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Biomedical subjects

M Miyahara

Publications and source records attributed to M Miyahara.

At least 109 records · Page 6Linked to original sources

An autopsy case of intracranial hemorrhage during tissue plasminogen activator infusion.

We describe an autopsy case of severe intracranial hemorrhage which occurred during the infusion of tissue plasminogen activator (t-PA) for acute myocardial infarction. A 75-year-old man was admitted with substernal chest pain of 3-h duration and electrocardiographic changes consistent with an acute inferior myocardial infarction. Physical examination was unremarkable, except for an initial blood pressure reading of 160/96 mmHg. The patient received 3,000 IU intravenous heparin followed by a 2.4 x 10(6) IU bolus dose of tissue plasminogen activator (t-PA) (Alteplase). This was followed by a drip infusion of 21.6 x 10(6) IU of t-PA over 1 h (total dose 41 mg). Thirty minutes after the infusion of t-PA was initiated, the patient suddenly lost consciousness and began to have violent convulsions, followed by cardiac arrest. Autopsy revealed massive hemorrhage in the bilateral cerebrum and brain stem. To our knowledge, this is the first case of sudden death during t-PA infusion therapy.

Aged↗

[Structure-activity relationship of flavonoids in suppressing rat liver lipid peroxidation].

145 flavonoids were studied for their inhibitory effects on the iron-induced lipid peroxidation in mitochondria obtained from rat livers. Of these compounds tested, 30, 57, 59, 67, 70, 72, 77, 102 and 110 (ED50 < or = 0.5 nmol/mg prot) showed distinctly more potent inhibitory activity than baicalein (ED50 < or = 5 nmol/mg prot) and 59 and 72 (ED50 < or = 0.05 nmol/mg prot) exhibited the most potent activity. In order to elucidate the relationships between substituents on the flavonoid skeleton and the biological activity, the quantitative structure-activity relationships (QSAR) were analyzed by the adaptive least-squares (ALS) method for 142 flavonoids. The analysis has shown that the presence of the 1,4- and 1,2-hydroquinone in A-ring and/or B-ring of flavonoids and hydrophobicity of the molecule are responsible for the in vitro inhibitory activity.

Animals↗

Cisplatin, vindesine, pepleomycin and combined radiation therapy for inoperable esophageal carcinoma.

Sixteen inoperable esophageal cancer patients, including six over 80 years of age, were given combined chemoradiation therapy. The treatment consisted of radiation therapy (50-60 Gy for 6-7 wk on days 1 to 46) combined with cisplatin (50 mg/m2 i.v. on days 22 and 50), vindesine (3 mg/m2 i.v. on days 22 and 50) and pepleomycin (5 mg i.m. on days 23 to 27 and 51 to 55). The treatment was well-tolerated. The overall response rate was 56%, with three complete responses and six partial responses. For 10 patients with loco-regional disease (stage II-III), the response rate was 70%. The overall median survival was 7 mo and the survival rate was 31% at one year and 23% at two years. For loco-regional disease, the one and two-year survival rates were 40 and 27%, respectively, with a median survival of 8 mo. The protocol is worthy of being considered for treating inoperable, poor-risk esophageal cancer patients.

Actuarial Analysis↗

Effect of indomethacin and aspirin on the TNF-alpha-induced priming and protein tyrosyl phosphorylation of human neutrophils.

Receptor-mediated superoxide (O2-.)-generation in human peripheral neutrophils (HPPMN) is enhanced by various priming agents, such as granulocyte colony stimulating factor (G-CSF) and tumor necrosis factor (TNF-alpha). We previously reported that this enhancement occurred in parallel with the priming agent-induced increase in protein tyrosyl phosphorylation which is sensitive to tyrosine kinase (TK) inhibitors [Akimaru K. et al. Arch. Biochem. Biophys. 298:703, 1992]. We describe here that nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and aspirin, modulate the priming and tyrosine phosphorylation of HPPMN. The enhancement by TNF-alpha of formylmethionyl-leucyl-phenylalanine (FMLP)-induced O2-. generation was not inhibited by 5 microM azide, whereas that of FMLP-induced luminol chemiluminescence (LCL) was sensitive. Enhancement of FMLP-induced O2-. generation and LCL by priming agents was inhibited by both aspirin and indomethacin in a concentration dependent manner. This inhibition by the NSAIDs was much stronger than that for FMLP-induced O2-. generation without priming. The half-inhibition dose of indomethacin and aspirin were 50 microM and 1.5 mM, respectively. The priming-induced enhancement of tyrosyl phosphorylation of some neutrophil proteins, such as that of 108 and 115 kDa, was also inhibited by aspirin and indomethacin in a dose-dependent manner. However, dose dependent inhibition of the enhanced O2-. generation by the NSAIDs was not completely similar to that of enhanced tyrosyl phosphorylation. However, PKC-mediated O2-. generation, which has little sensitivity to TNF-alpha or G-CSF, was rather stimulated by the NSAIDs. These findings suggest that aspirin and indomethacin inhibit also the early steps of neutrophil activation as reflected by their ability to inhibit priming and the related tyrosyl phosphorylation of neutrophil proteins.

Animals↗

[Restriction endonucleases: their characteristics and distribution in pathogenic bacteria].

Restriction endonucleases have been widely employed in almost all fields of genetic engineering including DNA mapping, cloning, sequencing, hybridization, amplification and diagnosis. The general characteristics of restriction endonucleases and their reactions are reviewed in this paper, together with their distribution in pathogenic bacteria. Many restriction endonucleases with novel specificity have been found in these bacteria in our laboratory. Some of them are commercially available and have been employed for the molecular biologist. Rapid method for detection of restriction endonucleases in pathogenic bacteria is also described.

Bacteria↗

Organ function index: a predictive marker of operative mortality based on multiple organ dysfunctions in patients with esophageal cancer.

To evaluate the risk of transthoracic esophagectomy for cancer based on the overall impairment of vital organs, we examined pulmonary, cardiac, renal and hepatic functions using 18 markers in 35 patients between 1982 and 1984. A discriminant analysis proved useful in determining whether or not the patients would be at risk of operative mortality (operative death and hospital death), based on the overall impairment of vital organs. The accuracy of the prediction of operative mortality by this model, the organ function index (OFI), was 91.4%. The OFI was then applied to 66 patients seen between 1986 and 1991. During this period, a change in policy for performing transthoracic esophagectomy and perioperative care on patients with impairment of multiple organs was associated with a decrease in operative mortality. We conclude the OFI to be beneficial in evaluating the risk of operative mortality based on mild to moderate dysfunctions of multiple vital organs in patients with esophageal cancer.

Aged↗

[Preoperative evaluation of malignant potential in esophageal carcinoma by nuclear DNA contents].

Employing surgically resected specimens from patients without preoperative radiation therapy, we measured the nuclear DNA contents in order to evaluate the malignant potential of esophageal carcinoma. The association of the DNA index (DI) > or = 1.7 and the intratumoral DNA heterogeneity of biopsy specimens from patients with or without preoperative radiotherapy was also analyzed in relation to problems related to preoperative evaluation of nuclear DNA contents using biopsy specimens and the influence of irradiation on nuclear DNA contents. Esophageal carcinomas in 128 cases were studied. Nuclear DNA content was measured for biopsy specimens as well as surgically resected tumors by flow cytometry according to the method of Hedley and colleagues. HET was found in 42% of surgically resected specimens, but in only 18% of biopsy specimens. In 90% of cases, dominant DI of the resected tumor was also found in the biopsy specimens. Cases of DI > or = 1.7 showed a poorer prognosis than those with DI < 1.7 in cases with preoperative radiotherapy (p < 0.05) as well as in those without it. These results indicated that DI can be an indicator for highly malignant potential of esophageal carcinoma when measuring nuclear DNA contents using not only biopsy specimens but also specimens from irradiated cases.

Cell Division↗

[The intensity of hst-1 gene amplification and malignant potential of esophageal carcinoma in relation to intratumoral heterogeneity].

Amplification of hst-1 gene is associated with poor prognosis in patients with esophageal carcinoma. Since there is a high frequency of DNA stem-line heterogeneity, we studied intratumoral heterogeneity of hst-1 amplification, and evaluated whether or not the intensity of hst-1 amplification is associated with the malignant potential of esophageal carcinoma. A total of 73 patients with esophageal carcinoma who had undergone esophagectomy were studied. Intratumoral heterogeneity of hst-1 amplification was examined in two to four sections of tumour specimens which showed mainly DNA heterogeneity in 27 of these patients. The judgement of hst-1 amplification in the same tumor was identical in all of the 27 patients, although its intensity was not identical in some cases. And in 73 patients, postoperative recurrence in organs showed a high incidence (78%) in the hst-1 amplification group with a high intensity (over 7-fold). Therefore, hst-1 amplification exceeding 7-fold can serve as an indicator to predict the high grade of malignant potential of esophageal carcinoma.

DNA, Neoplasm↗

Isolation and characterization of new restriction endonucleases from Vibrio parahaemolyticus: VpaK32I enzyme with the class-IIS heptanucleotide specificity, GCTCTTCN1/N4.

Six restriction endonucleases (ENases), classified into four different specificities, were found in a screen among 68 reference strains of Vibrio parahaemolyticus of human origin. Five of these ENases are isoschizomers of well-known ENases, while the remaining one, designated VpaK32I, is a novel and highly efficient class-IIS ENase with the hepatanucleotide recognition site, 5'-GCTCTTC(1/4)-3'.

Base Sequence↗

Impaired neutrophil bactericidal activity correlates with the infection occurring after surgery for esophageal cancer.

We examined whether or not preoperative impaired bactericidal activities of polymorphonuclear neutrophils (PMN) are associated with infections following surgery for esophageal cancer. Intracellular killing (KI), superoxide anion-producing capacity (SOP), and myeloperoxidase (MPO) activity were measured in 22 patients with esophageal cancer, 27 with gastric cancer, and 13 age-matched controls. The average level of KI was significantly depressed in patients with esophageal cancer or with gastric cancer, to a similar extent, compared to findings in controls, but SOP was not. In esophageal cancer patients, the SOP level was significantly higher in those with postoperative septic complications than in those without such problems, whereas the KI level was depressed to a similar extent in both. Therefore, a depression of KI with elevation of SOP of PMN may serve to predict complications of infection following surgery in patients with esophageal cancer.

Adult↗

Adenoma of the nipple.

We report herein a case of a 42 year old woman with adenoma of the nipple of her left breast. The diseased nipple was enlarged, reddened and a hard elastic mass was palpable within its substance. There was an area of eczematoid erosion on the surface. Incisional biopsy revealed a picture of adenoma and therefore the nipple was excised. Five years postoperatively, there has been no recurrence of the disease. To our knowledge, only thirteen cases of adenoma of the nipple have been reported in the Japanese literature. Some clinical features and treatments are discussed in a review following the case report. Although rare, adenoma of the nipple should be borne in mind to avoid a misdiagnosis of malignancy and unnecessarily extensive surgery.

Adenoma↗

Factors contributing to deficiencies in cell-mediated immunity in esophageal cancer patients.

Based on the previous data which indicated a preoperative decrease in cell-mediated immunity (CMI) is associated with the occurrence of infectious complications following surgery on patients with esophageal cancer, we examined possible factors contributing to a decrease in CMI levels. A multiple linear regression analysis was made on data from 76 patients with esophageal cancer and 53 with gastric cancer as the control. In patients with esophageal cancer, both protein-calorie malnutrition (PCM) and age factor contributed to a decrease in CMI, although the contribution of the latter was weak while the stage of the cancer and the grade of dysphagia showed no such contribution. The PCM and stage of the cancer were contributing factors in patients with gastric cancer. Thus, these results indicate that PCM and old age, and not the presence of malignant tumors, play a significant role in deficiency in CMI in patients with esophageal cancer.

Age Factors↗

Increases in immunoglobulin and complement in patients with esophageal or gastric cancer.

Based on data providing evidence that the enhancement of serum IgG and IgA is associated with the occurrence of infectious complications following surgery in patients with esophageal cancer, we examined the possible factors contributing to alterations in the serum IgG, IgA, IgM, C3, C4, and CH50 levels. A multiple linear regression analysis was made on data obtained from 71 patients with esophageal cancer and 57 with gastric cancer. In the patients with esophageal cancer, age and protein-calorie malnutrition (PCM) were related to the elevation of IgG levels while the stage of cancer was linked to that of IgA. The sex and IgM levels were also seen to be related. Age and the stage of cancer were associated with reductions in C3, C4, and CH50 levels, although in the patients with gastric cancer, the stage of cancer and elevations of these complement levels were related. Thus, age, PCM, and tumor malignancy are all factors related to the enhancement of IgG or IgA in patients with esophageal cancer.

Adenocarcinoma↗

Primary anorectal malignant melanoma.

A case of primary anorectal malignant melanoma seen in a 46 year old woman is presented herein. Her most marked symptoms were bloody stools and anal pain. Endoscopic examination indicated a tumor with ulceration but without pigmentation in the anorectal region. Histologic examination of the biopsied specimens showed spindle-shaped cells with atypia proliferating in a bandlike arrangement, as in leiomyosarcoma. An abdominoperineal resection was done and detailed histological examination of the tumor confirmed the nature of the tumor to be malignant melanoma. The postoperative immunochemotherapy consisted of Dimetyl-Triazeno-Imidasole-Carboxamide (DTIC), Amino-Methyl-Pyrimidinyl-Methyl-Chlorethyl-Nitrosourea-Hydrochlori de (ACNU), Vincristine (VCR) and OK-432. The patient has been well without recurrence for fifteen months following her operation through the continuous administration of these agents.

Antineoplastic Agents↗

Experimental study on Reye's syndrome: inhibitory effect of interferon alfa on acetylsalicylate-induced injury to rat liver mitochondria.

Viral infection and acetylsalicylate (ASA)-induced mitochondrial aberration have been reported to play important roles in the pathogenesis of Reye's syndrome. We report that increasing amounts of ASA (0 to 250 mumol/L) resulted in increases in state 4 respiration and decreases in state 3 respiration in rat liver mitochondria in vitro when using alpha-ketoglutarate and/or beta-hydroxybutyrate as respiratory substrates, but not when using succinate as substrate. Interferon alfa (IFN-alpha) (1.5 to 5 x 10(4)IU/mL, approximately 1/100 the therapeutic dosage for humans) and interleukin-1 (IL-1) (1.5 to 2 x 10(4)IU/mL, nearly equivalent to the therapeutic dosage) decreased the severity of the above effects via interaction with mitochondrial membranes. Interferon gamma (IFN-gamma) and interleukin-2 (IL-2) had no such protective effect. Electron microscopic observation indicated that IFN-alpha prevented the induction of mitochondrial swelling by ASA. These results suggest that IFN-alpha may prove to be effective for the treatment of Reye's syndrome.

Animals↗

The influence of chloro-substituent sites of hexachlorobiphenyl on the respiration of rat liver mitochondria.

The actions of three hexachlorobiphenyls (HCBs) 2,3,4,2',3',4'-, 2,3,4,3',4',5'- and 3,4,5,3',4',5'-HCBs, on the respiration of rat liver mitochondria with succinate as the substrate were compared, and the effect of chloro-substitution sites in HCB on the respiration was examined. 2,3,4,2',3',4'-HCB strongly inhibited both state 3 and 2,4-dinitrophenol (DNP)-stimulated respiration with 50% inhibition dose of 52 and 54 microM for state 3 and DNP-stimulated respiration, respectively. The inhibitory action of 2,3,4,3',4',5'-HCB on both respiration was approximately half as potent as that of 2,3,4,2',3',4'-HCB. On the other hand, 3,4,5,3',4',5'-HCB did not inhibit any respiration at all. These results indicate that both inside (ortho) and outside (meta or para) positions in each phenyl ring of the biphenyl molecule should be replaced with chlorines for HCB to be an effective inhibitor. Either the actual position of chloro-substituent or steric conformation caused by its substitution or both can be considered as factors affecting the inhibition. On the basis of the conformational energy, calculated by AM1 (Austin model 1) method, with increases in chlorine number in ortho position, HCB molecule became angulated. Furthermore, calculated probability of the conformation distribution for HCB indicated that the probability of nonplanarity was higher for effective HCB than for less effective HCB. These structural features suggest the significance of steric conformation as well as chloro-substituent sites in determining the inhibitory ability of HCB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗