Biomedical subjects
Publications and source records attributed to H Homma.
The literature on MRI of orbital schwannomas is limited. The appearances in three patients with an orbital schwannoma were reviewed. A superior orbitotomy through a subfrontal craniotomy revealed a schwannoma in all cases. MRI characteristics of very low signal on T1-weighted images and homogeneous postcontrast enhancement may be helpful for differentiating schwannomas from other intraconal masses.
A case is presented of an adult chylous cyst of the mesentery that was preoperatively diagnosed to be a pancreatic cystadenoma. A 66-year-old asymptomatic male was followed up for 15 months under the diagnosis of a benign pancreatic cyst. On October 1997, computed tomography showed a 45 x 40 mm cystic mass in the upper abdomen which came in contact with the pancreas. Endoscopic ultrasonography revealed a multilocular mass with a 7 x 4 mm elevated lesion. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed the cystic mass to be unrelated to the pancreatic duct. The preoperative diagnosis was a pancreatic cystadenoma or cystadenocarcinoma. A laparotomy showed a 50 x 40 mm cystic mass containing chylous fluid, that arose from the mesentery of the upper part of the jejunum. The pathological diagnosis was a chylous cyst of the mesentery. The preoperative diagnosis in this case was very difficult because the chylous cyst appeared to be attached to the pancreas and this phenomenon is considered to be extremely rare.
Most cases of cholangiocarcinoma have reached an unresectable stage by the time they are discovered despite significant progress of diagnostic modalities. Many of these patients with obstructive jaundice are often treated by biliary drainage using stents to relieve the jaundice. However, the stent patency period is as short as 3 to 9 months because of tumor ingrowth or overgrowth, and mean survival is at most 12 months. Therefore, both continuous relief of obstructive jaundice and local control of the tumor are required in the treatment for advanced cholangiocarcinoma. In this investigation, we developed a new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin-coated tube; CCT). CCT continuously released a fixed amount of carboplatin for 4 weeks and showed an antitumor effect on human cholangiocarcinoma cell line HuCC-T1 in vitro. When CCT was embedded in subcutaneous tumor inoculated in nude mice, a significant reduction of tumor size with no apparent damage to normal adjacent tissue was observed. On the basis of these studies, 5 patients with inoperable cholangiocarcinoma were treated with CCT for 4 weeks. Overall efficacy rate of 5 patients with cholangiocarcinoma was 60% (partial response in 3 and no change in 2). No apparent side effect was observed in these patients. Thus, CCT may provide a new treatment modality for this disease. Randomized controlled trials comparing CCT therapy with palliative stenting are required to confirm these results.
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Our previous studies demonstrated that the octacalcium phosphate (OCP) causes new appositional bone formation on the OCP when implanted into the subperiosteal region of murine calvaria. The OCP may stimulate the cell population committed to the osteoblastic differentiation in the periosteum and have them express the phenotype. The present study was designed to investigate which periosteal cell population is involved in bone formation on the OCP with applying the OCP implants on top of and underneath the periosteum. The periosteum of the rat parietal bones was flapped and the OCP was implanted on top of or underneath the periosteum, in which the implantation sites were defined using the membrane filter. The histology was examined to see if new appositional bone formation occurs on the OCP implant under each condition. New bone was deposited on the OCP on the bone surface separated from the periosteum by the filter, whereas no bone was formed either under the periosteum separated from the bone surface by the filter or on the periosteum. The present study suggests that the OCP acts on osteoblasts, bone lining cells and/or their closely committed progenitors on the bone surface to express the phenotype and deposit new bone on the OCP implant.
Rat pituitary gland and retina were probed with anti-D-aspartate (D-Asp) antibody previously prepared in this laboratory [Lee et al., Biochem. Biophys. Res. Commun., 231 (1997) 505-508]. D-Asp immunoreactivity (IR) was observed only in the posterior lobe of the pituitary gland of 3-day-old rats, whereas the anterior and posterior lobes were also positive in 3-week and 6-week-old rats, respectively. In the anterior lobe, intense IR was scattered throughout the lobe and the D-Asp-positive cells appeared to be prolactin-containing cells or some other very closely related type of cell. In the retina, D-Asp IR was observed only in the ganglion cell and nerve fiber region of 3-day-old rats. In contrast, during the transient increase in D-Asp levels in 7-day-old rats, D-Asp IR was additionally evident in regions where differentiating bipolar cells had begun to make contact with other types of cells. The functional relevance of D-Asp localization in these tissues is discussed.
D-aspartate and human chorionic gonadotropin act synergistically to increase testosterone production in purified rat Leydig cells, and D-aspartate stimulates testosterone synthesis even in the absence of human chorionic gonadotropin stimulation. In addition, D-aspartate enhances steady-state cellular mRNA and protein levels of steroidogenic acute regulatory protein, which is a key regulatory factor in gonadal and adrenal steroidogenesis. D-aspartate therefore appears to increase testosterone production in rat Leydig cells by stimulating steroidogenic acute regulatory protein gene expression. To our knowledge, this is the first report demonstrating a direct effect of D-aspartate on gene expression in mammalian cells.
D-Aspartate increases human chorionic gonadotropin-induced testosterone production in purified rat Leydig cells. L-Aspartate, D-,L-glutamate or D-,L-asparagine could not substitute for D-aspartate and this effect was independent of glutamate receptor activation. Testosterone production was enhanced only in cells cultured with D-aspartate for more than 3 h. The increased production of testosterone was well correlated with the amounts of D-aspartate incorporated into the Leydig cells, and L-cysteine sulfinic acid, an inhibitor of D-aspartate uptake, suppressed both testosterone production and intracellular D-aspartate levels. D-Aspartate therefore is presumably taken up into cells to increase steroidogenesis. Intracellular D-aspartate probably acts on cholesterol translocation into the inner mitochondrial membrane, the rate-limiting process in steroidogenesis.
Nicardipine, a dihydropyridine type calcium channel blocker, was infused at two flow-rates into spontaneously hypertensive (SH) and control normotensive Wistar-Kyoto (WKY) rats (young, 6-week-old and adult, 23-week-old, n = 5) under pentobarbital anesthesia, to cause hypotension. Mean arterial blood pressure and the concentrations of plasma amino acids and norepinephrine (NE) were measured before infusion and at each step of the infusion. The reduction in blood pressure caused by nicardipine induced a decrease in plasma L-arginine concentration in both young and adult SH rats, this effect being larger in adult rats. There was no significant change in plasma levels of L-arginine in age-matched WKY rats. The concentration of other amino acids did not change in both rat strains. On the contrary, there was an increase in plasma NE concentration in both SH and WKY rats after infusion with nicardipine. Plasma L-arginine concentration showed a good inverse correlation with the logarithm of plasma NE concentration in SH and WKY rats and the correlation was expressed as Y = -alpha log(X) + m (Y, plasma L-arginine concentration (nmol/mL); X, plasma NE concentration (pmol/mL); alpha, a slope; and m, an intercept). alpha, 43.0 and 4.35 for 23-week-old SH and WKY rats, respectively, and 17.0 and 4.0 for 6-week-old SH and WKY rats, respectively. The present data together with previous data suggest a direct noradrenergic stimulation of the synthesis of nitric oxide (NO) from L-arginine. The findings also indicate an impairment of the L-arginine metabolism or pools in SH rats compared with WKY rats. The deficiency of L-arginine increases with the age of SH rats and could be related to the development and maintenance of hypertension due to inefficient production of NO.
Enantiomeric separation and detection of D,L-aspartic acid (Asp) derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) by capillary electrophoresis (CE) using modified cyclodextrins as chiral selectors was studied. Heptakis(2,3, 6-tri-O-methyl)-beta-cyclodextrin(TM-beta-CD) was most effective for enantiomeric separation of NBD-D,L-Asp with optimum conditions of 30 mM TM-beta-CD in 50 mM phosphate buffer (pH 4.0) and the limit of detection (LOD) attained was 100 nM for each enantiomer. The method proposed in the present study was convenient for both D- and L-Asp determination since the other amino compounds migrated differently and D-Asp in bio-samples such as rat pineal gland and foods was determined with a simple sample pretreatment and a short analysis run time.
In a previous report (Hamase, K. et al., Biochim Biophys Acta 1134: 214-222 (1997)), we showed that the rat pineal gland contains D-leucine (D-Leu) as well as D-aspartic acid (D-Asp). In this communication we report alterations in the content of these D-amino acids during anesthesia. The D-Asp content was significantly increased from 2.8 to 5.0, 4.8 and 5.8 nmol/pineal gland by administration of ether, urethane and pentobarbital, respectively. In contrast, the D-Leu content was decreased by administration of urethane or pentobarbital. The D-Leu content decreased from 4.2 to 2.2 pmol/pineal gland 4 hours after administration of urethane, although the content remained unchanged until 1.5 hours after administration. The content of the L-enantiomers of these amino acids were not affected by anesthesia. The urethane-induced decrease in D-leucine content was almost completely suppressed by a beta-agonist, (-)-isoproterenol, whereas the agonist itself had no effect.
BACKGROUND: Portal hypertensive gastropathy causes some gastric mucosal microcirculatory disorders in cirrhotic patients, but the nature of the rheologic dysfunction in the gastric microcirculation remains to be clarified. METHODS: To examine the rheologic properties of the gastric microcirculation, we subjected 112 cirrhotic patients and 51 control subjects to endoscopic laser Doppler flowmetry and measured multiple variables of flow, red blood cell volume, and velocity. Furthermore, based on these results, we analyzed the shear rate which reflects the status of the microcirculatory system. To validate the laser Doppler flowmetry, we derived the relationship between red blood cell volume and cross-sectional areas of submucosal collecting venules; near-infrared endoscopy was used to evaluate this relationship. RESULTS: Analysis of shear rate according to the severity of portal hypertensive gastropathy showed that the mucosa was exposed to strong hemokinetic stress in severe cases, characterized by a higher shear rate than in control subjects or in mild cases. Nitroglycerin, administered by intravenous infusion (1.0 microg/kg/min), reduced blood flow and restored shear rate to control levels in patients with severe portal hypertensive gastropathy. CONCLUSION: This rheologic study of the gastric mucosa suggests that a disorder of the shear rate control mechanism in the microcirculation is associated with severe portal hypertensive gastropathy.
BACKGROUND: A dorsum sellae meningioma is a rare occurrence. It is difficult to evaluate dorsum sellae meningiomas preoperatively from the viewpoint of neuroimaging. We report a rare case of dorsum sellae meningioma mimicking pituitary macroadenoma in a 73-year-old woman. CASE PRESENTATION: The patient presented with bitemporal hemianopsia and panhypopituitarism. Magnetic resonance imaging demonstrated a bright, homogeneously enhancing intra- and suprasellar mass and a hypointense region in this mass, which was interpreted as a dorsum sellae. Transsphenoidal extirpation was used because of a suspicion of nonsecreting pituitary macroadenoma. Histopathologically, the tumor was diagnosed as a meningioma. Superselective external carotid angiography before the second surgery revealed that the mass was supplied by the left accessory middle meningeal artery and appeared to originate from dorsum sellae. After preoperative embolization, the patient developed hyponatremia. The tumor was subtotally removed via a transcranial route, and the attachment to the dorsum sellae was coagulated extensively. She did well after a second surgical procedure. CONCLUSION: These radiologic findings may be useful in differentiating dorsum sellae meningioma from pituitary macroadenoma.
OBJECTIVE: The purpose of this study was to determine whether there is a relationship between synovial fluid levels of nitric oxide and clinical and arthroscopic findings of synovitis or cartilaginous degeneration. STUDY DESIGN: Arthroscopic surgery was performed on 20 joints in 15 female patients with internal derangement and osteoarthritis of the temporomandibular joint. Synovial fluid aspirates were obtained immediately before arthroscopy. Synovial fluid was also obtained from 14 joints of 11 female asymptomatic volunteers. The concentration of nitrite in the fluid recovered from each temporomandibular joint was measured through use of a highly sensitive and specific chemiluminescence detection method, calibrated per 1 mg of synovial fluid protein and expressed as nitric oxide; the result was then compared with clinical and arthroscopic findings of synovitis and cartilaginous degeneration. RESULTS: Significantly higher levels of nitric oxide (median, 0.331 micromol/mg) were seen in the patients with internal derangement and osteoarthritis than in the control group (median, 0.001 micromol/mg; P<.0001). Synovial fluid from joints with pain in the joint area had significantly higher levels of nitric oxide than did fluid from joints without such pain. Synovial fluid from joints with degenerative changes (median, 0.467 micromol/mg) had significantly higher levels of nitric oxide than did fluid from joints without osteoarthritis (median, 0.057 micromol/mg; P<.05). Although the levels of nitric oxide in synovial fluid aspirates were markedly elevated in some joints with synovitis, there was no correlation between the levels of nitric oxide and the presence of synovitis. CONCLUSIONS: The findings indicate that increased levels of nitric oxide are involved in the pathogenesis of cartilaginous degeneration of the temporomandibular joint.
The occurrence of free D-amino acids and aspartate racemases in several hyperthermophilic archaea was investigated. Aspartic acid in all the hyperthermophilic archaea was highly racemized. The ratio of D-aspartic acid to total aspartic acid was in the range of 43.0 to 49.1%. The crude extracts of the hyperthermophiles exhibited aspartate racemase activity at 70 degrees C, and aspartate racemase homologous genes in them were identified by PCR. D-Enantiomers of other amino acids (alanine, leucine, phenylalanine, and lysine) in Thermococcus strains were also detected. Some of them might be by-products of aspartate racemase. It is proven that D-amino acids are produced in some hyperthermophilic archaea, although their function is unknown.
Synthetic octacalcium phosphate (OCP) enhances bone formation if implanted into the subperiosteal region of murine bone. Such implanted OCP may be resorbed and replaced by bone with time. We hypothesized that OCP could be used as an effective bone substitute. To test this hypothesis, we designed the present study to investigate if bone repair in a rat skull defect is enhanced by the implantation of OCP. Rats were divided into two groups: OCP-treated animals and untreated controls. Six rats from each group were fixed at 4, 12, and 24 weeks after implantation. A full-thickness standardized trephine defect was made in the parietal bone, and synthetic OCP was implanted into the defect. After being examined radiographically, the specimens were decalcified and processed for histology. OCP implantation significantly promoted bone repair compared with the controls. A statistical analysis showed an increase in the area of radiopacity within the skull defect between week 4 and week 12. Histologically, bone was formed on the implanted OCP and along the defect margin at week 4. At week 12, the implanted OCP was surrounded by newly formed bone. At week 24, the defect was almost completely filled with bone. In the control, bone formation was observed only along the defect margin. The present results demonstrate that OCP could be used as an effective bone substitute.
The rat embryonic brain was probed with anti-d-aspartic acid (d-Asp) antiserum at different stages of development. At gestational day (E) 12, weak immunoreactivity (IR) of d-Asp was apparent at the hindbrain, midbrain and caudal forebrain, whereas it became more intense and extended over the whole brain at E20. However, IR markedly decreased after parturition. In the region of the immature forebrain at an early stage of development (E12), IR was mainly a characteristic of the cytoplasm of the neuronal cells, while in the more mature hindbrain it was localized in the axonal zone. In the more differentiated forebrain at a later stage of development (E18), the IR became restricted to zones which mainly consisted of axons and processes. Consequently, in the rat central nervous system, d-Asp first emerges during embryonic development as a feature of the cytoplasm and thereafter spreads into the axonal regions of neuronal cells, before disappearing almost completely after parturition.
In this communication, we demonstrate that D-aspartate (D-Asp) is synthesized in pheochromocytoma cells (PC12). To our knowledge this is the first report of biosynthesis of D-Asp in mammalian cells. Synthesis of D-Asp was demonstrated by its time-dependent accumulation in the cell culture, and by the fact that this accumulation was proportional to the number of inoculated cells. D-Asp in PC12 cells was identified by (i) co-elution with authentic D-Asp on two different HPLC columns, an octadesyl silica column and a Pirkle-type chiral column, (ii) reversed elution order of D-Asp and L-Asp on another Pirkle-type chiral column with an opposite configuration, and (iii) sensitivity to D-Asp oxidase. In the cells the amount of D-Asp was approx. 12-14% of total Asp and no other investigated D-amino acid was detected. The amount of D-Asp did not increase during the culture of mouse 3T3 fibroblasts and human neuroblastoma NB-1 cells. Immunocytochemical staining with anti-D-Asp antiserum demonstrated that D-Asp synthesized is present in the cytoplasm of the cells.