Inhibition of TGF-ß and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1.

BACKGROUND: Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas. METHODS: Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migratory abilities of cells in response to MALT1 were determined by wound-healing assay and time-lapse analysis. RESULTS: Totally, 2933 genes upregulated or downregulated in MALT1-expressing cells were identified. The subsequent pathway analysis implicated the inhibition of epidermal growth factor and transforming growth factor-ß signalling gene expression, and highlighted the involvement in the cellular movement. Wound closure was suppressed by wild-type MALT1 (66.4%) and accelerated by dominant-negative MALT1 (218.6%), and the velocities of cell migration were increased 0.2-fold and 3.0-fold by wild-type and dominant-negative MALT1, respectively. CONCLUSION: These observations demonstrate that MALT1 represses genes activating the aggressive phenotype of carcinoma cells, and suggest that MALT1 acts as a tumour suppressor and that the loss of expression stimulates oral carcinoma progression.

Thallium-201 scintigraphy to assess effect of chemotherapy in osteosarcoma.

UNLABELLED: Imaging results in patients with high-grade osteosarcoma of the extremities were reviewed to determine whether scintigraphic appearance correlated with histologic response to preoperative chemotherapy. METHODS: Histologically, the percent tumor necrosis in specimens from 30 patients were classified into three grades: grade 1 = necrosis less than 60%, grade 2 = 60%-89% necrosis and grade 3 = diffuse necrosis greater than 90% based upon whole transverse sections. Scintigraphically, we analyzed 201TI uptake before and after preoperative chemotherapy. The changes in the tumor-to-background ratio were defined by an alteration ratio. RESULTS: Of the 11 patients with a grade 1 response, the ratio showed -67.1% +/- 45.4% (mean +/- s.d.). Of the 9 patients with a grade 2 response, the ratio showed 37.9% +/- 29.9% of the 10 patients with a grade 3 response the ratio showed 105.5% +/- 12.4%. The ratios correlated well with the histologic grades (p < 0.0001; analysis of variance). CONCLUSION: Thallium-201 scintigraphy accurately assesses the effect of chemotherapy on osteosarcoma.

Regional metabolic changes in the pedunculopontine nucleus of unilateral 6-hydroxydopamine Parkinson's model rats.

The pedunculopontine nucleus (PPN) located in the mesopontine tegmentum is innervated by descending projections from nuclei in the basal ganglia. The present study was performed to determine whether nigrostriatal dopaminergic neuron degeneration is associated with changes in PPN metabolic activity. Unilateral nigrostriatal lesioning was performed by injecting 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta in 10 rats. Six of these animals exhibited apomorphine-induced rotations contralateral to the lesion and were included in the experimental group for determination of regional cerebral metabolic rate for glucose (rCMRglucose) along with five sham-lesioned and five normal controls. All studies were performed 13-15 days after lesioning using [14]C-2-deoxyglucose autoradiography. Significant hemispheric differences in metabolic activity were observed only in the 6-OHDA lesioned animals. Increased rCMRglucose was found in the globus pallidus (+63%) ipsilateral to the lesion as compared to the contralateral hemisphere, and reduced rCMRglucose in the primary motor, sensory, and auditory cortex (-7%, -12% and -7%, respectively), and in the subthalamic nucleus (-6%). Metabolic activity within the PPN ipsilateral to the lesion was significantly greater than the contralateral hemisphere (P<0.05; lesion 57+/-8, nonlesion 52+/-5), and significantly greater than the sham-lesioned side of the sham rat (P<0.05; sham lesion 47+/-5). No hemispheric differences were observed in the lateral dorsal tegmental nucleus. These observations offer further support for a role of the PPN in Parkinson's and for the utility of the rodent unilateral 6-OHDA model in defining the pathophysiologic significance of the mesopontine tegmental striatal-motor interfaces in basal ganglia disease.

The results, indications, and physiology of posteroventral pallidotomy for patients with Parkinson's disease.

In the past, stereotactic surgical intervention for Parkinson's disease was considered indicated only in those patients with active motor manifestations that were refractory to pharmacological therapy, manifestations such as tremor, rigidity, dystonia, and dyskinesia. With the reintroduction and refinement of Leksell's posteroventral pallidotomy, both akinetic and hyperkinetic symptoms are now amenable to surgical treatment. We have analyzed the results of 126 patients who underwent either unilateral (n = 58) or bilateral (n = 68) posteroventral pallidotomies. The Unified Parkinson's Disease Rating Scale and Hoehn and Yahr Staging Scale were used for preoperative and postoperative objective assessments. Postoperative follow-up evaluation occurred initially at 1 week and subsequently at intervals between 1 and 12 months (mean = 4.5 months) after surgery. Although individual motor subscores on the Unified Parkinson's Disease Rating Scale were significantly reduced (n = 126, P < or = 0.01), the most dramatic findings were the reversal of akinetic symptoms and the elimination of dyskinesia and profound "off" periods. These clinical results, combined with intraoperative microelectrode records revealing pallidal neuronal hyperactivity, suggest a reconsideration of the pathophysiology of akinesia and point to possible mechanisms of akinesia improvement by posteroventral pallidotomy in some parkinsonian subgroups.

Oxidative metabolism during and following ischemia of cat spinal cord.

Spinal cord ischemia was produced by an occlusion of the thoracic descending aorta on experimental cats for the periods of 3, 5, 10, and 15 minutes. The reduction/oxidation (redox) ratio of cytochrome a,a3 was measured in vivo by reflectance spectrophotometry, simultaneously with the measurement of the following: blood pressure in the aorta distal to the occlusion; relative blood volume in the cord; oxygen tension in cord tissue; and cord potential in response to dorsal root stimulation. During aortic occlusion, the maximum increase in the redox ratio was reached somewhat more slowly than the maximum decrease in blood pressure, blood volume, and oxygen tension. Interneuron potentials began to decrease as the redox level increased, and completely disappeared soon after the redox ratio increased, and completely disappeared soon after the redox ratio increased maximally. During ischemia, therefore, oxygen consumption in the mitochondria was slightly lower than the decrease in oxygen tension; impairment of ADP phosphorylation, and accordingly that of ion pump, occurs simultaneously with the increase in the redox ratio. Recovery of the redox ratio after completion of aortic occlusion was also slightly slower than the recovery of blood pressure, blood volume, and oxygen tension. Complete recovery of interneuron potentials was much more delayed than that of the redox ratio; after 15-minute ischemia, uncoupling of ADP phosphorylation was noted. It can be concluded that the spinal cord function and metabolism are severely impaired after 15-minute occlusion.

EEG frequency patterns in the cat prepyriform cortex during sleep and waking.

The cellular populations in the prepyriform cortex are a primary processing station for sensory information from the olfactory bulb. These populations are also influenced from forebrain and other brain systems involved in behaviour. Recording electrodes can be precisely placed in this cortex compared to many other brain structures. This permits straddling the cortical superficial pyramidal cell layer with a bipolar recording configuration and the ability to obtain information about awake-vigilant and other state conditions from this brain structure. Methadone, a vigorously arousing drug in the cat, and a short acting barbiturate was administered to compare the differences of EEG patterns obtained during normal awake and sleep conditions. Fourier analysis was used in this study and combined with computer profiles of spectra to show time relationships of the state conditions in the cortex. Good separation of the spectra, between the major states in the cat, were observed using this technique for both natural and drug-induced changes.

Simultaneous bilateral pallidoansotomy for idiopathic dystonia musculorum deformans.

A 17-year-old Russian male with a 9-year diagnosed history of dystonia musculorum deformans manifested as severe tortipelvis, lordosis, and axial and appendicular spastic dystonia, refractory to medical therapy, is reported. This patient underwent a simultaneous bilateral pallidoansotomy with dramatic results. Postoperative evaluation revealed sustained alleviation of all dystonic symptoms and abnormal movements. Rapid recovery of useful strength in all limbs as well as dramatic improvement in coordination occurred. Bilateral posteroventral pallidotomy and pallidoansotomy in the past have proven effective in alleviation of all parkinsonian symptoms, including dyskinesia and dystonia, without the concurrent risk of intransigent side effects associated with bilateral thalamotomy or other stereotactic surgical procedures. Pallidoansotomy may prove to be the treatment of choice for idiopathic torsion dystonia and merits further investigation.

Effects of water-soluble hemicellulose from soybean hull on serum antibody levels and activation of macrophages in rats.

Effects of soybean hull water-soluble hemicellulose (WSHC) on serum immunoglobulin (Ig) concentration and production of NO and IL-1beta from peritoneal macrophages were examined and compared with those of Agaricus blazei in the rat system. WSHC consisted of arabinose, galactose, xylose, glucose, and rhamnose, and the molecular weight was approximately 500000. Rats were ip administrated each sample at a dose of 0.67, 13.4, or 26.9 mg/kg/day for 14 days. The administration of WSHC resulted in significantly higher productions of IgM (p < 0.01 on day 6, p < 0.05 on day 14) and IgG (p < 0.05 on day 6) than those in other groups. When peritoneal macrophages were stimulated with various concentrations of sample (0.67, 13.4, or 26.9 mg/mL), WSHC significantly increased both NO and IL-1beta productions only at the concentration of 13.4 (mg/mL) compared with those of a saline group. These findings demonstrate that WSHC enhances humoral immunity and activation of macrophages, thereby leading to the augmentation of immune responses in rats.

Risk factors for the prevalence of porcine cysticercosis in Mbulu District, Tanzania.

To estimate prevalence of and risk factors for the prevalence of porcine cysticercosis in Mbulu District, Tanzania, 770 live pigs were examined by lingual examination in 21 villages. Structured observations and questionnaire interviews were used to assess pig rearing practices and household use of latrines. Associations between factors were analyzed using a Bayesian hierarchical model to obtain prevalence odds ratio (OR) and 95% Bayesian Credible Intervals (95% BCI). Prevalence was 17.4% (village-specific range 3.2-46.7%). Prevalence of porcine cysticercosis was considerably higher in pigs reared in households lacking latrines than in those reared in households that were using latrines (OR = 2.04; 95% BCI = 1.25, 3.45). About 96% of the pigs were kept under free-range conditions. This study suggests the need for further studies in order to design and implement effective prevention and control measures for porcine cysticercosis in Mbulu District, Tanzania.

Prevalence of Cryptosporidium spp. oocysts in cattle and wildlife in Morogoro region, Tanzania.

Prevalences of Cryptosporidium spp. oocysts in cattle (n = 486) on five selected farms in Morogoro municipality and three species of herbivorous wildlife (n = 87) from Mikumi National Park, Morogoro, Tanzania, were determined using the modified Ziehl-Neelsen staining technique. Of 486 bovine faecal samples, 5.3% were positive for Cryptosporidium spp. The prevalence of Cryptosporidium was higher in calves less than 3 months of age compared to weaned calves and adults. Cryptosporidium spp. oocysts were detected in both diarrhoeic and non-diarrhoeic animals, but there was a significantly higher prevalence (P < 0.001) of oocyst shedding in diarrhoeic than in non-diarrhoeic animals. Of the 87 faecal specimens from the wildlife species, 36 were from the African buffaloes (Syncerus caffer), 25 from zebra (Equus zebra) and 26 from the wildebeest (Connochaetes gnou). Cryptosporidium spp. oocysts were detected in eight (22%) buffaloes, seven (28%) zebras and seven (27%) wildebeests. Confirmation of the diagnosis was performed using anti-Cryptosporidium monoclonal antibody specific for Cryptosporidium muris. Cryptosporidium parvum and Cryptosporidium baileyi (Pathasure Cryptosporidium test kit).

Experimental single and trickle infections of cattle with Taenia saginata: studies of immunodiagnosis.

Two groups of 12 calves were given either a single infection dose of 30,000 Taenia saginata eggs (group A) or trickle infected with 12 x 2500 T saginata eggs (group B). The calves were killed 16, 22 or 54 weeks after infection and the numbers of viable and dead parasites were counted by slicing selected organs and muscles of half of the carcases. The total numbers of cysts and the numbers of viable cysts were higher in group A than in group B. Within the two groups there were no significant differences between the numbers of cysts at the three dates of slaughter. Comparable results were obtained by using an ELISA and a dot blot procedure for the detection of antibody in the serum of the infected calves; an initial increase in response during the first 10 weeks after infection was generally followed by a gradual decline. When using a monoclonal antibody-based ELISA for the detection of circulating antigens, the sera from all the 14 animals which had no viable cysts or only dead cysts at slaughter did not react with the monoclonal antibodies. Calves 122 and 123, which harboured two and 122 viable cysts, respectively, reacted positively during the late phase of the infection to the antigen-detecting ELISA. However, several other animals which harboured between two and 41 viable cysts at slaughter did not react.

Lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone Japanese quail.

The purpose of this study was to characterize the lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone (HAP) Japanese quail. HAP and commercially available (CA) Japanese quail were fed either a semi-purified diet containing 1% cholesterol or a cholesterol-free diet for two weeks. The lipoproteins of CA and HAP quail fed cholesterol-free diet were composed of two fractions: densities ranging from 1.02 to 1.09 and from 1.09 to 1.21. The lipoprotein distribution patterns obtained from both strains showed an HDL-predominant pattern. A protein of 26 kDa was the major apoprotein in the entire density range of the lipoprotein class. Marked increases in the cholesterol ester levels were observed in the lower density fractions (1.006 < d < 1.055: chylomicron and VLDL fractions) of the cholesterol-fed quail, accounting for 46% of the total lipids in CA quail and 54% in HAP quail. In addition, the presence of a protein of 470 kDa was exclusively observed in the lower density fractions (1.006 < d < 1.055) of the cholesterol-fed HAP quail. The fatty-acid compositions of the chylomicron and VLDL fractions were affected by the dietary cholesterol in both strains: a decrease in concentration of 16: 0 and increase in 18: 0 (weight %). However, cholesterol feeding had no effect on the level of cholesterol, chemical composition or fatty-acid composition of the HDL fractions in either strain. Although the lipoprotein and apoprotein profiles of HAP quail showed resemblances to those of the CA quail, expression of the 470 kDa protein in the lipoproteins (d < 1.055) appeared to be pronounced in HAP quail. The relevance of these lipoprotein and apoprotein profiles to the genesis of atherosclerosis was discussed in this study.

Design for a micropowered multichannel PAM/FM biotelemetry system for brain research.

A design for a 12-channel pulse amplitude-modulated/FM biotelemetry system is described. The biotelemeter mounts on an animal's head close to the electrode probes to record and transmit brain electrical data. The size of the unit is 4.5 x 6.5 x 2 cm and it weighs about 60 g. It is designed to acquire EEG and other physiological data where the requirement is to obtain bioelectrical activity without cable encumbrance or confining behavioral restrictions. The telemeter consumes about 800 muW of power and operates for approximately 3 continous days before it is necessary to exchange the utilization of complementary metal oxide semiconductor (CMOS) integrated circuits. Transmission range is typically about 10 m.

Endothelium-dependent vascular smooth muscle relaxation activated by electrical field stimulation.

Electrical field stimulation (EFS) produced relaxation of contracted arteries in the presence of tetrodotoxin. In the present study the contributions of vascular smooth muscle repolarization and endothelial release of nitric oxide to the relaxation response were investigated using isolated rat tail arteries and bovine aortic endothelial cells (BAEC). Intact and endothelium-denuded rings or intact, pressurized artery segments were contracted with either phenylephrine or KCl prior to EFS. Electrical field stimulation induced a small relaxation in denuded, phenylephrine contracted rings that was inhibited by the K+ channel blockers glibenclamide and BaCl2. In intact, phenylephrine-contracted rings, EFS induced significantly larger relaxations that were inhibited by BaCl2 as well as by L-NAME, an inhibitor of nitric oxide (NO) synthase, and methylene blue. EFS-induced relaxations were completely inhibited when BaCl2 and L-NAME or methylene blue were combined. Exposure to Ca(2+)-free buffer or diltiazem also inhibited the relaxation while ascorbic acid had no effect. Effluent from electrically stimulated BAEC caused denuded, phenylephrine contracted rings to relax. The ability of the effluent to cause relaxation was almost completely blocked by exposure of the BAEC to L-NAME or exposure of the recipient vascular smooth muscle to methylene blue; glibenclamide caused partial blockade. Simultaneous measurements of membrane potential and intraluminal pressure showed that EFS-induced membrane repolarization preceded changes in steady-state pressure. It is concluded that (1) the smooth muscle cells possess an endothelium-independent repolarization mechanism, (2) EFS causes endothelial cells of intact arteries to release NO and possibly a hyperpolarizing factor, (3) EFS of BAEC causes release of NO, and (4) EFS-induced relaxation depends on vascular smooth muscle cell membrane repolarization and endothelial cell release of vasoactive substances.