Vascular and brain dopamine beta-hydroxylase activity in young spontaneously hypertensive rats.

Dopamine beta-hydroxylase activity was higher in mesenteric vessels, adrenal glands, and serum of 3-week-old spontaneously hypertensive rats but lower in the locus coeruleus than it was in the control Wistar-Kyoto rats. The results support the concept that the nervous system is an important regulator of blood pressure.

Risk factors for clustering of tuberculosis cases: a systematic review of population-based molecular epidemiology studies.

BACKGROUND: Many molecular epidemiology studies have been conducted to identify risk factors for clustering of tuberculosis (TB) cases in the population. OBJECTIVE: To estimate the impact of commonly investigated risk factors on TB clustering. METHODS: Ten electronic databases were searched up to January 2006 along with a hand search of the International Journal of Tuberculosis and Lung Disease and bibliographies of review articles. Meta-analyses of odds ratios (ORs) for various risk factors were conducted using random effect models, stratified by TB incidence. Meta-regressions were employed to account for the heterogeneity in clustering proportions and the magnitudes of risk. FINDINGS: The TB clustering proportion varied greatly (7.0-72.3%) among 36 studies in 17 countries. In multiple meta-regression analyses, high TB incidence, mean cluster size and conventional contact tracing were significantly associated with higher clustering. The pooled ORs (95%CIs) for low and high/intermediate TB incidence studies, using a cut off of 25/100000 per year, were 3.4 (2.7- 4.2) and 1.6 (1.3-2.1) for local-born status, 1.6 (1.5-1.7) and 1.7 (1.3-2.2) for pulmonary TB and 1.2 (1.1-1.3) and 1.3 (1.1-1.7) for smear-positive cases, respectively. Male sex, local birth, alcohol abuse and injection drug use were significantly higher risks in low TB incidence studies than in the high/intermediate ones. INTERPRETATION: Meta-analyses yielded significant estimates of ORs for several risk factors across both levels of TB incidence. Alcohol abuse, injection drug use and homelessness--all characteristics of marginalized populations--were found to be consistently significant in populations of low TB incidence. More research is needed to better understand TB transmission dynamics in high-burden countries.

Biomechanical behaviour of a French femoral component with thin cement mantle: The 'French paradox' may not be a paradox after all.

OBJECTIVE: Cement thickness of at least 2 mm is generally associated with more favorable results for the femoral component in cemented hip arthroplasty. However, French-designed stems have shown favorable outcomes even with thin cement mantle. The biomechanical behaviors of a French stem, Charnley-Marcel-Kerboull (CMK) and cement were researched in this study. METHODS: Six polished CMK stems were implanted into a composite femur, and one million times dynamic loading tests were performed. Stem subsidence and the compressive force at the bone-cement interface were measured. Tantalum ball (ball) migration in the cement was analyzed by micro CT. RESULTS: The cement thickness of 95 % of the proximal and middle region was less than 2.5 mm. A small amount of stem subsidence was observed even with collar contact. The greatest compressive force was observed at the proximal medial region and significant positive correlation was observed between stem subsidence and compressive force. 9 of 11 balls in the medial region moved to the horizontal direction more than that of the perpendicular direction. The amount of ball movement distance in the perpendicular direction was 59 to 83% of the stem subsidence, which was thought to be slip in the cement of the stem. No cement defect and no cement breakage were seen. CONCLUSION: Thin cement in CMK stems produced effective hoop stress without excessive stem and cement subsidence. Polished CMK stem may work like force-closed fixation in short-term experiment.Cite this article: Y. Numata, A. Kaneuji, L. Kerboull, E. Takahashi, T. Ichiseki, K. Fukui, J. Tsujioka, N. Kawahara. Biomechanical behaviour of a French femoral component with thin cement mantle: The 'French paradox' may not be a paradox after all. Bone Joint Res 2018;7:485-493. DOI: 10.1302/2046-3758.77.BJR-2017-0288.R2.

Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction.

It has been reported that individuals with the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene are at greater risk for myocardial infarction (MI), especially among subjects normally considered to be at low risk. However, little is known about the mechanism by which the ACE polymorphism affects the risk of MI. Coronary artery spasm (CAS) is considered to be one possible mechanism for developing MI. We therefore examined the ACE polymorphism relation to CAS to determine if this was the mechanism by which the DD genotype influences MI. We studied 150 angiographically assessed Japanese males, all more than 60 yr old. CASs were detected using intracoronary injection of ergonovine maleate. Subjects were divided into three groups: those with CAS (group 1), those without CAS, but with fixed organic stenosis (group 2); and those without CAS and no organic stenosis (group 3). DD subjects were significantly represented in group 1 when compared with groups 2 (P = 0.002) and 3 (P = 0.026). These results suggest that the DD genotype relates to the greater risk for MI in the patients with CAS.

The influence of cement thickness on stem subsidence and cement creep in a collarless polished tapered stem: When are thick cement mantles detrimental?

OBJECTIVES: Favourable results for collarless polished tapered stems have been reported, and cement creep due to taper slip may be a contributing factor. However, the ideal cement thickness around polished stems remains unknown. We investigated the influence of cement thickness on stem subsidence and cement creep. METHODS: We cemented six collarless polished tapered (CPT) stems (two stems each of small, medium and large sizes) into composite femurs that had been reamed with a large CPT rasp to achieve various thicknesses of the cement mantle. Two or three tantalum balls were implanted in the proximal cement in each femur. A cyclic loading test was then performed for each stem. The migration of the balls was measured three-dimensionally, using a micro-computed tomography (CT) scanner, before and after loading. A digital displacement gauge was positioned at the stem shoulder, and stem subsidence was measured continuously by the gauge. Final stem subsidence was measured at the balls at the end of each stem. RESULTS: A strong positive correlation was observed between mean cement thickness and stem subsidence in the CT slices on the balls. In the small stems, the balls moved downward to almost the same extent as the stem. There was a significant negative correlation between cement thickness and the horizontal:downward ratio of ball movement. CONCLUSION: Collarless polished tapered stems with thicker cement mantles resulted in greater subsidence of both stem and cement. This suggests that excessive thickness of the cement mantle may interfere with effective radial cement creep.Cite this article: E. Takahashi, A. Kaneuji, R. Tsuda, Y. Numata, T. Ichiseki, K. Fukui, N. Kawahara. The influence of cement thickness on stem subsidence and cement creep in a collarless polished tapered stem: When are thick cement mantles detrimental? Bone Joint Res 2017;6:-357. DOI: 10.1302/2046-3758.65.BJR-2017-0028.R1.

Characterization of mucin antigens recognized by monoclonal antibodies raised against human colon cancer cells.

Two monoclonal antibodies, MLS 102, which recognizes cancer-associated mucin antigens, and MLS 103, which recognizes normal mucin, were used to isolate, by immunoaffinity chromatography, the corresponding antigens from cell lysates and spent medium of a human colorectal carcinoma cell line, LS 180. The MLS 102 antigen contained serine, threonine, and proline as major amino acids. The carbohydrate chains of the MLS 102 antigen were composed of O-linked NeuAc alpha 2----6GalNAc (56%), N-acetylgalactosamine (25%), and longer oligosaccharide chains. The MLS 103 antigen differed from the MLS 102 antigen in both amino acid and carbohydrate composition. Most O-linked oligosaccharides of the MLS 103 antigen were longer than the disaccharide found in the MLS 102 antigen. Immunostaining of LS 180 cells using MLS 102 and MLS 103 revealed that the cells are heterogeneous with respect to the expression of the antigens.

Effects of stereochemical structures of tetrahydrobiopterin on tyrosine hydroxylase.

1. Four stereochemical isomers of tetrahydrobiopterin, i.e., 6-L-erythro-, 6-D-erythro-, 6-L-threo-, or 6-D-threo-1,2-dihydroxypropyltetrahydropterin, have been synthesized and used as cofactors for tyrosine hydroxylase (EC 1.14.18.-) purified from the soluble fraction of bovine adrenal medulla. The L-erythro- (the putative natural cofactor) and D-threo isomers showed a striking similarity in their cofactor activities for tyrosine hydroxylase; the remaining two isomeric tetrahydrobiopterins, D-erythro and L-threo isomers, also had very similar cofactor characteristics. 2. The Km values of the L-erythro and D-threo isomers as cofactor were found to be dependent on their concentrations. When their concentrations were below 100 muM, the Km values of the L-erythro and D-threo isomers were fairly low (about 20 muM). However, the Km values were markedly higher (about 150 muM) at concentrations above 100 muM. The same kinetic behavior was also observed with the tetrahydrobiopterin prepared from a natural source (bullfrog). In contrast, the Km value of the L-threo or D-erythro isomer was found to be independent of the concentration and remained constant throughout the concentration examined. 3. The Km values of tyrosine did not show much difference (from 20 muM to 30 muM) with respect to the structure of the four isomeric cofactors. At high concentrations tyrosine inhibited the enzymatic reaction with any one of the four tetrahydrobiopterin cofactors. 4. Oxygen at high concentrations was also inhibitory with any one of the four stereochemical isomers as cofactor. Approximate Km values for oxygen with the tetrahydrobiopterins as cofactor were 1-5%. 5. In contrast to the four isomers of tetrahydrobiopterin, when 6-methyltetrahydropterin or 6,7-dimethyltetrahydropterin was used as cofactor tyrosine or oxygen did no inhibit the enzymatic reaction at high concentrations, and the Km values toward the pterin cofactor, tyrosine, and oxygen were significantly higher than the Km values with the tetrahydrobiopterins as cofactor.

A new acidic protein in porcine brain.

An extremely acidic protein has been isolated in a purified form from porcine rain extract, by (NH4)2SO4 fractionation followed by column chromatography on DEAE-Sephadex A-50 and on Sephadex G-75. The purified protein was tentatively named as glutamic acid-rich protein because it was characterized by its remarkably high content of glutamic acid which accounted for 49% of the total amino acid composition. The protein appeared to be a single polypeptide chain with a molecular weight of 56 000-58 000, and had an isoelectric point of 4.6. The N-terminal amino acid sequence was Asp-Glu-Pro-Pro-Ser-Glu-Gly. The immunochemical analysis using rabbit antiserum prepared to the porcine protein has suggested that it is present in the brain of human, cow, cat, dog and goat as well as in various goat organs including liver, kidney, heart, small intestine and spleen.

Involvement of agouti-related protein, an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action.

To understand the role of agouti-related protein (AGRP), an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action, we produced a full-length recombinant AGRP and examined its effect on the satiety effect of leptin. We also studied leptin's regulation of hypothalamic AGRP mRNA expression. A single intracerebroventricular (i.c.v.) injection of AGRP significantly increased cumulative food intake and body weight in a dose-dependent manner in rats. The leptin-induced inhibition of food intake and body weight was reversed by co-injection of AGRP in a dose-dependent manner. Hypothalamic AGRP mRNA expression was upregulated in leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice and downregulated in lethal yellow agouti mice (KKAy mice) with hyperleptinemia. A single i.c.v. injection of leptin reversed the increased AGRP mRNA levels in ob/ob mice but not in db/db mice. In control mice and KKAy mice, AGRP mRNA expression was upregulated during fasting, when plasma leptin concentrations were decreased. No significant increase in AGRP mRNA expression was noted during fasting in control mice and KKAy mice treated with leptin. This study provides the first direct evidence that AGRP is a negative regulator of leptin action, and leptin downregulates hypothalamic AGRP production. Because leptin is shown to increase hypothalamic alpha-melanocyte stimulating hormone (alpha-MSH) production, our data suggest that its action via the hypothalamic melanocortin system is determined by the balance between the levels of its agonist and antagonist, alpha-MSH and AGRP.

Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion.

Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a primary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997). To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ventromedial hypothalamus (VMH), Arc, paraventricular nucleus (PVN), and dorsomedial hypothalamus (DMH) in rats. To further assess whether sympathetic activation of leptin is mediated via the VMH, we also examined the effects of a single intravenous injection of leptin in VMH-lesioned rats. A single injection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 pg i.c.v./rat) increased plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a dose-dependent manner. Plasma NE and EPI concentrations were increased significantly when leptin was injected directly into the VMH but were unchanged when injected into the Arc, PVN, and DMH. Plasma NE and EPI concentrations were unchanged in VMH-lesioned rats that received a single intravenous injection of leptin. The present study provides evidence that a leptin-induced increase in catecholamine secretion is mediated primarily via the VMH and suggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.

Mucin-carbohydrate directed monoclonal antibody.

To raise monoclonal antibodies recognizing cancer-associated alterations of the carbohydrate structure of glycoproteins, Balb/c mice were immunized with human colonic cancer cells (LS 180 from ATCC). One of the generated hybridomas produced a monoclonal antibody that bound to the carbohydrate moiety of mucin-type glycoproteins from LS 180. The antibody did not bind to glycoproteins from another colonic cancer cell line, SW 1116, or to glycolipids from any of the colonic cancer cell lines. The antibody bound to ovine and bovine submaxillary mucins (OSM and BSM). NeuAc alpha 2----6Ga1NAc seemed to be involved in the epitope.

The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. II. Cartilage composition and proteoglycan metabolism.

A model of early osteoarthritis (OA) induced in ovine joints by medial meniscectomy was used to study the effects of two hyaluronan (HA) preparations (AHA and DHA) on cartilage composition and proteoglycan (PG) metabolism. DHA was an HA preparation with an average molecular weight (MW) of approximately 2.0 x 10(6) d, and AHA had an MW of approximately 8.0 x 10(5) d. Both preparations were administered intraarticularly once a week for 5 weeks starting 16 weeks after meniscectomy, and animals (n = 5) were killed 5 weeks after the last injection. Meniscectomized, saline-injected (n = 5) and nonoperated (n = 5) animals were used for controls. At necropsy, 3-mm-diameter full-depth cartilage plugs were sampled under sterile conditions from specific locations on the medial and lateral femoral condyles, tibial plateaus, patella, and trochlear groove. The cartilage plugs were cultured in Hams-F12 medium supplemented with 10% fetal calf serum for 24 hours, then for a further 48 hours in the presence of H2(35)SO4 to determine the biosynthesis of PGs. The percentage of 35S-PGs and sulfated glycosaminoglycans released into the media was also ascertained. The cartilage adjacent to the plugs was analyzed for collagen and proteoglycan content and differential extractability with guanidine hydrochloride (GuHCl) solutions. The extractability of PGs with 0.4 mol/L GuHCl (nondissociative conditions) was lower from the medial femoral cartilages of the DHA-treated group than from the corresponding saline-treated group. In contrast, the release of 35S-PGs from the tibial cartilages of the DHA-treated animals was higher than in the saline-treated group. The biosynthesis of 35S-PGs, determined in vitro, for cartilage derived from the medial compartment was generally lower than for the lateral regions of the meniscectomized joints. The biosynthetic activity was further reduced in joints injected with the two HA preparations, but DHA reduced 35SO4 incorporation into PGs more than AHA. It was concluded that reduced biosynthesis of 35S-PGs and secretion into media was a consequence of increased loading of joints in the HA-treated animals rather than a direct effect of these preparations on chondrocyte metabolism.

Cytotoxicity of a novel indoloquinone eo9 in hypoxic non-small-cell lung-cancer cell-lines.

3-Hydroxymethyl-5-aziridinyl-1-methyl-[1H-indole-4,7-dione]-prop-beta-en -alpha-ol (EO9) is a bioreductive anticancer agent active for non-small cell lung cancer (NSCLC) and structurally related to mitomycin C (MMC). DT-diaphorase (DTD) is regarded as a two electron reductase that plays an important role in the biotransformation of MMC to antitumor metabolites. To evaluate the role of DTD as a bioactivator of EO9 in NSCLC cell lines under oxic and hypoxic conditions, we examined the inhibitory effect of dicumarol which was regarded as a selective inhibitor of DTD on the sensitivity to EO9 in vitro. In this study, we used an MMC-resistant NSCLC cell line (PC-9/MC4) which was established from a PC-9 cell line as a parent cell line by continuous exposure to MMC in our laboratory. We reported previously that the subline PC-9/MC4 was 6.7-fold more resistant to MMC than PC-9 with decreased DTD activity. The IC50 value of PC-9 against EO9 was significantly increased by co-incubation with dicumarol under oxic conditions. EO9 was more cytotoxic against PC-9/MC4 than against PC-9 cells and the enhancement was impaired by tempol under hypoxic conditions. These findings suggest a suppressive role of DTD against one-electron reduction pathway in the bioactivation of EO9 under hypoxic conditions and EO9 may be more active against oxygen-deficient solid tumors especially in MMC-resistant NSCLC cells with low levels of DTD activity.

Modulation of sensitivity to mitomycin C and a dithiol analogue by tempol in non-small-cell lung cancer cell lines under hypoxia.

We examined the mechanisms involved in the bioactivation of mitomycin C (MMC) and a newly developed MMC analogue: 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)mitomycin C, KW-2149, in non-small-cell lung cancer (NSCLC) cell lines under aerobic and hypoxic conditions. To investigate these mechanisms, we used MMC-resistant non-small-cell lung cancer cell lines (PC-9/MC4) that had been established in our laboratory from the parent PC-9 cell line by continuous exposure to MMC. We previously reported that the MMC-resistant cell line (PC-9/MC4) was poor in NAD(P)H dehydrogenase (quinone) activity and approximately 6-fold more resistant than the parent cells (PC-9) to MMC on 2-h exposure under aerobic conditions. In this study, the subline PC-9/MC4 was 6.7-fold more resistant to MMC than PC-9, the parent cell line, under aerobic conditions, and 5.2-fold more resistant under hypoxic conditions after 2-h exposure to MMC. However, on co-incubation with tempol, an inhibitor of the one-electron reduction pathway, the sensitivity of PC-9/MC4 to MMC was impaired under hypoxic conditions, but the impairment was not evident under aerobic conditions. KW-2149, the newly developed MMC analogue, was cytotoxic for both PC-9/MC4 and PC-9 cells, and the sensitivity of both cell lines to KW-2149 was not changed by exposure to hypoxic conditions or by coincubation with tempol. There were no significant differences in the intracellular uptake of MMC and the activities of cytosolic detoxification enzymes between the PC-9 and PC-9/MC4 cell lines. These results support the hypothesis that the one-electron reduction pathway plays a partial role in the bioactivation of MMC, but not of KW-2149, and that KW-2149 is excellent at circumventing resistance to MMC in NSCLC.

Comparison of protein sulfation in control and virus-transformed baby hamster kidney cells.

Protein sulfation in baby hamster kidney cells (BHK) and their polyoma virus transformants (PY-BHK) was studied comparatively. On in vivo labeling, [35S]-sulfate was incorporated into the 50K protein and proteins in the 100-180K range, represented by the 155K protein. The incorporation into both the 50K and 155K protein was elevated 2-3 fold in PY-BHK cells compared to in BHK cells. Tyrosine-O-sulfate was the only identifiable sulfated amino acid in both proteins. On in vitro labeling with [35S]3'-phosphoadenosine 5'-phosphosulfate (PAPS), at least 6 radioactive protein bands were discernible on gel electrophoresis. Of these, sulfation of the 57K and 60K proteins was elevated in PY-BHK cells compared to in BHK cells, whereas sulfation of the 39K protein was depressed in PY-BHK cells. Tyrosine-O-sulfate was the only identifiable sulfated amino acid in these proteins.

A monoclonal antibody that recognizes sialyl-Lea oligosaccharide, but is distinct from NS 19-9 as to epitope recognition.

A murine monoclonal antibody, designated as MSW 113, was generated using a human colonic cancer cell line, SW 1116, as the immunogen. MSW 113 was shown to be directed mainly to mucin-type oligosaccharide with sialyl-Lea antigens. The reactivity of MSW 113 to sialyl-Lea was stronger than that of NS 19-9, which is believed to be raised against the same determinant group. MSW 113 binds to sialyl-Lea-ol, LS-tetrasaccharide a, and disialyllacto-N-tetraose with higher affinities, compared to NS 19-9. These two antibodies could clearly be distinguished in that MSW 113 bound to sialic acid but not to fucose, whereas NS 19-9 bound to fucose but not to sialic acid. Thus, MSW 113 is directed more toward sialic acid-containing terminal structures while NS 19-9 is directed toward fucose-containing internal structures. MSW 113 was found to be useful for detecting antigens in the bloodstream of patients, especially those with pancreas cancer. Even NS 19-9 negative patient sera were positive for MSW 113.

Immunoaffinity isolation of a sialyl-Le(a) oligosaccharide from human milk.

A cancer-associated antigen, sialyl-Le(a) oligosaccharide, was isolated from human milk using a monoclonal antibody recognizing carbohydrate moieties of mucin-type glycoproteins. The structure was identified as: (Formula: see text) based on 500-MHz 1H-NMR spectroscopy. This oligosaccharide comprises 0.07% of sialyloligosaccharides in human milk. The NMR spectra of two fellow oligosaccharides, Le(a) oligosaccharide (or lacto-N-fucopentaose II) and LS-tetrasaccharide a, are also given.

Varied value of urinary N-acetyl-beta-D-glucosaminidase isoenzyme B in males of reproductive age.

A reliable enzyme-linked immunosorbent assay designed to detect N-acetyl-beta-D-glucosaminidase isoenzyme B (NAG-B) was used to determine distribution and variation of urinary NAG-B in normal and pathologic urine. NAG-B values varied over a much broader range in urine from male than in that from female subjects under different conditions of sampling. Because NAG-B values are markedly high in the semen (5800.2 micrograms/liter on the average), contamination of the urine with NAG-B from genital tissues occurs at urination, when it enters urine containing NAG-B of renal origin. The clinical significance of NAG-B and total NAG enzymatic activity as a renal tubular marker should be carefully evaluated when analyzing urine of males from reproductive age.

Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system.

Leptin is an adipocyte-derived blood-borne satiety factor that decreases food intake and increases energy expenditure, thereby leading to a substantial decrease in body weight. To explore the possible roles of the hypothalamic melanocortin system in leptin action, we examined the effects of intracerebroventricular (i.c.v.) injection of leptin with or without SHU9119, a potent antagonist of alpha-melanocyte stimulating hormone, on food intake, body weight, and mitochondrial uncoupling protein-1 (UCP-1) mRNA expression in the brown adipose tissue (BAT) in rats. A single i.c.v. injection of leptin decreased cumulative food intake and body weight gain, and increased UCP-1 mRNA expression during 3 h at the onset of the dark phase. Inhibition of food intake and body weight change with leptin was reversed by co-injection of SHU9119 in a dose-dependent manner. Co-injection of SHU9119 also inhibited completely the leptin-induced increase in UCP-1 mRNA expression in the BAT. Treatment with SHU9119 alone did not affect food intake, body weight, and UCP-1 mRNA expression in rats. The present study provides evidence that the hypothalamic melanocortin system plays a central role in both satiety effect and sympathetic activation of leptin.

Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain.

The activities of tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), and monoamine oxidase (MAO) with serotonin and phenylethylamine as substrates were measured in catecholaminergic regions of human brain from 10 controls and 3 patients with Parkinsonism. PNMT activity was detected in hypothalamus, thalamus and cerebellar nucleus of the control human brain, and was reduced in hypothalamus of Parkinsonian cases. Type A (with serotonin as substrate) and type B (with phenylethylamine as substrate) MAO activities were high in all brain regions with little individual variations in controls and Parkinsonian cases. TH activity was high in the controls and was markedly decreased, in substantia nigra, caudate nucleus, putamen and in pallidum, in all three cases of Parkinsonism. DDC activity in these regions was also decreased in 2 patients. However, one Parkinsonian case had only decreased TH and normal DDC activities. DBH activity in hypothalamus was also reduced in the Parkinsonian cases.