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Biomedical subjects

T Hashida

Publications and source records attributed to T Hashida.

At least 37 records · Page 2Linked to original sources

[Chemotherapy for B lymphoid malignancy in childhood--results in BLK88 protocol].

Ten cases of newly diagnosed pediatric B cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia (B-NHL, stage I & II 6 cases, stage III & IV 2 cases/ALL 2 cases) experienced during the last 7 years (1987-1994) were treated by BLK88 protocol, which consisted of HD-CPM (1,200 mg/m2), and HD-MTX (1,000 mg/m2) with VCR, ADR, and/or AraC combination, and CNS prophylaxis by triple intrathecal injection. The therapy duration was 24 weeks for B-NHL (36 weeks for B-ALL). The results showed that while one of the six cases in stage I & II relapsed, and other 4 cases of stage III & IV B-NHL/ALL remained in complete remission. On the other hand, all of the four cases in stage III & IV in historical controls had relapsed. Neutropenia and liver dysfunction were observed during therapy, but they were tolerable. We conclude that BLK88 is a very useful protocol for B-NHL/ALL in childhood.

Adolescent↗

A proposal of FK506 optimal dosing in living related liver transplantations.

We analyzed the relation between FK506 trough levels (ELISA: patients 1-41, IMx: patients 42-70) and rejection and/or viral infection episodes, retrospectively, in the first 70 consecutive cases of living related liver transplantation. Twenty patients (28.6%) had rejection episodes. Of the 13 patients who had evidence of rejection during the first 3 months, 6 patients without infection and 7 patients with viral infection showed low concentrations of FK506 (< 5 ng/ml). Twelve patients were treated and improved with high dose steroid administration and an increase in the FK506 dosage. One patient died of refractory rejection. Nine patients had evidence of rejection after the first 3 months. In 3 patients, weaning from FK506 initiated the rejection episodes. Five patients repeated rejection and 4 patients required a third immunosuppressant (azathioprine). Viral infection included CMV (11 cases), EBV (13 cases), HZV (3 cases), and HSV (1 case). Excess immunosuppression might have been the cause, but no clear correlation was found. We propose that the optimal dosage of FK506 obtained by monitoring the trough levels using the IMx method should maintain a 10-20 ng/ml level during the first month, and a 5-10 ng/ml level at the second and third months.

Adolescent↗

Serum and urine beta-2-microglobulin in hemophagocytic syndrome.

BACKGROUND: Previous reports suggesting a correlation between lymphoproliferative disease and serum levels of beta-2-microglobulin (beta-2M) and in vitro data indicating a role of cytokines in the production of beta-2M prompted a study of serum and urine beta-2M concentration in patients with hemophagocytic syndrome (HPS), because no data were previously available for HPS, a pathologic state associated with excessive cytokines secreted from activated reactive/malignant lymphocytes and histiocytes. METHODS: Serum and urine beta-2M levels were measured in six children with HPS during active and convalescent phase and in other diseases. RESULTS: Serum and urine beta-2M levels during active phase HPS were significantly high not only in serum (median, 7.5 mg/l; range, 2.3-16.0 mg/l; P < 0.01), but also in urine (median, > 31,650 micrograms/gram Creatinine (gCr); range, 8179-236,333 micrograms/gCr; P < 0.01), compared with levels during convalescent phase HPS (median, 2.0 mg/l; range, 0.9-2.5 mg/l in serum and median, 338 micrograms/gCr; range, 223-585 micrograms/gCr in urine) and in control subjects with diseases such as acute lymphocytic leukemia (median, 2.3 mg/l; range, 1.0-2.8 mg/l in serum and median, 327 micrograms/gCr; range, 48-2684 micrograms/gCr in urine), infectious mononucleosis (median, 2.9 mg/l; range, 2.5-5.5 mg/l in serum and median, 348 micrograms/gCr; range, 80-1325 micrograms/gCr in urine), and Kawasaki disease (median, 2.8 mg/l; range, 1.5-3.3 mg/l in serum and median, 1016 micrograms/gCr; range, 214-4500 micrograms/gCr in urine). Noteworthy was the observation that urine beta-2M levels correlated closely with HPS disease activity. CONCLUSIONS: Urine beta-2M appears to be a useful marker for assessing disease activity in patients with HPS.

Adolescent↗

Change of salivary IgA secretion and caries development in irradiated rats.

Xerostomia is a serious side-effect of radiotherapy for head and neck cancer and often enhances caries activity. However, the relationship between caries induction and the IgA level in saliva in rats subjected to irradiation of the salivary glands is unclear. The effect of salivary gland irradiation on salivary function was examined in specific pathogen-free Sprague-Dawley rats infected with or without Streptococcus mutans MT8148R (serotype c). The flow rate of saliva and the protein concentration in saliva were significantly reduced in irradiated rats, regardless of infection of S. mutans. The caries activity was enhanced in these rats, and and irradiation level of 50 Gy significantly increased the caries score. However, longitudinal study indicated that the salivary concentration of IgA reactive with S. mutans whole cells maintained similar or significantly higher levels in irradiated rats, when compared with those of nonirradiated rats. In addition, there was no negative correlation between the caries score and the salivary concentration of IgA reactive with S. mutans. These findings suggest that the secreted IgA against S. mutans may not play a significant role in the caries induction of hyposalivated rats.

Animals↗

Genomic structure of the human caldesmon gene.

The high molecular weight caldesmon (h-CaD) is predominantly expressed in smooth muscles, whereas the low molecular weight caldesmon (l-CaD) is widely distributed in nonmuscle tissues and cells. The changes in CaD isoform expression are closely correlated with the phenotypic modulation of smooth muscle cells. During a search for isoform diversity of human CaDs, l-CaD cDNAs were cloned from HeLa S3 cells. HeLa l-CaD I is composed of 558 amino acids, whereas 26 amino acids (residues 202-227 for HeLa l-CaD I) are deleted in HeLa l-CaD II. The short amino-terminal sequence of HeLa l-CaDs is different from that of fibroblast (WI-38) l-CaD II and human aorta h-CaD. We have also identified WI-38 l-CaD I, which contains a 26-amino acid insertion relative to WI-38 l-CaD II. To reveal the molecular events of the expressional regulation of the CaD isoforms, the genomic structure of the human CaD gene was determined. The human CaD gene is composed of 14 exons and was mapped to a single locus, 7q33-q34. The 26-amino acid insertion is encoded in exon 4 and is specifically spliced in the mRNAs for both h-CaD and l-CaDs I. Exon 3 is the exon that encodes the central repeating domain specific to h-CaD (residues 208-436) together with the common domain in all CaD (residues 73-207 for h-CaD and WI-38 l-CaDs, and residues 68-201 for HeLa l-CaDs). The regulation of h- and l-CaD expression is thought to depend on selection of the two 5' splice sites within exon 3. Thus, the change in expression between l-CaD and h-CaD might be caused by this splicing pathway.

Alternative Splicing↗

A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs.

Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.

Animals↗

Effects of hyposalivation on the oral microflora of rats fed sucrose or wheat flour diets.

The effects of hyposalivation on the induction of dental caries and on the composition of the oral microflora were examined in specific pathogen-free Sprague-Dawley rats fed either a sucrose or a wheat flour diet with or without inoculation of Streptococcus mutans. Significant dental caries was induced in hyposalivated rats fed diet 2000 containing 56% sucrose, irrespective of infection by S. mutans. Diets containing 56% wheat flour did not induce dental caries in either hyposalivated or sham-operated rats, irrespective of infection by S. mutans. Bacteriological examinations at the end of the experiment demonstrated that the total numbers of lactobacilli and staphylococci increased in hyposalivated rats irrespective of the diet given, while the inoculated stain of S. mutans decreased significantly in hyposalivated rats. These findings suggest that some acidogenic microorganisms such as lactobacilli and staphylococci that can utilize sucrose or glucose but not wheat flour may also promote dental caries in hyposalivated rats.

Animals↗

Preliminary nuclear magnetic resonance studies on human saliva.

Of gustatory-stimulated human whole, parotid, submandibular and sublingual saliva only parotid saliva, a serous rather than mucous secretion, presented a relatively well-resolved proton NMR spectrum with satisfactory signal-to-noise ratio in a short time (30 min). The proton signal intensities showed significant circadian rhythms related to the circadian rhythms of protein concentrations in saliva. Age- and sex-associated differences in spectra were not observed for healthy saliva. On the other hand, marked differences in the spectra were observed for patients with suspected sialoadenitis.

Adult↗

Induction of chromosome abnormalities in mouse and human epidermal keratinocytes by the human papillomavirus type 16 E7 oncogene.

Cytogenetic abnormalities associated with human papillomavirus (HPV) type 16 were studied using primary human and mouse epidermal keratinocytes. The E7 transforming gene of HPV-16 was found to induce chromosome duplication in epidermal keratinocytes; little or no detectable chromosome disorganization was associated with the function of the E6 gene. These results suggest that the E7 gene-linked cytogenetic effect reflects HPV-16-associated pathogenicity in the early phase of transformation.

Aneuploidy↗

Dental caries induction in hyposalivated rats.

The effects of hyposalivation on the induction of dental caries and on the oral microflora were examined in SPF Sprague-Dawley rats with or without inoculation of oral streptococci. Significant dental caries was induced in hyposalivated rats, irrespective of the infection with oral streptococci including Streptococcus mutans. In addition, bacteriological analyses demonstrated that the total number of lactobacilli increased significantly at the expense of the inoculated streptococci. These findings suggest that opportunistic infections may be induced in the oral cavity of hyposalivated rats and some acidogenic microorganisms including lactobacilli may promote the induction of dental caries.

Animals↗

Casein kinase II activities related to hyperphosphorylation of human papillomavirus type 16-E7 oncoprotein in epidermal keratinocytes.

The present study describes hyper-phosphorylation of E7-oncoprotein of human papillomavirus (HPV) type 16 in epidermal keratinocytes. We found that highly phosphorylated E7-oncoprotein was present in epidermal keratinocytes but little in fibroblasts. The E7 oncoprotein contains serine residues (Ser-Ser-Glu-Glu-Glu) capable of being phosphorylated by casein kinase II (CK II). Extracts from various cell lines including human origins transformed by HPV 16 were examined for the casein kinase activity. The results showed that CK II activity was present at significantly high levels in keratinocytes but little or no detectable levels of the activity in human fibroblasts. These differential CK II activities in host cells may play a part in the differential transforming activity by E7-oncoprotein.

Amino Acid Sequence↗

Effect of experimental hyposalivation on the induction of dental caries in rats infected with Streptococcus mutans.

The effects of hyposalivation on the induction of dental caries were examined in specific pathogen-free Sprague-Dawley rats infected with Streptococcus mutans MT8148R and fed the caries-inducing diet 2000. Hyposalivation was induced by either irradiation or surgical removal of salivary glands in 30-day-old rats. After either procedure, severe dental caries was induced in the rats when examined at 84 days of age, and a statistically significant correlation was found between caries scores and flow rates of saliva. However, the recovery of strain MT8148R from hyposalivated rats was not always high, and it is possible that microorganisms other than the inoculated S. mutans strain MT8148R may have played a role in promoting dental caries.

Animals↗