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Biomedical subjects

Y Yamamoto

Publications and source records attributed to Y Yamamoto.

At least 91 records · Page 5Linked to original sources

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Bacillus subtilis↗

A novel hypoxia-dependent 2-nitroimidazole KIN-841 inhibits tumour-specific angiogenesis by blocking production of angiogenic factors.

Tumour angiogenesis is initiated by angiogenic factors that are produced in large amounts by hypoxic tumour cells. The inhibition of this step may lead to tumour-specific antiangiogenesis because normal tissues are not usually hypoxic. On the other hand, blocking a biological function of endothelial cells is known to result in angiogenic inhibition. To produce a tumour-specific and powerful antiangiogenesis, we determined whether potent angiogenic inhibition could be achieved by inhibiting the production of angiogenic factors by hypoxic tumour cells and simultaneously blocking certain angiogenic steps in endothelial cells under normoxia. We focused on the 2-nitroimidazole moiety, which is easily incorporated into hypoxic cells and exhibits its cytotoxicity as hypoxic cytotoxin. We designed and synthesised 2-nitroimidazole derivatives designated as KIN compounds, and investigated their antiangiogenic activities under normoxia using a chick embryo chorioallantoic membrane. KIN-841 (2-nitroimidazole 1-acetylhydroxamate) showed a potent angiogenic inhibition in a dose-dependent manner. This compound inhibited the proliferation of bovine pulmonary arterial endothelial (BPAE) cells more strongly than that of tumour cells, such as Lewis lung carcinoma (3LL) cells, under normoxia. The inhibition of cell proliferation by KIN-841 under hypoxia increased about five-fold compared to that under normoxia. Moreover, under hypoxia, KIN-841 significantly decreased the excessive production of vascular endothelial cell growth factors induced by 3LL cells as determined by tritium-labelled thymidine ([(3)H]thymidine) incorporation into BPAE cells and by ELISA. Intraperitoneal administration of KIN-841 suppressed 3LL-cell-induced in vivo angiogenesis in the mouse dorsal air sac system. These results indicate that the regulation of the production of angiogenic factors by hypoxic tumour cells is a useful target for tumour-specific angiogenesis inhibition, and that KIN-841, which causes simultaneous direct inhibition of endothelial cell function and production of angiogenic factors by hypoxic tumour cells, is a very potent inhibitor of tumour-specific angiogenesis. Thus, the potential for clinical use of KIN-841 as an antitumour drug is very high.

Angiogenesis Inhibitors↗

The glutamate AMPA receptor antagonist, YM872, attenuates regional cerebral edema and IgG immunoreactivity following experimental brain injury in rats.

We previously reported the neuroprotective effects of the glutamate AMPA receptor antagonist YM872 on neurobehavioral motor function and cortical tissue loss (lesion volume) in a brain-injured rat model. Here we examined its effect on brain edema and the breakdown of the blood-brain barrier (BBB). Rats subjected to severe right lateral (parasagittal) fluid-percussion brain injury or sham injury received a 4-hr intravenous infusion of YM872 (20 mg/kg/ hr, 20 mg/3 ml) or normal saline starting at 15 min post-injury. At 48 hr we removed their brains and evaluated the cerebral regional edema by the wet weight/dry weight method. Another group of rats was transcardially fixed with 10% formalin at 2 weeks after injury. Serial brain sections were immunostained for endogenous IgG and the extent and intensity of staining were evaluated. The administration of YM872 resulted in a significant reduction in regional cerebral edema in the injured parietal cortex and a markedly reduced area of IgG immunoreactivy in the injured cortex. Our results indicate that the post-traumatic administration of YM872 may be neuroprotective by reducing BBB breakdown and regional cerebral edema.

Animals↗

In vivo activation of pro-form Bombyx cysteine protease (BCP) in silkmoth eggs: localization of yolk proteins and BCP, and acidification of yolk granules.

The present study was designed to investigate the process of acidification of yolk granules during embryogenesis. In oocytes of mature Bombyx mori silkmoth, yolk proteins and a cysteine protease (pro-form BCP) were found in yolk granules. BCP was localized in small sized yolk granules (SYG, 3-6 microm in diameter) and yolk proteins in large sized granules (LYG, 6-11 microm in diameter), which might result in a spatial separation of protease and its substrates to avoid unnecessary hydrolysis. The granules were isolated on Percoll density gradient centrifugation. Although separation of LYG and SYG was incomplete, the granules sedimented in different fractions when using unfertilized egg extract, in which LYG was recovered from heavier fractions and BCP from lighter fractions. Acid phosphatase, as well as other lysosomal marker enzymes tested, was recovered from LYG-containing fractions. When extracts were prepared from developing eggs (day 3), some BCP-containing granules co-sedimented with LYG. The inactive pro-form BCP was activated in vivo, in parallel with yolk protein degradation, and as demonstrated previously in vitro under acidic conditions (). These results suggest that acidification occurs in yolk granules during embryogenesis. This was also confirmed using acridine orange fluorescent dye. In early development, most yolk granules were neutral, but became acidic during embryonic development. SYG were progressively recovered in heavier density fractions, displaying acidic interior. In this fraction, BCP-containing granules seem to be associated with larger granules (6-11 microm in size). In addition, SYG (BCP containing granules) were likely to be acidified earlier than LYG. Our results suggest that acidification initiates yolk degradation through activation of pro-form BCP.

Animals↗

Follicular dendritic cell tumor in the oro-pharyngeal region: report of a case and a review of the literature.

A case of follicular dendritic cell tumor (FDC tumor) arised in the aro-pharyngeal region is reported in a 16-year-old Japanese boy. He had a swelling in the right retromolar trigone and soft palate. Clinical examination disclosed a 25 mm x 30 mm, elastic hard, ulcerated mass. CT scans showed a low density lesion in the right medial parapharyngeal area. The biopsy specimen revealed a low-grade malignant tumor. The patient underwent a tumorectomy which was extended to include the adjacent palatine tonsil. The tumor cells, with a clear cytoplasm and oval nucleus, were immunoreactive for S-100 (N/A), CD 21 (1F8), fascin (55K-2) and FDC (CNA42). The fascicular sheet pattern arrangement of the tumor cells was partly characteristic. The final diagnosis was an follicular dendritic cell tumor. Three courses of adjuvant chemoradiotherapy were administered postoperatively. Clinical features, pathological diagnosis and immunohistochemical markers for distinguishing FDC tumor are reviewed.

Adolescent↗

Explanations for the smoking paradox in Japan.

The prevalence of cigarette smoking among Japanese men has been consistently high compared with Western males over the past 30 years. However, during the same period, the incidence of and mortality rates for lung cancer have consistently been lower in Japan than in Western countries ('Japanese smoking paradox'). The odds ratio/relative risk of cigarette smoking for lung cancer mortality/incidence relative to the same number of cigarettes smoked per capita in Japan, were apparently lower than those in Western countries. This must be the cause driving the 'Japanese smoking paradox'. Furthermore, low carcinogenic ingredients in Japanese cigarettes and a congenitally-related resistance to smoking-related lung carcinogenesis emerged as the main factors which have brought the 'Japanese smoking paradox'.

Adolescent↗

Immunohistochemical evaluation of the muscularis mucosae in the ruminant forestomach.

The muscularis mucosae and condensed fibrous layer of the ruminant forestomach were studied by immunohistochemistry using specific antibodies against alpha-smooth muscle actin (alphaSMA) and gamma-smooth muscle actin (gammaSMA). The specimens were collected from the rumen, reticulum and omasum of cattle, water buffalo, sheep, goat, Barbary sheep, Japanese serow, sika deer and mouse deer. The muscularis mucosae showed immunoreactivity for both alphaSMA and gammaSMA. On the other hand, the condensed fibrous layer appearing between the propria mucosa and tela submucosa was immunoreactive only for alphaSMA except for that in the goat and Barbary sheep reticulum which is intermingled with gammaSMA immunoreactivity. The distribution of muscularis mucosae and/or condensed fibrous layer varied among the compartments of forestomach and ruminant species. In the rumen, only the condensed fibrous layer was detected. On the other hand, the omasum contained only the muscularis mucosae. In the reticulum, both were detected. The amount of the condensed fibrous layer in the reticulum varied among different species in the following order of abundance: goat > Barbary sheep > sika deer> sheep > water buffalo > cattle and Japanese serow. Smooth muscle cells of external muscle layer were immunoreactive for alphaSMA and gammaSMA whereas those of blood vessels and pericytes were immunoreactive only for alphaSMA. The present findings on the actin immunoreactivity and distribution profile of muscularis mucosae and the condensed fibrous layer provide additional knowledge to further understand the histophysiological specialization of the different compartments of the ruminant forestomach.

Actins↗

The role of ultrasonographically guided puncture of the human rete testis in the therapeutic management of nonobstructive azoospermia.

We attempted to characterize the cells collected from the rete testis via ultrasonographically guided puncture. Unilateral puncture of the rete testis was performed in nine men with obstructive azoospermia and 51 men with nonobstructive azoospermia. All the aspirated samples from the rete testis were observed via confocal scanning laser microscope and some of them after fluorescent in situ hybridization techniques. Then therapeutic testicular biopsy was performed in the punctured testis of each man. Spermatozoa were found in all rete testis samples and all biopsy samples from obstructed men. Twenty-two nonobstructed men demonstrated absence of spermatozoa in biopsy samples. Twenty-nine nonobstructed men showed spermatozoa in biopsy material and 24 of these men (82%) had demonstrated spermatozoa in rete testis samples. There were no significant differences in fertilization and cleavage rate between intracytoplasmic sperm injection trials using biopsy spermatozoa and rete testis spermatozoa both in obstructed and nonobstructed men. Considering that puncture of the rete testis does not reduce the volume of testicular parenchyma, is less invasive and apparently causes less detrimental effect on testicular vasculature than biopsy, puncture of rete testis is recommended as first line approach for the treatment of azoospermic men. If puncture is negative for spermatozoa in nonobstructed men, biopsy is indicated.

Biopsy↗

An artificial testis for production of rat haploid cells.

PURPOSE: We attempted to apply the microgravity cell culture system for rat testicular germ cell maturation in vitro. METHODS: Primary spermatocytes were isolated from immature male rat by sedimentation velocity. Sertoli cells were isolated from another immature male by enzyme digestions. Sertoli cell aggregates were plated into conventional tissue culture flasks and incubated at 37 degrees C for 48 hours. These pretreated Sertoli-enriched monocultures were used in preparing Sertoli cell-primary spermatocyte cocultures. And then, primary spermatocytes and Sertoli cells were cocultured in a microgravity cell culture device for 28 days. RESULTS: Cell viability rate is more than 50 % after a 28-day long period of incubation. Furthermore, about 23 % haploid germ cells are observed. CONCLUSIONS: These results using primary spermatocyte coculture with Sertoli cell aggregates under microgravity show that it is possible to mature these cells up to the round spermatid and even to elongating/elongated steps. It may be possible to overcome the male sterility due to maturation arrest at the primary spermatocyte stage.

Animals↗

Warming by resistive heating maintains perioperative normothermia as well as forced air heating.

BACKGROUND: Even mild perioperative hypothermia is associated with several severe adverse effects. Resistive heating has possible advantages compared with other active warming systems because it can heat several fields independently. To assess this new warming system, we measured core temperature in patients during surgery who were warmed with circulating water mattresses, forced air covers or resistive heating covers. METHODS: Twenty-four patients undergoing laparoscopic cholecystectomy were randomly assigned to (i) circulating water mattress (38 degrees C), (ii) forced air warming (set to 'medium') or (iii) carbon-fibre resistive warming (38 degrees C). Warming was applied throughout anaesthesia and surgery. The groups were compared using one-way ANOVA and Student-Newman-Keuls tests. RESULTS: Confounding factors were similar among the groups. Core temperatures in each group decreased for 20 min, but subsequently increased in the forced air and resistive heating groups. There was no significant difference between the forced air and resistive heating groups at any time. In contrast, core temperature in the circulating water group continued to decrease. Consequently, core temperature in the circulating water group was significantly lower than in the other groups 30 min after anaesthetic induction and at later times. CONCLUSIONS: Resistive heating maintains core body temperature as well as forced air heating and both are better than circulating water. Resistive heating offers the advantage of adjustable heating pods.

Adult↗

99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative assessment of hepatectomy in relation to percutaneous transhepatic portal embolization.

We have devised an original predictive residual index (PRI) using 99mTc diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) liver dynamic SPET for the pre-operative assessment of hepatectomy, including the prediction of residual liver function before hepatectomy. The aim of this study was to evaluate the usefulness of the PRI by using 99mTc-GSA liver dynamic SPET before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe, and to compare the results with the prognosis after hepatectomy. The subjects included eight patients with cholangiocellular carcinoma, five with gallbladder cancer, four with hepatocellular carcinoma and three with metastatic liver cancer. 99mTc-GSA liver dynamic SPET was performed immediately before and 2 weeks after PTPE. Dynamic SPET with 35 continuous rotations was performed to obtain the k-value according to the accumulation curve in each voxel (0.54 cm x 0.54 cm x 1.08 cm) of the liver immediately after a bolus injection of 185 MBq 99mTc-GSA. Each rotation consisted of 180 degrees turn in 64 steps in a 64 x 64 matrix. The acquisition time of each rotation was 35 s. We devised an original PRI by combining the k-value with functional liver volume which were measured by liver dynamic SPET. Hepatectomy was performed following the second SPET. The correlation between the PRI and post-operative patient prognosis was investigated retrospectively. The functional liver volume of the remnant lobe and the PRI significantly increased after PTPE compared with respective values before PTPE (P<0.005 and P<0.0001, respectively). Regarding the relationship between the PRI and the clinical course following surgery, post-operative complications were observed in only two patients. The PRI values of these two patients were 0.323 and 0.394. When the PRI was above 0.400, no patient had symptoms of hepatic failure. The results of this study suggest that, when the PRI value is above 0.400, there is a low probability of hepatic failure after hepatectomy. We conclude that the PRI devised in this study is useful in the pre-operative assessment of hepatectomy after PTPE.

Adult↗

Comparative whole-body 201Tl and bone scintigraphies for the detection of bone marrow involvement in multiple myeloma.

The objectives of this study were to investigate the role of whole-body 201Tl-chloride scintigraphy in comparison with bone scintigraphy in the detection of bone marrow involvement in patients with multiple myeloma and to assess the follow-up evaluation using 201Tl-chloride. Twenty-one patients with untreated multiple myeloma were evaluated. 201Tl-chloride images were acquired 10 min (early) and 2 h (delayed) after the injection of 111 MBq 201Tl-chloride. Bone images were acquired 3 h after the intravenous injection of 740 MBq 99mTc-hydroxymethylene diphosphonate (HMDP). The 201Tl-chloride scan patterns were classified as normal, diffuse (presence of bone marrow), focal (localized areas of uptake) and diffuse+focal. The bone scan patterns were classified as normal and abnormal. Eight of the 21 patients also underwent 201Tl-chloride scintigraphy after chemotherapy for the evaluation of the therapeutic response. On the early 201Tl-chloride image, two patients showed a normal, 13 a diffuse, two a focal and four a diffuse + focal pattern. On the delayed 201Tl-chloride image, nine patients showed a normal, six a diffuse, four a focal and two a diffuse + focal pattern. Bone scintigraphy showed an abnormal accumulation in only five of the 21 patients. Of the eight patients who underwent follow-up 201Tl-chloride studies, the abnormal diffuse pattern was changed to a normal pattern on post-treatment scintigraphy in three, and the degree of abnormal 201Tl-chloride accumulation decreased in comparison with the pre-treatment scan in three. These six patients were considered to be in clinical remission. In the two remaining patients, the degree of abnormal 201Tl-chloride accumulation increased in comparison with the pre-treatment scan, and they were considered to be in clinical progression. 201Tl-chloride scintigraphy is a non-invasive tool, which may be more useful than bone scintigraphy for the diagnosis of multiple myeloma, and may be helpful in the follow-up of multiple myeloma.

Aged↗

Similar effects of cocaine and immobilization stress on the levels of heat-shock proteins and stress-activated protein kinases in the rat hippocampus, and on swimming behaviors: the contribution of dopamine and benzodiazepine receptors.

Cocaine (COC) has been reported to cause effects similar to physiological stressors in the brain neuroendocrinal system, including heat-shock protein (HSP) expression, although these effects have not been elucidated in detail. In the present study, we examined the effects of repeated (4 days) treatments with cocaine hydrochloride (35 mg/kg, i.p.) and 10 min immobilization stress (IM) on the distribution of HSP (HSP27, HSP60, HSP70, HSC70) and stress-activated protein kinase (SAPK) (SAPKalpha, SAPKbeta, SAPKgamma) immunoreactive nerve cells (positive cells) in the rat hippocampus. The swimming behaviors of the rats in the forced swimming test were also examined. In both COC and IM groups, an early enhancement (5 h time point) of hippocampal HSP (HSP27, HSP60, HSP70, HSC70) and SAPK (SAPKbeta, SAPKgamma) positive cells was observed, whereas a recovery (SAPKs) or attenuation (HSP60 and HSC70) was observed at the 24 h time point. In both groups, a depression of the swimming behaviors (attenuation in the activity counts and time until immobility) below the control level was observed at the 5 h point, but a recovery was observed at the 24 h time point. At the 48 h time point, all parameters returned to the control level. These alterations in the levels of HSPs and SAPKs, and the swimming behaviors were similar to those observed in the stress (IM) group, and were characteristic in that all of these alterations were attenuated by the benzodiazepine inverse agonist, Ro 15-4513 (5 mg/kg, i.p.), and the dopamine D1 receptor antagonist, SCH23390 (0.5 mg/kg, i.p.), which was not observed in the groups treated with another stressor-like drug (bicuculline).

Animals↗

Development of predictive equations for body density of sumo wrestlers using B-mode ultrasound for the determination of subcutaneous fat thickness.

OBJECTIVE: To develop an equation for predicting the body density of sumo wrestlers. METHODS: The following were measured: subcutaneous fat thickness measured at nine sites using B-mode ultrasound equipment; circumference at seven sites; hand to leg bioelectrical impedance. The subjects consisted of 24 college sumo wrestlers (mean age 19.7 years, mean body weight 111.2 kg) and 24 matched obese controls (mean age 19.1 years and mean body weight 111.2 kg). In addition, body density was measured by the underwater weighing method, and the percentage of fat was calculated from the measured body density. RESULTS: Linear regression analysis was used to estimate the relation between body density and other variables, and a predictive equation for the body density was derived: y = 1.088-0.00036 x (fat thickness at nine sites) (r(2) = 0.90) for the sumo wrestler group and y = 1.083-0.00033 x (fat thickness at nine sites) (r(2) = 0.91) for the control group. A multiple regression analysis was performed using the body density as the objective variable, and other measured items as the explanatory variables. This was used to derive a predictive equation: y = 1.121-0.00038 x (fat thickness of abdomen)-0.00043 x (circumference of hips)-0.00142 x (fat thickness of triceps) (r(2) = 0.94) for the sumo wrestler group, and y = 1.076-0.00070 x (fat thickness of abdomen)-0.00140 x (fat thickness of tibialis) (r(2) = 0.91) for the control group. The difference between the two equations was due to the difference in body fat distribution. Neither of these predictive equations is applicable to non-overweight non-athletes. CONCLUSION: This is the first predictive equation developed for the body density of sumo wrestlers.

Adipose Tissue↗

Effects of static magnetic fields on bone formation in rat osteoblast cultures.

Although the promotional effects on osteoblasts of pulsed electromagnetic fields have been well-demonstrated, the effects of static magnetic fields (SMF) remain unclear; nevertheless, magnets have been clinically used as a 'force source' in various orthodontic treatments. We undertook the present investigation to study the effects of SMF on osteoblastic differentiation, proliferation, and bone nodule formation using a rat calvaria cell culture. During a 20-day culture, the values of the total area and the number and average size of bone nodules showed high levels in the presence of SMF. In the matrix development and mineralization stages, the calcium content in the matrix and two markers of osteoblastic phenotype (alkaline phosphatase and osteocalcin) also showed a significant increase. Accordingly, these findings suggest that SMF stimulates bone formation by promoting osteoblastic differentiation and/or activation.

Alkaline Phosphatase↗

Hypertriglyceridemia associated with decreased post-heparin plasma hepatic triglyceride lipase activity in hypoxic rats.

Exposure of sated rats to 45% N2 in air for 5h increased serum triglyceride levels by 212% over the levels in normoxic rats. This increase in triglyceride levels was accompanied by a decrease in plasma triglyceride hydrolase activity after intravenous injection of heparin. Further fractionation of the activity by inhibition of lipoprotein lipase indicated that the low triglyceride hydrolase activity is mainly due to a reduction in hepatic triglyceride lipase, which is inversely correlated with the serum triglyceride level. The hypoxic exposure decreased the arterial blood [acetoacetate]/[beta-hydroxybutyrate] ratio in the sated rats, which is believed to reflect the oxidation-reduction state in hepatic mitochondria, but did not affect the level of serum enzymes indicative of tissue damage. On the other hand, triglyceride levels did not change during hypoxic exposure in fasted rats. Thus, hypertriglyceridemia in sated rats following exposure to hypoxia may result from impaired removal of circulating triglycerides by hepatic triglyceride lipase located in the sinusoidal surface of the liver.

Animals↗