysosomal degradation. The endocytic uptake of GA-LDL by these cells was competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore, incubation of GA-LDL with these macrophages and Chinese hamster ovary cells overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal macrophages from MSR-knockout mice, led to the intracellular accumulation of cholesteryl esters (CE). These results raised the possibility that AGE-modified LDL, if available in situ, is taken up by macrophages mainly via MSR and then contributes to foam cell formation in early atherosclerotic lesions.

Acetaldehyde↗

PubMed1998

High mobility group proteins 1 and 2 can function as DNA-binding regulatory components for DNA-dependent protein kinase in vitro.

The DNA-dependent protein kinase (DNA-PK) holoenzyme consists of a 470-kDa catalytic subunit (DNA-PKcs), a DNA-binding regulatory component known as Ku protein, and double-stranded DNA (dsDNA) with ends. We previously reported that the activity of DNA-PK in vitro is stimulated by non-histone chromosomal high mobility group proteins (HMG) 1 and 2 comprising two similar repeats, termed domains A and B, and an acidic C-terminal. Here we demonstrate that in vitro HMG1 and 2 can completely replace Ku protein as the DNA-binding regulatory component of DNA-PK. DNA-PKcs and Ku protein were separately purified from Raji nuclear extracts, and reconstituted into the DNA-PK holoenzyme in the presence of dsDNA. DNA-PKcs alone catalyzed DNA-dependent phosphorylation at a very low but significant level, and HMG1 and 2 markedly stimulated the phosphorylation of alpha-casein and a specific peptide substrate in a DNA-dependent manner. The HMG2-domains (A+B) polypeptide devoid of the C-terminal acidic region was more effective for DNA-PKcs stimulation than the full-length HMG2, and HMG2-domain A and -domain B polypeptides. Anti(Ku protein) antibodies inhibited the DNA-dependent phosphorylation activity of the DNA-PKcs:Ku protein complex, but not that of DNA-PKcs alone or when it was complexed with HMG1 or 2. These results demonstrate that HMG1 and 2 can function as the DNA-binding regulatory component for DNA-PKcs in vitro, and imply that a conformational change of dsDNA, which is elicited by regulatory components, is important for the stimulation of DNA-PK activity of DNA-PKcs.

Amino Acid Sequence↗

PubMed1998

Structural studies of the vacuolar H(+)-pyrophosphatase: sequence analysis and identification of the residues modified by fluorescent cyclohexylcarbodiimide and maleimide.

We determined the amino acid residues of the H(+)-translocating inorganic pyrophosphatase (H(+)-PPase) of pumpkin which are covalently labeled by two fluorescent labeling reagents; N-cyclohexyl-N'-[4-(dimethyl amino)-alpha-naphthyl] carbodiimide (NCD) and N-pyrenylmaleimide (NPM). NCD and NPM are fluorescent analogues of N,N-dicycrohexylcarbodiimide and N-ethylmaleimide, respectively, and inactivate H(+)-PPase activity. Excess Mg2+ protected the H(+)-PPase from the inactivation by these reagents. Furthermore, we identified the cDNA clone encoding the pumpkin H(+)-PPase in order to determine the position of labeled residues. The nucleotide sequence of the cDNA clone contains a 2,304 bp open reading frame encoding a polypeptide with 768 amino acids. Chemical sequence analysis of fluorescent peptide fragments revealed that Glu749 located in the C-terminal putative transmembrane alpha-helix was a NCD-labeled residue, and Cys632 was a NPM-labeled residue located in a putative cytosolic domain. The amino acid sequence of the region that includes Glu749 is highly conserved in H(+)-PPases from other plants and it also shows some sequence similarity with the region of the carbodiimide-reactive Glu (or Asp) of F0F1-ATPase c-subunit. The reactive glutamic acids in these proteins are located at the last C-terminal transmembrane alpha-helix. We also found that the H(+)-PPase shows significant amino acid sequence similarity to Kdp-ATPase A chain of E. coli. This similarity between the two different proteins suggest that they have evolved from a common ancestor and may utilize a common basic mechanism for ion transport.

Amino Acid Sequence↗

PubMed1998

The lipoxygenase inhibitor, nordihydroguaiaretic acid, inhibits ovulation and reduces leukotriene and prostaglandin levels in the rat ovary.

Eicosanoids, the active metabolites of arachidonic acid, are grouped into cyclooxygenase products (prostaglandins [PGs] and thromboxanes) and lipoxygenase products (leukotrienes [LTs] and lipoxins). Numerous studies suggest a role for the lipoxygenase system in ovulation. The aim of this study was to further characterize the effects of lipoxygenase inhibition and the interactions of the lipoxygenase and cyclooxygenase systems in the rat ovary during ovulation. The lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), was administered in vivo and in the isolated perfused rat ovary to determine its effect on ovulation rate. The in vivo study confirmed the inhibitory effect of NDGA, and in the perfusion experiments, NDGA caused a dose-dependent reduction in the ovulation rate. To further define the interaction between the lipoxygenase and cyclooxygenase systems, a second set of perfusions was performed with NDGA (10 microM) and the combination of NDGA (10 microM) plus a nonselective cyclooxygenase inhibitor, indomethacin (10 microM). NDGA significantly reduced the number of ovulations compared to that in controls. The ovulation rate for the combination of NDGA+indomethacin was also significantly lower than in controls but not different from that in the NDGA-treated group. Steroidogenesis was decreased only in the NDGA+indomethacin perfusions. Ovarian tissue PGE2 and PGF2alpha levels in the NDGA-treated ovaries were significantly suppressed compared to those in controls. Almost a complete block of PGE2 and PGF2alpha was seen in the NDGA+indomethacin group. LTB4 levels in the 10-h-perfused ovarian tissues were significantly decreased by NDGA compared to those in control tissues. Furthermore, LTB4 (3 microg added twice) completely reversed the inhibitory effect of 0.1 microM NDGA on ovulation rate and partially reversed the effect of 10 microM NDGA in the perfusion model. These results demonstrate that the products of the lipoxygenase pathway, especially LTB4, are important in the process of ovulation in this cyclically ovulating species. The interconnected lipoxygenase and cyclooxygenase pathways may optimize ovulation and facilitate steroidogenesis.

Animals↗

PubMed1998

Effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker, on adrenal catecholamine secretion in anesthetized dogs.

We investigated the effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker possessing blocking actions on N-type and L-type voltage-dependent Ca2+ channels (VDCCs), in comparison with the L-type VDCC blocker nifedipine, on adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. Ca2+ channel blockers and cholinergic agonists were infused and injected, respectively, into the adrenal gland through the phrenicoabdominal artery. Cilnidipine (0.3-3 microg/min) inhibited increases in both epinephrine (EPI) and norepinephrine (NE) output induced by SNS (2 Hz), ACh (1.5 microg), and DMPP (0.2 microg). However, cilnidipine inhibited increase in NE output induced by muscarine (1 microg) without affecting increase in EPI output. Nifedipine (0.3-3 microg/min) inhibited the ACh- and DMPP-induced increases in EPI and NE output without affecting the SNS- and muscarine-induced increases in EPI and NE output. From these results, it seems likely that the inhibition by cilnidipine of the SNS-induced EPI and NE secretion and of the muscarine-induced NE secretion is related to its blocking action on N-type VDCCs.

Acetylcholine↗

PubMed1998

Current surgical trends in Japan for managing chronic pancreatitis.

The main aims of surgery for treating chronic pancreatitis are to relieve the patient's persistent pain and to preserve pancreatic functioning. The indications for surgery include treating complications, such as the presence of pancreatic pseudocysts or biliary stenosis associated with chronic pancreatitis or both. A resection, ductal drainage, or both, may commonly be required. Furthermore, some surgeons recommend pancreatic denervation. We analyze the details of 2,936 patients with chronic pancreatitis who were treated surgically and were listed in the 1985 National Statistics in Japan. We have also evaluated the present surgical methods for treating chronic pancreatitis in Japan. In addition, we discuss a new surgical method being used to treat chronic pancreatitis. This is a recently improved technique involving a complete duodenum-preserving resection of the head of the pancreas, which also preserves the biliary and alimentary tracts.

Chronic Disease↗

PubMed1998

Characterization of mRNA expression of IkappaB alpha and NF-kappaB subfamilies in primary adult T-cell leukemia cells.

Tax protein of HTLV-1 activates the transcriptional capacity of the NF-kappaB family, resulting in up-regulation of various genes, which are linked to phenotypic alterations of HTLV-1-infected T cells. To understand NF-kappaB regulation in HTLV-1-infected leukemic cells in vivo, we analyzed expression of NF-kappaB and IkappaB alpha in primary cells isolated from ATL patients. Using competitive polymerase chain reaction, we observed an elevated expression of IkappaB alpha mRNA in all four ATL cases tested. In contrast to the elevated mRNA levels, the levels of IkappaB alpha protein were remarkably reduced in some of these cases, suggesting destabilization of IkappaB alpha protein. On the other hand, mRNA expression of p50/p105 and p65, subfamilies of NF-kappaB, was enhanced in primary cells isolated from some ATL patients. Furthermore, the expression patterns of NF-kappaB subfamily were variable among patients and also different from those in T cells isolated from uninfected individuals. Although the number of cases analyzed was limited, we can conclude from these observations that activation of NF-kappaB is restricted to a few subfamilies in vivo. These findings in vivo are strikingly different from those in HTLV-1-infected T cell lines in vitro, in which Tax is responsible for NF-kappaB activation. It is therefore suggested that the elevation of NF-kappaB expression in leukemic cells of ATL patients might not be supported mainly by the viral protein Tax.

Blotting, Western↗

PubMed1998

Effects of zaprinast on renal nerve stimulation-induced anti-natriuresis in anaesthetized dogs.

1. We examined whether zaprinast, a putative cGMP-specific phosphodiesterase inhibitor, affects neural control of renal function in pentobarbital-anaesthetized dogs. 2. Renal nerve stimulation (1 Hz, 1 ms duration) reduced urine flow rate, urinary Na+ excretion (UNaV) and fractional excretion of Na+ (FENa) with little change in either renal blood flow (RBF) or glomerular filtration rate (GFR). 3. Intrarenal arterial infusion of zaprinast (10 and 100 micrograms/kg per min) increased basal urine flow rate, UNaV and FENa but not RBF or GFR. Zaprinast infusion (100 micrograms/kg per min) also increased renal venous plasma cGMP concentration and urinary cGMP excretion. 4. Renal nerve stimulation-induced reductions in UNaV and FENa were attenuated during zaprinast infusion, whereas the reduction in urine flow rate was resistant to zaprinast. 5. Renal nerve stimulation increased the renal venous plasma noradrenaline concentration and renal noradrenaline efflux, which remained unaffected during infusion of zaprinast (100 micrograms/kg per min). 6. The results of the present study suggest that zaprinast induces natriuresis and counteracts adrenergically induced antinatriuresis by acting on renal tubular sites in the dog kidney in vivo.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats.

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.

Animals↗

PubMed1998

Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle.

BACKGROUND: Temiverine (p-INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC-36, on isolated human bladder. METHODS: Effects of temiverine and RCC-36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric field stimulation were evaluated using the muscle-bath technique, and compared with the effects of atropine and oxybutynin. RESULTS: Atropine (10(-9) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of the concentration-response curves to acetylcholine stimulation. The rank order of pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)-induced contractile responses. Rank order of maximum inhibition was RCC-36 = temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent inhibition of electric field-induced contraction with or without 10(-6) mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were significantly greater than that of oxybutynin. CONCLUSION: Atropine, oxybutynin, temiverine, and RCC-36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the atropine-resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.

Acetylcholine↗

PubMed1998

Leukocytapheresis therapy by extracorporeal circulation using a leukocyte removal filter.

Leukocytapheresis therapy has been used to try to treat such intractable diseases as autoimmune and neurologic diseases, achieving good results. However, a number of problems have been identified in leukocyte removal by thoracic duct drainage or continuous centrifugal separation; namely the high risk, expensive cost, and complicated operation. Asahi Medical Co. has developed an innovative solution for such conventional problems. Its new leukocyte removal filter (Cellsorba) is capable of removing white blood cells by perfusion of whole blood by means of simple extracorporeal circulation. Leukocytapheresis therapy using the Cellsorba column is being confirmed as extremely effective for many inflammatory diseases, as well as in autoimmune and neurologic diseases. This paper outlines information about the Cellsorba column and introduces several reports on therapeutic results.

Autoimmune Diseases↗

PubMed1998

A new device for selective removal of CD4+ T cells.

To control antigen (Ag)-specific immune cells is important in the treatment of autoimmune diseases. In particular, a direct solution may be obtained by controlling the CD4+ cell function that controls the immune response of autoimmune T cells. Thus, a technique to selectively remove CD4+ cells has been developed, based on the consideration that the immune system may possibly be modified by selectively removing the CD4+ cells by means of extracorporeal circulation. The currently developed device to selectively remove CD4+ cells uses a material made of nonwoven fabric with monoclonal antibodies immobilized on the surface. With this device, removal of only CD4+ cells from human mononuclear cells suspension can be accomplished. Moreover, CD4+ cells can be specifically removed from peripheral whole blood by direct perfusion. This review outlines a series of procedures for selective cell removal and the results of our research.

Animals↗

PubMed1998

Immusorba TR and Immusorba PH: basics of design and features of functions.

Immusorba was reported by Yamazaki et al. to be the world's first practical immunoadsorbent in 1982. Since then, this immunoadsorbent has accumulated an abundance of clinical achievements. Immusorba has such unique functions that it is used in treating various diseases and holds possibilities for application to more diseases. Immusorba was designed as an artificial receptor for rheumatoid factor (RF) based on structural analysis of heat-denaturated globulin. Subsequently, new substances that it can adsorb have been found as seen in reports on the adsorption performance of Immusorba to anti-acetylcholine receptor antibodies (anti-AChR Abs) and antiganglioside antibodies. Along with this, Immusorba has been used in treating a wide range of diseases. The greatest characteristic of Immusorba is that its adsorption capability is selective rather than specific, making it effective against a great number of diseases.

Acetylcholine↗