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Biomedical subjects

T Kawaguchi

Publications and source records attributed to T Kawaguchi.

At least 361 records · Page 20Linked to original sources

[Alteration of endothelin-1 receptor in the choroid plexus of rats with kaolin-induced experimental hydrocephalus].

Specific binding sites for endothelin-1 (ET-1) in the choroid plexus of rats with kaolin-induced hydrocephalus were analyzed using quantitative receptor autoradiographic technique with 125I-ET-1. Unlabeled ET-1 and its natural analog ET-3 inhibited the binding of 125I-ET-1 to the choroid plexus of control rats with similar high potencies. However, possibly related substances, such as ion channel regulators (omega-conotoxin GVIA, nitrendipine, verapamil, diltiazem, alpha-bungatmtoxin, aconitine, apamin), ouabain and atrial natriuretic peptide did not affect the binding. Scatchard analysis revealed the presence of a single class and high affinity binding sites for ET-1 in the choroid plexus. The number of 125I-ET-1 binding sites in the choroid plexus of rats with kaolininduced hydrocephalus was significantly lower, when compared with those in the age-matched control rats; maximum number of binding sites (Bmax) was 16.3 +/- 0.6 and 36.2 +/- 2.5 fmol/mg, respectively (p less than 0.01, n = 5). There was no significant difference in the binding affinities; affinity constants (Ka) was 2.6 +/- 0.3 x 10(9) M in control rats and 3.5 +/- 0.5 x 10(9) in hydrocephalic rats (n = 5). These results suggest that ET receptors may play a role in the regulation of cerebrospinal fluid production.

Animals↗

Dermatomyositis and pregnancy. Case report and review of the literature.

Dermatomyositis is a rare disease complicating pregnancy. We treated a patient in whom two pregnancies were complicated by dermatomyositis. In the first of the two gestations, a mild form of the disease arose in the last trimester. In the second gestation, the disease was inactive following treatment with 0.3 mg/kg/day prednisolone. Both the mother and two children have since been doing well.

Adult↗

Xeroderma pigmentosum patients belonging to complementation group F and efficient liquid-holding recovery of ultraviolet damage.

A 73-year-old woman with xeroderma pigmentosum (XP), XP107TO, was assigned to complementation group F. The fibroblast of this patient showed a reduced level (19%) of unscheduled DNA synthesis (UDS) compared with normal cells. XP107TO cells were 2.3 times more hypersensitive to ultraviolet C (UVC) than normal cells and in the same range of other XPF cells. A clinical case report of 2 patients belonging to XP group F is also described; together with these clinical findings, the characteristics of XP group F are discussed. These patients manifested mild clinical symptoms, developing skin cancer in later age, although acute sun sensitivity was observed in early age (usually a few months after birth). Fibroblasts derived from these patients showed a substantially reduced level of UDS, considering its mild clinical features. To analyze the discrepancy of low UDS level and late onset of skin cancer in XPF cells, we examined the UV sensitivity under density-inhibited condition using XPF cells. XP cells belonging to complementation group F showed marked enhancement of UV survival when they were held in a density-inhibited condition for 1-4 d after UV irradiation. The enhancement was also observed in normal and XP group A cells, but the recovery in these cell lines was less than that in XP group F cells. XP group F cells have been shown to possess slow and long-lasting excision repair capacity and this type of repair might be stimulated by holding through time of the repair process within one cell cycle.

Adult↗

[Efficacy and some complications of programmable pressure valve].

Twenty-five patients with hydrocephalus were treated using Sophy programmable pressure valve. The valve pressure is adjustable percutaneously with a magnet. This valve was very useful for management cases presenting overdrainage and high-risk cases of shunt dysfunction such as aqueductal stenosis and idiopathic normal pressure hydrocephalus. It was also useful for hydrocephalus after subarachnoid hemorrhage because it was difficult to know the most adequate pressure before the shunt operation. Two patients developed acute subdural hematoma of arterial origin after the shunt operation. The causative factor appeared to be low intracranial pressure and rupture of small arterial branches. This complication may be more frequent in cases using this system than in cases using other systems. We must pay attention to this complication and it is necessary to improve the shunt system. One bed-ridden patient developed necrosis of the skin because of this valve, and it had to be removed. We should place this valve so that it is at the anterior of the chest.

Acute Disease↗

[Altered metabolism of membrane glycosphingolipids in erythrocytes of paroxysmal nocturnal hemoglobinuria].

Paroxysmal nocturnal hemoglobinuria (PNH) is currently accepted to be a stem-cell disorder of a clonal nature with increased susceptibility to autologous complement attack. Consequent hemolytic feature has been partly explained by lack of complement regulatory membrane proteins such as decay-accelerating factor (DAF) or C8-binding protein that anchored to membrane via glycosyl-phosphatidyl inositol (GPI) lipids. Recent reports suggest essential PNH lesion is the synthetic defect of sugar moiety of the PI-anchor. In PNH, the abnormal expression of C3b/C4b receptor (CRI) glycoproteins, or glycophorin-alpha have been also pointed out. These altered expression of glycoproteins and glyceroglycolipids, especially in the carbohydrate structures, prompted us to analyze biochemically the membrane glycosphingolipids as one of major glycoconjugates in PNH. As results, PNH erythrocytes showed altered metabolism of gangliosides in comparison to control erythrocytes from healthy donors. IV6 NeuAc-nLc4 Cer and highly polar gangliosides variably disappeared in PNH erythrocytes, partly due to impaired sialylation of glycolipids. These results suggest metabolic disorder of carbohydrates of membrane glycoconjugates as a new aspect of PNH.

Adult↗

[Factors relating to postoperative infections in cancer patients].

Some factors relating to the increasing prevalence of postoperative infections after gastroenterological surgery were investigated from the standpoint of both patients profile and isolated bacteria. Data were collected from 542 cancer patients comprising 39 with esophagus cancer, 229 with gastric cancer, 149 with hepato-biliary tract and pancreatic cancer and 125 with colon cancer. Respiratory infections after operations were most frequently caused by aging, disturbance of glucose tolerance and respiratory dysfunction, whereas with intraabdominal abscess the major factors were disturbance of glucose tolerance, hepatic dysfunction and respiratory dysfunction in this order. Two factors in the management of patients during operation were singled out as mainly contributing to infection: these were prolonged operative time as in the case of esophagus cancer or hepato-biliary tract and pancreatic cancer, and massive intraoperative bleeding as in hepato-biliary tract, pancreatic and gastric cancer. As isolated bacteria, the most frequent clinical isolates were MRSA, Enterococcus, P. aeruginosa and Enterobacter, and it is noteworthy that all of these were strongly resistant to all antimicrobial agents. The greater emphasis on prevention control of postoperative infections, therefore, should be focussed on aging, preoperative risk factors, surgical stress and the kinds of antimicrobial agents administered.

Bacterial Infections↗

[A case of bilateral multiple pulmonary arteriovenous fistula treated by the right fistula plication and resection of the left lingual lobe with use of microwave tissue coagulator (MTC)].

A 53-year-old man with the history of brain abscess and multiple cerebral arterio-venous malformations underwent the staged operation for bilateral multiple pulmonary arterio-venous fistulas (PAVF). Right fistula plication and the resection of the left lingular lobe using MTC were performed through posterolateral thoracotomy. Postoperatively, the patient showed the right residual fistula, but, he has been doing well without PAVF complications such as polycythemia and hypoxemia. In conclusion, 1) PAVF with central nervous system complications should be treated aggressively either by surgery or by embolization. 2) MTC was useful for the resection of the lung because of no air leak and bleeding coming from the resected section.

Arteriovenous Fistula↗

[Serum deoxythymidine kinase activity in adult T-cell leukemia].

Serum deoxythymidine kinase activities (s-TK) of the patients with adult T-cell leukemia (ATL), carriers and healthy persons were measured, using a recently developed TK assay with 125I-iodo-deoxyuridine as a substrate. The mean s-TK values were 3.3 +/- 2.7 U/l (n = 21) in normal subjects (HTLV-1(-)), 4.7 +/- 5.0 U/l (n = 35) in carriers, 9.8 U/l (n = 3) in smoldering ATL and 26.7 U/l (n = 6) in chronic ATL. In the patients with acute ATL, the mean s-TK values before and after chemotherapy were 80.9 U/l (n = 2) and 11.6 U/l (n = 4), respectively. In the follow-up studies of the patients with acute ATL, the changes of s-TK levels revealed earlier than those of serum LDH levels. It is suggested that s-TK activity is more useful than LDH as a parameter of monitoring treatment in ATL.

Biomarkers, Tumor↗

Stimulation of Mn-superoxide dismutase expression by tumor necrosis factor-alpha: quantitative determination of Mn-SOD protein levels in TNF-resistant and sensitive cells by ELISA.

Marked increase in protein levels of Mn-superoxide dismutase (Mn-SOD) was found in TNF-resistant cell lines after treatment with Tumor Necrosis Factor (TNF). No such increase was observed in Cu,Zn-superoxide dismutase (Cu, Zn-SOD) protein in either TNF-resistant or sensitive cells. These results support the data that the Mn-SOD is one of the rescue proteins required for resistance to TNF cytotoxicity in these cell lines (Wong et al., Cell 58, 923-931, 1990). Mn-SOD was also responsive to TNF stimulation in KURAMOCHI, a human ovarian adenocarcinoma cell line. This may explain our previous result that Mn-SOD protein is highly expressed in epithelial ovarian cancer (Ishikawa et al. Cancer Res. 50, 2538-2542, 1990).

Adenocarcinoma↗

A heteromeric transcription factor required for mammalian RNA polymerase II.

A general transcription factor, FC, essential for specific initiation of in vitro transcription by mammalian RNA polymerase II was identified and a procedure developed to purify it to near homogeneity from HeLa cell nuclei. Purified FC is composed of two polypeptides of apparent molecular masses 80 kDa and 30 kDa, on SDS-PAGE, and has a native size of 280 kDa estimated by gel filtration column. Both polypeptides were shown to be essential for reconstituting in vitro transcription activity. Biochemical analysis showed that the 80 kDa and 30 kDa components were present in a 1:1 molar ratio. FC was also demonstrated to interact directly or indirectly with purified RNA polymerase II. Similarities between FC and transcription factors reported by others from human, rat or Drosophila cells are discussed.

Chromatography, High Pressure Liquid↗

Side-to-side choledochoduodenostomy: a reappraisal based on a study of 70 patients.

We experienced a total of 70 side-to-side choledochoduodenostomy cases and 80% of them were indicated for gallstone disease patients. There were no early postoperative complications, but intrahepatic gallstones developed in 2 cases. The size of the stoma and the width of the common duct were reduced about 30% within 3 postoperative months. Although clinical cholangitis did not occur in the presence of an adequate stoma, histological cholangitis was constantly seen throughout 10-year-follow-up period. Strictness of operative indications, and periodical and long term follow-up study of postoperative patients are mandatory to obtain better clinical results.

Bile Ducts, Intrahepatic↗

Serum-manganese-superoxide dismutase: normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by an enzyme-linked immunosorbent assay using a monoclonal antibody.

An enzyme-linked immunosorbent assay (ELISA) has been developed for human manganese-superoxide dismutase (Mn-SOD), using a specific monoclonal antibody raised against the purified enzyme. The Mn-SOD molecule comprises four identical sub-units and this permitted the development of a symmetrical assay, using the same monoclonal antibody as both capture and detector. The assay offers a specific, sensitive and convenient means of measuring immunoreactive Mn-SOD in human sera. Under optimum conditions, the sensitivity of the assay permits the detection of 2-200 ng of purified Mn-SOD from human liver. The mean serum Mn-SOD levels of normal healthy males and females were 99.8 +/- 24.8 (mean +/- SD) and 88.8 +/- 20.8 (mean +/- SD), respectively. A high level of the enzyme was found in the sera of patients with acute myocardial infarction as well as malignant diseases such as acute myeloid leukemia, primary hepatoma and gastric cancer. This is the first report of an ELISA using a monoclonal antibody specific for a distinct epitope of Mn-SOD.

Adult↗

Ester prodrugs of zidovudine.

Ten novel ester prodrugs of zidovudine (azidothymidine; AZT) were synthesized with aliphatic acids (acetic-stearic), and the enzymatic regeneration of AZT from the prodrugs was investigated both in vitro and in vivo. The enzymatic hydrolysis rates of the AZT esters in the presence of mouse enzyme systems (plasma, liver, and intestine, and kidney) were highly dependent on the lengths of the acyl chains of the prodrugs. The caprate or caprylate of AZT showed the highest reactivity to three of the four enzyme systems; either the decrease or the increase in the acyl chain length resulted in the decrease of the reactivity to the enzymes. Zidovudine (AZT) and three of the prodrugs (acetate, caprate, and stearate) were administered to mice intraperitoneally, and the plasma concentrations of AZT and a corresponding prodrug were measured. The AZT concentrations in plasma following the acetate administration rapidly decreased with a half-life of 14.5 min. This tendency is similar to that shown in direct AZT administration. On the other hand, the concentrations following the caprate or stearate administration decreased slowly and were maintained for as long as 4 h after dosing. The prodrug concentrations in plasma after the prodrug administration were under the detection limit (0.01 micrograms/mL), except for acetate. The absence of the caprate and stearate in plasma may be attributed to the high hydrophobicity or favorable tissue distribution of the ester derivatives.

Animals↗

Controlled release of 3',5'-diester prodrugs of 5-fluoro-2'-deoxyuridine from poly-L-lactic acid microspheres.

Poly-L-lactic acid (MW 6000) microspheres (PLA-MS) containing 5-fluoro-2'-deoxyuridine (FUdR) or four ester prodrugs of FUdR were prepared and examined with regard to the in vitro release kinetics. The incorporation efficiency of the lipophilic prodrugs into the PLA-MS was higher than that of FUdR or the hydrophilic prodrugs. The release of the lipophilic FUdR prodrugs from PLA-MS was sustained as compared with that of FUdR from PLA-MS. The release kinetics of the FUdR prodrugs appears to fit the Higuchi, Baker, and Lonsdale model in the early stage of the release process. The slope of the Baker and Lonsdale plots of the release of divaleryl-FUdR from PLA-MS decreased as the initial drug loading was decreased. The order of the release rates of FUdR prodrugs from PLA-MS with the same prodrug content was similar to that of the water solubilities of the prodrugs. These results suggest that the ester prodrugs could be released from PLA-MS by diffusion through water-filled capillaries or a series of pores rather than by diffusion through the PLA matrix.

Chemical Phenomena↗

Flunarizine treatment in poor-grade aneurysm patients.

A cerebral Ca2+ overload blocker--flunarizine hydrochloride--was used with excellent results for prophylaxis of delayed ischaemic neurological deficit (DIND) in severe subarachnoid haemorrhage. The drug was administered orally at a dose of 10 mg, four times daily for four days, followed by three times daily for three days and twice daily for 14 more days. Of 72 patients treated with flunarizine, only one developed permanent DIND. 37 consecutive patients who were in Fisher's group III and were treated with flunarizine from immediately after early surgery were compared retrospectively with the 37 consecutive Control Group patients, who also belong to Fisher's group III. Among the Control Group patients, eight died from DIND and ten developed infarction from DIND, while flunarizine strongly prevented (p less than 0.001) DIND. Furthermore, the only one DIND was attributable to failure of administration of flunarizine. There were no side-effects from flunarizine. The association of severe angiographic vasospasm was less frequent in the Flunarizine Group (18% vs 57%, p less than 0.02). From this evidence, it might be concluded that flunarizine significantly inhibits the occurrence of severe neurological deficit due to delayed vasospasm. This highly beneficial effect on severe delayed vasospasm might be attributable to its intense inhibitory action on intracellular Ca2+ overloads especially in severe pathological situations.

Adult↗

Alteration of atrial natriuretic peptide receptors in the choroid plexus of rats with induced or congenital hydrocephalus.

Specific binding sites for atrial natriuretic peptide (ANP) in the choroid plexus of rats with induced or congenital hydrocephalus were examined using in vitro quantitative receptor autoradiographic methods. The number of 125I-ANP binding sites in the choroid plexus of rats with kaolin-induced hydrocephalus was significantly higher as compared to findings in the control rats, whereas no differences in the binding affinity were observed 3 days and 3 weeks after the intracisternal injection of kaolin. Conversely, rats with congenital hydrocephalus (LEW-HYR and HTX rats) had a small number of binding sites for 125I-ANP in the choroid plexus, as compared to findings in the control rats. These alterations may relate to the pathophysiology of hydrocephalus. The possibility that atrial natriuretic peptide may be involved in the regulation of cerebrospinal fluid production in the choroid plexus must be considered.

Animals↗

Effect of purified recombinant human erythropoietin on anemia in rats with experimental renal failure induced by five-sixth nephrectomy.

Recombinant human erythropoietin (rHuEPO) was purified from the conditioned media of Chinese hamster ovary cells with a transfected human erythropoietin gene. We investigated the effects of the rHuEPO in rats with renal anemia induced by partial nephrectomy. Five-sixth nephrectomy resulted in renal failure with anemia. Twenty-five days after the operation plasma urea nitrogen was increased about 2.5 times, and the red blood cell count, hematocrit, and hemoglobin concentration fell to 85% of normal. The reticulocyte count and plasma erythropoietin level did not change such as they do in patients with anemia due to chronic renal failure. Both total red blood cell volume and the plasma iron turnover rate were depressed in five-sixth nephrectomized rats compared with normal rats. The five-sixth nephrectomized rats were injected with rHuEPO (60 IU/kg) intravenously every second day for a total of six injections. After three injections of rHuEPO, circulation volume of total red blood cells was increased from 9.9 ml to 14.6 ml, and the plasma iron turnover rate was increased from 1.03 mg/kg/day to 2.12 mg/kg/day, and the reticulocyte count was also increased. After six injections, a marked increase of the red blood cell count, hematocrit, and hemoglobin concentration were observed. Plasma urea nitrogen and the creatinine levels as indications for renal function did not change after rHuEPO administration in both normal and five-sixth nephrectomized rats. In conclusion rHuEPO has a potent erythropoietic action and it is possible to cure the anemia caused by renal failure.

Anemia↗