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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 397 records · Page 22Linked to original sources

Fundamental and clinical evaluation of chest computed tomography imaging in detectability of pulmonary nodule.

Fundamental and clinical evaluation of chest CT imaging in detectability of pulmonary nodules was carried out in comparison with projection chest radiography including conventional screen-film system, advanced multiple beam equalization radiography (AMBER System), and computed radiography with imaging plate (CR). Detectability of simulated nodules in the fundamental study and of metastatic pulmonary nodules in ten patients in the clinical study was analysed by five radiologists. CT found the greatest number of nodules and also showed the highest sensitivity in detecting nodules of less than 5 mm in both the fundamental and clinical studies. The ability of computed tomography to visualize small pulmonary nodules may make it a possible substitute for chest radiography as the primary mass screening method, and as the examination method for small metastatic nodules (less than 5 mm) in patients with extrathoracic malignancy. There was no significant difference between conventional radiography, AMBER, and CR in the number of detected nodules.

Humans↗

[Lung transplantation from non-heart-beating donor following brain death in canine model].

Candidates for pulmonary transplantation have been limited because of extreme susceptibility to lung infections and pulmonary edema in the brain-dead donor. To ameliorate the donor shortage, two possibilities for expanding the donor source have been presented, i.e. xenotransplantation and transplantation from cardiac-dead donors. The present study was conducted to evaluate the possibility of lung transplantation from a non-heart-beating donor following brain death, using a canine model. Six mongrel dogs were put into a state of brain death by elevating intracranial pressure with a balloon catheter. Following the intravenous administration of methylprednisolone and heparin used for 6-hour management following brain death mechanical ventilation was discontinued leading to cardiac arrest with in a few minutes. Excision of the left lung was scheduled for twenty minutes after cardiac arrest, followed by washing out the pulmonary vasculature with cold Ep4 solution, and orthotopic transplantation into the recipient animal. Immunosuppression was achieved with methylprednisolone and azathioprine. A right pulmonary arterial occlusion test (RPAO) was performed to assess graft function immediately and 7 days postoperatively. All but one animal survived and three animals had an uneventful postoperative course, with the transplants alone according to immediate and 7 day postoperative, respectively, RPAO results. These outcomes indicate the possible feasibility of lung transplantation from non-heart-beating donors following brain death.

Animals↗

Immunoblastic lymphadenopathy in a five-month-old girl: successful treatment with immunosuppressants.

A five-month-old girl developed high fever, erythema, hepatosplenomegaly and generalized lymphadenopathy. Laboratory examinations revealed elevated peripheral leukocyte counts, C-reactive protein, lactate dehydrogenase and serum ferritin level. Pathologic examination of the lymph nodes revealed immunoblastic lymphadenopathy (IBL) on the basis of the complete effacement of the normal architecture, replacement by a diffuse infiltrate composed of immunoblasts, plasmacytoid cells and small lymphocytes, and an abortive proliferation of blood vessels. B-cells and T-cells were nearly equally mixed throughout the lymph nodes. No rearrangements of the B-cell immunoglobulin and T-cell receptor genes were detected. The patient was initially treated with alpha-interferon with dramatic efficacy. After relapse, however, the disease was well controlled with cyclosporin A (CyA) and subsequently with combination regimens of CyA, deoxyspagarin and azathioprine with fair success. An alternating regimen of 6-mercaptopurine, cyclophosphamide and methotrexate was then instituted which continued the complete remission for 12 months. The effects of immunosuppressants in the treatment of IBL merit investigation.

Azathioprine↗

[Risk factors for retroperitoneal lymph node metastasis in ovarian cancer].

The incidence and significant risk factors for retroperitoneal lymph node metastasis were investigated in 48 patients with primary epithelial ovarian cancer. Twenty-four (50.0%) of the 48 patients had para-aortic and/or pelvic lymph node metastases. In retroperitoneal lymphadenectomy at primary cytoreductive surgery, all patients with lymph node metastases were found to have both para-aortic and pelvic lymph node metastases. It is possible that the lymphatic extension, from the pelvic lymph node to the para-aortic lymph node, is one of the routes of retroperitoneal lymph node metastases in primary epithelial ovarian cancer. The incidence of lymph node metastases significantly increased with the spread of the abdominal tumor, peritoneal cytology, peritoneal metastasis, omental metastasis, involvement of both ovaries and poor histological grade. In the multiple analysis, the spread of the abdominal tumor, positive peritoneal cytology and poor histological grade were found to be the most important risk factors for retroperitoneal lymph node metastasis in ovarian cancer.

Cystadenocarcinoma, Serous↗

[An experience of suprahyoid release for resection and reconstruction of the lower part of trachea].

An experience of suprahyoid release for resection and reconstruction of the lower part of trachea was reported. 51-year-old woman, complaining of continuous stridor, was diagnosed as tracheal tumor at another hospital and was transferred to our hospital for consecutive examination and surgical treatment. The size of the tumor was about 3 cm in longitudinal diameter and the distance between tracheal carina and lower edge of the tumor was estimated about 2 cm by tomography. At operation, following suprahyoid release in supine position, 6 tracheal rings were resected and reconstructed by end-to-end anastomosis through right posterolateral incision. Patients neck was forced to bend for three weeks and intravenous byperalimentation without oral intake was employed for two weeks to avoid misswallowing and dysphagia postoperatively. Oral intake was started at two weeks after operation and parenteral nutrition was no more necessary at 3 weeks after surgery. Misswallowing and dysphagia were not encountered at all. The tumor was diagnosed as adenoid cystic carcinoma pathologically and residual tumor was demonstrated in submucosal space at the oral margin of the resected specimen as well. She discharged from the hospital uneventfully after postoperative radiotherapy. The recurrence of the tumor has not been observed for 3 years postoperatively. It was confirmed that suprahyoid release is an useful technique and should be ready to introduce in the extensive resection of the trachea because of its little influence on laryngeal function.

Anastomosis, Surgical↗

Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe: implications for transferrin iron release.

Members of the transferrin family of proteins are involved in Fe3+ transport (serum transferrins) and are also believed to possess antimicrobial activity (ovotransferrins and lactoferrins). The structure of the monoferric N-terminal half-molecule of hen ovotransferrin, reported here at 2.3-A resolution, reveals an unusual interdomain interaction formed between the side-chain NZ atoms of Lys 209 and Lys 301, which are 2.3 A apart. This strong interaction appears to be an example of a low-barrier hydrogen bond between the two lysine NZ atoms, both of which are also involved in a hydrogen-bonding interaction with the aromatic ring of a tyrosine residue. Crystals of the protein were grown at pH 5.9, which is well below the usual pKa approximately 10 for a lysine side chain. We suggest that the pKa of either one or both of these residues lies below the pH of the structure determination and is, therefore, not positively charged. This finding may serve to explain, on a molecular basis, the pH dependence of transferrin Fe3+ release. We propose that uptake of the Fe(3+)-transferrin complex into an acidic endosome (viz., pH approximately 5.0) via receptor-mediated endocytosis will result in the protonation of both lysine residues. The close proximity of the two resulting positive charges, and their location on opposite domains of the N-lobe, might well be the driving force that opens the two domains of the protein, exposing the Fe3+ ion and facilitating its release.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Oxidative regeneration and selective reduction of native disulfide bonds in the N-terminal half-molecule of ovotransferrin.

The denatured, disulfide-reduced form of the N-terminal half-molecule of ovotransferrin was reoxidized with either oxidized dithiothreitol or GSSG and analyzed for the localization of disulfide bonds. Chemical analyses of the reoxidized proteins revealed that the disulfide peptides corresponding to the six native protein disulfides (SS-I, SS-II, SS-III, SS-IV, SS-V, and SS-VI) are all regained in the reoxidized protein. The peptide recoveries from the reoxidized proteins were, however, about half of those from the native protein with respect to the two inner disulfides (SS-IV and SS-V) in the kringle bridges, but all the disulfide peptides corresponding to the remaining disulfides (SS-I, SS-II, SS-III, and SS-VI) were recovered at almost equivalent yields in the native and reoxidized proteins. In addition, on searching for a nonnative disulfide peptide, the two disulfides, Cys171-Cys174 and Cys174-Cys182, which can be accounted for by mispaired bridges of sulfhydryls in SS-IV and SS-V, were detected in the protein reoxidized with oxidized dithiothreitol. Upon disulfide reduction of the native protein with reduced dithiothreitol, both SS-IV and SS-V were selectively cleaved under the same buffer and temperature conditions as in the oxidative refolding. The lower stabilities of the two inner disulfide bonds in the kringle may be related to the lower recoveries of the disulfide peptides from SS-IV and SS-V and the generation of the nonnative disulfide bonds.

Amino Acid Sequence↗

The 2.0-A resolution structure of soybean beta-amylase complexed with alpha-cyclodextrin.

New crystallographic findings are presented which offer a deeper understanding of the structure and functioning of beta-amylase, the first known exo-type starch-hydrolyzing enzyme. A refined three-dimensional structure of soybean beta-amylase, complexed with the inhibitor alpha-cyclodextrin, has been determined at 2.0-A resolution with a conventional R-value of 17.5%. The model contains 491 amino acid residues, 319 water molecules, 1 sulfate ion, and 1 alpha-cyclodextrin molecule. The protein consists of a core with an (alpha/beta)8 supersecondary structure, plus a smaller globular region formed by long loops (L3, L4, and L5) extending from beta-strands beta 3, beta 4, and beta 5. Between the two regions is a cleft that opens into a pocket whose floor contains the postulated catalytic center near the carboxyl group of Glu 186. The annular alpha-cyclodextrin binds in (and partly projects from) the cleft with its glucosyl O-2/O-3 face abutting the (alpha/beta)8 side and with its alpha-D(1 --> 4) glucosidic linkage progression running clockwise as viewed from that side. The ligand does not bind deeply enough to interact with the carboxyl group of Glu 186. Rather, it occupies most of the cleft entrance, strongly suggesting that alpha-cyclodextrin inhibits catalysis by blocking substrate access to the more deeply located reaction center. Of the various alpha-cyclodextrin interactions with protein residues in loops L4, L5, L6, and L7, most notable is the shallow inclusion complex formed with Leu 383 (in L7, on the core side of the cleft) through contacts of its methyl groups with the C-3 atoms of four of the ligand's D-glucopyranosyl residues. All six residues of the bound alpha-cyclodextrin are of 4C1 conformation and are joined by alpha-1,4 linkages with similar torsional angles to form a nearly symmetrical torus as reported for crystalline inclusion complexes with alpha-cyclodextrin. We envision a significant role for the methyl groups of Leu 383 at the cleft entrance with respect to the productive binding of the outer chains of starch.

Amino Acid Sequence↗

Inhibition by dehydroepiandrosterone of butylated hydroxyanisole (BHA) promotion of rat-bladder carcinogenesis and enhancement of BHA-induced forestomach hyperplasia.

The effects of dehydroepiandrosterone (DHEA) with/without ribonucleoside (RNs) supplementation on butylated hydroxyanisole (BHA) bladder-tumor promotion and forestomach carcinogenesis were investigated. Male F344 rats were given N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and then received basal diet or diet containing BHA, DHEA, a mixture of RNs, BHA + DHEA or BHA + DHEA + RNs for 32 weeks. The occurrences of papillomas and carcinomas in the urinary bladder were increased in the groups given BHA or BHA + DHEA + RNs, as compared with control group values. In comparison with the BHA group, the BHA + DHEA group incidences and numbers of these tumors were decreased. However, the incidence and multiplicity of papillomas in the group given BHA + DHEA + RNs were again elevated. DNA synthesis levels in normal-appearing bladder epithelium, but not tumor cells, were closely correlated with the observed level of promotion in most groups. The case of DHEA alone proved exceptional in that DNA synthesis was markedly decreased without any significant influence on lesion development. In the forestomach, DHEA, which itself was associated with slight although non-significant hyperplasia, enhanced BHA-induced epithelial lesions, characterized by marked basal-cell proliferation and keratin-cyst formation, independently of additional RNs administration. Our results suggest that the anti-promoting effects of DHEA in the bladder depend on a deficiency in the pentose phosphates necessary for production of nucleosides. Organ-specific modulation is indicated by the enhancing effects of DHEA on BHA-induced forestomach hyperplasia.

Animals↗

Effects of sodium nitrite and catechol, 3-methoxycatechol, or butylated hydroxyanisole in combination in a rat multiorgan carcinogenesis model.

Effects of simultaneous treatment with NaNO2 and butylated hydroxyanisole, catechol, or 3-methoxycatechol were examined in a rat multiorgan carcinogenesis model. Groups of 15 animals were given a single i.p. injection of 100 mg/kg of body weight diethylnitrosamine, 4 i.p. injections of 20 mg/kg of body weight N-methylnitrosourea, 4 s.c. injections of 40 mg/kg of body weight dimethylhydrazine, p.o. treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for the first 2 weeks and p.o. treatment with 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine in the drinking water for the next 2 weeks of the initial 4-week initiation period. Starting 3 days after the completion of these carcinogen treatments, animals were given diets containing 2% butylated hydroxyanisole, 0.8% catechol, 2% 3-methoxycatechol, or basal diet either alone or in combination with 0.3% sodium nitrite until week 28, when complete autopsy was performed. Histological examination showed that NaNO2 strongly enhanced development of forestomach lesions but inhibited that of glandular stomach lesions in rats simultaneously given catechol or 3-methoxycatechol with or without prior carcinogen exposure. 3-Methoxycatechol promoted esophageal carcinogenesis either with or without NaNO2, but promoting effects of catechol were evident only in the presence of NaNO2. In addition, treatment with NaNO2 after carcinogen exposure enhanced forestomach carcinogenesis. These results indicate that NaNO2 can modify phenolic antioxidant-induced cell proliferation and/or carcinogenesis, particularly in the upper digestive tract.

Animals↗

Modification of hepato- and renal carcinogenesis by catechol and its isomers in rats pretreated with N-ethyl-N-hydroxyethylnitrosamine.

Modifying effects of catechol, resorcinol, and hydroquinone on second stage hepato- and renal carcinogenesis was investigated in rats pretreated with N-ethyl-N-hydroxyethyl-nitrosamine (EHEN). Groups of twenty 6-week-old Wistar/Crj male rats were treated with 0.1% EHEN in the drinking water for 3 weeks. Starting 1 week after the termination of EHEN treatment, they were given a diet containing 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone or basal diet for 36 weeks. Further groups of 15 rats were each treated with the same doses of phenolic compounds or basal diet alone without EHEN pretreatment. All surviving animals were killed at the end of week 40 when histopathological assessment revealed significant reduction of the numbers per rat of hepatocellular adenomas and hepatocellular carcinomas by resorcinol, whereas hydroquinone significantly enhanced the numbers per rat of renal microadenomas and renal cell tumors. On the other hand, the number of alpha 2u-globulin positive tubules in the animals treated with hydroquinone was significantly lower than controls, without any alteration in bromodeoxyuridine (BrdU) incorporation. Lipid peroxidation, as evaluated by thiobarbituric acid reactive substance (TBARS), was at control levels in the kidneys of rats treated with hydroquinone throughout the experiment. The results showed that the known renal carcinogen hydroquinone potently enhances the second stage of EHEN-induced renal carcinogenesis, while its isomer resorcinol inhibited hepatocarcinogenesis. alpha 2u-Globulin and lipid peroxidation may not play roles in hydroquinone-associated promotion of renal carcinogenesis.

Adenoma↗

Actin and myosin deposition around bile canaliculi: a predictor of clinical outcome in biliary atresia.

The role of pathological changes of the intrahepatic bile canaliculi in determining postportoenterostomy bile drainage in biliary atresia (BA) patients remains unestablished. It is known that canalicular contraction contributes an active force for bile flow in normal ductal systems. This motility is controlled by the bile canalicular membrane-associated filaments (BCMF), particularly actin and myosin. Wedge resected specimens of liver from 13 patients with BA were studied using histopathological markers of BCMF in order to clarify the morphological and functional changes of bile canaliculi. Histopathological data were also compared with clinical outcomes after portoenterostomy. Patients who showed sufficient bile flow after the operation showed an almost normal shape and level of BCMF accumulation around bile canaliculi, whereas there was markedly increased BCMF volume in patients who did not exhibit bile flow after surgery. The clinical staining patterns of BCMF in BA patients appears closely related to clinical outcome. These findings suggest that BCMF plays an important role in determining the rate of postoperative bile flow in BA patients.

Actins↗

Subchronic toxicity study of methyl hesperidin in mice.

A subchronic toxicity study of methyl hesperidin was performed using B6C3F1 mice. The flavonoid was administered to groups of ten males and ten females in dietary levels of 0, 0.3, 0.6, 1.25, 2.5 and 5.0% for 13 weeks. No significant treatment-related differences were found in data for body weights, food and water consumption, hematology, clinical chemistry and organ weights. Furthermore, no effects of treatment were observed on gross and histopathological examination of the major organs. The present experiment thus demonstrated that methyl hesperidin exerts no obvious toxic effects in mice of either sex when administered at a level as high as 5.0% in the diet.

Administration, Oral↗

Modification of carcinogenesis by alpha-tocopherol, t-butylhydroquinone, propyl gallate and butylated hydroxytoluene in a rat multi-organ carcinogenesis model.

Effects of the dietary antioxidants alpha-tocopherol (alpha-Toc), t-butylhydroquinone (TBHQ), propyl gallate (PG) and butylated hydroxytoluene (BHT) were examined using a multi-organ carcinogenesis model. Groups of 20 F344 male rats were treated with a single intragastric administration of 100 mg/kg body weight N-methyl-N'-nitro-N-nitrosoguanidine, a single intragastric administration of 750 mg/kg body weight N-ethyl-N-hydroxyethylnitrosamine, two subcutaneous injections of 0.5 mg/kg body weight N-methylbenzyl-nitrosamine and four subcutaneous injections of 40 mg/kg body weight 1,2-dimethylhydrazine. At the same time the rats were given 0.1% N-dibutylnitrosamine for 4 weeks and then 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine for 2 weeks in the drinking water, for a total carcinogen exposure period of 6 weeks. Starting 3 days thereafter the rats received 1% alpha-Toc, 1% TBHQ, 1% PG or 0.7% BHT in the diet, or basal diet alone. Further groups of 10-15 animals each were treated with antioxidant alone or basal diet alone as controls. Surviving animals were killed at the end of week 36. Histopathological examination showed that alpha-Toc increased the incidence of glandular stomach atypical foci but reduced the incidence and multiplicity of kidney atypical tubules. TBHQ significantly elevated the incidences of esophageal papillary or nodular (PN) hyperplasias and papillomas, as well as forestomach papillomas, but significantly decreased the multiplicity of colon adenocarcinomas. PG was only effective in reducing the multiplicity of kidney atypical tubules. BHT enhanced the development of thyroid hyperplasias, but strongly reduced the incidence and multiplicity of colon adenocarcinomas. This compound was also associated with lowered incidence and multiplicity of renal cell tumors. None of the agents studied was unequivocal in exerting either positive or negative influence.

1,2-Dimethylhydrazine↗

Enhancing effect of concomitant L-ascorbic acid administration on BHA-induced forestomach carcinogenesis in rats.

The effects of the synthetic antioxidant butylated hydroxyanisole (BHA) and naturally occurring antioxidants such as L-ascorbic acid (AsA; vitamin C), citric acid, benzoic acid or gallic acid in combination, on the development of rat forestomach epithelial lesions were investigated. A dietary level of 2.0% was selected for all antioxidants and the experimental period was 1 year. As compared with BHA alone, treatment with AsA in combination with BHA increased the severity of the hyperplasia in the mid-region, but not in the prefundic region of the forestomach epithelium, as well as the multiplicity of forestomach tumors. Furthermore, incidences of squamous cell carcinomas (SCCs) in the forestomach were significantly elevated in this group, while papilloma development only showed a tendency to increase. In addition, SCC invasion into the muscle layer of the forestomach was observed only in the BHA + AsA group. Treatment with the other antioxidants did not affect BHA-induced forestomach lesion development. The present study demonstrated that AsA can clearly enhance BHA forestomach carcinogenesis.

Animals↗