Biomedical subjects
Publications and source records attributed to K Nemoto.
A successful anterior spinal fusion using vascularized fibula graft in the case of a 17-year-old male with severe cervical kyphosis due to neurofibromatosis is reported. Anterior spinal fusion at C2-7 using the fibula graft was performed with spinous process wiring. The kyphosis was corrected from 85 to 38 degrees. Bony fusion was obtained in 5 months without loss of correction.
Cholesteryl esters (CE) in lipid droplets undergo a continual cycle of hydrolysis and reesterification by neutral cholesterol esterase (N-CEase) and acyl CoA:cholesterol acyltransferase (ACAT), respectively. The mechanism by which HDL mobilizes CE from lipid droplets in J774 A.1 cells was investigated, focusing on N-CEase activity. We asked whether HDL enhances the activity and, if so, what signals induce the change of the activity. An incubation of cells with HDL enhanced the decline of cholesteryl-[l-14C]-oleate in foam cells and increased N-CEase activity in the supernatant of cell homogenate in a concentration-dependent manner, whereas incubation with LDL decreased the activity. In addition, N-CEase activity was fivefold higher when cells were cultured in 10% lipoprotein-deficient serum (LPDS) medium (2 micrograms cholesterol/mL) than when cultured in 10% fetal calf serum medium (31 micrograms cholesterol/mL), suggesting that changes in N-CEase activity are mediated by cholesterol. An addition of cholesterol (0 to 30 micrograms/mL) in LPDS medium markedly inhibited N-CEase activity with a concomitant increase in cellular cholesterol concentration. This inhibitory effect of cholesterol was also observed in mouse peritoneal macrophages. In vitro addition of cholesterol did not affect N-CEase activity. Treatment of cells with HMG-CoA reductase inhibitors enhanced N-CEase activity, whereas ACAT inhibitor decreased the activity. Northern blot analysis of N-CEase mRNA showed that the expression was not altered by the presence of cholesterol in LPDS medium. These results suggest that cholesterol downregulates N-CEase activity, probably through cholesterol-dependent appearance of some factors.
From 1980 to 1994, 59 patients with a diagnosis of lowgrade astrocytoma were treated in our hospital. We analyzed survival, prognostic factors and quality of life (QOL) in survivors who had been recurrence free for at least 2 years. The overall 2-, 5- and 10-year survival rates were 75, 65 and 49 % respectively. The major prognostic factors were field size (the smaller, the better) and age (the younger, the better) according to Cox regression analysis. Quality of life was evaluated in the 20 patients who had survived at least 2 years without tumor regrowth. Performance status was good in most of the patients, and 17(85%) patients were intellectually and physically normal. Headache, fatigue and memory difficulties were the major clinical complaints of these patients and were observed in 7(35%), 6(30%) and 7(35%) of the patients, respectively, although severe symptoms were rare.
The host-defense mechanisms against cancers are known to be modulated by changing the environmental factor(s). The spontaneous incidence of myeloid leukemia is about 1% in C3H/He mice, and the incidence increases up to 23.3% when a single dose of radiation, 3 Gy X-ray, is exposed to a whole-body. Since calorie restriction was known to reduce the incidence of spontaneous tumors, a question as to whether such radiation induced-increase of myeloid leukemia would be also decreased by calorie restriction, was aimed to answer to elucidate possible mechanism of radiation-induced myeloid leukemia. By the calorie restriction, the incidence of myeloid leukemia was significantly decreased. In addition, the latent period of the myeloid leukemia in the groups for calorie restriction was significantly extended at a greater extent as compared with the control diet groups. Number of hemopoietic stem cells, the possible target cells for radiation-induced leukemias, in the groups for the calorie restriction demonstrated a significant decrease, especially in the spleen, as compared with that in the control, when the evaluation was made at the time of radiation exposure.
Single breath-hold gradient echo images were obtained before and immediately after bolus intravenous administration of Gd-DTPA (dynamic MR imaging) in the study of the pancreas. Of 37 patients with pathologically proved pancreatic ductal adenocarcinoma, seventeen patients who underwent both dynamic MR imaging studies and curative surgery were included in this study. Correlations between histologic findings in the resected specimens and MR images were analyzed as to tumor extension and staging according to the General Rules for the Study of Pancreatic Cancer (4th Edition) published by the Japan Pancreas Society. In comparison with conventional MR images, dynamic MR imaging improved the detectability of pancreatic carcinoma and delineation of the vasculature by clarifying the margin of the tumor and the vessels. Nonenhanced T1-weighted imaging is the best sequence to estimate peripancreatic tumor extension, because the contrast between the tumor and peripancreatic fat deteriorates with the use of contrast material. There is a tendency to overestimate vascular invasion on MR images, the reason for which is considered to be the contractive nature of fibrotic change induced by pancreatic carcinoma. The diagnostic efficacy of lymph node metastasis remains insufficient on MR images because some cases show no enlargement of lymph nodes in spite of the existence of pathological metastasis. Our results suggest that dynamic MR imaging has the advantage of improving the conspicuity of the tumor and the vasculature.
Between 1994 and 1996, 24 patients with esophageal carcinoma were entered in a randomized clinical trial comparing radiotherapy (RT) only (arm A) versus RT and a daily low dose of CDDP (5 mg/m2) (arm B). For arm B group, CDDP was injected within 30 min after irradiation. All patients were irradiated with a total dose of 60 Gy /30fr. at first, and some patients were boosted. An overall response rate of 75.0% (complete response rate of 25.0%) was observed in arm A and 91.7% (complete response rate of 16.7%) in arm B, respectively. The survival rate at 1 year was 23.8% in arm A and 40.0% in arm B. Median survival time was 7 months in arm A and 9 months in arm B. Toxicity was acceptable and no significant difference was noted between arm A and arm B.
Deoxyspergualin (DSG) is an immunosuppresive agent of proven effectiveness in the prevention and treatment of transplant rejection; its most frequent side effect is reversible bone marrow suppression. To clarify the mechanisms of bone marrow suppression induced by DSG, we monitored the numbers of peripheral blood and marrow stem cells in C3H/HeN mice receiving 14 days of DSG injections at a highly immunosuppressive dose of 10 mg/kg/day. In the peripheral blood cells, DSG induced severe anemia and mild leukopenia because of a decrease in granulocyte counts, although these phenomena were reversible. During DSG administration, nucleated cell counts in the femur also markedly decreased, whereas the absolute numbers of various stem cells and progenitor cells, except for erythroid colony-forming units (CFU-E), remained normal or increased; CD34- or c-kit-positive and lineage-negative cell levels markedly increased on the day DSG administration ceased. These findings indicate that DSG-induced anemia and leukopenia are not initiated by a generalized killing of these stem cells, but rather by a transient suppression of their ability to mature. Significantly, the severe anemia induced by DSG resembles pure red cell aplasia in humans, because there were marked decreases in peripheral reticulocytes, marrow CFU-E, and erythroblasts, with no decrease in renal erythropoietin mRNA expression. Furthermore, DSG-induced anemia was completely ameliorated by treatment with human recombinant erythropoietin.
We performed an anterior spinal fusion using a vascularized fibular bone graft combined with posterior fusion for a patient with severe cervical kyphosis due to neurofibromatosis. The kyphosis was corrected from 85 degrees preoperatively to 38 degrees postoperatively. A vascularized fibular bone graft is a useful surgical procedure in selected patients to obtain successful bony union.
Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced by brain ischemia, such as in stroke. In the present study we found a missense mutation in the trkB gene from all of the five substrains of stroke-prone spontaneously hypertensive rats (SHRSP) that were examined. This mutation was not found in six out of seven hypertensive but stroke-resistant ancestral strains (SHR) of SHRSP, nor in any of seven strains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to be more susceptible to ischemic damage in SHRSP than in either SHR or normotensive, stroke-resistant controls. The association of a mutated trkB gene with the stroke-prone genotype found in this study suggests that the trkB gene merits further study as a promising candidate gene for stroke.
We previously reported a missense mutation in the low affinity nerve growth factor receptor (LNGFR) gene of spontaneously hypertensive rats (SHR), proposing this gene as a promising candidate in genetic hypertension. In this study we provide further support for implicating this gene in genetic hypertension using two new inbred strains, WKHT and WKHA rats. These strains originated from crossbreeding SHR rats with normotensive Wistar-Kyoto rats (WKY): WKHT rats are hypertensive but not hyperactive, and WKHA rats are hyperactive but not hypertensive. Nucleotide sequence analysis of the LNGFR gene revealed that WKHT has the same mutation as SHR, whereas WKHA has the normal sequence, as seen in WKY. These results support our original hypothesis that the mutated LNGFR gene is linked to hypertension, since the mutation had co-segregated with the hypertensive trait, and not hyperactivity trait of SHR.
Explore the source record for details and available documents.
To develop a more effective adhesive primer, it is imperative to understand the adhesion mechanisms of the resin to the demineralized dentin through a dentin primer. When the bonding agent was directly applied to the dentin etched by 40 wt % phosphoric acid without a primer pretreatment, the bond strength of the resin to the dentin was 5 MPa. Conversely, when the demineralized dentin was pretreated with the N-methacryloyl glycine (NM alpha A) primer solution with a pH value of 1.5, the bond strength increased considerably to 15 MPa. However, the bond strength dropped dramatically from 15 to 3 MPa when the sodium salt of NM alpha A was added, thereby increasing the pH value of the NM alpha A primer solution from 3.2 to 5.0. When the pH value was increased above 3.5 (pKa value), the number of ionized NM alpha A species increased in the solution. As a result, the bond strength of the resin fell to approximately 3 MPa. This result was obtained despite the 5-micron-thick hybrid layer that was created in the subsurface of the intertubular dentin. The number of unionized NM alpha A species increased by lowering the pH value below 3.5. As a result, the NM alpha A primer provided a higher bond strength of the resin to the demineralized dentin. In contrast, when 10 wt % citric acid containing 3 wt % ferric chloride was applied to the dentin, maximum bond strength was obtained when the pH value of the NM alpha A primer solution was 3.5. The pH dependency of the bond strength obtained following 10 wt % citric acid containing 3 wt % ferric chloride etching is different from the results obtained from 40 wt % phosphoric acid etching. This can be attributed to the difference in the characteristics of the demineralized collageous layer.
We have shown previously that prostaglandin (PG) production in 7-day-old neonatal mouse calvarial cultures is regulated largely by changes in prostaglandin G/H synthase-2 (PGHS-2) expression and to a lesser extent by changes in arachidonic acid (AA) release. In this study, we examined the effects of interleukin-4 (IL-4), and its interactions with other cytokines and with parathyroid hormone (PTH), on mRNA levels of PGHS-2, PGHS-1, and cytosolic phospholipase A2 (cPLA2) and on medium protaglandin E2 (PGE2) levels in calvarial cultures. IL-1 and tumor necrosis factor-alpha (TNF-alpha), both at 1-100 ng/ml, and PTH at 0.1-10 nM increased PGHS-2 and cPLA2 mRNA and medium PGE2 levels dose-dependently after 4 h of treatment. IL-6 and IL-11 at 1-100 ng/ml did not affect mRNA or PGE2 levels. IL-4 at 1-100 ng/ml decreased PGHS-2 and cPLA2 mRNA and PGE2 levels in control as well as IL-1, TNF-alpha, and PTH-stimulated cultures. The inhibition of PGHS-2 and cPLA2 mRNA expression by IL-4 (10 ng/ml) was present at 1 h, reached a maximum at 4 h, and persisted for 24 h. The effects were maintained in the presence of cycloheximide. IL-4 also decreased PGHS-2 protein levels in control and IL-1-stimulated cultures. PGHS-1 mRNA levels were not stimulated by any of the factors studied nor inhibited by IL-4. IL-4 partially inhibited control and PTH-stimulated 45Ca release from prelabeled mouse calvariae at 4 days. However, neither the inhibition of resorption by IL-4 nor the stimulation by IL-1 and PTH were altered by indomethacin (1 microM). We conclude that (1) IL-1, TNF-alpha, and PTH, but not IL-6 nor IL-11, can increase the expression of PGHS-2, cPLA2, and PGE2 production in cultured mouse calvariae; (2) IL-4 inhibits PGE2 production in both control and stimulated calvarial cultures by inhibiting PGHS-2 and cPLA2; and (3) IL-4 has an inhibitory effect on bone resorption which is independent of PG production.
Deoxyspergualin (DSG), an analogue of spergualin produced by B. laterosporus, has a strong immunosuppressive effect in various transplantation models. We have investigated the mechanism of donor-specific prolongation of survival time in rat kidney grafting by donor-specific blood transfusion (DST) and a short course of DSG. Lewis (LEW) kidney allografts were transplanted into fully allogeneic BN rats. Fresh, whole LEW blood 1.0 ml, was injected i.v. into BN rats 2 days prior to transplantation. Then, DSG, 6 mg/kg per day, was administered by i.m. injection on days 0, 1, and 2 after transplantation. The recipients were divided into five groups: group 1 (n = 6) no treatment: group 2 (n = 6) DST only; group 3 (n = 7) DSG only; group 4 (n = 7) DST and DSG; and group 5 (n = 6), third party (ACI rats) blood transfusion and DSG. Lymphocytes (cervical lymph nodes) and serum were harvested from BN recipients on day 7 postgrafting. For suppressor cell assays, lymphocytes from BN recipients in each group were added as a third cell to the mixed lymphocyte reaction (MLC) between nontransplanted BN lymphocytes (responder) and LEW or other third party (PVGC, ACI, WKA rats) lymphocytes (stimulator). Antidonor lymphocytotoxic antibody (ADLA) was checked by microcytotoxicity assays. Median survival times (MST) for each group were: group 1, 10 days; group 2, 10 days; group 3, 13 days; group 4, 75 days; and group 5, 13 days. Remarkable prolongation of MST was only noted in group 4. In the suppressor cell assay, group 4 showed significant suppression (40%; P > or = 0.05); the other groups did not show any suppression. This suppressive activity in group 4 was effective only during the MLC between BN and LEW, not during the MLC of third party-BN combinations. Thus, suppressor cells from DST/DSG-treated BN recipients appear to be donor-specific. In the microcytotoxicity assay, the only group that showed any ADLA was group 2, which was not treated with DSG. These results clearly show that both induction of donor-specific suppressor cells and inhibition of ADLA production are associated with the remarkable donor-specific prolongation of kidney allograft survival in DST/DSG-treated recipients.
We investigated the in vitro and in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the proliferation of two murine leukemic cell lines. The rhG-CSF stimulated leukemic colony formation of the promyelocytic leukemic cell line L-8801 in methylcellulose culture and increased the number of L-8801 cells in liquid culture. However, rhG-CSF treatment prolonged the median survival period of mice implanted with L-8801 cells and the emergence of the leukemic blast cells in peripheral blood. Meanwhile, rhG-CSF had no influence on that of the megakaryoblastic leukemic cells L-8057 and failed to prolong the median survival period of L-8057 leukemic mice. Receptor binding analysis revealed that L-8801 cells expressed a G-CSF receptor (Kd=125 pM, 479 binding sites/cell) and L-8057 cells had no G-CSF receptors. Then, we examined the growth potential of these cells. The median survival period was longer for mice implanted with L-8801 cells cultured with rhG-CSF for 72 h in vitro than for cells grown without rhG-CSF. Furthermore, the median survival period of mice implanted with spleen cells from L-8801 leukemic mice treated with rhG-CSF was prolonged compared with those from leukemic mice without rhG-CSF. In contrast, there was no effect of rhG-CSF on the growth potential of the spleen from L-8057 leukemic mice. The results of our present study demonstrate that rhG-CSF reduced the growth of L-8801 leukemic cells in vitro and in vivo mediated through G-CSF receptors, thereby suppressing the development of leukemia.
Forty-three trigger thumbs and fingers in 33 children (15 boys and 18 girls, average age 2 years and 4 months) were treated using a polyethylene splint. Affected digits included 40 thumbs, one index finger, and two middle fingers. The IP joint was stabilized in maximum extension via a strap on the dorsal side. The splint was applied only at night and during day-time naps. Twenty-four digits recovered completely in an average of 10 months, seven digits improved, and two digits required surgery. Eight patients (10 digits) dropped out of treatment. Splint therapy is effective in treating trigger thumbs and fingers in children.
A variant alkaline phosphatase (ALP), with heat-sensitivity characteristics similar to that of the bone type, was found in the serum of a patient suffering from lung cancer. In disc polyacrylamide gel electrophoretic studies most of this enzyme had migrated to the region corresponding to liver ALP, with the remainder affecting bone ALP. Like kidney ALP, this ALP was markedly inhibited by 0.5 mmol/l L-cysteine. The K(m) of this ALP for p-nitrophenylphosphate was 0.39 mmol/l, similar to that of kidney ALP. The sugar moiety of this enzyme bore greater resemblance to that of kidney ALP than liver or bone ALP. However, immunoprecipitation of this particular ALP was strong with a monoclonal antibody against liver ALP and moderate with an antibody against bone ALP.
PURPOSE: To characterize the CT findings of dermatofibrosarcoma protuberans. MATERIAL AND METHODS: CT and pathologic specimens of 6 patients with dermatofibrosarcoma protuberans (5 in the trunk and 1 in the leg) were retrospectively reviewed. RESULTS: CT clearly defined the tumors in the dermis and subcutaneous tissue with a characteristic, if not pathognomonic, protrusion. On postcontrast CT, 3 tumors showed marginal enhancement and central low density, while the others showed homogeneous enhancement. Pathologically, the marginal enhancement on CT corresponded to fibrosarcomatous changes, and the central low density to necrosis. The tumors with homogeneous enhancement had no sarcomatous changes. CONCLUSION: CT allows detection and precise anatomic localization of dermatofibrosarcoma protuberans. Marginal enhancement with central low density on CT may suggest a relatively poor prognosis.