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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 451 records · Page 25Linked to original sources
PubMed1994

Development of glycosylated human interleukin-1 alpha, neoglyco IL-1 alpha, coupled with D-mannose dimer: synthesis and biological activities in vitro.

Interleukin 1 (IL-1) is a nonglycosylated cytokine with pleiotropic effects on various cell types. In order to investigate the effect of carbohydrate introduction on IL-1 activity and to develop IL-1 with less deleterious effects recombinant human IL-1 alpha was chemically coupled with mannose dimers, alpha-D-Man1-6-D-Man[Man2(alpha 1,6)] and alpha-D-Man1-4-D-Man[Man2(alpha 1,4)]. About 5 molecules of mannose dimers were introduced per molecule of IL-1. Anti-IL-1 alpha antibody reacted only weakly with the glycosylated IL-1s. Conversely, antibody against the mannose dimer reacted with only glycosylated IL-1. The effect of glycosylation on IL-1 activity was evaluated by measuring a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on melanoma cells, stimulatory effect on IL-6 synthesis by melanoma cells, and stimulatory effect on prostaglandin E2 synthesis by fibroblast cells. Glycosylated IL-1s exhibited reduced activities, which were 10-fold to more than several hundred-fold lower than those of the original IL-1 alpha depending upon different aspects of activities addressed. Man2(alpha 1,6)-introduced IL-1 exhibited lower activity than Man2(alpha 1,4)-introduced IL-1. The competitive binding of 125I-IL-1 alpha to mouse T cells with unlabeled IL-1s suggests that the reduced activity of glycosylated IL-1s is due, at least partially, to the decrease of their receptor binding abilities.

Animals↗
PubMed1994

Protective effect of the calcium antagonist NKY-722 against renal and arterial injuries in Dahl salt-sensitive rats.

OBJECTIVE: To study the effect of long-term administration of NKY-722 and nicardipine on renal dysfunction and morphological changes in the kidneys and arteries in Dahl salt-sensitive (Dahl-S) rats. DESIGN: Vehicle, NKY-722 and nicardipine were administered orally to Dahl-S rats fed a high-salt diet for 6 weeks. METHODS: Systolic blood pressure was measured once a week. At the last week blood and urine were collected and an autopsy was carried out. RESULTS: NKY-722 (1 mg/kg per day) lowered blood pressure reproducibly for 6 weeks, whereas nicardipine (3 mg/kg per day) showed a similar effect at week 1 only. NKY-722 tended to decrease blood urea-nitrogen, and reduced plasma creatinine and renin activity significantly. NKY-722 increased urine volume, urinary sodium, creatinine and protein excretions, but did not affect urinary N-acetyl-beta-D-glucosaminidase activity significantly. NKY-722 increased the glomerular filtration rate and reduced glomerulosclerosis and renal arterial injury morphologically. Nicardipine did not affect blood or urinary parameters, but reduced glomerular injury significantly. NKY-722 but not nicardipine reduced cerebral arterial injury. A lower dose of NKY-722 (0.3 mg/kg per day) did not affect blood pressure, blood or urinary parameters, but reduced glomerulosclerosis and renal arterial injury significantly. NKY-722 (1 mg/kg per day) and nicardipine (3 mg/kg per day) increased urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and PGE2. NKY-722 but not nicardipine increased the 6-keto-PGF1 alpha:thromboxane B2 ratio in the thoracic aorta. CONCLUSIONS: NKY-722 improved the renal dysfunction, and reduced glomerular, renal and cerebral arterial injuries in Dahl-S rats. The effect of NKY-722 on glomerulosclerosis and arterial injuries is, at least partly, independent of blood pressure, and is probably related to the effect on eicosanoid metabolism.

Animals↗
PubMed1994

[Clinical analysis of MRSA pneumonia. Niigata Research Group of MRSA.ABK].

Aged or immuno-compromised patients were mostly affected, by pneumonia caused by infection of MRSA, and more than half of the cases were superinfected with glucose-nonfermentative Gram-negative rods including Pseudomonas aeruginosa. These patients were treated with a monotherapy of arbekacin (ABK) by intravenous drip administration or with a combination of ABK and imipenem/cilastatin, ceftazidime or antifungals. The clinical efficiencies were 55.6% in 11 monotherapy cases and 83.3% in combined therapy. MRSA was eradicated in 31.9% of the patients. These results are comparable with, or superior to the vancomycin therapy in the treatment of MRSA pneumonia. When MRSA is isolated from sputum of pneumonia patients, the discrimination between colonization and infection is important, but the diagnosis is very difficult in many clinical cases before the initiation of chemotherapy. The number of bacteria and the grade of inflammation should be carefully scored before starting a chemotherapy.

Aged↗
PubMed1994

Cocaine abuse in Japan.

During the past several years, Japan has seen an emergence of cocaine abuse. Although there were only 43 cocaine-related arrests in 1988, the number in 1989 jumped to 96-more than double the previous year. In 1991, the number increased to 122. National Police Agency data shows that about 50% of methamphetamine (MAP) violators had been arrested for drug use. In comparison, only about 5% of cocaine arrests were for drug use, whereas about 50% were for possession, a pattern more similar to that of marijuana violators than MAP violators. More violators were in their 20's for cocaine and marijuana violations than for MAP violations. The percentage of foreigners involved was about 27% for cocaine and about 10% for marijuana, figures greater than the percentage for MAP (about 4%). The first cocaine patients to emerge were the two reported in a 1989 nationwide psychiatric hospital survey. This came two years after the first reporting of marijuana patients. In a similar 1991 survey, two more cocaine patients were reported. Three of the four cocaine patients had abused marijuana prior to abusing cocaine. Marijuana patients and MAP patients have the following demographic differences: about 57% of marijuana patients but only about 4% of MAP patients had enrolled in junior colleges, colleges or universities; and about 71% of marijuana patients but only about 5% of MAP patients were from high income families. Only about 14% of marijuana patients but about 74% of MAP patients had previously been apprehended. These patterns suggest that, demographically, cocaine abusers in Japan are more similar to marijuana abusers than MAP abusers.

Adult↗
PubMed1993

Two functionally different domains of rabphilin-3A, Rab3A p25/smg p25A-binding and phospholipid- and Ca(2+)-binding domains.

Rabphilin-3A is a putative target molecule for rab3A p25/smg p25A, which is a member of a ras p21-related small GTP-binding protein and implicated in neurotransmitter release from the synapse. Rabphilin-3A has two copies of an internal repeat that are homologous to the C2 domains of protein kinase C, synaptotagmin, and phospholipase A2, which are known to bind to phospholipid in a Ca(2+)-dependent manner. In the current study, we have investigated the functional domains or rabphilin-3A by use of three recombinant proteins as follows: full rabphilin-3A (1-704 amino acids), an N-terminal fragment (1-280 amino acids), and a C-terminal fragment containing the C2 domains (281-704 amino acids). Both rabphilin-3A and the C-terminal fragment bound to phospholipid in the presence of Ca2+, but the N-terminal fragment did not bind to phospholipid. 45Ca2+ bound to rabphilin-3A and the C-terminal fragment only in the presence of phospholipid but did not bind to the N-terminal fragment. The GTP gamma S-bound form of rab3A p25 bound to both rabphilin-3A and the N-terminal fragment but did not bind to the C-terminal fragment. These results indicate that rabphilin-3A has at least two functionally different domains, the N-terminal rab3A p25-binding and C-terminal phospholipid- and Ca(2+)-binding domains.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Expression of non-hepatic-type S-adenosylmethionine synthetase isozyme in rat hepatomas induced by 3'-methyl-4-dimethylaminoazobenzene.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, non-hepatic-type and liver-type enzymes, which are the products of two different genes. We have examined the expression of two AdoMet synthetase isozyme proteins and mRNAs in rat hepatomas induced by 3'-Me-DAB. The levels of non-hepatic-type enzyme protein and mRNA are clearly induced by 3'-Me-DAB feeding. On the other hand, the levels of liver-type enzyme protein and mRNA are nearly the same or slightly decreased during hepatocarcinogenesis. These results indicate that the expression of the non-hepatic-type isozyme gene is obviously influenced with the progression of carcinogenesis and that the non-hepatic-type isozyme is useful as a oncodevelopmental marker in the liver.

Amino Acid Sequence↗
PubMed1993

Intrahepatic cholangiocarcinoma with sarcomatous change. Clinicopathologic and immunohistochemical evaluation of seven cases.

BACKGROUND: Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure. METHODS: Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin-biotin-peroxidase complex method were performed on these cases. RESULTS: The tumor showed both mucin-producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease-free for 3 years after surgery. CONCLUSIONS: These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Adenocarcinoma, Mucinous↗
PubMed1993

Effects of tracheostomy on electrically induced vocalization in decerebrate cats.

Electrical stimulation delivered to the rostral pons induced well coordinated activity of the intralaryngeal muscles and the ventilatory muscles for vocalization in unanesthetized, decerebrate cats. The stimulation reset the normal respiratory rhythm and induced vocalization with a newly developed rhythm. Continuous opening of the tracheostomy decreased the breathing cycle during induced vocalization. Opening of the prepared tracheostomy during vocalization caused a sudden decrease in the subglottic pressure, but the expiration phase was not abruptly terminated. These findings suggested that vagal feedback from pulmonary stretch receptors plays a more significant role in the maintenance of the breathing cycle during electrically induced vocalization than the laryngeal feedback from the laryngeal mucosa.

Animals↗
PubMed1993

Phorbol ester stimulates the activity of a protein tyrosine phosphatase containing SH2 domains (PTP1C) in HL-60 leukemia cells by increasing gene expression.

The affinity-purified antibody to a protein tyrosine phosphatase (PTP) containing two src homology 2 domains (PTP1C) was generated. The antibody recognized two types of PTP1C (PTP1C-alpha and -beta) of which the molecular sizes were 66 (alpha) and 62 kDa (beta), respectively, and these two types were expressed differentially in various cell types. The immune complex phosphatase assay using the antibody demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) and a vitamin D metabolite increased the PTP activity of immunoprecipitated PTP1C to 230 and 150% of control, respectively. By contrast, neither dimethyl sulfoxide nor retinoic acid significantly affected the PTP activity of PTP1C in HL-60 cells. The time course increment by TPA of PTP1C activity was closely correlated with that of the acquisition by HL-60 cells of a macrophage-like phenotype. In addition, TPA increased the amount of PTP1C detected by immunoblotting and immunoprecipitation and raised the level of expression of PTP1C mRNA in HL-60 cells. The increase of PTP1C mRNA induced by TPA treatment was inhibited by cycloheximide, suggesting that new protein synthesis is required for the increase by TPA of PTP1C mRNA expression. Furthermore, TPA increased the rate of transcription of the PTP1C gene without affecting the stability of PTP1C mRNA. These results suggest that (i) two subtypes of PTP1C may exist and function in various cell types, and (ii) TPA stimulates the PTP activity of PTP1C by increasing the transcription rate of PTP1C gene expression. The possible role of PTP1C in the macrophage differentiation will be also discussed.

Base Sequence↗
PubMed1993

Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig.

The mediators of photochemically induced thrombosis in the femoral artery of guinea pig were investigated. The femoral artery was occluded by a thrombus about 7 min after the initiation of photochemical reaction between rose bengal and green light. Pretreatment with a specific thromboxane (TX) A2 receptor antagonist, vapiprost, a platelet-activating factor (PAF) antagonist, WEB-2086, and ADP-induced platelet aggregation inhibitor, ticlopidine, prolonged the time to occlusion. Within the range of doses used, platelet aggregation in whole blood, which was induced by U-46619, PAF and ADP ex vivo, was inhibited by vapiprost, WEB-2086 and ticlopidine, respectively. In contrast, argatroban, a thrombin inhibitor, had no effect on the time to occlusion, although the dose of argatroban was sufficient to delay the prothrombin time and the activated partial thromboplastin time and to inhibit thrombin-induced platelet aggregation ex vivo. These results suggest that TXA2, PAF and ADP are involved in photochemically induced thrombosis of the guinea pig femoral artery, although the coagulation cascade does not play an important role.

Adenosine Diphosphate↗
PubMed1993

Fate of odontoblasts and blood capillaries in the incisal region of the rat incisor pulp.

Transmission electron microscopy of thin sections of the rat incisor pulp revealed that in the middle region of the incisor there were fenestrated capillaries in the "predentinal plexus" and that this region contained the tallest odontoblasts. The odontoblasts gradually became shortened in the incisal part of this region; the fenestrated capillaries in the predentinal plexus changed to continuous type capillaries. Almost all the odontoblasts had degenerated near the incisal end of the tooth. The predentinal plexus disappeared in this region, but the "subodontoblastic capillary plexus" persisted. In a specific region just beneath the worn incisal end, numerous macrophages and polymorphonuclear neutrophils appeared and scavenged the degenerating cells, possibly including the odontoblasts.

Animals↗
PubMed1993

1-(Tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur) determined in rat hair as an index of drug exposure.

The fluorescence derivatization of 1-(tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur, FT) with 4-bromomethyl-6,7-dimethoxycoumarin (BrMdmc) with 18-crown-6 as catalyst was utilized for a sensitive and selective liquid chromatographic method to determine the concentration of FT in hair. Hair samples collected from rats, which had received FT intraperitoneally for 1 to 4 weeks, were dissolved in 1 M NaOH by heating at 80 degrees C for 30 min. A three-step extraction procedure for FT in the dissolved hair was used before and after the derivatization of FT with BrMdmc. The detection limit achieved was < 0.16 ng/mg hair. A dose-dependent accumulation of FT was evident in the rat hair (r = 0.914, p < 0.001): 0.24 +/- 0.07, 1.35 +/- 0.39, and 2.85 +/- 0.74 ng/mg hair (mean +/- SD, n = 4-5) at the doses of 5, 15, and 50 mg/kg/day for 4 weeks, respectively. In the rats that had received the highest dose of FT, the accumulation of FT in the hair depended also on the duration of FT administration: 0.82 +/- 0.33 (1 week), 1.52 +/- 0.38 (2 weeks), and 2.85 +/- 0.74 (4 weeks) ng/mg hair (n = 4-5). These findings suggest that the analysis of an oral antineoplasmic FT in the hair may be useful for assessing the degree of exposure to the drug.

Animals↗
PubMed1993

Changes in plasma and urinary 11-dehydrothromboxane B2 in healthy subjects produced by oral CS-518, a novel thromboxane synthase inhibitor.

When 50 mg CS-518, a novel thromboxane (TX) A2 synthase inhibitor, was orally administered to healthy male volunteers, the plasma concentration of CS-518 peaked after 0.5 h and then decreased with a half-life of 0.44 h. There was no significant change in the plasma concentration of circulating TXB2, whereas that of circulating 11-dehydrothromboxane B2 (11-dhTXB2), an enzymatic metabolite of TXB2, was significantly decreased from 0.5 h to 24 h after administration; the maximal decrease to about 25% of the pre-dose value was found at 6 h. After CS-518 100 mg b.d. for 4.5 days, plasma 11-dhTXB2 was suppressed to the same extent as after the single dose of 50 mg from 6 h after the initial dose throughout the administration period. The urinary excretion of 11-dhTXB2 corrected for the creatinine level was significantly decreased by 70-84% throughout the treatment. These results suggest that CS-518 causes long-lasting inhibition of TXA2 synthase despite its rapid elimination from plasma, and that circulating 11-dhTXB2 in plasma and its urinary excretion can serve as a quantitative index of TXA2 synthase inhibition in vivo by CS-518.

Administration, Oral↗
PubMed1993

Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5'-deoxy-5-fluorouridine.

The present study shows that various cytokines such as tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interferon-gamma (IFN gamma) make tumor cells much more susceptible to the cytostatic 5'-deoxy-5-fluorouridine (5'-dFUrd) than to 5-fluorouracil (5-FUra) and other cytostatics. These three cytokines increased the susceptibility of human cancer cell lines (COLO201, MKN45 and WiDr) but did not affect that of normal fibroblast WI38 cells. The cytokine mixture induced a 50-fold increase in the susceptibility of COLO201 to 5'-dFUrd, whereas a 12-fold increase and a less than 5-fold enhancement in the susceptibility to 5-FUra and other cytostatics, respectively, were observed. The increased susceptibility would be a result of the induction of thymidine phosphorylase (TdR Pase), which is the essential enzyme for the conversion of 5'-dFUrd to 5-FUra. The cytokine mixture increased TdR Pase activity by up to 47 times and greatly induced its mRNA expression in the cancer cell lines. These results suggest that the therapeutic benefit of 5'-dFUrd would be improved by its use in combination with the cytokines.

Antineoplastic Agents↗
PubMed1993

Idiopathic chronic calcifying pancreatitis with diabetes mellitus. Analysis of pancreatic stone protein gene.

We present a case of a 27-year-old female suffering from chronic calcifying pancreatitis with diabetes mellitus. Radiographic examinations and exocrine pancreatic function tests revealed considerable dilatation of pancreatic ducts with large intraductal calculi and exocrine pancreatic insufficiency, respectively. Recent literature indicates that a decrease in the activity of pancreatic stone protein (PSP), which inhibits CaCO3 crystal formation in pancreatic juice, is closely related to the development of chronic calcifying pancreatitis. The patient had no apparent cause or family history of pancreatitis. We therefore investigated the possibility that alterations in the PSP gene might explain the chronic pancreatitis seen in this patient. Six exons of the PSP gene amplified by polymerase chain reaction were directly sequenced, but there was no apparent base mutation observed. Furthermore, Southern blot analysis revealed neither rearrangement nor deletion of the PSP gene in the genomic DNA of this case. However, this genetic approach will be useful for future study of the etiology of hereditary pancreatitis.

Adult↗
PubMed1993

PGE2 protects isolated cells against injury through multiple mechanisms.

In order to clarify how PGE2 regulates gastric mucosal integrity, we examined the effects of PGE2 on ethanol-caused injury of isolated gastric chief cells, cultured gastric mucous cells from guinea pigs and Balb/c 3T3 fibroblasts. Pretreatment of these cells with PGE2 reduced ethanol-caused injury of the cells. Furthermore, pretreatment of gastric mucous cells with indomethacin enhanced ethanol-caused injury, suggesting that endogenous PGE2 may be involved in the cell protection. PGE2 stimulated an increase in diacylglycerol (DG) accumulation in chief cells and treatment of chief cells with synthetic DG reduced the injury of the cells. However, DG accumulation was not observed in gastric mucous cells treated with PGE2. Therefore PGE2 may protect the cells from injury through a variety of mechanisms. In addition, PGE2 enhanced the survival of the quiescent fibroblasts cultured in the absence of serum, while PGE2 had no survival enhancing effect on gastric mucous cells. These results suggest that the mechanism by which PGE2 preserves the cell viability may depend on not only cell types used but also how the cells are injured.

Animals↗
PubMed1993

Activities of the intralaryngeal muscles during electrically induced vocalization in decerebrate cats.

Electromyograms were recorded from the intralaryngeal muscles (the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles) and the ventilatory muscles (the diaphragm (DA) and abdominal (RA) muscle) during electrically induced vocalization in precollicular postmammillary decerebrate cats. Electrical stimulation (rectangular pulses, 0.2 ms, 10-60 microA, 100 Hz, lasting 5-10 s) delivered to the rostral pons (Horsley-Clarke coordinates, A 1.0 to P 2.0, L or R 3.0 to 5.0, H -4.5 to -6.0) induced alternate inspiration and vocalization. The normal respiratory rhythm was reset to a new one and the intralaryngeal and ventilatory muscles were coordinately activated to produce vocalization. During the period of the electrical stimulation, preceding activity of PCA to DA and postinspiratory activity of DA, which were normally observed during quiet breathing, disappeared. These results suggested that the tonic electrical stimulation delivered to the rostral pons acted as a command signal to alter teh pattern generation of the ventilatory and laryngeal systems from quiet breathing to vocalization.

Animals↗