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Biomedical subjects

K Kuroda

Publications and source records attributed to K Kuroda.

At least 181 records · Page 10Linked to original sources
PubMed1996

[Analysis of genetic changes in progression of colorectal cancer].

To investigate whether genetic changes of the p53 gene and genetic defects in DNA-mismatch repair systems are involved in progression of colorectal carcinomas (CRCs), we examined loss of heterozygosity (LOH) on 17p and mutations in exon 5 through 8 of the p53 gene as well as replication errors (RER) at four microsatellite loci in DNAs from 108 CRCs at all clinical stages (20 Dukes A, 40 Dukes b, 48 Dukes C). We observed that LOH on 17p and/or p53 mutation were detected in 93% of Dukes A carcinomas and in 84% of Dukes C carcinomas, suggesting that the p53 gene is mutated and/or deleted before carcinoma has been produced. RER-positive phenotype was observed in approximately 30% of CRCs, irrespective of clinical stage. These results suggest that genetic instability is likely to play an important role in development of a subpopulation of sporadic CRCs, but not in progression of CRCs. In addition, we found no significant association between genetic alterations and progression of CRCs. We consider that genetic defects in DNA-mismatch repair pathway do not necessarily promote genomic instability at the p53 sequences in CRCs.

Chromosomes, Human, Pair 17↗
PubMed1996

[A case of cervical liquorrhea with headache in and around the area of the great occipital nerve].

We report a 44-year-old man who had sudden-onset severe pain with ardor at the left occipital and nuchal region without trauma in July, 1992. Severe pain disappeared soon after, but dull pain continued intermittently. Four months later, he was referred to our hospital. Neurological examination showed no abnormalities. Cervical CT scan and myelography disclosed liquorrhea. Digital subtraction myelography confirmed cerebrospinal fluid leakage from the level of C1/2 disc. He underwent laminectomy of C1 and C2, and dural plasty on April 6, 1993 with subsequent disappearance of headache. We suppose that this headache was due to rupture of the root sleeve and compression to the root and dorsal root ganglia by outflowed liquor.

Adult↗
PubMed1996

[A nationwide investigation needs for rehabilitation of schizophrenic outpatients--the patients' attribute and actual conditions of living].

In Japan we are very short of community resources for persons with mental disability. The authors, a board of resettlement, thought patients' actual conditions of living and needs for rehabilitation to let them live in the community had to be evaluated. Then in March 1993 the actual conditions of living and needs for rehabilitation of schizophrenic outpatients were investigated nationally. This article is the report on the patients' actual conditions of living. Investigation papers were sent to 358 institutions (286 hospitals and 72 clinics) which agreed to cooperate with the investigation. The 5186 investigation papers were received from 313 institutions. All of the papers except 18, which were lack of their ages, were analyzed. All of the schizophrenic outpatients, who consulted psychiatrists on one day during investigation, were considered objects of this research. Those who consented were included the research and psychiatrists filled in investigation papers. These institutions had a policy of intensive social resettlement activities and so on. Male patients were 55% and females were 45%. There were patients in the forties and females were older than males. Thirty-nine percent of them had been hospitalized once or twice. Thirty-four percent of them had been hospitalized for less than one year. Eighteen percent of them had not been hospitalized. Fifty percent of patients answered there was no friend and acquaintance, and had a tendency to stand alone. Fifty-three percent of patients lived with their parents, 21% with their spouses, and 17% alone. But 32% of females lived with their husbands. Sixteen percent worked for full-time jobs, 8% worked part-time jobs, 12% attended day care center 4% went to sheltered-workshops and only 1% went to rehabilitation-workshops for outpatients. While 13% didn't have a right to receive disability pension, the sources of income were job (30%), disability pension (30%), and welfare benefits (12%). Regarding the ability for living, both socially independent patients and daily independent were 36%. On the other hand, patients who needed support in daily life were 27%. This ability wasn't related to sex and age significantly (chi-square test). It is clear most of the patients were in isolation and depended on their families, so they needed support in income, accommodation and daily life.

Adult↗
PubMed1996

Protein-tyrosine phosphorylation and p72syk activation in human platelets stimulated with collagen is dependent upon glycoprotein Ia/IIa and actin polymerization.

In human platelets treated with acetylsalicylic acid, collagen induced protein-tyrosine-phosphorylation of several proteins. The major 75 kDa band included cortactin and auto-phosphorylated p72syk. p72syk activity rapidly increased upon collagen stimulation, whereas p60c-src activation was below detectable levels. A combination of inhibitors to remove the effects of extracellular and intracellular Ca2+, released ADP, and fibrinogen binding to GPIIb/IIIa delayed and attenuated the major 75 kDa band. By contrast, p72syk activation was not inhibited by these treatments. Cytochalasin D completely inhibited protein tyrosine phosphorylation and p72syk activation. It also potently inhibited aggregation and [Ca2+]i elevation. Anti-GPIa/IIa MoAb in a concentration-dependent manner partially attenuated protein tyrosine phosphorylation and p72syk activation. Its inhibitory effects on intracellular Ca2+ mobilization, release of intracellular granule contents, and aggregation also were partial. No tyrosine kinase activity was coprecipitated with GPIa/IIa. These results suggest that p72syk activation lies upstream of protein tyrosine phosphorylation, Ca2+ mobilization, ADP release, thromboxane A2 production and aggregation. GPIa/IIa plays a key role in p72syk activation induced by collagen, but other collagen receptors may work in synergy to fully activate p72syk. Actin polymerization is a prerequisite for both p72syk activation and other intracellular signal transduction pathways.

Actins↗
PubMed1996

[A case of ectopic amylase-producing lung cancer].

A case of amylase-producing lung cancer is reported. A 58-year-old man was admitted to our hospital because of abnormal shadow on chest X-rays. Transbronchial lung biopsy showed adenocarcinoma at the right upper lobe. Amylase levels were elevated to 915 IU/l in the serum and 960 IU/l in urine. Amylase isozyme pattern identified "salivary-type" amylase. Right upper lobectomy was performed. Both serum and urine, amylase levels were decreased within normal limits after operation. Enzyme labeled immunoperoxidase method on this specimen proved that tumor cells were producing amylase ectopically.

Adenocarcinoma↗
PubMed1996

[Mortality of SMON patients in relation to their disabilities].

The relationship between mortality and disability, was studied in SMON patients, who had participated in the questionnaire survey in 1980, by following them for 10 years through municipal resident registration information offices. Eighty deaths were observed among 409 subjects during the follow-up period. The effect of each disability on the mortality of SMON was estimated by applying the Cox proportional hazard model. The presence of severe gait disturbance and low levels of activities of daily living (ADL) were associated with significantly higher risk of death after adjustment for age and sex. The relative risk of visual disturbance was not significant after adjusting for age, sex and other kinds of disability. Those who complained of continuous dysesthesia at the time of the initial survey showed better prognosis than those without such dysesthesia. Among subjects who died during the follow-up period, those who had reported low levels of ADL at the time of the initial survey had a greater proportion of deaths attributable to heart failure and pneumonia than those who had reported high levels of ADL.

Activities of Daily Living↗
PubMed1996

Successful treatment with topical PUVA of nodular cutaneous plasmacytosis associated with alopecia of the scalp.

We obtained a successful response to PUVA therapy in a 51-year-old Japanese man who had multiple nodules of the trunk, extremities and scalp along with polyclonal hypergammaglobulinaemia; the scalp lesions were associated with extensive alopecia. Examination of skin biopsies showed a dense infiltrate of mature plasma cells in the dermis and hair follicles; no systemic disease or functional involvement of other organs was detected. The clinical and histological findings were compatible with cutaneous plasmacytosis and treatment with topical PUVA gradually reduced the size and number of the lesions.

Alopecia↗
PubMed1995

Fc gamma II receptor-mediated platelet activation induced by anti-CD9 monoclonal antibody opens Ca2+ channels which are distinct from those associated with Ca2+ store depletion.

Anti-human platelet CD9 mAb, NNKY1-19, induced platelet activation in a Fc gamma RII-dependent manner in terms of aggregation and secretion of intracellular granule contents. These responses were considerably suppressed by aspirin. [Ca2+]i elevation in the absence of extracellular Ca2+ ([Ca2+]e), which represents the amount of Ca2+ released from intracellular Ca2+ ([Ca2+]i) stores, was also greatly reduced, whereas Ca2+ influx was sustained at similar levels. We thus investigated the mechanism that leads to the opening of Ca2+ channels in platelets incubated with aspirin. IP3 production and Ca2+ efflux were below detectable levels. 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid loading of platelets to chelate [Ca2+]i did not reduce Ca2+ influx, as assessed by 45Ca2+ measurement. These findings suggested that NNKY1-19 induces Ca2+ channels to open without [Ca2+]i mobilization or by depleting the [Ca2+]i stores. The magnitude of Ca2+ influx was evaluated by adding [Ca2+]e to a platelet suspension activated by various agonists in the absence of [Ca2+]e. The dose dependence of the Ca2+ influx on [Ca2+]e concentrations differed according to the mode of activation. The ED50 value of Ca2+ after thrombin or thapsigargin stimulation was 0.6 mM, whereas that of NNKY1-19 activation was about 3 mM. The addition of anti-Fc gamma RII mAb, IV.3, even 10 min after the initiation of platelet activation induced by NNKY1-19, inhibited the Ca2+ influx. These findings suggest that the Fc gamma RII-dependent activation of platelets induced by NNKY1-19 directly opens Ca2+ channels, which are distinct from those opened by thrombin or thapsigargin.

Antibodies, Monoclonal↗
PubMed1995

Induction of cytochrome P450-dependent monooxygenase in serum-free cultured Hep G2 cells.

We examined the induction of cytochrome P450-dependent mixed-function monooxygenase (MFO) in the human hepatoma cell line Hep G2 by means of several factors. The MFO activities induced in the cells cultured in medium containing five commercial sera varied significantly, and the activity in the cells cultured in the absence of serum was about twice as high as that in cells supplemented with serum. The activity of ethoxycoumarin O-deethylase was highest 12 hr after adding 3-methylcholanthrene, and it was induced by several polycyclic aromatic hydrocarbons such as benzo(a)anthracene and benzo(a)pyrene, which are usually found in urban air as environmental contaminants. Furthermore, an extract from the total suspended particles collected using a high volume air sampler, which was mutagenic in the Ames assay using Salmonella typhimurium TA98, induced the same enzyme activities in Hep G2 cells. These findings suggest that serum-free culture allows the stable and highly sensitive measurement of induced MFO activity, and that studies of MFO induction by environmental samples using human hepatoma Hep G2 cells should provide helpful information regarding the risk associated with environmental contaminants.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1995

Novel muteins of human tumor necrosis factor with potent antitumor activity and less lethal toxicity in mice.

Eight muteins of recombinant human tumor necrosis factor-alpha (rhTNF; 1SSSRTP...29RR...155L), in which 29Arg was replaced by another amino acid, were prepared and their anti-tumor effects in BALB/c mice bearing Meth A fibrosarcoma were evaluated. The therapeutic indices, which mark the extent of the therapeutically effective dose, of V29 (29Arg-->Val) and D29 (-->Asp) were 3.5 and 3.2, respectively, whereas that of rhTNF was 1.4. Clearly, the therapeutically effective range of these muteins was extended along with a decrease in lethal toxicity. V29 did not produce hypotension in the rat system, but D29 did. In addition, V29 showed potent anti-tumor activity (Tumor Volume Inhibition Rate = 81% on day 15 after implantation) in 3 consecutive injection schedules despite the decreases in toxicity compared with rhTNF. The relative receptor binding constant was determined using HEp-2 cells (expressing mainly 55-kDa-TNF receptor; p55R) and HL60 cells (expressing mainly 75-kDa-TNF receptor; p75R), and revealed that the reduced toxicity of V29 in mice was due to the reduced binding to p55R (34% of rhTNF). On the other hand, the ratio of the constants HEp-2/HL60 of V29 was 11 in comparison with the value of 1.0 for rhTNF, suggesting that this mutein binds preferentially to p55R. The biological activities in human cell lines (HEp-2 and HL60 cells) correlated well with the binding activities to each receptor in vitro. Therefore, the much lower toxicity and the potent anti-tumor activity of this mutein suggest that V29 merits further investigation in pre-clinical and clinical trials.

Amino Acid Sequence↗
PubMed1995

Anti-CD9 monoclonal antibody activates p72syk in human platelets.

NNKY 1-19, anti-CD9 monoclonal antibody (MoAb), induced protein tyrosine phosphorylation of 125-, 97-, 75-, 64-, and 40-kDa proteins in human platelets, whereas F(ab')2 fragments of NNKY 1-19 did not, suggesting that the stimulation of Fc gamma II receptors is required for the induction of protein tyrosine phosphorylation. Tyrosine-phosphorylated proteins of 97 and 125 kDa were associated with aggregation, while NNKY 1-19-induced protein tyrosine phosphorylation was completely inhibited by prostaglandin I2 (PGI2). The activity of p72syk was assessed in immunoprecipitation kinase assays to determine at which step the signal transduction pathway leading to protein tyrosine phosphorylation was suspended. NNKY 1-19 induced a rapid and transient increase in the p72syk-associated tyrosine kinase activity that peaked at 10 s and subsided to the original level 2 min after stimulation. Coinciding with this time course, p60c-src transiently associated with p72syk. In platelets preexposed to GRGDS peptides or PGI2, NNKY 1-19 also increased the p72syk-associated tyrosine kinase activity and led to the association of p60c-src with p72syk. However, in contrast to the control without any inhibitor, the elevated tyrosine kinase activity and the associated state of the two tyrosine kinases persisted as long as 5 min after stimulation. F(ab')2 fragments of NNKY 1-19 induced changes similar to those observed with the effects of GRGDS peptides or PGI2 treatment on intact IgG NNKY 1-19 stimulation. F(ab')2 fragments of another CD9 MoAb, PMA2, had effects on p72syk essentially similar to those of NNKY 1-19. These findings suggest that the binding of anti-CD9 MoAb to CD9 on the platelet membrane per se induces an increase in the p72syk-associated tyrosine kinase activity but that Fc gamma II receptor-mediated signal(s) is required for the full activation of platelets and the appearance of tyrosine-phosphorylated proteins. The elevated intracellular cAMP level induced by PGI2 acts at a step distal to the activation of p72syk and inhibited the signal transduction pathway leading to protein tyrosine phosphorylation and aggregation. p72syk activation occurs in the absence of aggregation, but aggregation appears to reduce the elevated p72syk activity induced by anti-CD9 MoAb.

Antibodies, Monoclonal↗
PubMed1995

Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens.

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.

Acetyltransferases↗
PubMed1995

A precise and fast temperature mapping using water proton chemical shift.

A new temperature measurement procedure using phase mapping was developed that makes use of the temperature dependence of the water proton chemical shift. Highly accurate and fast measurements were obtained during phantom and in vivo experiments. In the pure water phantom experiments, an accuracy of more than +/- 0.5 degrees C was obtained within a few seconds/slice using a field echo pulse sequence (TR/TE = 115/13 ms, matrix = 128 x 128, number of slices = 5). The temperature dependence of the water proton chemical shift was found to be almost the same for different materials with a chemical composition similar to living tissues (water, glucide, protein). Using this method, the temperature change inside a cat's brain was obtained with an accuracy of more than +/- 1 degree C and an in-plane resolution of 0.6 x 0.6 mm. The temperature measurement error was affected by several factors in the living system (B0 shifts caused by position shifts of the sample, blood flow, etc.), the position shift effect being the most serious.

Animals↗