Pathological correlate of the slitlike changes on MRI at the putaminal margin in multiple system atrophy.
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Atrophy↗
Biomedical subjects
Y Goto
Publications and source records attributed to Y Goto.
The effect of tranilast on experimental proliferative vitreoretinopathy.
BACKGROUND: Tranilast has been clinically used for various allergic diseases. Recently, it has also been found to inhibit excessive scarring in wound healing processes. In this study, we examined the effects of tranilast on the treatment for experimental proliferative vitreoretinopathy (PVR). METHODS: Cultured rabbit conjunctival fibroblasts were injected intravitreously (50000 cells/eye) into the rabbit vitreous to induce experimental PVR. Immediately after that, tranilast (0.5-5 mg/ml, 0.1 ml/eye) was injected into the vitreous. Injection of vehicle solution was used as a negative control. PVR was clinically evaluated by masked observers using ophthalmoscopy and graded into six stages: 0 (no PVR) to 5 (severe PVR). The amount of transforming growth factor beta1 (TGF-beta1) in the vitreous was measured by ELISA method. Functional and morphological changes induced by 5 mg/ml tranilast were sought by electroretinography, light microscopy, and electron microscopy on day 28. RESULTS: The average stage of PVR in the eyes treated with tranilast (1 or 5 mg/ml) was significantly lower than that in the control group on days 14 and 28. There was no difference between the eyes treated with low-dose tranilast (0.5 mg/ml) and the control group. The amount of TGF-beta1 in the vitreous of tranilast-treated eyes was significantly lower than in the control group. The morphological and functional studies did not show any deleterious effect of tranilast on the retinal function and morphology. CONCLUSION: Tranilast effectively inhibits the progression of PVR without showing apparent toxicity of the eye. This agent has therapeutic value for PVR.
Animals↗
Systemic granulomatous arteritis associated with Epstein-Barr virus infection.
A 61-year-old woman initially presented with symptoms and findings reminiscent of infectious mononucleosis, and her illness then took a rapidly fatal course. Autopsy revealed widespread granulomatous arteritis, with multinucleated giant cells but without eosinophils and fibrinoid necrosis, affecting small arteries and arterioles and infiltration of haemophagocytic histiocytes into many organs. In situ hybridization with Epstein-Barr virus (EBV)-specific oligonucleotide probes showed positive signals in the infiltrating immune cells and epithelial and endothelial cells of the affected organs. EBV-associated haemophagocytic syndrome (EBV-AHS) with systemic granulomatous arteritis was diagnosed. From the immunophenotypes of the infiltrating immune cells, a possible role of CD4+ T-cells in the pathogenesis of this haemophagocytic syndrome and granulomatous vasculitis was suggested.
Arteritis↗
Possible role of an endovascular provocative test in the diagnosis of glossopharyngeal neuralgia as a vascular compression syndrome.
We utilized endovascular provocative techniques to identify the indications for microvascular decompression surgery in a serious case of glossopharyngeal neuralgia. This is the first reported case in which an endovascular provocative test was applied for diagnosis of glossopharyngeal neuralgia as a vascular compression syndrome. A 68-year-old woman presented with severe paroxysmal facial pain which could not be controlled by medical therapy. Partial effectiveness to carbamazepine led us to wonder whether or not the selection of microvascular decompression surgery would be appropriate. Pre-operative angiography was performed. During the examination a microcatheter was inserted into the right posterior inferior cerebellar artery (PICA), and an attack of typical glossopharyngeal neuralgia occurred. The patient thus underwent microvascular decompression surgery. The PICA was verified to compress the glossopharyngeal nerve and therefore was moved to induce decompression. The patient has since experienced no further pain for one year postoperatively. The diagnosis of glossopharyngeal neuralgia is sometimes complex and it is difficult to select the most appropriate surgical modality. In such cases this endovascular provocative technique may thus be useful for making a definitive decision or microvascular decompression surgery.
Aged↗
Inhibitory effect of methylene blue-induced photooxidation on intimal thickening of vein graft.
BACKGROUND: We have previously speculated that methylene blue-induced photooxidation of adventitial surface for 5 minutes can completely inhibit the intimal and medial growth of surgically prepared saphenous vein in vitro. In this study, inhibitory effect of methylene blue-induced photooxidation on intimal thickening of vein graft in vivo was investigated. METHODS: Jugular vein grafts were photooxidized in 0.01% methylene blue solution for 5 minutes, and interposed into arterial circulation for 4 weeks in rabbits. Vein grafts were studied by morphometry and immunohistochemistry. RESULTS: The intimal thickening of photooxidized vein grafts were suppressed significantly compared with those in the nonphotooxidized group. Proliferated cell nuclear antigen (PCNA) index (total PCNA-positive cells/total cell count x 100%) of vein graft was significantly higher in the nonphotooxidized group than those in the photooxidized group. CONCLUSIONS: Methylene blue-induced photooxidation is effective in the inhibition of intimal thickening of vein graft interposed in the arterial circulation for 4 weeks in vivo.
Animals↗
Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan.
Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.
Adult↗
Possible involvement of nitroglycerin converting step in nitroglycerin tolerance.
Nitroglycerin (GTN) produces a dilation of vascular smooth muscle by releasing NO through a putative GTN-converting step. However, the response to GTN is markedly attenuated after prolonged or repeated exposure, resulting in tolerance. We investigated the mechanisms of GTN tolerance, employing exogenous and endogenous NO in rat aorta. In endothelium-denuded rat aortic strips, the GTN-induced relaxation response was attenuated by preceding exposure to either GTN or sodium nitroprusside (SNP). In contrast, the SNP-induced relaxation response was not affected by this protocol of GTN or SNP preexposure. Preincubation of aortic strips with lipopolysaccharide (LPS) +/- L-arginine for 12 h also caused attenuation of GTN-induced responses such as relaxation, cGMP production and nitrite/nitrate formation. The attenuating effect of LPS abolished in aortic strips co-incubated with LPS and cycloheximide or N(G)-nitro-L-arginine. These results suggest that GTN tolerance is predominantly associated with the reduction of NO release from GTN, which is caused through inhibition of a GTN-converting step due to preceding exposure to NO itself.
Animals↗
The comparative benefits of glaucoma filtering surgery with an electric-pulse targeted drug delivery system demonstrated in an animal model.
PURPOSE: To evaluate the safety and effectiveness of glaucoma filtering surgery performed with the adjunctive use of bleomycin administered in conjunction with electric pulses (EP). DESIGN: Experimental study in rabbits. CONTROLS AND METHODS: Trabeculectomies were performed on pigmented rabbits (2 to 2.5 kg) using the following adjunctive treatments: 5 microM of topical bleomycin and EP (5V, 50 msec, 8 pulses) (group A: B+E+, n=15); bleomycin but no EP (group B: B+E-, n=15); 5 ,uM mitomycin C (MMC) and EP (group C: M+E+, n= 10); MMC but no EP (group D: M+E-, n=10); EP alone (group E: E+, n=10); and no adjunctive treatment (group F: E-, negative control, n=10). MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured regularly for 60 days after the operation. Bleb formation and the condition of the conjunctiva, cornea, and retina were also regularly evaluated. Histologic studies were performed by light microscopy, and retinal functions were evaluated by electroretinography. RESULTS: Postoperative IOP was significantly lower than the preoperative level in all the animals until day 7. However, in groups E and F (the negative control) it returned to the preoperative level after day 7, and in groups B, C, and D after 15 days. The IOP of group A remained lower even on day 40. The average amount IOP was lowered or increased on day 20 was -6.4 mmHg (P < 0.05) in group A; -0.2 mmHg in group B; +1.2 mmHg in group C; and -3.25 mmHg in group D. The survival rate of the filtering blebs on day 20 was significantly higher in group A than in the other groups. Clinical and histologic studies uncovered no pathologic findings in any intra- or paraocular tissues. Electroretinographic evaluation of retinal function in group A showed no apparent change over the 60 days of the study. CONCLUSION: Glaucoma filtering surgery in rabbits with the adjunctive use of bleomycin in conjunction with EP significantly lowered IOP for up to 40 days without clinically, morphologically, or functionally harming intraocular tissues.
Animals↗
Skin manifestations of a patient with mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS syndrome).
Skin abnormalities in a patient with newly diagnosed MELAS syndrome are reported. He presented with scaly, pruritic, diffuse erythema with reticular pigmentation on his entire body. Moderate hypertrichosis was also noted on the lower extremities. Thickened arrector muscles with longitudinal and cross sections were seen in the dermis. Analysis of mitochondrial DNA in a biopsy specimen from the biceps brachii disclosed the presence of an A-to-G point mutation at nucleotide pair 3243. Electron microscopy revealed marked increase in the number of morphologically abnormal mitochondria in the arrector muscles of the involved skin. This is the first report of a MELAS syndrome patient with skin manifestations and evidence of morphologically abnormal mitochondria.
Adult↗
Analysis of flash echo from contrast agent for designing optimal ultrasound diagnostic systems.
Microbubble-based contrast agents can enhance echoes in areas of low blood flow, but the bubbles are extremely sensitive and collapse easily when exposed to ultrasound (US) irradiation. An experimental study of bubble collapse was carried out to design new functions for US diagnostic systems to detect echoes from microbubbles more efficiently. For contrast agent (Levovist) solution, a high-intensity, but momentary, echo (flash echo), was observed in the first frame image after a several-second suspension of transmission, but was not seen in the second frame image. These "flash echo" signals were analyzed and categorized based on microscopic observation, and the results showed that the longevity of the microbubbles was reduced by conditions such as B-mode imaging. Next, a numerical simulation of the bubbles in liquid was performed under the same conditions as in the in vitro experiment. The results showed that even bubbles less than 1 microm in diameter expand and collapse within one pulse drive, which would generate flash echoes. The flash echo imaging system described here permits flexible intermittent scanning with variable intervals, with a variable number of frames at the trigger, and with simultaneous monitoring at low power output. Animal experiments were also conducted to evaluate the system. As the interval between frames was increased, the flash echoes gradually increased, and perfusion in the parenchyma was clearly observed with an interval of 4 s.
Animals↗
Differences in evoked potential characteristics between DRPLA patients and patients with progressive myoclonic epilepsy: preliminary findings indicating usefulness for differential diagnosis.
The characteristics of evoked potentials in patients with dentatorubral-pallidoluysian atrophy (DRPLA) were investigated. Twelve patients with DRPLA and three patients with progressive myoclonic epilepsy (PME) attributable to other causes participated in the study. In 11 out of the 12 patients, the diagnosis of DRPLA was genetically confirmed, based on a 56-75 CAG triplet repeat expansion on chromosome 12p; in the remaining patient, the diagnosis was not genetically confirmed but the patient was clinically diagnosed as having DRPLA and was within the same pedigree as one of the 11 genetically confirmed patients. Two out of the three patients with PME, who had been tested for dodecamer repeat expansion in the cystatin B gene, were genetically confirmed as having Unverricht-Lundborg disease (UL); the remaining patient was also clinically diagnosed as having UL, but the patient did not have the aforementioned genetic abnormality. Somatosensory evoked potentials (SEPs) and brainstem auditory evoked responses (BAERs) were recorded. The amplitudes of the SEPs were determined as the peak-to-peak amplitudes between P2 and N2 deflections. The results revealed that high-amplitude SEPs were not evoked in any of the DRPLA patients; on the other hand, high-amplitude SEPs were evoked in all the patients with UL. Moreover, BAERs were absent in seven out of the 12 patients with DRPLA; on the other hand, all UL patients showed BAERs in which all peaks, from I to V, were distinguishable. These results suggest differences in pathophysiology between DRPLA, which predominantly affects the brainstem and subcortical regions, and PME, characterized by cortical hyperexcitability. Thus, evoked potential measurements may be useful to differentiate DRPLA patients from those with progressive myoclonic epilepsy.
Adolescent↗
Improved efficacy with nonsimultaneous administration of netilmicin and minocycline against methicillin-resistant Staphylococcus aureus in in vitro and in vivo models.
The effect of combined administration of netilmicin and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) was investigated by using in vitro and in vivo models. Thirty one isolates of MRSA were tested for sensitivity to netilmicin, minocycline, and combination of both by the chequer board method. We used then a dynamic in vitro system, which simulates in vivo serum kinetics, to assess the effect of various combination regimens of these antibiotics against an MRSA isolate with a fractional inhibitory concentration index of 0.25. The following dose regimens were compared: netilmicin given alone; minocycline given alone; both antibiotics given simultaneously; netilmicin followed by minocycline at 2 h; or minocycline followed by netilmicin at 2 h. Netilmicin showed a stronger activity than minocycline. On the other hand, their combination was synergistic against 19% of isolates and additive against 77% of isolates. Against one isolate only, it was indifferent, and no antagonism was observed. In the auto-simulation system, the combination of antibiotics was generally more effective than single drugs, with the regimen netilmicin followed by minocycline at 2 h showing the highest antibacterial effect. In the mouse model of pulmonary infection, the bacterial counts and histopathological findings of the lungs improved by treatment with this regimen. This regimen led also to a significantly high survival rate of mice with systemic infection compared to the other treatment regimens. Therefore, it was concluded that administration of netilmicin followed by minocycline at 2 h may be an effective combination against MRSA infection.
Animals↗
Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections.
In vitro and in vivo anti-Candida albicans and anti-Aspergillus fumigatus activities of NND-502, a new imidazole-antimycotic, were compared with those of fluconazole (FCZ), itraconazole (ITZ) and/or amphotericin B (AmB). NND-502 exhibited strong in vitro antifungal activity against both fungal species; its MIC against C. albicans was 1-4 times lower than that of FCZ, and its MIC against A. fumigatus was at least 60-2000 times lower than that of ITZ and AmB. In vivo antifungal treatments with each drug were initiated 1 h after inoculation in the experimental models, so that antifungal potential reflected prophylactic activity rather than therapeutic activity. The oral regimen of NND-502 in a murine model of systemic C. albicans infection was much less effective than that of FCZ. In vivo anti-A. fumigatus activity of oral NND-502 in a murine model of systemic infection was apparently superior to that of FCZ and ITZ in terms of prolonging survival. In addition to the murine model of systemic aspergillosis, intravenous NND-502 was shown to be highly effective in a rat model of pulmonary aspergillosis compared with intravenous AmB; 90% of animals survived at a dose of 2.5 mg/kg per day of NND-502 while only 30% of animals escaped death when 5 mg/kg per day of AmB was used. This potent efficacy of NND-502 was also confirmed in a sublethal challenge study in which the administration of the agent at a dose as low as 1.25 mg/kg per day resulted in the significant reduction of organisms in the lung; no comparable effect of AmB was found.
Amphotericin B↗
Alcohol-induced denaturation of beta-lactoglobulin: a close correlation to the alcohol-induced alpha-helix formation of melittin.
Alcohols denature the native structure of proteins and induce alpha-helical structure. The potential of alcohols causing such effects varies substantially depending on the alcohol species. With beta-lactoglobulin as a model protein, we compared the effects of various alcohols and observed the additive contribution of each group constituting the alcohol molecules. Whereas the hydrophobic hydrocarbon group promotes the transition according to their size, hydrophilic hydroxyl group suppresses the transition. Halogen groups promote the transition depending on their type and number. It has been known that alcohols induce the alpha-helical structure on the short peptides such as melittin. There is a close correlation between the potentials of alcohol in denaturing beta-lactoglobulin and those in inducing the helical structure in melittin, indicating that the underlying mechanisms of the two phenomena are the same.
Alcohols↗
Markedly high eosinophilia and an elevated serum IL-5 level in an infant with cow milk allergy.
BACKGROUND: Interleukin-5 (IL-5) promotes the production and function of eosinophils, and an increase in the serum soluble CD23 (sCD23) level is suggestive of enhanced type-2 helper T-cell activity. The secretion of a large amount of the proinflammatory cytokine, tumor necrosis factor alpha (TNF-a), has been reported to alter the intestinal barrier capacity. OBJECTIVE: To determine whether or not distinct profiles of cytokine production were involved in the marked peripheral eosinophilia of as high as 20,000/mm3 and the gastrointestinal symptoms seen in an infant with cow milk allergy. METHODS: The levels of IL-5, sCD23, and TNF-alpha in serum and the culture supernatants of mononuclear cells were compared with those in infants with anaphylaxis to cow milk and nonallergic infants. RESULTS: Interleukin-5 was detected in the serum (19 pg/mL) but became undetectable after 2 weeks on a milk-free diet together with clinical remission. A kinetic decrease in the serum sCD23 level was also observed during the administration of a milk-free diet with improvement of the eosinophilia in 2 months. The TNF-alpha produced in vitro after stimulation with cow milk protein was not different from in controls. CONCLUSION: It seems likely that the allergic inflammation due to cow milk can induce marked eosinophilia with an associated increase in IL-5 production.
Animals↗
A case of hereditary amyloidosis transthyretin variant Met 30 with amyloid cardiomyopathy, less polyneuropathy, and the presence of giant cells.
Transthyretin-Met 30 (TTR-Met 30) is a variant of transthyretin and is usually associated with familial amyloid polyneuropathy. It is rare that patients with TTR-Met 30 will primarily develop amyloid cardiomyopathy. This report presents a patient with late-onset TTR-Met 30 who primarily developed amyloid cardiomyopathy, with less amyloid polyneuropathy in the peripheral nervous system than is usually seen. An autopsy was performed, and histological examination revealed many foreign-body giant cells and macrophages in the area of amyloid deposition that was found in nearly all of the organs.
Aged↗
Microsatellite analysis of childhood leukemia: correlation of 9p and 12p chromosome abnormalities with expression of related genes.
BACKGROUND: Loss of heterozygosity (LOH) and DNA replication error (RER) have been thought to be involved in carcinogenesis, but have not been investigated in childhood leukemia and lymphoma. METHODS: Eighty samples from 65 patients with childhood leukemia and lymphoma were examined using seven different microsatellite markers for RER analysis. Additionally, LOH in two chromosome regions (9p and 12p) was investigated. Furthermore, expression of the TEL, TEL/AML1 and p27(KIP1) genes on 12p and the p16 gene on 9p were detected by reverse transcriptase polymerase chain reaction. RESULTS: Replication errors were detected in 5/65 patients (7.7%). Most (4/5 patients) RER were preferentially located in the 9p and 12p regions. There were two patients who had DNA abnormalities in both 9p and 12p, one with common acute lymphoblastic leukemia (ALL) showed 9p LOH and the TEL/AML1 fusion gene on 12p and the other with common ALL and 12p RER had diminished expression of both the p27(KIP1) gene on 12p and the p16 gene on 9p. CONCLUSIONS: Combined DNA alterations on 9p and 12p, involving LOH, RER and/or gene mutation and chromosomal translocation, were found in childhood acute leukemia, especially in common ALL.
Child↗
Analysis of prognostic factors related to primary superficial bladder cancer tumor recurrence in prophylactic intravesical epirubicin therapy.
PURPOSE: The aims of the present study were to examine the effects of intravesical instillation of epirubicin on tumor recurrence and to identify tumors that are at a high risk of recurrence. METHODS: Forty-five patients with primary superficial bladder cancer were treated with prophylactic intravesical epirubicin following transurethral resection of the bladder tumor (TUR-BT). Epirubicin (20 mg) was administered intravesically every second week for 4 months and then once a month or every 2 weeks for next 8 months. Patients were analyzed with respect to prognostic factors related to tumor recurrence. RESULTS: The overall recurrence-free rate, calculated using the Kaplan-Meier method, was 76.1 and 52.3% at 2 and 5 years after operation, respectively. These results were better than those reported for patients treated with TUR-BT alone. A univariate analysis demonstrated that high-grade, T1, sessile, large (> or = 2 cm) and multiple tumors were a significantly high risk for recurrence. A multivariate analysis performed by using the Cox proportional hazard model with stepwise selection showed that morphologic features (pedunculated or sessile) were the most prognostic factors for recurrence. This was followed by age and tumor size. The remaining four factors were not found to contribute significantly to recurrence. CONCLUSIONS: Epirubicin appears to be effective in preventing the recurrence of superficial bladder cancer. Morphologic features, patient age and size of the tumor were considered independent risk factors. The risk of recurrence for each tumor should be taken into consideration when the intravesical adjuvant therapy protocol is being selected.
Administration, Intravesical↗