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Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 451 records · Page 25Linked to original sources

Intraarterial infusion chemotherapy with [Sar1,Ile8]angiotensin II for bladder cancer.

Thirty-three patients with primary bladder cancer (nine stage T1 with multifocal tumors and 24 stage T2-4) were treated with intraarterial infusion chemotherapy including cisplatin, doxorubicin, and [Sar1,Ile8]Angiotensin II(AT II). Of the 32 evaluable patients, 12 had pathologically proven complete response (CR), 19 showed partial response (PR), and one showed no change (NC); the overall response rate (CR + PR) was 97%. The blood pressure increased in response to the administration of [Sar1,Ile8]AT II in all the patients; the mean increase in the systolic blood pressure was 36 mmHg. Most of the side effects were mild to moderate in severity, transient in nature, and included nausea/vomiting (100%), alopecia (84%), leukopenia (66%), headache (9%), nephrotoxicity (6%), diarrhea (3%), skin pigmentation (3%), and neurotoxicity (3%). One patient who dropped out of the study developed hemiplegia as a result of cerebral infarction. The findings indicate that it is necessary to exercise caution in selecting the patients to be subjected to this therapy. We conclude that intraarterial infusion chemotherapy combined with a vasoconstrictor has a significant effect not only against multifocal superficial bladder cancer but also against invasive bladder cancer.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Dying back type axonal degeneration of sensory nerve terminals in muscle spindles of the gracile axonal dystrophy (GAD) mutant mouse.

A disorder of the gracile axonal dystrophy (GAD) mutant mouse is characterized by a neuromuscular disease with sensory ataxia (detectable 30 days after birth) and paresis of the hindlimbs (detectable at 80 days). In the sensory ataxia stage, histological study of the primary sensory system shows that, in addition to the lesions in the central nervous system, peripherally projecting axons have also started to degenerate at their distal ends in muscle spindles. Although the structure of Ia fibre endings appear normal until 15 days after birth, initial changes in the annulo-spiral structure are detected around the 20th day by a degeneration of the terminal axons. Degeneration then progressed proximally and the secondary endings also start to degenerate. Neuron cell bodies located in the dorsal root ganglia are morphologically intact until the later stages. Chronological studies indicate that, although axonal degeneration progresses throughout life, it is accentuated during the rapid somatic growth period. Around 50 days of age, transient regeneration takes place at axonal endings when somatic growth has attained a plateau. Such primary sensory endings tend to be restored by fine, multiple axons which gain access to the intrafusal fibres through the original endoneurial tubes. Ultrastructural observations at the fully affected stage show intrafusal muscle fibres lying scattered within spindles due to loss of the fine network of inner capsule layers and an almost complete loss of sensory endings from the surface of intrafusal muscle fibres. These results indicate that this mutant mouse is a useful model for naturally occurring 'dying back' type axonal degeneration or 'central and peripheral distal axonopathies', and would provide significant information about the complete evolution of the pathological processes involved.

Animals↗

Ornithine and histidine decarboxylase activities in mice sensitized to endotoxin, interleukin-1 or tumour necrosis factor by D-galactosamine.

1. An injection of D-galactosamine (GalN) into mice together with a lipopolysaccharide (LPS or endotoxin), interleukin-1 (IL-1) or tumour necrosis factor (TNF), sensitized the mice and induced fulminant hepatitis with severe congestion resulting in rapid death. Since LPS and these cytokines induce ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) in the liver and spleen of mice, the effects of GalN on the induction of ODC and HDC in these organs were examined. 2. The induction of ODC by LPS, IL-1 or TNF was suppressed by GalN in the liver, and this suppression preceded the hepatic congestion. There was good agreement between the degree of hepatic congestion and the suppression of ODC induction by various amounts of GalN. The induction of ODC in the spleen was suppressed only at the highest dose of GalN examined. 3. GalN is known to deplete uridine 5'-triphosphate (UTP), resulting in the suppression of RNA and protein synthesis. An injection of uridine, the precursor of UTP, diminished the GalN-induced suppression of ODC induction by LPS and prevented the hepatic congestion and death. 4. LPS-pretreatment before injection of LPS plus GalN prevented the suppression of ODC activity and prevented the hepatic congestion and death. 5. An injection of putrescine, the product of ODC, prolonged survival time and delayed the development of hepatic congestion. However, injection of an ODC inhibitor into the mice given LPS did not produce hepatic congestion. 6. The induction of HDC in the liver by LPS, IL-1 or TNF was not suppressed by GalN and, at high doses, the response to LPS was enhanced. An inhibitor of HDC neither prevented the hepatic congestion nor enhanced the protective effect of putrescine.7. Although GalN in combination with IL-la induced a markedly higher HDC activity than was observed when it was combined with TNFa, and suppressed the induction of ODC, the former combination at the doses used did not produce hepatic congestion or death. However, the sensitization to TNFa by GalN was markedly potentiated by IL-la.8. These results suggest that suppression of the induction of ODC by GalN may be one cause of the sensitization to LPS, IL-1 or TNF, and that the induction of HDC, i.e. histamine formation, may not be involved in this sensitization.9. These results are consistent with the hypothesis that both IL-1 and TNF are involved in the sensitization to LPS.

Animals↗

Structural identification of an epitope of antigenic factor 5 in mannans of Candida albicans NIH B-792 (serotype B) and J-1012 (serotype A) as beta-1,2-linked oligomannosyl residues.

In previous articles, we reported the presence of phosphate-bound beta-1,2-linked oligomannosyl residues in the mannans of strains of Candida albicans serotypes A and B and Candida stellatoidea. To identify the antigenic factor corresponding to this type of oligomannosyl residue, a relationship between chemical structure and antigenic specificity in the mannans of C. albicans NIH B-792 (serotype B, B-strain) and C. albicans J-1012 (serotype A, J-strain) was investigated by using a combination of two-dimensional 1H nuclear magnetic resonance spectroscopy of H-1, H-2, and H-5 regions in the mannans and an enzyme-linked immunosorbent assay that employed concanavalin A-coated microtiter plates. It was shown in the present 1H nuclear magnetic resonance study that an examination of chemical shifts not only in the H-1 region but also in the H-5 region was useful for the quantitative determination of the phosphate-bound beta-1,2-linked oligomannosyl residues. In the enzyme-linked immunosorbent assay using concanavalin A-coated plates, it was revealed that, of factor sera 1, 4, and 5, only factor serum 5 showed a reactivity proportional to the densities of the beta-1,2-linked oligomannosyl residues of the mannan subfractions of different phosphate contents that had been prepared from the bulk B-strain mannan by DEAE-Sephadex chromatography. The above results indicate that the phosphate-bound beta-1,2-linked oligomannosyl residues, Manp beta 1----(2Manp beta 1----)n2Man (n = 0-5), correspond to antigenic factor 5.

Antigens, Fungal↗

Isolation of novel lignans, heteroclitins F and G, from the stems of Kadsura heteroclita, and anti-lipid peroxidative actions of heteroclitins A-G and related compounds in the in vitro rat liver homogenate system.

From the stems of Kadsura heteroclita, two new lignans named heteroclitins F and G were isolated and their structures were determined by various spectroscopic means including an X-ray diffraction method. Dibenzocyclooctadiene type lignans and related compounds isolated from the stems of K. heteroclita, potently inhibited the lipid peroxidation in the rat liver homogenate stimulated by Fe(2+)-ascorbic acid, CCl4-reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine 5'-diphosphate-NADPH.

Animals↗

Constituents of a fern, Davallia mariesii Moore. II. Identification and 1H- and 13C-nuclear magnetic resonance spectra of procyanidin B-5, epicatechin-(4 beta----8)-epicatechin-(4 beta----6)-epicatechin, and epicatechin-(4 beta----6)-epicatechin-(4 beta----8)-epicatechin-(4 beta----6)-epicatechin.

Procyanidin B-5 (1), epicatechin-(4 beta----8)-epicatechin-(4 beta----6)-epicatechin (2), and epicatechin-(4 beta----6)-epicatechin-(4 beta----8)-epicatechin-(4 beta----6)-epicatechin (3), which showed an inhibitory effect toward protein kinase C, were isolated from the rhizomes of Davallia mariesii Moore. Detailed analyses of their 1H- and 13C-nuclear magnetic resonance spectra were carried out by the use of two-dimensional nuclear magnetic resonance techniques.

Biflavonoids↗

Metabolism by rat liver cytosol of illudin S, a toxic substance of Lampteromyces japonicus. II. Characterization of illudin S-metabolizing enzyme.

1. Enzyme systems responsible for formation of cyclopropane ring-cleavage metabolites (M1 and M2) of illudin S in rat liver were characterized. 2. The enzymes were localized in the cytosol fraction and utilized NADPH alone as electron donor; they were not affected by oxygen and had low pH optima. 3. Formation of metabolites M1 and M2 was inhibited completely by dicumarol (10(-4) M), an inhibitor of DT-diaphorase. 4. Menadione (10(-4) M) and quercetin (10(-4) M) both inhibited formation of M1 and M2 by 35% and 15%, respectively, but quinacrine, barbital, pyrazole and p-chloromercuribenzoic acid had no significant effect. 5. Results show that the enzyme systems may differ from DT-diaphorase, aldehyde oxidase, xanthine oxidase, ketone reductase, aldose reductase, aldehyde reductase and alcohol dehydrogenase, known cytosolic enzymes responsible for xenobiotic metabolism.

Animals↗

Developmental expression of S-antigen in fetal human and rat eye.

Development expression of S-antigen and its mRNA in human and rat fetal retina was studied by immunocytochemical and in situ hybridization techniques. Immunocytochemistry indicated that S-antigen was present after 4 months gestation in the fetal human retina. In the rat, S-antigen was detected in the retina only after birth. In situ hybridization studies indicated that the S-antigen mRNA was present at 13 weeks gestational age in the human and at 15 days in the rat embryo. S-antigen mRNA was expressed not only in the retina but also in ocular tissues of neural crest origin in the fetus.

Adult↗

Identification of bone morphogenetic protein-2 in early Xenopus laevis embryos.

Polyclonal antibodies capable of reacting with amphibian bone morphogenetic protein (BMP-2 and -4) were raised in rabbits by immunization with a synthetic 21 amino acid peptide which corresponds to a sequence residing in the mature protein of Xenopus BMP-2 (xBMP-2). The antibodies recognized an embryonic BMP as well as mammalian and bacteria expressed recombinant xBMPs. The antibodies detected, under reducing conditions, a 30 kDa protein in the extract of oocytes and embryos during early development. Interestingly, acidification of the extract from each developmental stage yielded a protein band of smaller molecular weight of 18 kDa, which is similar in size to reduced form of mature BMPs purified from mammalian species. Two-dimensional electrophoresis employed to examine the molecular weight of unreduced forms using the antibody, revealed that both molecular forms are monomeric in the embryos. The result suggests that at least BMP-2 mRNA previously detected in early embryos, is translated into peptide but the dimerization may be incomplete or strictly limited in these embryos.

Amino Acid Sequence↗

[67kDa-laminin receptor in human lung cancer].

Complimentary DNA for the 67kDa-laminin receptor was cloned from the cDNA library derived from a human lung cancer cell line, and the nucleotide sequence was determined. Expression of the gene was estimated by Northern analysis in various types of human lung cancer. As a result, increased expression of the laminin receptor was demonstrated especially in the cell types of small cell cancer and bronchioloalveolar cell cancer, which are aggressive biologically. Antibody raised against a partial sequence of the polypeptide was prepared for immunodetection of 67kDa-laminin receptor. It was shown that immunohistochemistry with the antibody could be applied to diagnostic use in lung cancer. The results also suggest that the laminin receptor polypeptide is not necessarily a membrane-associated protein and may function without further processing to the receptor.

Cloning, Molecular↗

Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: characterization of tumor and assessment of effect of treatment.

To evaluate glucose metabolism in patients with tumors involving the liver, 35 patients with liver lesions had PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG (148 MBq) was injected and radioactivity of the tumor was scanned dynamically by PET. The rate constants (k1, k2, k3, k4) of FDG in a metabolic model were calculated. The results were compared to hexokinase activity in the excised tumor specimens. k3 was found to reflect tumor hexokinase activity. When k3 was used as an index (cut-off value: 0.025), it was possible to distinguish benign and malignant tumors. k4 was significantly higher in hepatocellular carcinoma. By using k3 and k4 as indices, one could assess the degree of differentiation of hepatocellular carcinoma. After treatment, k3 decreased according to the effectiveness of therapy and thus may be a useful index for quantitatively assessing tumor viability.

Adenoma, Bile Duct↗

[Anti-bacterial zeolite balloon catheter and its potential for urinary tract infection control].

We present here a production of anti-bacterial zeolite balloon catheter and investigated its potential for controlling urinary tract infection. This anti-bacterial balloon catheter showed a bactericidal effect against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli in vitro studies. The antibacterial effects were correlated with the concentration of anti-bacterial zeolite and size of catheter. We tried this catheter for 11 various urological patients who needed a long-term indwelling of a balloon catheter for lower urinary tract obstruction and neurogenic bladder. All patients were already indwelled silicon balloon catheter for 3 to 6 months and suffered with complicated urinary tract infection. Nine patients who had this anti-bacterial zeolite balloon catheter indwelled for 3 to 7 months and exchanged every 2 to 4 weeks, and no patient was taking antibiotics during this trial. Two patients (22.2%) showed good results by the urinary tract infection (UTI) criteria and 5 patients (55.4%) showed good effects by doctor's judgment. This anti-bacterial zeolite balloon catheter might be useful for patients who need long-term balloon catheter indwelling.

Aged↗

Anti-hepatitis C virus immunoglobulin M antibody in patients with chronic hepatitis type C.

Anti-hepatitis C virus immunoglobulin M antibody titers were measured by enzyme-linked immunosorbent assay in 28 patients with chronic hepatitis C. Nine patients were treated with alpha-interferon at a dosage of 3 MIU/day for 4 weeks. Anti-HCV IgM was positive in 12 of the 28 patients, and these 12 patients also had significantly higher anti-HCV antibody titers than those patients who were negative for anti-HCV IgM. Among the 9 patients treated with alpha-interferon, anti-HCV IgM positivity was significantly lower in 4 good responders than in 2 non-responders and 3 transient responders at 12 months after the completion of treatment (p < 0.01). These results suggest that anti-HCV IgM titers might be useful for monitoring the antiviral effect of interferon treatment in CH C.

Adult↗

Intrahepatic lymphocyte subpopulations and HLA class I antigen expression by hepatocytes in chronic hepatitis C.

The lymphocyte subpopulations in the peripheral blood and liver were studied in 17 patients with chronic active hepatitis type C (CAH C) by immunoenzymatic and immunofluorescence techniques, using mono-specific T cell antibodies and other reagents. The peripheral blood subsets showed no significant differences between the patients with CAH C and normal controls. In the liver, CD8-positive cells were predominant over CD4- and Leu 7-positive cells. Leu 7-, CD4-, and CD11-positive lymphocytes were all few in number. HLA class I antigen was expressed diffusely on the cell surfaces of the hepatocytes. Serum levels of soluble interleukin 2 receptor (sIL2R) in the CAH C patients were significantly higher than in normal controls (p less than 0.01). In CAH C, sIL2R levels were higher during exacerbations than during remissions (p less than 0.01). These results suggest that cytotoxic T cells (CD8- positive, CD4-negative, and CD11-negative) may play an important role in the pathogenesis of hepatocyte injury in patients with CAH C.

Antibodies, Monoclonal↗

[Clinical significance of respiratory infections associated with lung cancer patients].

An attempt was made to interpret the clinical significance of secondary infections associated with lung cancer. The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer in our institution in 1988 and 1989, and almost all of them had respiratory infections caused by commonly encountered bacteria. The incidence of infection was high in lung cancer of cell types other than adenocarcinoma, and in those with hypoalbuminemia, impaired cellular immunity and obstruction of the airway. The prognosis in patients with infection was much poorer than that in patients without infection. Major pathogens responsible for infection were Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp. and Pseudomonas aeruginosa. These pathogens, except for H. influenzae, were isolated in the terminal stage in cases with airway obstruction and post cancer chemotherapy. The efficacy rate of 194 therapeutic regimens against infection was 57.7%. It was thus found that the efficacy rate in 1988 and 1989 exceeded that in the 1970s. The effectiveness was very poor for infections caused by S. aureus and P. aeruginosa, and for cases with airway obstruction and marked impairment of pulmonary blood flow. The efficacy rate of single-drug regimens was 57.1% (80/140) and that of combined regimens was 59.3% (32/54). The above results indicate that a new combined therapy which includes a beta-lactam antibiotic as well as measures to improve the general health of compromised hosts are required in the treatment of secondary infections in these patients.

Adult↗

[Emergency manual aspiration for severe hypertensive cerebellar hemorrhage].

We treated 16 patients with hypertensive cerebellar hemorrhage and coma, or deep coma. Their ages ranged from 44 to 79 years (mean age: 66.3 years). Manual aspiration was performed in 9 patients and suboccipital craniectomy was performed in 7 patients. The difference in outcome between the manual aspiration group and the suboccipital craniectomy group with severe hypertensive cerebellar hemorrhage was then evaluated. Manual aspiration was performed for 4 patients in coma, and 5 in deep coma, with a mean age of 69.0 years. The average size of the hematoma was 48.7mm and the mean volume was 31. 7ml on CT scan. The mean interval from admission to operation was about 60 minutes. The mean aspiration rate was 79.6% and 7 patients (77.8%) had a good response to drainage. The suboccipital craniectomy patients included 5 in coma, and 2 in deep coma, with a mean age of 63.4 years. The average size of the hematoma was 51.1 mm and the mean volume was 33.1 ml on CT scan. The mean interval from admission to operation was about 112 minutes and the mean evacuation rate was 86.4%. The results were as follows: 1) After manual aspiration, 5 patients (55.6%) had a good outcome and 2 patients (40%) with deep coma showed good recovery. In contrast, after suboccipital craniectomy only 2 patients (28.6%) had a good outcome and all of the deep coma patients showed poor recovery. 2) The outcome may be most strongly influenced by the duration from admission to operation. 3) All patients with a hematoma volume of over 30 ml had a poor outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Acute subdural hematoma caused by mild head trauma in the aged].

We encountered 8 cases of acute subdural hematoma caused by mild head trauma in the aged. In this report, these cases were analyzed, taking into consideration clinical symptoms, CT scan, operative findings and outcome. The age ranged from 70 to 92 years (mean age of 79.7 years). 4 patients were male and 4 female. Head trauma was caused by falls in 4 patients, but in the other 4 patients the causes were unknown. Initial symptoms were headache, nausea and vomiting in 5 patients and mild disturbance of consciousness with lucid intervals in 3 patients. Seven patients had more than 100 on JCS and less than 9 on GCS on admission. Small craniotomy (HITT) was performed in 4 patients. Large craniotomy was performed in 2 patients, and decompressive craniectomy was carried out in 2 patients. The bleeding focus came from the cortical artery of the middle cerebral artery in 4 patients, cerebral contusion in 2 patients, and was unknown in 2 patients for HITT. CT scan on admission showed mixed density area of acute subdural hematoma in all of the patients, and intraventricular hemorrhage, intracerebral hemorrhage and subarachnoid hemorrhage in 3 patients. CT scan after operation revealed a new area of cerebral contusion in 3 patients, delayed traumatic intracerebral hematoma (DTICH) in 2 patients, and hypertensive intracerebral hemorrhage in 1 patient. Two patients recovered to good and fair without general complication. But the outcome in 5 patients with general complication was poor for 3 patients and fatal for 2 patients. In conclusion, large craniotomy is recommended because of bleeding from the cortical artery of the middle cerebral artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Complications and their management in intraarterial infusion chemotherapy].

Complications and its management were evaluated in intraarterial infusion chemotherapy for 188 patients with advanced carcinoma of the digestive organs from 1975 to Sept. 1991. Subjects were divided into four groups: Group I was 62 patients in whom the tip of the catheter without knots was established in the abdominal aorta via celiac axis, Group II consisted of 72 patients with the tip of the catheter without knots in the common hepatic artery. Group III had 35 patients with the tip of the catheter with knots (Anthron catheter) in the common hepatic artery. Group IV was 19 patients with the tip of the anthron catheter connected to the Infuse A-Port in the common hepatic artery. The most frequent complications seen among Group I, II and III were caused by catheter thrombosis (11.3%) in Group I, spontaneous dislodgement of catheter (26.4%) in Group II and extravasation (20%) in Group III. By using 16 gauge Toray Anthron catheter with Heparin coating on its inner and outer surfaces, the number of complications in Group I and II was kept smaller. Extravasation, on the other hand, has been less frequently seen in Group III by establishing the tip of the catheter at the branching site of the gastroduodenal artery from the common hepatic artery. Complications in Group IV (19 patients) were noted only in 3 patients, i.e., extravasation, subcutaneous necrosis and subcutaneous abscess, respectively. Therefore, we concluded that Group IV showed the most favorable intraarterial infusion chemotherapy with the most infrequent complications.

Aorta↗