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Biomedical subjects

R Matsui

Publications and source records attributed to R Matsui.

At least 19 recordsLinked to original sources

Effect of pH on skin permeation enhancement of acidic drugs by l-menthol-ethanol system.

The effect of pH on the skin permeation enhancement of three acidic drugs by the l-menthol-ethanol system was investigated. The total flux of acidic drugs from the system remarkably varied over the pH range 3.0-8.0, and the permeation enhancement factor depended on the system pH and drug. A skin permeation model, which consists of two permeant (unionized and ionized) species, two system (oily and aqueous) phases, and two permeation (lipid and pore) pathways, was developed. The assumptions were made that only the unionized species can distribute to the oily phase and transport via the lipid pathway. The model explained the relationship between the concentration of drug in the aqueous phase and system pH. The skin permeability data were also described by the model and permeability coefficients corresponding to the physicochemical properties of permeant were calculated for the lipid and pore pathways. The model simulation showed that the permeation of acidic drugs occurred from the aqueous phase and the oily phase acted as a reservoir. Whether the total flux increased with increase of pH was dependent on the lipophilicity of drug. These results suggest that the pH of l-menthol-ethanol system should be given attention to elicit the maximum permeation enhancement.

Animals↗

Reduced sarco/endoplasmic reticulum Ca(2+) uptake activity can account for the reduced response to NO, but not sodium nitroprusside, in hypercholesterolemic rabbit aorta.

BACKGROUND: Hypercholesterolemia (HC) impairs acetylcholine-induced relaxation but has little effect on that caused by the NO donor sodium nitroprusside (SNP), suggesting that acetylcholine releases less NO from the endothelium in HC. The relaxation to authentic NO gas, however, is also impaired in HC aortic smooth muscle, indicating an abnormal smooth muscle response. NO relaxes arteries by both cGMP-dependent and -independent mechanisms, and the response involves calcium (Ca(2+)) store refilling via the sarco/endoplasmic reticulum calcium ATPase (SERCA). We studied the involvement of cGMP and SERCA in the smooth muscle response to NO and SNP in HC rabbit aorta. METHODS AND RESULTS: A selective guanylyl cyclase inhibitor, 1H-[1,2,4]-oxadiazole-[4,3-a]quinoxalin-1-one, eliminated SNP-induced relaxation but only partially blocked NO-induced relaxation in both normal and HC aorta. The residual relaxation to NO was still less in HC and, in both normal and HC aorta, was abolished by concomitant administration of the SERCA inhibitor cyclopiazonic acid (CPA). In contrast, CPA did not affect SNP-induced relaxation in either normal or HC aorta. SERCA activity measured by (45)Ca(2+) uptake was markedly decreased in HC, although SERCA2 protein expression did not change significantly. CONCLUSIONS: These data suggest that NO-induced relaxation but not that to SNP is partially mediated by cGMP-independent Ca(2+) uptake into sarco/endoplasmic reticulum and that reduced sarco/endoplasmic reticulum Ca(2+) pump function can account for the impaired response to NO in HC.

Acetylcholine↗

Technetium-99m MIBI single photon emission computed tomography as an indicator of prognosis for patients with lung cancer-preliminaly report.

PURPOSE: We performed technetium-99m hexakis-2-methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) in 23 patients with primary lung cancer between July 1993 and March 1996. We evaluated the relationships among the uptake ratio, retention index and the prognosis after radiation therapy and/or chemotherapy. MATERIALS AND METHODS: Tc-99m MIBI SPECT was performed at 30 minutes and at 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A/HG) on transverse SPECT images. Regions of interest were set in the area of abnormal uptake of Tc-99m MIBI and in the contralateral normal lung. The ratio of uptake in the lesion to that in the contralateral normal lung was obtained on early images (early ratio; ER) as well as delayed images (delayed ratio: DR). The retention index (RI) was calculated as follows: RI = (DR - ER)/ER x 100. The ratio was compared with survival time and prognostic factors. RESULTS: There was no correlation between ER and DR. The patients with high RI survived longer than those with low RI (median survival, 19.4 months vs. 9.4 months; p = 0.0104 by the Mantel-Cox test). CONCLUSION: These results suggest that RI is the most useful among Tc-99m MIBI indices of primary lung cancer in predicting prognosis.

Adult↗

[Clinical symptoms and characteristic MR spectroscopic findings in Pelizaeus-Merzbacher disease].

Clinical symptoms and MR spectroscopic findings were studied on 4 cases of Pelizaeus-Merzbacher disease including 1 autopsy case. Common symptoms were severe mental retardation and spastic tetraplegia. These cases had nystagmus, and one had involuntary athetotic movement. Genetical diagnosis revealed in 2 cases, duplication of proteolipid protein (PLP) and deletion in 1, whereas one case had no abnormality of PLP gene. MRI indicated the reversal of signal intensities on T1- and T2-weighed images, a characteristic finding of PMD MR spectroscopy demonstrated a pattern of NAA in 3 cases. This was specific to PMD because other white matter diseases show a decrease in NAA. In conclusion, MRS was useful to differentiate PMD from other white matter diseases.

Adult↗

Esophageal varices before and after endoscopic variceal ligation: evaluation using helical CT.

The purpose of this study was to demonstrate the utility of helical CT in assessing the therapeutic effects of endoscopic variceal ligation (EVL). Twenty-four patients with esophageal varices were examined. Helical scanning was initiated 60 s after intravenous injection (Iopamidol 300 mgI/ml, total 120 ml, 3 ml/s) was started. Esophageal varices were clearly depicted as high-density areas. Multiplanar reformation and 3D images demonstrated collateral circulation three-dimensionally. After EVL, mucosal high-density areas had diminished markedly, but collateral veins around the esophagus, and gastro- and/or spleno-renal shunts, were unchanged in all patients. Of 21 patients with collateral circulation, esophageal varices recurred endoscopically in 6 patients within 12 months. In 3 patients without collateral circulation, esophageal varices did not recur within 12 months. From these findings, we conclude that helical CT is a useful method for assessing the therapeutic effects of EVL.

Collateral Circulation↗

FGF-2 induces surfactant protein gene expression in foetal rat lung epithelial cells through a MAPK-independent pathway.

Fibroblast growth factors (FGFs) play important roles in diverse aspects of animal development including mammalian lung epithelial cell proliferation, differentiation, and branching morphogenesis. We developed an in vitro lung epithelial cell culture system to study functions and mechanisms of FGFs in regulating growth and differentiation of primary foetal rat lung epithelial cells. In comparison with other growth factors such as IGF-I, EGF, and HGF, FGFs were the most potent mitogens in stimulating lung epithelial cell proliferation. In the presence of FGF-1, 2, or 7, the primary lung epithelial cells could be propagated for generations and grown for more than two mo in vitro. Among the three FGFs tested, FGF-7 showed the strongest stimulation in cell growth. FGF-2, on the other hand, is the most effective inducer of lung epithelial cell-specific surfactant protein gene expression (SP-A, -B, and -C). FGF-2 upregulated SP-C expression in a dose-dependent manner. More interestingly, the induction of surfactant protein gene expression by FGF-2 appeared to be independent of MAPK pathway, since the SP-C expression was not inhibited but rather augmented by MEK1 inhibitor which inhibited MAPK activation and cell proliferation. Similar effects were observed for the expressions of surfactant protein genes SP-A and SP-B. In contrast to MAPK, FGF-2-induced SP-C expression was partially inhibited by PI 3-kinase inhibitor wortmannin. These data suggest dynamic roles and complex signalling mechanisms of FGFs in regulating lung epithelial cell proliferation and differentiation. While a MAPK-dependent pathway is essential for all three FGFs to stimulate cell proliferation, a MAPK-independent pathway may be responsible for the FGF-2-induced surfactant protein gene expression. PI 3-kinase may play an important role in mediating FGF-2-induced lung epithelial cell differentiation during development.

Animals↗

Angiosarcoma of the tongue: report of a case with immunohistochemical findings.

A case report of angiosarcoma of the tongue is presented. The specimen revealed single and clustered large, pleomorphic, and spindle-shaped cells with a markedly hemorrhagic background. Tumor cells showed expression of thrombomodulin and E-selectin, but no expression of Factor VIII-related antigen, Ulex europaeus agglutinin-1, vascular endothelial growth factor, and CD34. In the current study, immunohistochemical results using antibodies against thrombomodulin and E-selection supported the diagnosis of angiosarcoma.

Aged↗

[Evaluation of 99mTc-MAG3 (mercaptoacetyltriglycine) renography for pediatric patients].

It is difficult to evaluate renal function with 99mTc-MAG3 renography in both adult and pediatric patients. We examined 109 pediatric patients with various renal diseases using 99mTc-MAG3 renography. Tenal diseases were classified as follows: 9 vesicoureteral reflux, 4 ureteropelvic junctional stenosis, 3 double pelvis, 23 hydronephrosis, 4 glomerulonephritis, 4 nephrotic syndrome, 24 hemolytic uremic syndrome, 10 others; and 24 patients without abnormal findings on other examinations. After hydration and sedation, 100-200 MBq of 99mTe-MAG3 was injected intravenously. All patients were placed in the supine position, and dynamic data acquisition at 12 sec/frame x 100 frames was performed from the back. The renograms were prepared with the ROIs (regions of interest) set to include the entire kidney. Tmax and T1/2 of renograms were measured for 26 kidneys with no abnormal findings. The correlations between Tmax or T1/2 and age (days after birth) were determined by a linear or logarithmic function. The logarithmic function (Y = 7.49 - 0.56 logeX, r2 = 0.134) yielded a higher correlation than did the linear function (Y = 5.16 - 0.00194X, r2 = 0.089) between Tmax and age. For T1/2 and age (days after birth), the linear function (Y = 8.07 - 0.00451X, r2 = 0.222) yielded a higher correlation than the logarithmic function (Y = 11.9 - 0.986 logeX, r2 = 0.192). Our findings suggest that prolonged Tmax is normalized more rapidly than T1/2 after birth in infants. A delayed excretion phase is not suggestive of renal dysfunction, but is characteristic of renograms in pediatric patients. Abnormality was detected in all patients with hydronephrosis using 99mTc-MAG3 renography. On the other hand, a quantitative study was required because renography detected no abnormality for some of patients with disorders of renal parenchyma.

Adolescent↗

[Quantitative assessment of 201Tl-SPECT in tumors of bone and soft tissue].

201Tl-SPECT was performed to diagnose the malignancy of bone and soft tissue tumors by visual and quantitative assessment in 48 patients (17 malignant lesions and 31 benign lesions). SPECT images were obtained in the early phase (15 min after injection) and the delayed phase (240 min). By visual assessment a tumor was considered malignant if high accumulation was found in the tumor in the early phase and the accumulation was confirmed in the delayed phase. Tumors which did not meet these criteria were considered benign. For quantitative assessment, the ROI (region of interest) accumulation ratios of the tumor to the contralateral normal tissue in the early phase (ER) and in the delayed phase (DR), the ROI accumulation ratio of the delayed phase to the early phase of the tumor (Td/Te), and the ROI accumulation ratio of the delayed phase to the early phase of the contralateral normal tissue (Nd/Ne) were obtained. Sixteen patients with malignant tumors each had a high accumulation each but 12 of 31 benign lesions had no high accumulation on visual assessment. Furthermore, the accuracy was 85.4%, sensitivity 94.1%, and specificity 80.6%. Quantitative assessment was performed for 36 cases of high accumulation. The ER of malignant and benign lesions was 5.51 +/- 3.73 and 2.75 +/- 2.17, respectively, and the ER of malignant lesions was significantly higher than that of benign lesions. The DR did not demonstrate a significant difference. If the tumor having an ER greater than 3.9 was assumed to be malignant, the accuracy for differentiating malignant lesions from benign lesions was 85.4%. The Td/Te of benign lesions (0.97 +/- 0.28) was higher than that of malignant lesions (0.77 +/- 0.09). The Nd/Ne of normal tissue which contained muscles in both lesions were higher than 1.4. In conclusion, 201Tl-SPECT was very useful for the differential diagnosis of benign or malignant bone and soft tissue tumors. The ER was important for quantitative assessment, but a delayed image was necessary for visual assessment.

Adolescent↗

[A case of a traumatic anterior cerebral artery aneurysm following the penetration of the skull base by an iron rod].

A 61-year-old male fell from a position 1 m high when building a house. An iron rod, which protruded upward from a solid base in cement, penetrated this patient's neck 15 cm to the head and was successfully extracted by himself. On admission, he complained of headache and vomiting. General examination disclosed nasal bleeding, intraoral bleeding, and L figured skin laceration in the left side of his neck at the level of the thyroid cartilage. Mild disorientation (JCS2) was noted. Otolaryngological examination disclosed hyperemia on the left side of the vocal cord as well as at the dome of the superior pharynx. Plain skull film disclosed pneumocephalus and that a piece of bone fragment of the planum sphenoidale had penetrated the brain. CT demonstrated air in the subarachnoid space, ventricular hemorrhage, intracerebral hematoma in the right frontal lobe, and subarachnoid hemorrhage in the anterior interhemispheric fissure. CAG detected neither cerebral vascular abnormalities nor cerebral aneurysm. While staying in our department, he developed mild fever and CSF rhinorrhea. The diagnosis of bacterial meningitis was made from the CSF finding and was well controlled with conservative therapy. CSF rhinorrhea stopped spontaneously with conservative treatment. Sagittal MRI continuously demonstrated contusional hematoma in the base of the right frontal lobe just above the fractured planum sphenoidale and genu of the corpus callosum following the course of the intracranially invading iron rod. The right CAG on Day 10 demonstrated vasospasm on the A1 and a 1 cm sized saccular cerebral aneurysm at the proximal right fronto-polar artery. CAG on Day 17 again showed the persistent presence of the aneurysm. For the purpose of preventing delayed rupture of the aneurysm, radical surgical treatment was planned. Microsurgical dissection disclosed that the aneurysm was located just behind the elevated fracture of the planum sphenoidale. Severe arachnoid adhesion was noted around the aneurysm. The aneurysm was successfully clipped with preservation of the parent artery without inducing new neurological deficits. From the general, otolaryngological, neuroradiological, and operative findings, this aneurysm was diagnosed as a traumatic cerebral artery aneurysm following the penetration of the skull base by the iron rod. The CAG performed at 8 months postoperatively demonstrated the patency of the parent artery and that there was no recurrence of the aneurysm. An unusual case of a traumatic cerebral artery aneurysm following the penetration of the skull base by an iron rod was thus reported.

Accidents, Occupational↗

[Collection conditions of ECG-gated myocardial SPECT].

In ECG-gated myocardial SPECT, we evaluated the effects of data acquisition and imaging conditions on the parameters of left ventricular cardiac function by a phantom experiments and in patients (n = 50) and normal controls (n = 15). Data acquisition was performed under the following conditions: (1) matrix size, 64 x 64 or 128 x 128; R-R interval, 8 or 6 frames; (3) presence or absence of attenuation and scatter corrections; and (4) changes in the accumulation rate of the radioactive tracer (information content) in the myocardium. When the matrix size was 64 x 64 and an R-R interval was divided into 8 frames, end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were 98.30 +/- 13.74 ml, 44.20 +/- 7.45 ml, and 54.91 +/- 2.84%, respectively, for normal controls. These values were slightly lower than those under other conditions. When attenuation and scatter corrections were not performed, the values of the above parameters were even lower. In patients with high accumulation of the radioactive tracer in the liver affecting the myocardial area, the cardiac function parameters were markedly decreased. In phantom experiments in which a decreased accumulation of the radioactive tracer was assumed, the left ventricular volume increased.

Adult↗

Assessment of proliferating cell nuclear antigen immunostaining in parotid tumors.

We evaluated the prognostic value of immunostaining proliferating cell nuclear antigen (PCNA) by using a monoclonal antibody (PC10) in patients with parotid tumors. Twenty-seven cases were studied. Immunohistochemical studies were carried out on paraffin-embedded tissues from the patients, and the PCNA index was calculated as the percentage of positively staining tumor cells. The PCNA index ranged from 0.1 to 65.3%. We divided the 27 lesions into three groups histologically: group A with benign pleomorphic tumors (11 cases), group B with low-grade malignant tumors (5 cases), and group C with high-grade malignant tumors (11 cases). The mean PCNA index was 0.7% in group A, 2.0% in group B, and 23.1% in group C. The clinical data revealed a significantly higher local tumor recurrence and mortality rate in group C than in groups A and B. We conclude that PCNA may be used as an important indicator for determining clinical prognosis in parotid tumors.

Adenoma, Pleomorphic↗

[Clinical usefulness of scatter and attenuation correction for brain single photon emission computed tomography (SPECT) in pediatrics].

This investigation was undertaken to study clinical usefulness of scatter and attenuation correction (SAC) of brain SPECT in infants to compare the standard reconstruction (STD). The brain SPECT was performed in 31 patients with 19 epilepsy, 5 cerebro-vascular disease, 2 brain tumor, 3 meningitis, 1 hydrocephalus and psychosis (mean age 5.0 +/- 4.9 years old). Many patients was necessary to be injected sedatives for restraining body motion after Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was injected at the convulsion or rest. Brain SPECT data were acquired with triple detector gamma camera (GCA-9300 Toshiba Japan). These data were reconstructed by filtered backprojection after the raw data were corrected by triple energy windows method of scatter correction and Chang filtered method of attenuation correction. The same data was reconstructed by filtered backprojection without these corrections. Both SAC and STD SPECT images were analyzed by the visual interpretation. The uptake ratio of cerebral basal nuclei was calculated by the counts of the thalamus or lenticular nuclei divided by the cortex. All images of SAC method were excellent than that of STD method. The thalamic uptake ratio in SAC method was higher than that of STD method (1.22 +/- 0.09 > 0.87 +/- 0.22 p < 0.01). The lenticular nuclear uptake ratio in SAC method was higher than that of STD method (1.26 +/- 0.15 > 1.02 +/- 0.16 p < 0.01). Transmission scan is the most suitable method of absorption correction. But the transmission scan is not adequate for examination of children, because this scan needs a lot of time and the infants are exposed by the line source radioisotope. It was concluded that these scatter and absorption corrections were most suitable method for brain SPECT in pediatrics.

Adolescent↗

Evaluation of uptake and release of technetium-99m MIBI SPECT of pulmonary and mediastinal lesions.

We evaluated the uptake and release of Tc-99m MIBI in 7 benign and 30 malignant pulmonary and mediastinal lesions. Of the 37 patients, 13 underwent surgery; malignant involvement was examined in 21 mediastinal lymph nodes. Tl-201 SPECT was also performed in 10 patients. Tc-99m MIBI SPECT studies were performed on transverse SPECT images acquired 30 minutes and 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A). Regions of interest were set in the area of abnormal uptake of Tc-99m MIBI and in an area of normal tissue in the contralateral lung. The uptake ratio of the lesion in the contralateral normal lung was obtained on the early image (early ratio; ER) as well as the delayed image (delayed ratio; DR). The benign lesions showed significantly lower ER (1.6 +/- 0.3) and DR (1.4 +/- 0.4) than the malignant lesions (1.9 +/- 0.5 and 1.8 +/- 0.5, respectively; both p < 0.05). There was no significant difference in the retention index (RI), calculated as RI = (DR-ER)/ER x 100. The DR obtained with Tl-201 SPECT images was significantly higher than that obtained with Tc-99m MIBI SPECT (p < 0.05). For the detection of mediastinal lymph node metastases, the early images showed sensitivity, specificity, and accuracy of 85.7%, 100%, and 95.2%, respectively, for the delayed images these values were 85.7%, 92.9%, and 90.5%, respectively. These results suggest that the uptake ratio of Tc-99m MIBI is a useful index in assessing benign or malignant pulmonary and mediastinal lesions.

Aged↗

[Usefulness of 99mTc-tetrofosmin myocardial scintigraphy before and after coronary intervention].

Dipyridamole-loading 99mTc-tetrofosmin myocardial scintigraphy was performed for patients with coronary artery disease who underwent percutaneous transluminal coronary angioplasty (PTCA) in order to examine whether SPECT imaging prior to treatment is useful for the determination of prognosis after coronary intervention. Thirty-six patients including 9 with angina pectoris (AP), 22 with old myocardial infarction (OMI) and 5 OMI with AP were underwent dipyridamole-loading 99mTc-tetrofosmin myocardial SPECT before and after coronary intervention. The length of follow-up was 185 +/- 107 days after PTCA. Improvement of myocardial uptake was observed on myocardial SPECT in all cases with AP. Improvement of the myocardial uptake was observed 50% (4/8) of patients with OMI who had no myocardial viability. It was suggested that the improvement of myocardial uptake after PTCA was due to incomplete fill-in in cases with AP and that the presence of fill-in was important for level of fill-in in patients with AP. The improvement of myocardial uptake in the scar tissue in patients with OMI contributed to the hibernating myocardium. We concluded that correct detection of hibernating myocardium was difficult despite the superior imaging capability of 99mTc-tetrofosmin myocardial SPECT.

Aged↗

Evaluation of an artificial dermis full-thickness skin defect model in the rat.

An artificial dermis product was applied to full-thickness skin defects in rats and cell infiltration into the collagen matrix was investigated. Host fibroblasts and capillaries infiltrated as far as the upper end of the collagen matrix by day 14 after application. Determination of glycosaminoglycan levels in the matrix showed that hyaluronic acid was generated in a similar amount to that seen in the intact skin by day 14. An autologous thin split-thickness skin graft was placed onto the artificial dermis simultaneously or several days after its application to the defect. The take rate was 100% when a split-thickness skin graft was performed on day 14 after application of the artificial dermis. At 6 weeks after the skin defect was created, the wound area was 80% of the original area and the dermis at the grafted site was as thick as that of normal skin. These results suggested that the artificial dermis provides a good matrix for thin split-thickness skin graft and is useful for the reconstruction of full-thickness skin defects. This method is considered to be an alternative to the conventional procedure using thick skin grafts or skin flaps.

Animals↗

Histological evaluation of skin reconstruction using artificial dermis.

An artificial dermis, composed of a collagen matrix, was applied to a full-thickness skin defect prepared on the back of rats. Two weeks later, a thin split-thickness skin autograft was overlaid on the matrix at each recipient site. The dermal layer at the recipient sites was 1.02 mm thick with prior application of artificial dermis, as compared with the 0.46 mm thickness observed without such pretreatment. Histologically, the split-thickness skin graft normally lies with no gap on the artificial dermis, which looks like natural dermis. Six days after grafting, the epithelial basal cells in the grafts showed an active uptake of bromodeoxyuridine (a thymidine analogue), indicating high activity of cell proliferation. About 50 and 20% respectively of the artificial dermis remained at each recipient site at 12 and 20 weeks after its application (after the skin defect). This finding indicates that bovine collagen, which is a constituent of the artificial dermis, is gradually replaced by the host tissue.

Animals↗