Biomedical subjects

S Katayama

Publications and source records attributed to S Katayama.

At least 163 records · Page 9Linked to original sources

PubMed1997

Troglitazone has a scavenging effect on reactive oxygen species.

Troglitazone (CS-045), a newly developed antidiabetic thiazolidinedione that enhances insulin sensitivity, is similar in structure to several antioxidants, including alpha-tocopherol and probucol. The in vitro antioxidant activity of troglitazone has been demonstrated in alloxan-induced hyperlipoperoxidemic and hyperlipidemic mice. In this study, we found that troglitazone had a scavenging effect on reactive oxygen produced by xanthine-xanthine oxidase and generated by stimulated neutrophils and tends to be the radical form. Our results suggest that troglitazone is an antioxidant similar to alpha-tocopherol. However, under the same conditions, pioglitazone, another thiazolidinedione drug, did not have a scavenging effect. The antioxidant action of troglitazone, which is attributable to the similarity of its molecular structure to that of alpha-tocopherol, may be of benefit in preventing diabetic vascular complications, in addition to having hypoglycemic and hypolipidemic effects.

Antioxidants↗

PubMed1997

Acarbose controls postprandial hyperproinsulinemia in non-insulin dependent diabetes mellitus.

We investigated how fasting or postprandial insulin levels were altered by treatment with acarbose or sulfonylureas. Plasma glucose and serum insulin, C-peptide, and proinsulin levels were measured before as well as 1 and 2 h after breakfast in 23 patients with non-insulin-dependent diabetes mellitus and 17 patients with impaired glucose tolerance. In the diabetic patients, 12 weeks of acarbose therapy decreased the postprandial levels of glucose (1 h: -60.0%; 2 h: -67.6%), insulin (1 h: -67.5%; 2 h: -72.2%) and proinsulin (1 h: -55.2%; 2 h: -46.7%), and proinsulin (1 h: -20.9%; 2 h: -57.5%). In contrast, sulfonylurea treatment increased postprandial insulin and proinsulin levels. Since increased in the serum insulin or proinsulin levels are associated with a higher risk of cardiovascular disease, the present findings suggest that the acarbose-induced reduction of the postprandial serum insulin or proinsulin responses to food intake might be useful for preventing vascular complications in patients with diabetes.

Acarbose↗

PubMed1997

Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Abnormalities of the p53 gene can lead to the production of anti-p53 antibody in the serum of cancer patients. We evaluated the prognostic significance of anti-p53 antibody in 86 patients with hepatocellular carcinoma (HCC) in comparison with clinicopathological factors: age, sex, etiology, smoking and drinking habits, history of blood transfusion, presence of encephalopathy and ascites, Child classification, Pugh score, bilirubin, albumin, prothrombin time, indocyanine green retention time at 15 min (ICG), underlying liver disease, alpha-fetoprotein (AFP), tumor size, number of tumors, differentiation degree of HCC, presence of extrahepatic metastasis and therapy for HCC. METHODS: The serum anti-p53 antibody in 86 patients with HCC, 20 with chronic hepatitis (CH) and 20 with liver cirrhosis (LC) was measured by an enzyme-linked immunosorbent assay (ELISA). A single-strand conformation polymorphism-polymerase chain reaction (SSCP-PCR) analysis and loss of heterozygosity (LOH) study of the p53 gene were performed using 8 tissue samples of 8 HCC from four antibody-positive and four antibody-negative patients. The survival probabilities were assessed by the Kaplan-Meier technique, and a Cox regression analysis was used to identify the independent factors for prognosis. RESULTS: Anti-p53 antibody was positive in 32% (28 of 86) of the sera from patients with HCC, but in none of the 20 with CH and 20 with LC. p53 antibody positivity was associated with bilirubin and the number of tumors (p=0.027 and p=0.018, respectively). Overall survival was shorter in the HCC patients with p53 antibody than in those without p53 antibody (p<0.02). Bilirubin, p53 antibody, AFP and ICG were found to be significant prognostic factors by univariate analysis. A Cox multivariate analysis showed that bilirubin and p53 antibody were independent prognostic variables (p<0.0001 and p=0.003, respectively). In four antibody-positive patients, mutation and LOH of the p53 gene were detected in one patient and two patients, respectively. In contrast, only one of four antibody-negative patients exhibited LOH of the p53 gene. CONCLUSIONS: Serum anti-p53 antibody could be a useful prognostic factor in patients with HCC.

Adult↗

PubMed1997

Transplantable rat thyroid cancer cell line FRTC transformed with muramyl dipeptide.

A rat thyroid cancer cell line, FRTC, was established from the normal rat thyroid cell line, FRTL-5. FRTL-5 cells were cultured in vitro with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) for 4 days and were transplanted intraperitoneally into Fisher rats. Disseminated tumour formation in the peritoneum was found in ten out of ten rats in which MDP-treated FRTL-5 cells were transplanted. Colloid-like structures stained with anti-thyroglobulin (Tg) antibodies were observed in the tumours. On the other hand, no tumour was found in any of the rats in which untreated FRTL-5 cells were transplanted. No morphological changes were observed in FRTL-5 cells after long-term in vitro culture in the presence of MDP. MDP had no effect on thymidine incorporation, the production of cAMP or the expression of c-myc in FRTL-5 cells in vitro. Cells from the tumour (FRTC) secreted Tg in vitro and expressed Tg, thyroid peroxidase (TPO) and thyrotropin (TSH) receptor mRNA. The expression of TSH receptor mRNA increased in FRTC cells after TSH stimulation. FRTC cells produced cAMP in response to TSH stimulation in a dose-dependent manner. However, the growth of FRTC cells was TSH independent. Expression of c-myc and c-fos was observed in FRTC cells in vivo as well as in vitro. FRTC cells formed tumours in Fisher rats when transplanted subcutaneously. FRTC cells have several characteristics of differentiated thyroid cancer cells and may provide a good model for the study of human differentiated thyroid cancers.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1997

Free radicals in the cerebrospinal fluid are associated with neurological disorders including mitochondrial encephalomyopathy.

The free radical levels in the cerebrospinal fluid of 8 patients with neurological diseases and 9 undergoing lumbar anesthesia for surgery were measured. The ascorbate free radical level 10 min after lumbar puncture showed a positive correlation with the hydroxyl radical level. In the patient with mitochondrial encephalomyopathy, the levels of hydroxyl and ascorbate free radicals increased upon discontinuation of treatment and decreased upon its resumption, and the ascorbate free radical levels without therapy fell after lumbar puncture. The free radical levels in the cerebrospinal fluid may reflect the degree of oxidative stress in the central nervous system.

Aged↗

PubMed1997

Highly sensitive mutation assay for mutagenicity monitoring of indoor air using Salmonella typhimurium YG1041 and a microsuspension method.

A highly sensitive mutation assay for indoor mutagenicity monitoring was investigated by a combination of Salmonella typhimurium YG strains and the microsuspension method. Tester strains were YG1024, YG1029, YG1041 and YG1042. YG1041 gave the highest sensitivity in the mutagenicity test for the extracts of airborne particulates. The sensitivity of the microsuspension assay using S.typhimurium YG1041 in the absence of S9 mix was approximately 200 times higher than that of the preincubation assay using strain TA98, which has been widely used for mutagenicity monitoring of airborne particulates outdoors. Furthermore, a significant correlation was observed between mutagenicities determined by the microsuspension assay using S.typhimurium YG1041 and TA98, where mutagenicity assay was carried out for airborne particulates collected by a high volume sampler for 24 h every 12 days for 1 year. This new method was also useful for indoor mutagenicity monitoring in which a small amount of airborne particulates was collected by a low noise sampler for 12 h each of 6 consecutive days. The monitoring showed that mutagenicity in the daytime is generally higher than that in the night and that smoking is an important factor in increasing mutagenicity in indoor air.

Air Pollution↗

PubMed1997

Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N- and C-terminal peptides.

The effect of lambda-toxin, a thermolysin-like metalloprotease of Clostridium perfringens, on the inactive epsilon-prototoxin produced by the same organism was examined. When the purified epsilon-prototoxin was incubated with the purified lambda-toxin at 37 C for 2 hr, the 32.5-kDa epsilon-prototoxin was processed into a 30.5-kDa polypeptide, as determined by SDS-polyacrylamide gel electrophoresis. A mouse lethality test showed that the treatment activated the prototoxin: the 50% lethal doses (LD50) of the prototoxin with and without lambda-toxin treatment were 110 and 70,000 ng/kg of body weight, respectively. The lethal activity of the prototoxin activated by lambda-toxin was comparable to that with trypsin plus chymotrypsin and higher than that with trypsin alone: LD50 of the prototoxin treated with trypsin and trypsin plus chymotrypsin were 320 and 65 ng/kg of body weight, respectively. The epsilon-toxin gene was cloned and sequenced. Determination of the N-terminal amino acid sequence of each activated epsilon-prototoxin revealed that lambda-toxin cleaved between the 10th and 11th amino acid residues from the N-terminus of the prototoxin, while trypsin and trypsin plus chymotrypsin cleaved between the 13th and 14th amino acid residues. The molecular weight of each activated epsilon-prototoxin was also determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The C-terminus deduced from the molecular weight is located at the 23rd or 30th amino acid residue from the C-terminus of the prototoxin, suggesting that removal of not only N-terminal but also C-terminal peptide is responsible for activation of the prototoxin.

Amino Acid Sequence↗

PubMed1997

Prenatal diagnosis of Duchenne muscular dystrophy in the Japanese population by fluorescent CA repeat polymorphisms analysis.

OBJECTIVE: To investigate the efficacy of CA repeat analysis using fluorescence-labeled primers in the prenatal diagnosis of Duchenne muscular dystrophy in the Japanese population. METHODS: Allelic frequencies of polymorphic loci in the Duchenne muscular dystrophy gene were ascertained, and the polymorphic information content (PIC) was calculated. CA repeat analysis of 21 Japanese families with Duchenne muscular dystrophy was then performed. RESULTS: The STR 49 locus had the highest PIC, followed in decreasing order by the loci of STR 44, STR 45, STR 50, DYS III, DYS II, DYS I, and 3' CA. The diagnostic applicability increased to 0.999 when the PICs of all 8 loci were combined. When the highest PIC from each of the 5' end, exons near the 3' end and the 3' end were combined, the diagnostic applicability increased to 0.988. Of the 7 males examined prenatally, 1 was diagnosed as normal, and 6 were affected, while of the 9 females examined, 5 were diagnosed as carriers, and 4 as non-carriers. CONCLUSION: CA repeat analysis using fluorescence-labeled primers is useful in the prenatal diagnosis of Duchenne muscular dystrophy in the Japanese population.

Alleles↗

PubMed1997

Abdominal aortic aneurysm: rupture associated with the high-attenuating crescent sign.

PURPOSE: To determine the histopathologic features of the ruptured abdominal aortic aneurysm associated with the high-attenuating crescent sign on computed tomographic (CT) scans and to suggest a possible mechanism for the rupture. MATERIALS AND METHODS: Histopathologic examination was performed with specimens from six patients with a ruptured aneurysm associated with the high-attenuating crescent sign and from eight patients with a nonruptured aneurysm and in whom the high-attenuating crescent sign was not present. RESULTS: Acute hemorrhage in the mural thrombus or aneurysmal wall coincident with the high-attenuating crescent sign was present in all six patients with a ruptured aneurysm. Clefts with seeping blood in the mural thrombus were seen in four patients with a ruptured aneurysm; intact specimens of the mural thrombus were not obtained in two patients because the hemorrhagic thrombus was fragile. Clefts with seeping blood were scattered from the inner to the outer layers of the mural thrombus. In the eight patients with uncomplicated aneurysm, no hemorrhage in the mural thrombus or aneurysmal wall was noted, and no clefts were seen. CONCLUSION: The cause of high-attenuating crescents in a ruptured aneurysm may be attributed to hemorrhage in the mural thrombus or in the aneurysmal wall.

Adult↗

PubMed1997

Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enhanced gene expression and synthesis of skeletal muscle glucose transporter 4.

To clarify the relationship between blood pressure and insulin resistance, we studied the role of glucose transporter 4 (GLUT4) in skeletal muscle and the effect of angiotensin-converting enzyme inhibitor on insulin resistance. Blood pressure and plasma glucose and plasma insulin responses to glucose loading (2 g/kg, i.p.) were measured in spontaneously hypertensive rats (SHRs), Wistar-Kyoto rats (WKYs), and Wistar rats at 8, 12, and 20 wk of age. GLUT4 gene expression and plasma membrane protein content were also determined in the gastrocnemius muscle. SHRs and WKYs at the age of 8 wk had significantly higher plasma glucose levels than did age-matched control Wistar rats. Insulin response also tended to be higher. Glucose intolerance was also present in 12-wk-old SHRs, but normalized at the age of 20 wk. In contrast, WKYs were glucose intolerant at 12 and 20 wk. Gene expression and plasma membrane content of GLUT4 were augmented in both 8-wk-old SHRs and WKYs, indicating a compensatory increase in these variables. Effects of captopril (20-30 mg/kg/d from 8 to 20 wk) on GLUT4 were also investigated in these three strains. Captopril improved steady state plasma glucose levels in association with 1.2- to 2.5-fold higher GLUT4 gene expression and a 1.4-fold increase in skeletal muscle GLUT4 protein in SHRs and WKYs. Our results suggest that (1) not only SHRs but also WKYs may have glucose intolerance and hence insulin resistance; (2) gene expression and protein synthesis of skeletal muscle GLUT4 are probably increased compensatorily, indicating that abnormalities in GLUT4 do not have a pivotal role in the development of insulin resistance in SHRs and WKYs; and (3) captopril stimulates skeletal muscle gene expression and synthesis of GLUT4, providing further evidence of its beneficial effect on glucose metabolism.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Protective effect of glycoprotein gC-rich antigen against pseudorabies virus.

A trial vaccine containing pseudorabies virus (PRV) glycoprotein gC as the main component showed excellent protection against virulent virus infection in pigs. Glycoprotein gC-rich antigen was prepared by heparin affinity chromatography from PRV-infected cell lysates. The preparations were mixed with mineral oil adjuvant as a water-in-oil emulsion. Six-week-old pigs were immunized twice at two-week intervals with trial vaccines containing 128,000, 12,800 and 1,280 HA units per dose of gC antigen. They were then challenged with a virulent PRV at day 7 after the final immunization. Neutralizing (NT) antibodies were produced with increase of antibody titers after challenge. Pigs immunized with 128,000 HA units per dose of gC survived and showed no virus shedding during the 2-week experimental period after the challenge. The role of cell-mediated immunity was examined using BALB/c mice, and induction of gC-specific cytotoxic T lymphocytes (CTLs) was detected by 51Cr release assay. From these results with mice, it is inferred that cell-mediated immunity, especially CTL, may play an important role in the effectiveness of our trial vaccine in addition to humoral immunity.

Adjuvants, Immunologic↗

PubMed1997

A new method of bone tissue measurement based upon light scattering.

In recent years, time-resolved spectroscopy systems using near infrared pulsed laser have been applied to develop optical computed tomography. We applied this technique to measure the optical properties of osseous tissues. First, we gradually demineralized 10 mm blocks of bovine trabecular bone with EDTA, maintaining the absorption characteristics and structure but varying the hydroxyapatite content, thus creating specimens differing only in light scattering properties. We used computer densitograms to assess light penetration, and analyzed the correlation with bone mineral density (BMD) as with dual-energy X-ray absorptiometry scans. The light penetration increased with decreasing BMD. Second, using the above-mentioned pulsed laser time-resolved spectroscopy system, we investigated the correlation between the BMD and the time response waveforms of 10-mm blocks of bovine cortical bone, trabecular bone, and surrounding tissue as well as human trabecular bone. The human lumbar vertebral bone also displayed an inverse correlation between BMD and maximum light penetration and a positive correlation between BMD and peak time delay. This is the first demonstration of a correlation between BMD and light scattering properties showing that BMD can indeed be measured with light. Our results show the possibility of obtaining information on internal bone structure and composition in vivo through assessment of the waveforms obtained by a time-resolution system in the near infrared region.

Animals↗

PubMed1997

Hyperinsulinemia in relation to hypertension and other coronary risk factors in Japanese men.

In addition to obesity, abnormalities in glucose and lipid metabolism are common in hypertensives, indicating a possible link between hypertension and hyperinsulinemia. Since the frequency of obesity in Japanese is lower than that in Caucasians, the present study was designed to clarify the frequencies of hyperinsulinemia, glucose and lipid abnormalities, and obesity. We surveyed consecutively 470 men without a history of gastrectomy who visited a health clinic after excluding previously known hypertensives receiving hypotensive agents (4.2%) and diabetics (6.1%). Hypertensives with a blood pressure exceeding 150 and/or 90 mmHg (n = 62) had a significantly higher frequency of diabetes mellitus (6.5%) associated with hypercholesterolemia (24.2%) and mild obesity with a body mass index (BMI) of more than 25 (24.2%) than those of normotensives. When reanalyzed according to the presence or absence of hyperinsulinemia after 75 g oral glucose loading, hyperinsulinemic men demonstrated a higher blood pressure. The incidences of impaired glucose tolerance (67.1%), hypertriglyceridemia (64.4%), low HDL-cholesterol (53.4%), hypercholesterolemia (21.9%) and mild obesity (37.0%) were also significantly higher than those of normoinsulinemic subjects. Subjects with either hypertension and/or hyperinsulinemia had a significantly higher incidence of coexistence of these risk factors. Multiple regression analysis revealed that not only BMI, but also the plasma glucose and insulin response during the 75 g glucose loading test independently correlated with mean blood pressure. These results suggest that hypertensive and/or hyperinsulinemic subjects may be associated with excess cardiovascular risk and should be managed more carefully.

Antihypertensive Agents↗

PubMed1997

Cystic lymphoplasmacyte-rich meningioma--case report.

A 47-year-old female presented with an unusual cystic meningioma. Computed tomography and magnetic resonance imaging showed a cystic tumor with marked edema in the left parietal region of the brain, resembling a metastatic tumor. The tumor was totally removed. Histological examination revealed meningioma with dense lymphoplasmacytic infiltrates.

Female↗

PubMed1997

Evidence for association between the class I subset of the insulin gene minisatellite (IDDM2 locus) and IDDM in the Japanese population.

Although the shortest (class I) minisatellite (i.e., variable number of tandem repeats [VNTR]) alleles in the 5' region of the insulin gene are positively associated with IDDM in Caucasians, the majority of Japanese are homozygous for class I alleles. Here, we determined the exact length, in number of repeat units (RUs), of class I alleles in Japanese subjects. The distribution of class I alleles in Japanese was trimodal, with peaks located at 32/33, 41, and 44 RUs. The shortest component (i.e., 1S [25-38 RUs]) alleles were significantly increased in the IDDM group compared with the control group (54 vs. 46%; P = 0.040). The 1S/1S genotype was significantly increased in the IDDM patients (34 vs. 20%; P = 0.005; relative risk 2.1). Furthermore, the transmission disequilibrium test of Japanese families with 1S/1M or 1S/1L heterozygous parents confirmed the association of 1S alleles; 17 alleles of 1S and 6 alleles of 1M (39-41 RUs) or 1L (42-44 RUs) were transmitted to affected offspring (P = 0.022). In addition, we found tight linkage of 1S with allele 9 of the tyrosine hydroxylase gene microsatellite and allele (-) of the IGF-II gene Apa I polymorphism, but neither 9 nor (-) alleles were significantly associated with IDDM. The present study suggests that a class I subset may have a role in IDDM susceptibility in Japan. It was revealed that the difference between 1S alleles and 1M or 1L alleles is almost consistently characterized by a sequence variation generated by deletion of two copies of an ACAGGGGTCC CGGGG repeat element, implying that sequence variation of class I alleles may influence disease susceptibility.

Adolescent↗

PubMed1997

A case of renin-producing juxtaglomerular tumor: effect of ACE inhibitor or angiotensin II receptor antagonist.

We report a case of a renin-producing juxtaglomerular cell tumor and the effects of angiotensin-converting enzyme (ACE) inhibitor captopril or angiotensin II receptor antagonist TCV-116. A 19-year-old female visited our clinic because of hypertension (162/122 mmHg). Plasma renin activity (PRA) was 25 ng/ml/h and plasma aldosterone concentration (PAC) was 880 pg/ml. Abdominal sonography revealed a low echoic tumor in the center of the right kidney. The mass was shown to have isodensity on a computed tomography scan, iso- or slightly lower intensity on T1-weighted magnetic resonance imaging (MRI), and low intensity on T2-weighted MRI. Renal angiography disclosed a hypovascular tumor. Plasma renin activity was not decreased in response to oral administration of captopril (50 mg) or TCV-116 (4 mg), which is associated with a marked decrease in PAC and blood pressure. The average of the mean blood pressure determined by an ambulatory monitoring system every hour for 24 h was lowered from 118 +/- 10.6 (SD) to 85 +/- 11.4 mmHg by TCV-116. Plasma renin activity did not show any difference between the right and left renal vein. Removal of the tumor successfully decreased PRA to 0.3 ng/ml/h and PAC to 33 pg/ml, resulting in a decrease in 24-h average of the mean blood pressure to 78 +/- 16.9 mmHg. The tumor was well capsulated and stained with an antibody against mouse renin. In the tumor, but not normal tissues, renin mRNA was detected at 1.6 kb using rat renin cDNA. The content of active renin in the tumor amounted to 182 micrograms/g tissue, which is 109 times higher than that in normal tissue. The plasma- or tumor-inactive renin concentration was 3.6- or 1.8-fold the active renin concentration, respectively. These results suggest that the juxtaglomerular tumor had an MRI image of iso- to low intensity on T1 and low intensity on T2, and that renin secretion from the tumor may be due mainly to the constitutive pathway and angiotensin II receptor antagonist, as well as to ACE inhibitors, and may be very effective for lowering the blood pressure.

Administration, Oral↗

PubMed1997

[Chronic neuropathy, a high level of protein in cerebrospinal fluid, and vitamin B1 and folate deficiency in a patient with normal-pressure hydrocephalus].

A 67-year-old woman presented with a 1-year history of gradual weight loss, reduced mental activity, muscle weakness, and urinary dysfunction. Neurological examination revealed mild lethargy, severe muscular atrophy, and diminished deep tendon reflexes in the extremities. The levels of vitamin B1 and folate in blood were low: 1.9 micrograms/dl (normal range 2.0-7.2) and 0.7 ng/ml (normal range 4.0-12.0). respectively. A lumbar puncture was done. The pressure of the cerebrospinal fluid was within normal limits, the level of protein was very high (467 mg/dl), and only a few lymphocytes were seen. A nerve-conduction study showed low amplitudes of action potentials and slow conduction velocities in both the motor and sensory nerves. Myelin irregularity, "onion bulb formation", and axonal atrophy were seen in a specimen obtained by sural nerve biopsy. A T2-weighted magnetic resonance image of the brain showed ventricular dilatation, high-intensity signals around the lateral ventricles, and a flow-void sign of the cerebral aqueduct. Radioisotope cisternography (111In-DTPA) disclosed ventricular reflux and slow clearance of the tracer from the ventricles. These findings indicated the presence of chronic inflammatory demyelinating polyneuropathy, nutritional polyneuropathy, vitamin B1 deficiency, folate deficiency, and normal pressure hydrocephalus. In this patient, the high level of protein in the cerebrospinal fluid may have caused the hydrocephalus.

Aged↗

PubMed1997

[Objective measurement of motor activity in Parkinson's disease by actigraphy. Clinical assessment of akinesia].

Actigraphy measures physiological activity by using an acceleration sensor and RAM equipped with a data logger. Since actigraphy can continuously and easily record data over a long period of time without disturbing the normal activities of subjects, it is possible to analyze a large number of subjects. Actigraphy was performed in patients with Parkinson's disease who did not exhibit trembling. Results showed that the daily motor activity of patients was lower than that of the healthy individual. Daily motor activity was also found to be correlated with Hoehn-Yahr's classification. Furthermore, side-effects due to L-dopa, such as abnormal involuntary movement and on-off phenomenon, could be objective assessed. The results of long-term actigraphic examination, conducted after anti-Parkinsonian treatment, showed that akinesia improved with time. From these findings, it is concluded that actigraphy could quantitatively assess the degree of akinesia in Parkinsonian patients. Furthermore, actigraphy may be applied to the clinical assessment of drugs.

Antiparkinson Agents↗