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Biomedical subjects

K Kashima

Publications and source records attributed to K Kashima.

At least 217 records · Page 12Linked to original sources

Multiple aberrant splicing of the p53 transcript without genomic mutations around exon-intron junctions in a case of chronic myelogenous leukaemia in blast crisis: a possible novel mechanism of p53 inactivation.

We found three truncated p53 transcripts in a patient with chronic myelogenous leukaemia in blast crisis carrying chromosome 17 abnormalities. Sequencing of these transcripts revealed complete absence of the entire exons 7, 8 and 9 in one, exons 8 and 9 in another, and exon 10 in the other. Sequencing analysis of genomic DNA, however, revealed no mutation in exons 6-10 and their flanking introns. These results suggest that the aberrant p53 transcripts in this case might not result from splicing mutations but from an unknown affected splicing process.

Base Sequence↗

Immunocytochemical investigation of rat gamma-glutamyl transpeptidase in chemically-induced hepatocarcinogenesis using monoclonal antibody.

An immunocytochemical study using a monoclonal antibody showed the presence of gamma-glutamyl transpeptidase (gamma-GTP) in the bile duct epithelium of the normal adult rat liver, while a slight immunoreactivity for gamma-GTP could be observed on the membranes of bile canaliculi (the membranes of hepatocytes facing the lumen of bile canaliculi). In hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene, no immunoreactivity was detected in alpha-fetoprotein-positive cholangiolar "oval" cells, though it was detected on the membranes of bile canaliculi. In livers with hyperplastic nodules, gamma-GTP immunoreactivity was observed in clusters, with two different staining patterns. In one pattern, gamma-GTP was present not only on the membranes of bile canaliculi, but also on the membranes facing the Disse's space or the lateral cell surface of hepatocytes. In the other pattern, gamma-GTP immunoreactivity was seen on the membranes of the dilated bile canaliculi. In livers with developing hepatocellular carcinomas, the immunoreactivity was present on the membranes of irregularly dilated bile canaliculi in malignant cells.

Animals↗

Immunohistochemical localization of acidic and basic fibroblast growth factors in human benign and malignant thyroid lesions.

The localization of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) was investigated immunohistochemically in human benign and malignant thyroid lesions. Immunostaining for aFGF and bFGF displayed diffuse or granular deposits of the reaction products in the cytoplasm of neoplastic cells, especially in the marginal region of follicular adenoma, follicular carcinoma and papillary carcinoma. All lesions except for diffuse hyperplasia, which was completely negative in immunostaining for all antibodies, showed an increased immunostaining for bFGF (Ab-1) over that of aFGF and bFGF (Ab-2). Basement membranes of follicular and papillary structure and the fibroblasts located in the stromal tissues were free from immunostaining for all antibodies. The ratio of positive immunostaining for all antibodies was highest in papillary carcinoma, with an incidence of more than 80.0%, followed, in descending order, by widely invasive follicular carcinoma, minimally invasive follicular carcinoma, follicular adenoma and normal thyroid, in which some follicular cells exhibited weak reaction products. aFGF with a molecular weight of 18 kDa was identified in papillary carcinoma of the thyroid. From these data, we concluded that aFGF is synthesized in the neoplastic follicular cells of the thyroid, and aFGF and bFGF may have important roles in the neoplastic proliferation of follicular cells.

Adenocarcinoma, Follicular↗

[Side effects of interferon on endocrine and respiratory system in 545 cases of chronic hepatitis C].

We investigated the side effects of interferon (IFN) on the endocrine and respiratory system in 545 cases of chronic hepatitis C. Eleven of 494 (2.2%) patients with chronic hepatitis C who were treated with natural or recombinant interferon (IFN) developed thyroid disease while on treatment. Eight patients developed hyperthyroidism and 3 patients developed hypothyroidism. All 11 patients required definitive therapy, who became euthyroid after the therapy. Two patients received nIFN alpha and one patient received rIFN alpha 2b developed diabetes mellitus. Two patients received rIFN alpha 2a and rIFN alpha 2b, respectively, developed interstitial pneumonia 12 weeks and 24 weeks later, respectively. One patient showed positive reaction for RA test and LE factor and positive LE cell, and complained of fever, arthralgia and dry cough. These phenomenon disappeared after the cessation of IFN therapy.

Adult↗

[A phase III trial of subcutaneous administration of rhG-CSF in aplastic anemia].

To evaluate the efficacy and safety of subcutaneous administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in aplastic anemia (AA), 21 patients were given a daily subcutaneous dose of 200 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 400 micrograms/m2. A marked neutrophilic response was obtained in all 9 patients with non-severe AA and in 9 out of the 12 patients with severe AA, yielding a response rate of 85.7%. Adverse effects included lumbago in one patient and elevation of serum enzyme levels in 6 patients, but did not prohibit further treatment. These results suggest that subcutaneous administration of KRN8601 is safe and useful in improving neutropenia in AA.

Adolescent↗

[A phase III trial of subcutaneous administration of rhG-CSF in the myelodysplastic syndromes].

To evaluate the safety and efficacy of subcutaneous administration of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes (MDS), 20 patients were given a daily dose of 50 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 100 micrograms/m2. A marked neutrophilic response was obtained in 17 of the 18 evaluable patients (94.4%), irrespective of the MDS disease type. Five patients showed a platelet increase, 3 of which also showed an erythroid improvement. To maintain neutrophil levels greater than 1,000/microliters, 12 patients were treated with KRN8601 for 4 weeks. A dose of 25 to 50 micrograms/m2 3-4 times a week served to this end in 8 patients and 100 micrograms/m2 three times a week or daily in the remaining 4 patients. One patient with RAEB progressed to acute myeloid leukemia 8 weeks after KRN8601. The treatment was well-tolerated in the majority of patients with no severe toxicities. These results suggest that subcutaneous administration of KRN8601 is safe and useful in the treatment of cytopenias in MDS.

Adult↗

A cognitive-behavioral approach to temporomandibular dysfunction treatment failures: a controlled comparison.

The effects of cognitive-behavioral treatment for patients with temporomandibular disorders were studied by comparing active treatment to a wait-list control condition. Patients were predominantly women and had been referred to the study after having poor response to dental/physical medicine care. Patients' conditions were evaluated pretreatment and posttreatment based on self-report measures of pain, distress, and jaw function problems. They were examined by a dentist who assessed pain-free opening, muscle palpation pain, and tenderness of the temporomandibular joints. The 5-week cognitive-behavioral treatment included relaxation training, self-monitoring of stressors, and cognitive coping strategies. Treatment had its greatest impact on improving mood, especially anxiety; however, there were some effects on the patients' experiences of pain.

Adult↗

[B-lymphoma arising in the temporal muscle].

B cell lymphoma arising in skeletal muscle is described with the review of literature. A 72-year-old man visited our hospital on September 21st 1992, because of a right temporal mass which had grown gradually since one year previously. A CT scan and MRI showed a soft tissue mass adjacent to the temporal muscle expanding from the right temporal to infratemporal fossa. Physical examination on admission revealed that the mass at the right temporal region, was non-tender, elastic soft, and 5 x 2 cm in diameter. Some elastic hard masses at the right infraauricular region, approximately 1.5 x 1.2 cm in diameter, were also found. Histological examination of a biopsied specimen obtained from the temporal mass revealed B cell lymphoma, diffuse medium-sized cell type. Tests for surface markers using tumor cell suspension showed positive results for CD5, CD19, CD20, SmIg mu, delta, lambda, but negative for CD10. Chromosomal analysis revealed clonal aberrations, and the defining karyotype as 51, X, +X, -Y, +2, +3, +4, +8, +12. The patient achieved a complete remission after treatment with combination chemotherapy including doxorubicin, cyclophosphamide, vincristine, etoposide, vindesine, procarbazine, and prednisolone.

Aged↗

Combined effects of magnesium deficiency and an atherogenic level of low density lipoprotein on uptake and metabolism of low density lipoprotein by cultured human endothelial cells. II. Electron microscopic data.

The effects of magnesium deficiency on low density lipoprotein (LDL) transport by cultured endothelial cells with a high concentration of LDL (2 mg of LDL cholesterol/ml) were investigated by electron microscopy and by counting the radioactivity of [3H]-LDL transported across an endothelial monolayer grown on culture plate inserts. Electron microscopic examination showed that the number of pits/vesicles in the apical side was time-dependently increased for 24 h in both magnesium-deficient and magnesium-sufficient groups with the exception of 1 h under magnesium sufficiency. The number of pits/vesicles in the basal side was also increased for 8 h in both groups, though there was a decrease at 24 h in the two groups. No difference between either magnesium group at the same time point was statistically significant. [3H]-LDL transport was also time-dependently increased in both magnesium-deficient and magnesium-sufficient groups. In contrast to the results obtained by electron microscopy, the amount of LDL transported under magnesium deficiency was much larger for 24 h than under magnesium sufficiency. Differences in LDL transport between magnesium groups were statistically significant at 4 and 8 h. This finding indicates that magnesium deficiency increases LDL transport across the endothelial monolayer. The increase may be due to energy-dependent movement across endothelial cells, energy-independent movement between cells, or both. However, we conclude that magnesium deficiency increases the energy-dependent LDL transport to some degree since intercellular gap formations were rarely observed in either magnesium group. This LDL transported to the subendothelial space may lead to LDL accumulation and initiate atherosclerosis.

Arteriosclerosis↗

N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndrome.

We performed a longitudinal analysis of the karyotypes and N-ras gene configuration of bone marrow cells in 35 patients with myelodysplastic syndrome (MDS). Karyotypic evolution was found in eight patients, and was associated with disease progression, including leukemic transformation, in all the patients. We identified N-ras mutations in six patients, using a polymerase chain reaction (PCR) technique, in which oligonucleotide primers were constructed with induced mismatches, followed by endonuclease digestion. Direct sequencing confirmed single base substitutions at codon 12 in two patients and at codon 13 in four. The incidence of N-ras gene mutations was significantly higher in the karyotypically evolved group (five of eight patients) than in the stable group (one of 27 patients). All of five patients harboring both karyotypic evolution and an N-ras mutation showed concomitant disease progression to overt leukemia or refractory anemia with excess of blasts in transformation (RAEB-T). Two of four patients with either karyotypic evolution or N-ras mutation and six of 26 patients without any of these alterations also progressed to overt leukemia. Our results indicate that the accumulation of these genetic alterations is closely associated with leukemic transformation of MDS, although other genetic alterations may also play a key role in the remaining patients.

Adult↗

[Translocation t(11;14) (q13;q32) in six patients with lymphoid malignancies of mature B-cell phenotype].

We described six patients with t(11;14)(q13;q32) in lymphoid malignancies. Based on the histologic or morphologic findings of these patients, malignant lymphoma diffuse large cell (ML-DL) was diagnosed in two patients, small lymphocytic (SL) in one, mantle zone lymphoma (MZL) in one, prolymphocytic leukemia (PLL) in one, and chronic lymphocytic leukemia with > 10% prolymphocytes (CLL/PL) in one. Three cases showed involvement of the gastro-intestinal tract, and four were leukemic. Five cases were dead 12 to 25 months after the time of chromosomal analysis. Immunological studies revealed that all the patients were positive for CD5, CD20, HLA-DR, and only one was weak positive for CD10. Using probe b, SstI-Sst I segment, Southern blot analysis showed the rearrangement of BCL-1 gene in a patient with MZL. Our results suggested that t(11;14) is found in lymphoid malignancies with mature B-cell phenotype and that hepatosplenomegaly, gastrointestinal involvement, leukemic manifestation, and poor prognosis are common clinical features.

Aged↗

Experimental study of the reversibility of sinusoidal capillarization.

This study investigated the reversibility of sinusoidal capillarization in fibrotic rat liver induced by thioacetamide (TAA; 200 mg/kg body weight three times a week). Six weeks later, collagen fibers and hepatic lobular disarrangement were observed on light microscopy and basement membrane formation was noted in the space of Disse. Sinusoidal endothelial fenestrations (SEFs) were decreased in size and number (defenestration), and factor VIII-related antigen was observed in the cytoplasm. We also clarified the phenotypic reversibility of the sinusoidal endothelial cells. After 4 months following discontinuation of TAA exposure, the diameters and numbers of SEFs were increased. Six months later, the basement membrane in the space of Disse disappeared (as assessed by electron microscopy) and 12 months later, factor VIII-related antigen also disappeared. These results indicate that phenotypical changes in the sinusoidal endothelial cells and sinusoidal capillarization in hepatic fibrosis may be reversed.

Animals↗

Significance of pre-S region-defective hepatitis B virus that emerged during exacerbation of chronic type B hepatitis.

A defective form of the hepatitis B virus has been found in a patient with chronic type B hepatitis. Sequence analysis of the viral DNA after polymerase chain reaction amplification revealed a 117-base pair deletion (nucleotides 3129-53, subtype adr). This deletion includes the initiation codon of the pre-S2 region and a newly created in-frame stop codon in the pre-S1 region (nucleotide 3055) located 230 base pairs downstream from the pre-S1 initiation codon. This virus coexisted with the wild-type virus during the exacerbation period, as evidenced by an elevation of serum transaminase levels. It was not detected in the stable period, and the blood chemistry results were normal. We assayed antibodies against the mutation-related region by enzyme immunoassay in serial serum samples to clarify the mechanism of the emergence of this variant virus. Antibodies against the pre-S2 region were negative; however, the antibody response against the pre-S1 epitopes coincided with the appearance of the variant virus. These findings suggest that an activated T-cell and B-cell response had developed against the pre-S1 region during hepatic inflammation in this patient and that, consequently, selection occurred for a pre-S antigen-defective mutant strain of the virus that might be resistant to such an immune response.

Adult↗

Minimum views required to characterize cataracts when using the Scheimpflug camera.

We performed Scheimpflug slit lamp photography and computerized image analysis on 20 normal and 25 cataractous lenses using 18 slit images for each lens taken 10 degrees apart. The data gathered from the normals served as the reference to estimate the accuracy of representation of the cataracts by the least number of views (18 and less) using a Fourier interpolative algorithm. Using the error obtained with one view for the normals, our study suggests that the minimum number of views necessary for adequate characterization is two for cortical cataracts, two for nuclear cataracts, and six for posterior subcapsular cataracts. This information will be useful in longitudinal studies of cataracts, since most researchers presently use only one view, which may be adequate for normals but not for cataractous lenses. We found the Fourier interpolative algorithm useful in estimating the minimum views required for the current method of analyzing Scheimpflug images, and it can be easily applied to other similar images.

Algorithms↗

Hemodynamic characterization in experimental liver cirrhosis induced by thioacetamide administration.

Systemic and splanchnic hemodynamics in experimental liver cirrhosis in rats induced by thioacetamide were evaluated by the radioactive microsphere method. Cardiac output and regional blood flow were measured in conscious and anesthetized control and cirrhotic rats. The conscious thioacetamide-treated rats had hyperdynamic circulation with an increased cardiac index (300 +/- 10 vs 258 +/- 3 ml/min/kg body weight, P < 0.001) and increased portal venous inflow compared with the controls (64.60 +/- 2.4 vs 48.39 +/- 0.88 ml/min/kg body weight, P < 0.001). Under pentobarbital anesthesia, the hyperdynamic circulation of the cirrhotic rats was maintained, with an increased cardiac index (276 +/- 7 vs 229 +/- 5 ml/min/kg body weight, P < 0.001) and increased protal venous inflow compared with the controls (72.47 +/- 3.0 vs 54.08 +/- 1.2 ml/min/kg body weight, P < 0.001). Portal pressure, portal venous resistance, and portal systemic shunting increased significantly while splanchnic arterial resistance decreased significantly in cirrhotic rats. Thioacetamide-induced cirrhosis is a useful model for the hemodynamic study of portal hypertension and remains useful in hemodynamic studies in the basal state under pentobarbital anesthesia.

Anesthesia, General↗