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Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 163 records · Page 9Linked to original sources
PubMed1998

The benefits and risks of n-3 polyunsaturated fatty acids.

There is a growing number of animal models and clinical trials of n-3 polyunsaturated fatty acid (PUFAs) supplementation in disease. Epidemiologic and biochemical studies have suggested beneficial effects of n-3 PUFAs. But also, the use of n-3 PUFAs has some potential toxicological risks that can be circumvented by careless processing, storing, and preserving the PUFAs. The use of n-3 PUFAs is safe if appropriate preparations and dosages are selected. Much research is needed to clarify their use under different disease conditions. The newly established clinical and nutritional facts on n-3 PUFAs will induce industry to develop food products based on this knowledge.

Cardiovascular Diseases↗
PubMed1998

Induction chemotherapy followed by reduced-volume radiation therapy for newly diagnosed central nervous system germinoma.

OBJECT: Although curative, radiation, which is conventionally administered for germinomas, causes significant neurological sequelae. This study aimed at reducing the volume and dose of radiation to a localized level of 24 Gy by pretreating the patient with chemotherapy. METHODS: Seventeen patients were divided into two risk groups based on serological findings and the extent of tumor. They were treated with chemotherapy prior to receiving localized radiation therapy. Six patients with solitary pure germinomas were treated with three or four cycles of cisplatin and etoposide (EP regimen) followed by 24-Gy local radiation therapy. Eleven patients with human chorionic gonadotropin (HCG)-secreting, multifocal, or disseminated germinomas received four to five cycles of ifosfamide, cisplatin, and etoposide (ICE regimen) followed by 24-Gy local radiation therapy. Craniospinal ports were used only in three cases of germinomas with dissemination. Gross-total resection was performed in three patients. Fourteen patients were able to be evaluated for their responses to chemotherapy. All patients achieved a complete response within three cycles. At a median follow-up duration of 24 months, 16 patients (94%) were alive without recurrence. One patient with an HCG-secreting germinoma experienced recurrence 38 months after surgery. That patient underwent successful salvage therapy using the same protocol. Thus, all 17 patients became free of disease with a 70 to 100% Karnofsky Performance Scale status. Toxicities associated with this study's chemotherapy regimen were mostly transient. No patient showed neurological or endocrinological deterioration during the follow-up period. CONCLUSIONS: The EP and ICE regimens were highly effective in treating the central nervous system germinomas and permitted dose and volume reduction of the radiotherapy. Localized 24-Gy irradiation was sufficient for disease control.

Adolescent↗
PubMed1998

Teratomas of the central nervous system: treatment considerations based on 34 cases.

OBJECT: The optimum clinical management of central nervous system (CNS) teratomas, particularly postsurgical adjuvant therapy, is still unclear, partly as a result of the tumors' low incidence. In this study the authors analyze 34 cases of CNS teratomas so that they may adequately indicate management of these lesions. METHODS: The median age of the 34 patients was 13 years. Twenty-seven patients treated between 1970 and 1991 were retrospectively reviewed. Four of these 27 patients died as a result of radical surgery; each of them had a teratoma involving the hypothalamus. After initial treatment, which included radiation therapy, 20 patients (48%) had died. In all seven cases of mature teratomas there was no recurrence. In two cases of immature teratomas in which there was complete surgical resection there was recurrence; however, salvage therapies were effective. Seven of eight patients with highly malignant teratomas died; for these patients salvage therapies, including repeated radiation and chemotherapy, failed. Seven patients who presented with CNS teratomas between 1992 and 1996 received adjuvant chemotherapy and radiation therapy according to a prospective study protocol. All seven patients were free from recurrence with a 70 to 100% Karnofsky Performance Scale score at a median follow-up period of 41 months. Patients with CNS teratomas rarely responded completely to chemotherapy or radiation therapy; an effective adjuvant therapy produced a partial response at best. CONCLUSIONS: Because teratomas show various responses to adjuvant therapy, a misdiagnosis of their histological subtype will lead to inadequate therapy. A diverse therapeutic protocol based on histological diagnosis is necessary to plan appropriate management. Treatment recommendations are discussed in detail in the article.

Adolescent↗
PubMed1998

[Two cases of true hermaphrodite: the usefulness of laparoscopic gonadectomy in childhood. A case report].

Laparoscopic operation has been an alternative method in not only adults but children. We presented two children with true hermaphroditism who were performed by open gonadectomy and laparoscopic gonadectomy respectively. Both patients at the age of 4, and 2 years showed karyotypes of 46, XX, and were raised as girls. In the first case left ovary and right ovotestis were revealed by open gonadal biopsy and right ovotestis was removed by open surgery. In another case bilateral ovotestes were revealed by laparoscopic gonadal biopsy and resected by laparoscopic procedure. Laparoscopy was very useful for detecting the gonadal structures to confirm the diagnosis in intersex patients. True hermaphrodite is one of uncommon intersex anomalies, therefore the diagnosis should be made to demonstrate the coexistence of both ovarian and testicular tissues definitely. We estimated laparoscopic gonadectomy in pediatric true hermaphrodite and concluded that laparoscopic gonadectomy was as profitable as open gonadectomy.

Child, Preschool↗
PubMed1997

High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay.

To determine the timing and actual incidence of p53 mutations in oral epithelial lesions, we examined 33 primary squamous cell carcinomas (SCCs), 14 dysplasias and six hyperplasias from Japanese patients by a combination of yeast functional assay and DNA sequencing. The assay detects mutations of p53 mRNA between codons 67 and 347 on the basis of the DNA-binding activity of the protein. Twenty-six SCCs (79%) and five dysplasias (36%) were positive for p53 mutation, while all six hyperplasias were negative for the mutation. Human papillomavirus type 16 E6 mRNA was detected in one of seven p53 mutation-negative SCCs by reverse transcription polymerase chain reaction (RT-PCR). We further examined p53 mutations in 17 Sri Lankan oral SCCs using the yeast functional assay and the single-strand conformation polymorphism analysis of PCR-amplified DNA fragments (PCR-SSCP) of exon 5-8. The mutations were confirmed by DNA sequencing and the detection sensitivity was compared between the two methods. Six samples (35%) were positive for p53 mutation in PCR-SSCP analysis, while nine samples (53%) were positive in yeast functional assay. This suggests that the incidence of p53 mutations has been considerably underestimated in the conventional SSCP analysis. The present data indicate that p53 mutations are extremely frequent in oral cancers in the Japanese, and suggest that the timing and significance of p53 mutation in oral tumor progression vary in different ethnic populations and areas.

Adult↗
PubMed1997

Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells.

Genomic reprogramming of primordial germ cells (PGCs), which includes genome-wide demethylation, prevents aberrant epigenetic modifications from being transmitted to subsequent generations. This process also ensures that homologous chromosomes first acquire an identical epigenetic status before an appropriate switch in the imprintable loci in the female and male germ lines. Embryonic germ (EG) cells have a similar epigenotype to PGCs from which they are derived. We used EG cells to investigate the mechanism of epigenetic modifications in the germ line by analysing the effects on a somatic nucleus in the EG-thymic lymphocyte hybrid cells. There were striking changes in methylation of the somatic nucleus, resulting in demethylation of several imprinted and non-imprinted genes. These epigenetic modifications were heritable and affected gene expression as judged by re-activation of the silent maternal allele of Peg1/Mest imprinted gene in the somatic nucleus. This remarkable change in the epigenotype of the somatic nucleus is consistent with the observed pluripotency of the EG-somatic hybrid cells as they differentiated into a variety of tissues in chimeric embryos. The epigenetic modifications observed in EG-somatic cell hybrids in vitro are comparable to the reprogramming events that occur during germ cell development.

Alleles↗
PubMed1997

Nitric oxide as a carcinogen: analysis by yeast functional assay of inactivating p53 mutations induced by nitric oxide.

We have used a yeast p53 functional assay to study induction of mutations in the p53 tumor suppressor gene by nitric oxide and cytosine methylation. The yeast assay identifies only biologically important p53 mutations. p53 cDNA was treated with the nitric oxide donor sydnonimine, PCR-amplified and transfected into yeast. Sydnonimine produced a significant, dose-dependent increase in C:G-->A:T transversions. Many important p53 mutational hotspots are postulated to arise by deamination of methylCpG in tumors. We therefore examined nitric oxide induction of mutations in p53 cDNA methylated by PCR-mediated substitution of 5-methylcytosine for cytosine or by treatment with the SssI CpG methylase. Both methylation procedures increased the baseline mutation rate, and nitric oxide treatment produced a further increase in mutation yield. Sequence analysis showed that methylation alone led to C:G-->T:A transitions, whereas nitric oxide treatment simply produced more C:G-->A:T transversions. Thus the most important factor in C:G-->T:A transition at CpG sites identified in this experimental system is cytosine methylation, consistent with spontaneous conversion of 5-methylcytosine to thymine by deamination.

Carcinogens↗
PubMed1997

Phospholamban inhibitory function is activated by depolymerization.

Phospholamban (PLN), a homopentameric, integral membrane protein, reversibly inhibits cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity through intramembrane interactions. Here, alanine-scanning mutagenesis of the PLN transmembrane sequence was used to identify two functional domains on opposite faces of the transmembrane helix. Mutations in one face diminish inhibitory interactions with transmembrane sequences of SERCA2a, but have relatively little effect on the pentameric state, while mutations in the other face activate inhibitory interactions and enhance monomer formation. Double mutants are monomeric, but loss of inhibitory function is dominant over activation of inhibitory function. These observations support the proposal that the SERCA2a interaction site lies on the helical face which is not involved in pentamer formation. Four highly inhibitory mutants are effectively devoid of pentamer, suggesting that pentameric PLN represents a less active or inactive reservoir that dissociates to provide inhibitory monomeric PLN subunits. A model is presented in which the degree of PLN inhibition of SERCA2a activity is ultimately determined by the concentration of the inhibited PLN monomer.SERCA2a heterodimeric complex. The concentration of this inhibited complex is determined by the dissociation constant for the PLN pentamer (which is mutation-sensitive) and by the dissociation constant for the PLN/SERCA2a heterodimer (which is likely to be mutation-sensitive).

Animals↗
PubMed1997

Heterogeneous zonal distribution of sulfotransferase isoenzymes in rat liver.

By employing dual-digitonin-pulse perfusion technique, the cytosolic fractions were prepared from periportal (PP) and perivenous (PV) hepatocytes of male and female rat livers. Sulfotransferase (ST) activities toward 2-naphthol (2NAP) (at pH 5.5 and 7.4), 4-nitrophenol, dehydroepiandrosterone (DHEA), and cortisol were measured in each fraction. DHEA-ST activity was mainly localized in PP fraction in males, while in females it was slightly higher in PP fraction than in PV samples. In contrast, phenol ST activities were higher in PV fraction in both sexes. With anti-HS-ST and anti-P-ST antisera, the levels of immunoreactive ST polypeptides were compatible with the levels of ST activities except that in female PP fraction the level of immunoreactive P-ST polypeptide was low in spite of comparatively high levels of P-ST activities. Chromatofocusing of PP and PV fractions separated P-ST activities into three major fractions (I-III), which have distinct catalytic and electrochemical properties. Fraction I was localized only in the PP samples in both sexes and revealed ST activities toward 2NAP at pH 5.5 and 7.4, while fraction II was localized in the PP and PV samples in both sexes with 2NAP-ST activity only at pH 7.4. Fraction III which had ST activities at pH 5.5 and 7.4 was present only in the PV samples in female rats, whereas in male rats it was present in both PP and PV samples. With anti-P-ST antiserum, the immunoreactive polypeptide was present in fraction III, but no immunoreactive band was detected in fractions I and II, suggesting the presence of immunochemically and electrochemically different P-ST(s) in these fractions.

Age Factors↗
PubMed1997

Epstein-Barr virus infection in non-carcinomatous gastric epithelium.

Gastric tissue specimens from 20 patients with chronic atrophic gastritis, one of whom also had an early gastric carcinoma, were studied for evidence of Epstein-Barr virus (EBV) infection by Southern blot analysis, DNA and RNA in situ hybridization, and immunohistochemistry for the presence of the EBV-determined nuclear antigen 1 (EBNA-1) and the latent membrane protein 1 (LMP-1). EBV DNA was detected in two cases with chronic atrophic gastritis and in the case with early gastric carcinoma by Southern blot hybridization. DNA in situ hybridization showed EBV genomes in the epithelial cells of two other cases with chronic atrophic gastritis and in non-carcinomatous and carcinomatous epithelial cells of the early gastric carcinoma case. EBNA-1 was detected in all cases. LMP-1 was detected in areas of intestinal metaplasia in eight patients with chronic atrophic gastritis. EBV-encoded small RNA 1 (EBER-1) expression was limited to carcinoma cells. These results show that gastric epithelium is frequently infected with EBV and suggest that prolonged EBV persistence may contribute to the development of gastric carcinoma.

Adult↗
PubMed1997

Heat shock-induced manganese superoxide dismutase enhances the tolerance of cardiac myocytes to hypoxia-reoxygenation injury.

We evaluated the mechanism of the heat shock-induced tolerance to ischemia-reperfusion using a model of hypoxia-reoxygenation tolerance in neonatal rat cardiac myocytes. Myocytes exposed to heat shock (42 degrees C, 1 h) exhibited a 1.8-fold increase in levels of manganese superoxide dismutase (Mn-SOD) mRNA after 40 min v control cells. The concentration of Mn-SOD increased from 0.49+/-0.04 microg/mg protein to 0.68+/-0.05 microg/mg protein after 24 h (P<0. 05). Levels of heat shock protein 72 (hsp72; inducible form) mRNA and protein also increased markedly after heat shock exposure. The release of creatine kinase (CK) from the myocytes and the depletion of ATP level in the myocytes exposed to hypoxia (pO2: 7 mmHg, 3 h) and reoxygenation (pO2: 143 mmHg) were significantly reduced following heat shock pretreatment (CK: 1.18+/-0.14 U/l v 0.62+/-0.13 U/l, ATP: 11.9+/-1.1 nmol/mg protein v 16.2+/-1.0 nmol/mg protein, P<0.05). Treatment with antisense oligodeoxyribonucleotides to Mn-SOD (1.5 micromol/l) completely inhibited the heat shock-associated induction of Mn-SOD (0.47+/-0.05 microg/mg protein), but not hsp72, and abolished the heat shock-induced decrease in CK release (1.04+/-0.15 U/l, P<0.05) and depletion of ATP level (11. 2+/-1.1 nmol/mg protein, P<0.05). Results indicate that Mn-SOD induction, not hsp72 induction, plays a pivotal role in the heat shock-induced acquisition of tolerance to hypoxia-reoxygenation in neonatal rat cardiac myocytes.

Animals↗
PubMed1997

Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart.

We compared the time course of tolerance to myocardial ischemia-reperfusion injury with the time course of heat shock protein 72 (hsp72; inducible form) induction after heat stress in a rat model. The size of the infarct resulting from ischemia-reperfusion was increased 12 h after whole-body hyperthermia (42 degrees C for 15 min), but was significantly decreased 48 and 72 h after hyperthermia, compared with the sham control. The infarct size was decreased as late as 96 h after hyperthermia, although the infarct-limiting effect was smaller at that time. The myocardial content of hsp72 was markedly increased for 3-72 h after hyperthermic treatment, and was decreased after 72 h in association with an increase in the infarct size. The hsp72 content remained elevated during the period of tolerance to ischemia-reperfusion injury, but the infarct size decreased after the hsp72 content peaked. Pretreatment with a protein kinase C (PKC) inhibitor, chelerythrine chloride, immediately before hyperthermia, significantly suppressed the delayed cardioprotective effect of hyperthermia and reduced hsp72 induction. These results suggest that newly synthesized hsp72 through PKC activation after heat stress may have to be post-translationally modified and compartmentalized prior to assuming to the development of the delayed tolerance to ischemia-reperfusion injury in rats.

Animals↗
PubMed1997

99mTc-HSA-D scintigraphy in the diagnosis of protein-losing gastroenteropathy due to secondary amyloidosis.

Secondary amyloidosis frequently involves the gastrointestinal tract and may result in ulceration, hemorrhage, and protein-losing enteropathy. We report a patient with severe hypoalbuminemia in whom endoscopy revealed widespread ulceration of the small intestine. The protein-losing site was detected by 99mTc-diethylene triamine pentaacetic acid human serum albumin (99mTc HSA-D) scintigraphy. This evidence suggests that the ulcers and mucosal lesions associated with amyloidosis contribute to abnormal protein loss from the gastrointestinal tract.

Aged↗
PubMed1997

Osteoregenerative lateral suboccipital craniectomy using fibrin glue.

This report describes a simple technique of cranioplasty for suboccipital craniectomy and the results of a clinical study to assess the effects of fibrin glue on regeneration of the skull. Cranioplasty using a mixture of autologous bone chips and human allogenic fibrin glue was performed in 31 patients who received lateral suboccipital craniectomy. Long-term observations with three-dimensional CT showed satisfactory reconstruction of the mastoid-occipital bone plate in 25 patients (81%); among them, a nearly complete reconstruction of the occipital bone (plate) was found in 14 patients. Regeneration of the bone began 6 months after surgery on the inner surface, adjacent to the dura mater. In conclusion, the present technique provides a new simple method to restore an autologous bone plate in a cranial defect made by piecemeal craniectomy.

Adolescent↗
PubMed1997

Feasibility of the transparent cap-fitted colonoscope for screening and mucosal resection.

PURPOSE: A transparent plastic cap of 17 mm in outer diameter, 15 mm in inner diameter, and 10 mm in length can be easily attached to the tip of a colonoscope. By using the cap, a better view of the lesions hiding at the opposite side of the fold can be obtained. When a flat colonic lesion is found, a submucosal injection of saline solution is performed, the target mucosa is sucked inside the cap, snared under a full endoscopic suction, and resected by an electrical current. This procedure is called endoscopic mucosal resection using transparent cap-fitted endoscope (EMRC). Feasibility of the cap-fitted colonoscope for screening colonoscopic examination and mucosal resection was evaluated. MATERIALS AND METHODS: One hundred forty patients were randomly allocated for screening with a normal colonoscope (NCF) or that with the cap-fitted colonoscope (CCF). Average time for insertion up to the cecum, patients' discomfort during insertion expressed in 4 degrees, and average number of lesions found in one patient were compared. Thirty lesions randomly allocated for mucosal resection with conventional strip biopsy or EMRC were also evaluated. RESULTS: Time consumed for insertion up to the cecum with the CCF (12.4 +/- 6.6 minutes) was the same as that with the NCF (12.3 +/- 5.2 minutes), and there was no significant difference in patients' discomfort; however, the average number of lesions found in one patient was larger when using the CCF (0.86 +/- 0.96) than when using the NCF (0.58 +/- 0.81). For mucosal resection, 40 flat or wide-based lesions including 6 mucosal carcinomas were resected with EMRC. We experienced only one pinhole perforation of the ascending colon by heat damage, which was treated successfully by surgery. There was no other major complication or recurrence. CONCLUSION: The cap-fitted endoscope was equal in maneuverability, was excellent in sensitivity in comparison with the regular colonoscope, and was thought to be feasible both in screening and mucosal resection.

Aged↗