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Biomedical subjects

S Sakuma

Publications and source records attributed to S Sakuma.

485 records · Page 27Linked to original sources

Cerebellar vermis defect: a new neurological mutation in the rat.

A new neurological rat mutation showing hind-leg paralysis, cerebellar vermis defect, and cerebellar cortical dysplasia was named "cerebellar vermis defect" (CVD). Pathologically, affected animals already had a small-sized cerebellum in newborns and started to show hind-leg paralysis at approximately 14 days of age. The CVD rat was fertile in both sexes. Genetic analysis indicated that the CVD character is controlled by an autosomal recessive gene with 100% penetrance. The proposed gene symbol is Cvd.

Animals↗

Alignment of x-ray tube focal spots for spectral measurement.

A general method to align a diagnostic x-ray machine for x-ray spectrum measurement purpose was theoretically and experimentally investigated by means of the optical alignment of focal pinhole images. Focal pinhole images were obtained by using a multi-pinholed lead plate. the vertical plane, including the central axis and tube axis, was decided upon by observing the symmetry of focal images. the central axis was designated as a line through the center of focus parallel to the target surface lying in the vertical plane. A method to determine the manipulation of the central axis in any direction is presented.

Radiography↗

Immunohistochemical study of rat renal interstitial fibrosis induced by repeated injection of cisplatin, with special reference to the kinetics of macrophages and myofibroblasts.

Progressive renal interstitial fibrosis occurs following tissue injury, resulting in chronic renal failure. In the fibrogenesis, macrophages are speculated to induce myofibroblasts producing matrix protein. The kinetics of these cells in renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg body weight, once weekly) was investigated immunohistochemically. During the 10-wk injection period, epithelial damage of the proximal renal tubules in the corticomedullary junction was seen, followed by cystic dilation of the affected tubules. During the 8-wk recovery period following the seventh injection, the size of the dilated lumina was diminished and atrophic tubules lined by regenerating epithelial cells appeared. Morphometrical analysis revealed that fibrosis began to develop around the dilated renal tubules in the injection period and was more advanced in the following recovery period. Coinciding with development of fibrotic tissues, the number of alpha-smooth muscle actin-positive myofibroblasts was significantly increased in the areas compared to that of controls. In the injection period, despite a significant increase in myofibroblast number, an elevation of ED-1 (primary antibody)-positive macrophage number was not observed. In the recovery period, however, a significant elevation of macrophage number was noticed in markedly advanced interstitial fibrosis. This suggests that rapid expansion of the macrophage population, probably resulting from release from myelosuppression due to CDDP, might contribute in part to development of myofibroblasts, leading to the augmented fibrosis in the recovery period.

Acute Kidney Injury↗

Poorly differentiated carcinoma of the parotid gland in a six-week-old Sprague-Dawley rat.

A poorly differentiated spontaneous tumor was found in the parotid gland region of a 6-wk-old female Sprague-Dawley rat. The tumor consisted of undifferentiated cells forming dense clusters, well-defined nests, or compact sheets. In some areas, spindle-shaped cells were arranged in a fascicular fashion. Neither ductular nor acinar structures were seen. No keratinization was observed, either. Mitotic figures were frequent. All neoplastic cells were immunoreactive for pankeratin but negative for vimentin, alpha-smooth muscle actin and S-100 protein. Ultrastructurally, the tumor cells were characterized by desmosome-like junctional complexes, poorly developed cytoplasmic organelles, and microvilli-like cytoplasmic processes. Based on these findings and its anatomical location, the present tumor was diagnosed as a poorly differentiated carcinoma of the parotid gland.

Animals↗

Lysozyme-containing renal tubular hyaline droplets in F344 rats bearing a rat fibrosarcoma-derived transplantable tumor.

Renal tubular hyaline droplets developed in male and female F344 rats bearing a rat fibrosarcoma-derived transplantable tumor (SS). The droplets accumulated exclusively in the proximal renal tubular epithelia as eosinophilic granules of various sizes in hematoxylin and eosin-stained sections. The granules stained bright red with azan-Mallory stain. Immunohistochemically, the droplets were positive for lysozyme to various degrees but were negative for alpha 2u-globulin, albumin, and alpha 1-antitrypsin. These findings indicated the involvement of lysozyme, a low-molecular-weight protein, in the droplet formation. The morphological and immunohistochemical findings of the hyaline droplets bore a close resemblance to those reported in rats as a secondary lesion to spontaneous histiocytic sarcomas. Others have speculated that renal tubular hyaline droplets in histiocytic sarcoma-bearing rats are formed in lysosomes through cellular overload of lysozyme secreted excessively by the tumor cells. However, neoplastic cells of SS tumors were negative to lysozyme. The pathogenesis of renal hyaline droplets appearing in SS tumor-bearing rats remains to be investigated.

Animals↗

Immunohistochemical analysis of macrophages, myofibroblasts, and transforming growth factor-beta localization during rat renal interstitial fibrosis following long-term unilateral ureteral obstruction.

Renal interstitial fibrosis was induced in rats by chronic unilateral ureteral obstruction (UUO). To identify the mechanisms behind the fibrosis, macrophage influx, myofibroblast involvement, and the localization of transforming growth factor-beta (TGF-beta, a fibrogenic cytokine) were investigated immunohistochemically in rats euthanatized at 0 (controls), 3, 6, 9, 12, and 15 days after UUO. The number of alpha-smooth muscle actin-positive myofibroblasts began to increase significantly in the medulla from day 3, and the development of medullary fibrosis was confirmed from day 6 by morphometric analysis. From day 9, papillary fibrosis also developed in association with an increased number of myofibroblasts. These myofibroblasts showed a parallel orientation to the mucosal surface of the pelvis. In the medulla and papilla, from day 6 the number of ED1 (primary antibody)-positive macrophages began to increase significantly. There appeared to be a relationship between macrophage influx and myofibroblast involvement. By contrast, in the cortex there was no marked increase in myofibroblasts nor development of fibrotic tissues, regardless of increased number of macrophages from day 6. Immunohistochemically, no staining for TGF-beta was found in infiltrating macrophages or myofibroblasts. However, TGF-beta was localized on some cortical proximal renal tubules both of normal control and obstructed kidneys in the early stages on days 3, 6, and 9, suggesting that the possible origin of TGF-beta may be renal epithelia. However, the staining intensity for TGF-beta on the renal epithelia tended to be weakened in advanced obstructed kidneys on days 12 and 15. The likely contribution of TGF-beta to the advanced stages of UUO-induced renal fibrosis remains to be determined.

Actins↗

Antimicrobial effect of fluoride mouthrinse on mutans streptococci and lactobacilli in saliva.

PURPOSE: This study was designed to determine whether the long-term use of fluoride mouthrinse affects the salivary levels of mutans streptococci and lactobacilli. METHODS: The subjects consisted of 414 school children aged 7, 10, and 12 yrs. Among these subjects, 243 children had received fluoride mouthrinse since 5 years of age at nursery schools, and comprised the "mouthrinse group." The remaining 171 children, the "no mouthrinse group," had not received fluoride mouthrinse. All of the children received routine dental health education. The levels of mutans streptococci and lactobacilli for the subjects in both groups were measured using Dentocult SM Strip mutans and Dentocult LB Dip Slide, respectively. Dental examinations were conducted to obtain data on caries prevalence (dfs and DMFS). Logistic regression analysis was used to control confounding factors: age, dfs, DMFS, frequency of toothbrushing, sum of permanent tooth surfaces sealed, frequency of sweet snacks, frequency of sweet drinks, and the use of fluoridated toothpaste. RESULTS: There was a significant difference in mean DMFS between the mouthrinse group and no mouthrinse group at all ages. Children with fluoride mouthrinse had lower levels of mutans streptococci, and there was a significant association between the experience of fluoride mouthrinse and the score of Dentocult SM strip Odds ratio: 0.64, P < 0.05. However, there was no significant relation between the experience of fluoride mouthrinse and the score of Dentocult LB Dip Slide. The results of this study demonstrated that the long-term use of fluoride mouthrinse affected the detectable levels of mutans streptococci, but did not affect the levels of lactobacilli. CONCLUSIONS: These results suggest that fluoride mouthrinse might contribute to reducing the number of mutans streptococci.

Cariostatic Agents↗

Tetrahydrobiopterin inhibits copper-induced oxidation of low density lipoprotein.

The effect of tetrahydrobiopterin (BPH4) on Cu2+-induced oxidation of low density lipoprotein (LDL) prepared from rabbit plasma was examined. BPH4 (0.5-10 microM) inhibited the formation of thiobarbituric acid-reactive substances (TBARS) in LDL induced by 5 microM Cu2+ in a dose-dependent manner. BPH4 also suppressed the increase in relative electrophoretic mobility (REM) of LDL in the presence of 5 microM Cu2+. The potency of inhibitions of BPH4 on TBARS formation and REM was the same as or stronger than that of ascorbic acid and alpha-tocopherol, which are known as endogenous inhibitors of LDL oxidation. These results suggest that BPH4 could act as an efficacious endogenous inhibitor of atherogenic LDL modification.

Animals↗

Multi-directional positron imaging: evaluation of cancer detection with 2-(F-18)-fluoro-2-deoxy-D-glucose.

We developed a multi-directional positron imaging system for the whole body in order to evaluate the spatial distribution of radiopharmaceuticals. A positron emission tomography (PET) scanner with ring detectors was modified to provide 54 directional planar images with a three-dimensional appearance by using cinematic display. The initial clinical evaluation was performed on two normal volunteers and 17 cancer patients with 32 foci. Images were obtained approximately one hour after the intravenous administration of 2-(F-18)-fluoro-2-deoxy-D-glucose. In all 19 subjects, good quality images with a three-dimensional appearance were obtained. We were able to visualize 16 of 20 (80%) lesions that were three centimeters or more in greatest diameter. In contrast, only seven of 12 (58%) lesions less than three centimeters in greatest diameter were identified. The overall detectability of lesions was 72%. These results suggest that this system will be useful for tumor detection.

Aged↗

Influence of matrix size, vessel shape, vascular diameter, flow velocity, course of vessels on MR angiography.

Basic experiments were done to examine the influence of the extent of curve, direction of flow, vascular diameter, velocity of flow, and course of vessels on MR angiography. In the first experiment, two phantoms were constructed of vinyl tubing, a hairpin type and one with tubes bent to varying degrees. These phantoms were imaged in two matrices, different FOV, and of various velocities with a 1.5 Tesla system. Images of a normal volunteer were also obtained. In studies of the hairpin phantoms, a low intensity artifact appeared at the curve position, and the edge became fuzzy when the flow was perpendicular to the phase encoding direction. These phenomena were more apparent with a smaller matrix, smaller FOV, more gentle angle, larger diameter, and faster flow; in other words the component along the direction was dominant. In the phantom that used bent tubes, another low intensity artifact appeared on the medial side of the outflow portion. The results obtained from the volunteer corresponded well to those from the basic experiments. It was thought that the profile of flow was not well demonstrated due to the coarse matrix. In the second experiment, water flowed at various speeds through three-dimensional phantoms that were made of vinyl tubes of various diameters and directions. The phantoms were imaged with two- and three-dimensional time of flight and phase contrast angiography. The lower limits of detection of the phase contrast method were almost the same. In the coronal plane, the lower limit decreased to 2.5 mm for arteries and 9.5 mm for veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

Asymmetrical FDG-PET and MRI findings of striatonigral system in multiple system atrophy with hemiparkinsonism.

The asymmetry of the local cerebral metabolic rate for glucose (lCMRglc) and magnetic resonance (MR) imaging was studied in five patients with multiple system atrophy (MSA) presenting hemiparkinsonism. lCMRglc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in these patients and five normal control subjects. MR images were obtained in five patients and 11 control subjects. In all patients, T2-weighted MR images showed hypointense areas in the posterior lateral putamen. They were bigger or lower in intensity on the contralateral side than on the ipsilateral side. Significant glucose hypometabolism was found in the posterior putamen on the contralateral side to hemiparkinsonism. A significant decrease in size was found in the contralateral putamen, caudate nucleus, and pars compacta of the substantia nigra. However, no significant correlation was seen between PET and MRI data. In the control subjects, no apparent asymmetry was observed. PET and MR imaging demonstrated the characteristic asymmetry corresponding to the pathological findings reported in MSA.

Brain↗

Ultrasonographic and thermographic evaluation of the lower limb after transfemoral catheterization.

Ten adults undergoing routine transfemoral catheterization were randomly selected for study. Ultrasonography and thermography were performed within 48 hours before and after the catheterization procedure. Sites proximal and distal to puncture were assessed. There were no angiographic procedural complications in any case. Distal to the puncture, Doppler evaluation revealed a decrease in peak systolic velocity (PSV) in six cases, with four showing a greater than 30% fall, while three of the four cases with an increase had a less than 10% rise in PSV. Findings at the proximal site showed no distinct pattern. Changes in the resistive index at both sites were minimal. There was a significant increase in turbulence distal to the site of puncture in six cases. B-mode revealed arterial wall thickening compromising the lumen in half the cases. Thermography was done in four cases, and there was a tendency for an increase in limb temperature after the catheterization procedure. In view of the above-mentioned findings seen in "normal, uncomplicated" procedures, a larger study appears warranted to assess the significance of these findings and to attempt a correlation of the above results with the angiographic procedure.

Adult↗

Thin slice CT study of solitary pulmonary nodules with emphasis on the relation to vasculatures.

Thin (2 mm) and thick (10 mm) slice X-ray computed tomography (CT) scanning was performed in 49 and 31 patients, respectively, to assess the morphology of solitary pulmonary nodules or masses and to determine the relationship between the tumor and surrounding vasculature. When the pulmonary vein passed singly into the tumor or was larger than the artery (pattern I), 38 of 40 nodules (95%) were malignant (p less than 0.001). When the pulmonary artery passed singly into the tumor or was larger than the vein (pattern II) and when no pulmonary vessel passed into the tumor but when a pulmonary vessel was compressed by the tumor or passed through it (pattern III), only 11 of 19 nodules (58%) were malignant. Based on the morphology and vasculature patterns the accuracy of diagnosis with thin slice CT was 80.9% while that of thick slice CT was 67.7%. Thin slice CT can increase the diagnostic accuracy of primary lung cancer.

Adult↗

Isolation, identification, and biological activities of oxidative metabolites of FK506, a potent immunosuppressive macrolide lactone.

To characterize structures and biological activities of FK506 metabolites, FK506 was incubated with liver microsomes prepared from phenobarbital-treated rats in the presence of NADPH generating system under aerobic condition. Oxidative metabolites formed in the reaction medium were isolated and identified. Purified samples were analyzed by HPLC, mass spectrometry, and NMR spectroscopy. M-I, M-II, and M-III were the O-demethylated metabolites at the 13-, 31-, and 15-positions of FK506, respectively, and M-IV was the monohydroxylated metabolite at the 12-position. M-I was the dominant metabolite in this reaction system. M-II and M-III retained the tetrahydropyrane ring in their structures like FK506, but M-I and M-IV had rearranged structures in which the tetrahydropyrane ring was changed to a tetrahydrofuran ring. Measuring the immunosuppressive activity in the mouse mixed lymphocyte reaction system, IC50 values for M-I, M-II, M-III, M-IV, and FK506 were 1.65, 0.23, > 127, 5.52, and 0.15 nM, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocross-reactivity of M-I, M-II, M-III, and M-IV with the antibody were nil, 109.0, 90.5, and 8.8% of FK506, respectively. These results indicate that rat hepatic microsomes oxidatively metabolize FK506 to four metabolites, and some of them exhibit pharmacological activity.

Animals↗

Microglial cytokine gene induction after irradiation is affected by morphologic differentiation.

Microglia are known to play an important role in the CNS cytokine network, and their response after irradiation may be associated with the development of radiation-induced tissue damage. Radiation effects on this cytokine network have not yet been elucidated. We investigated the effect of gamma-irradiation on microglia stimulated with Zymosan A and lipopolysaccharide (LPS), which alone induce the expression of some cytokines and neurotoxic products by microglial cells. In the resting condition (ramified microglia), radiation had no effect on the mRNA level corresponding to cytokines such as IL1beta or IL-6, although TGF-beta1 mRNA was minimally enhanced by irradiation. However, in the activated microglia (amoeboid microglia) stimulated with Zymosan A, radiation-induced IL-6 mRNA expression was increased about two-fold in comparison with non-irradiation. IL-1beta was slightly induced by 2 Gy irradiation, but was not induced by higher doses. TGF-beta1 mRNA was not enhanced by radiation following Zymosan stimulation. In the LPS-stimulated condition, IL-6 mRNA was induced only by 2 Gy of irradiation, but no change in the expression of other genes was detected. These results suggested that radiation exerted different effects on cytokine gene transcription in microglia depending on their morphological state.

Animals↗