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Biomedical subjects

M Shinohara

Publications and source records attributed to M Shinohara.

At least 199 records · Page 11Linked to original sources

Hematopoietic cell transplantation in the twitcher mouse. The effects of pretransplant conditioning with graded doses of busulfan.

The effects of congenic hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) after graded doses of busulfan (BU), a myeloablative but nonimmunosuppressive alkylating agent, were evaluated in the twitcher mouse model of human galactosylceramidase deficiency, a demyelinating sphingolipid storage disease. C57BL/6 twitcher mice (immunophenotype Ly-5.1) were given 10 to 50 mg/kg of BU or total-body irradiation (9.0 Gy) at age nine days and HCT from congenic Ly-5.2 donors 24 hr later. The 30-day post-HCT survival, an indicator of tolerance of the preparative regimen, was at least 83% in twitcher mice given 45 mg/kg or less of BU, was 50% in recipients of 50 mg/kg BU and 75% in TBI-conditioned twitchers. The lifespan of twitcher mice given HCT after 10 or 20 mg/kg of BU was similar to that of untreated twitchers (median survival, 42 days; range, 30-47). In contrast, mice transplanted after 35 to 50 mg/kg of BU had significantly prolonged survival (median, 82 days; range, 56-208) and stabilization of hindlimb paralysis, similar to TBI-conditioned recipients. Post-HCT repopulation by donor Ly-5.2 cells was determined by flow cytometry. Thirty days after HCT, only 11-15% of lymphohematopoietic cells in blood, bone marrow, and spleens were of Ly-5.2 donor origin in twitcher mice transplanted after 10 mg/kg of BU but 60-80% were of Ly-5.2 donor origin in mice transplanted after higher doses of BU. These levels further increased to 70-90% by 90 days after HCT, comparable to that seen after TBI. Levels of galactosylceramidase in livers, spleens, and brains of twitchers transplanted after 35-50 mg/kg of BU or after TBI increased to 30-116% of normal control values by 90 days after HCT. Conditioning for HCT with as little as 35 mg/kg of BU provides minimal peritransplant mortality, rapid and sustained establishment of donor lymphohematopoiesis, replacement of lysosomal hydrolase, and prolonged survival in this murine model of human sphingolipidosis.

Animals↗

[Effects of local anesthetics on rat macrophage phagocytosis].

We examined whether phagocytosis by macrophages (M phi s) is affected by local anesthetics (lidocaine HCl, prilocaine HCl, mepivacaine HCl, tetracaine HCl and procaine HCl). Opsonized zymosan, fetal bovine serum and one local anesthetic were added to each M phi sample. After a 30-min incubation, M phi s were washed to make Giemsa stained slides for counting. The phagocytosis rate was calculated by counting the phagocytosizing M phi s per 200 cells with an optical microscope, and rates for the samples containing local anesthetics were compared with those for the non-treated samples. Inhibition of phagocytosis was reversible, dose-dependent and pH dependent for all local anesthetics. Tetracaine HCl inhibited phagocytosis most and procaine HCl, least. These results suggest that local anesthetics at the level of clinical use inhibit leukocyte phagocytosis and therefore may interfere with the normal function of cells fundamental to host defense.

Anesthetics, Local↗

[A survey of postoperative steroid replacement in 40 patients with Cushing's syndrome].

Adrenalectomy for Cushing's syndrome due to adrenocortical adenoma was performed on 40 patients at Tokyo University Hospital between 1960 and 1990. There were 32 women and 8 men aged 2 to 59 (mean 35.7) years. Three different operative approaches to the adrenal gland were employed: lumbar approach in 24 cases, dorsal in 8, and transabdominal in 8 of whom 7 patients were operated before 1970 without definite preoperative localization of the lesions. Postoperative administration of cortisone and hydrocortisone as a steroid replacement has been reduced in duration and dosage in recent 10 years. Average treatment period was 3 years and 1 month in the 1970's, and 9.5 months in the 1980's, respectively. The mean daily dosage of steroid hormone was 517.5 mg (mean) on the operative day and 43.1 mg after three weeks in the 1970's, while 187.5 mg and 18.4 mg in the recent five years, respectively. Nonetheless, even in the recent 6 patients, metabolic alkalosis and hypopotassemia because of steroid excess were observed in a few days after the surgery. These observations indicate that period and dosage of steroid replacement have been reduced in these years and could be further shortened by means of rapid tapering in the early postoperative phase.

Adenoma↗

[Intra-arterial chemotherapy with 5-FU (weekly high dose 5-FU HAI) for the prevention of tumor recurrence in residual liver after hepatic resection of metastasis from colorectal cancer].

Intra-arterial cancer chemotherapy using an implantable reservoir was performed for the prevention of tumor recurrence in residual liver after resection of a metastatic tumor from colorectal cancer. Four cases of synchronous hepatic metastases and one case of metachronous hepatic metastasis, which were in H1 (2 cases) and H2 (3 cases), were treated. 5-FU was administered in a dose of 1,000 mg/m2 5 hours weekly (weekly high dose 5-FU HAI). The longest survival obtained is 1Y 11M. Other cases have survived for 1Y 7M, 1Y 12M, 9M, and 3M. Tumor recurrence was not observed in all cases except one. This case had a residual tumor because the complete resection was impossible. The tumor recurrence rate in patients treated with surgery alone at Nikko Memorial Hospital (n = 11) was 63.6%. The 1- and 2-year survival rate in these patients was 60.6% and 26.9%, respectively. As compared to these rates, the results of this study were very favorable. Although mild nausea and abdominal discomfort were observed in 1 patient, this adverse effect was reduced by administration of an anti-ulcer agent. Only a slight decrease of WBC and PLT counts was observed. Consequently, for residual liver after resection of hepatic metastasis from colorectal cancer, this intraarterial chemotherapy with 5-FU is considered to be effective to prevent tumor recurrence and thus to prolong survival.

Aged↗

[Two cases of Marfan syndrome complicated with aortic dissection during pregnancy].

Two women with Marfan syndrome who developed aortic dissection during pregnancy are reported. Case 1: A 38-year-old woman had experienced severe back pain five years before (at the age of 33) when she was in the 38th week of gestation, followed by labour with no problem. Three years ago, she was examined in our hospital for enlarged thoracic aorta pointed out in a somatoscopy and was diagnosed as having Marfan syndrome and aortic dissection of DeBakey type IIIb. Because her aortic dissection has been growing larger recently, surgical repair is scheduled electively. Case 2: A 32-year-old woman, who had been diagnosed as having Marfan syndrome because of ectopia lentis at 10 years old, was referred to our department for a painful tumor with pulsation which had emerged at the right-hand side of her neck in the 32nd week of gestation. Acute aortic dissection of DeBakey type I complicated with acute aortic regurgitation was diagnosed, and emergency operation (Cesarean section, reconstruction of ascending aorta and aortic arch, replacement of aortic valve and aorto-coronary bypass to right coronary artery) was performed. Post-operative course was uneventful and the patient and her baby were discharged safely. In general, aortic dissection during pregnancy of patients with Marfan syndrome is of poor prognosis. Full consent by the patient and her family is necessary to decide whether the pregnancy should go on, and close cooperation among participating departments is indispensable for the treatment for this condition.

Adult↗

[Left ventricular rupture at an atypical place after mitral valve replacement: a case report].

Left ventricular rupture after mitral valve replacement (MVR) is a relatively rare, but a lethal complication. We report a case with this complication. The case was a 62-year-old woman with MSr, TR, and giant left atrium. She underwent MVR with SJM 29 mm, and TAP. During the operation, we found bleeding in the pericardial cavity, and confirmed left ventricular rupture. The place of the rupture was similar to Type I, but it was not posterior atrioventricular wall, but was lateral wall, left side of LAD. We thought that a manipulation during MVR was relevant to this event. Because, this place was opposite the anterolateral commissure of mitral valve to which the chordae tendineae and papillary muscles were adhered. It appeared that the annulus was injured at this point during the operative procedure.

Female↗

[A case of angina pectoris and aortic regurgitation combined with thymoma].

A case of a 72-year-old female with obstruction of LAD, stenosis of RCA, aortic regurgitation in moderate degree and an anterior mediastinal mass of 7 cm in diameter, is reported. Coronary artery bypass grafting, aortic valve replacement and thymectomy were simultaneously performed. On microscopic examination, the tumor was diagnosed as a mixed typed thymoma in the first stage of Masaoka's classification. She was making satisfactory progress without recurrence, after the operation. There was no case has been reported previously in the world in which simultaneous operations were performed for angina pectoris, aortic regurgitation and thymoma.

Aged↗

Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase.

Two species of lipoprotein containing apoA-I, one containing only apoA-I (LpA-I), and the other containing apoA-I and apoA-II (LpA-I/A-II), were tested for their effects on macrophage foam cells. Rat macrophages were converted to foam cells by incubation with radiolabeled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesteryl esters (CE) mass. However, the free cholesterol (FC) mass was only reduced by LpA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II; 39% of the excreted radioactivity was esterified in LpA-I and 10% in LpA-I/A-II. Upon complete inactivation of lecithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-II were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone. However, LpA-I re-isolated from the medium showed a lower esterification rate than did the re-isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that (i) the function of LpA-I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and (ii) LpA-I in concert with LpA-I/A-II induces a series of extracellular events; LCAT-mediated esterification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.

Adolescent↗

An iatrogenic foreign body (dental bur) in the maxillary antrum: a report of two cases.

Two cases of foreign bodies of the antrum are reported. One was a turbine bur which presumably entered through an oro-antral fistula after a tooth extraction. The other was also a turbine bur where the mode of entry was not clear (lack of oro-antral fistula), but it presumably entered through the socket of the extracted tooth. The mucosa of the antrum appeared normal in spite of the lengthy presence of the foreign body.

Adult↗

The existence of activin A/erythroid differentiation factor and its inhibitor in human serum: comparison of normal and chronic renal failure sera.

Activin A/EDF, initially found as a differentiation inducer of murine Friend erythroleukemia, also has a stimulatory effect on erythropoiesis in vitro and in vivo. Here we proved activin A/EDF activity in human serum. The activin A/EDF level in 18 normal human serum samples was measured by a specific bioassay and was found to be 8.3 +/- 4.6 ng/ml, indicating that there exists sufficient activity to affect erythropoiesis in normal serum. In contrast, activin A/EDF activity was reduced in the chronic renal failure patients and 23/26 serum samples examined showed levels below 1.2 ng/ml. Further analysis using HPLC revealed that chronic renal failure serum actually contained as much activin A/EDF as normal serum, and that the difference between normal and patient serum existed in the content of a specific inhibitor of activin A/EDF. This observation suggests the possibility that the inhibitor is participating in the regulation of activin A/EDF activity in vivo in chronic renal failure patients and also the possibility of activin A/EDF could be utilized in the therapy of the anemia of such patients.

Activins↗

Exposure of rat peritoneal macrophages to acetylated low density lipoprotein results in release of plasma membrane cholesterol. An efficient substrate for esterification by acyl-CoA:cholesterol acyltransferase.

In J774 macrophages and murine macrophages stimulated with acetylated low density lipoprotein (acetyl-LDL), the plasma membrane free cholesterol (FC) became accessible to acyl-CoA:cholesterol acyltransferase (ACAT) as substrate, the result being an accumulation of cholesteryl esters (CE) (Tabas, I., Rosoff, W. J., and Boykow, G. C (1988) J. Biol. Chem. 263, 1266-1272). As the route of delivery of FC to ACAT was not well characterized, we examined this route in the present study. In foam cells derived from rat peritoneal macrophages by preincubation with acetyl-LDL, esterification of the exogenously labeled [3H]FC was low (1.3% of total labeled cholesterol). In contrast, when cells were first labeled with exogenous [3H]FC and then chased with acetyl-LDL, the esterification was more extensive (9.2% of the total labeled cholesterol). During this experiment a significant portion of cellular [3H]FC was released into the medium (up to 33.4% of the total labeled cholesterol). In experiments using a two-compartment chamber in which cells in the lower and upper chambers were separated by filter paper yet the cells in both compartments could communicate without direct contact, [3H]FC released into the medium was biologically active and could serve as an efficient substrate for ACAT. Thus, when acetyl-LDL is not included in culture medium, FC delivery from the macrophage plasma membrane to ACAT is not enhanced, whereas in the presence of acetyl-LDL, plasma membrane FC released and bound to acetyl-LDL may re-enter the cells, possibly through the scavenger receptor. This would provide a significant route for CE synthesis in macrophages.

Animals↗

Oxygen availability and motor unit activity in humans.

Six men were studied to determine the interrelationships among blood supply, motor unit (MU) activity and lactate concentrations during intermittent isometric contractions of the hand grip muscles. The subjects performed repeated contractions at 20% of maximal voluntary contraction (MVC) for 2 s followed by 2-s rest for 4 min with either unhindered blood circulation or arterial occlusion given between the 1st and 2nd min. The simultaneously recorded intramuscular MU spikes and surface electromyogram (EMG) data indicated that mean MU spike amplitude, firing frequency and the parameters of surface EMG power spectra (mean power frequency and root mean square amplitude) remained constant during the experiment with unhindered circulation, providing no electrophysiological signs of muscle fatigue. Significant increases in mean MU spike amplitude and frequency were, however, evident during the contractions with arterial occlusion. Similar patterns of significant changes in the surface EMG spectra parameters and venous lactate concentration were also observed, while the integrated force-time curves remained constant. These data would suggest that the metabolic state of the active muscles may have played an important role in the regulation of MU recruitment and rate coding patterns during exercise.

Adult↗

Alveolar hydatid disease of the liver: computed tomography and transabdominal ultrasound with histopathological correlation.

The appearances of alveolar hydatid disease of the liver (AHDL) on computed tomography (CT) and ultrasound (US) were retrospectively compared with histopathological appearances in 67 patients with 100 separate lesions. The radiological features were correlated directly with the pathological specimens obtained from each patient. We conclude that the CT appearances are more specific, but that US has a role to play in mass screening in endemic areas, and intraoperatively.

Adolescent↗

Immunohistochemical detection of desmosomes in oral squamous cell carcinomas: correlation with differentiation, mode of invasion, and metastatic potential.

An expression of desmosomal glycoprotein 1 (DG 1) was immunohistochemically examined in 77 biopsies and 21 metastatic cervical lymph nodes of oral squamous cell carcinomas (SCC). In the primary tumors the DG 1 expression was significantly reduced at the invasive site of poorly differentiated and highly invasive tumors. In cases of metastases in cervical lymph nodes, the DG 1 staining at the invasive site of the primary tumor was significantly less than that of nonmetastatic cases. The DG 1 expression in the metastatic lymph nodes was as weak as that in the primary tumor. Thus, we suggest that immunohistochemical investigation of DG 1 expression in oral SCC is valuable in predicting tumor behavior.

Carcinoma, Squamous Cell↗

Heterotopic salivary gland tissue in lymph nodes of the cervical region.

The occurrence and composition of intranodal salivary gland tissue (ISGT) in the head and neck region were investigated. ISGT was mainly composed of mature acini, intercalated ducts and intralobular ducts but immature acini (20.8%) and immature small ducts (18.8%) were also observed. The latter resembled salivary gland tissue in an early developmental stage. Various histological changes of ISGT were observed including cyst formation (16.7%), oncocytic metaplasia (8.3%), oncocytic adenomatous hyperplasia (8.3%) and ductal proliferation (20.8%). Thus ISGT may contain immature components with a potential for differentiation and proliferation.

Adult↗