Molecular epidemiology of spinocerebellar ataxia type 6

We performed a population-based clinical and molecular genetic study of spinocerebellar ataxia type 6 (SCA6) in the northeast of England. The minimum point prevalence of SCA6 was 1.59 in 100,000 (95% confidence interval [CI], 1.04-2.14), and the number of individuals who either had SCA6 or are at risk of developing SCA6 was at least 5.21 in 100,000 (95% CI, 4.31-6.10), or 1 in 19,210. Microsatellite analysis of the CACNA1A gene indicated a founder effect for SCA6 within this region.     

Vitamin A levels and immunity in humans

In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 microg/dl), 34% had moderate deficiency (10 to <20 microg/dl), and 36% had normal levels (> or = 20 microg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 microg/dl, respectively). Vitamin A-deficient children (<20 microg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis, or other type 1 pathogens.     

The effect of forage quality and level of feeding on digestibility and gastrointestinal transit time of oat straw and alfalfa given to ponies and donkeys

Four donkeys and four ponies were fed molassed dehydrated alfalfa or oat straw, either ad libitum or restricted to about 70% ad libitum intake in a Latin-square design for four periods of 21 d. Measurements of apparent digestibility and gastrointestinal transit time were made on the last 7 d of each period. When the forages were provided ad libitum, all animals ate significantly more of the alfalfa than of the oat straw. Ponies consumed significantly more of both diets per unit live weight than donkeys. Higher apparent digestibilities of dietary DM, energy and fibre fractions were seen in donkeys, at both levels of feeding, compared with the ponies. This partly compensated for the lower intakes by the donkeys when fed ad libitum. When intake of alfalfa was restricted, the apparent digestibility of DM was higher compared with the corresponding values when fed ad libitum, but the reverse was true for straw. This may be because restriction of a low-quality diet reduced selection of the more digestible parts of the forage. Donkeys and ponies consumed more energy and protein than required when fed alfalfa ad libitum. Both oat straw treatments provided insufficient protein to meet the predicted requirements of ponies and donkeys. Straw intakes ad libitum exceeded the estimated energy requirement for ponies by 34-51%, but donkey energy requirements were only just met. When the amount of straw offered was restricted, 78-90% of the estimated energy requirement for donkeys was met compared with 90-105% for the ponies.     

Duodenal ulcer healing after presentation with haemorrhage.

Forty patients who were managed conservatively after haemorrhage from an endoscopically verified duodenal ulcer were randomised at discharge from hospital to enter a blind study of ranitidine therapy (150 mg bd) versus a placebo tablet. The patients were re-endoscoped after four weeks, ulcer status defined and the trial code broken revealing that five of 20 placebo patients had healed their duodenal ulcer compared with 16 of 20 ranitidine patients (p = 0.001). Lifestyle parameters of both groups improved during the study period but no directly related benefit in duodenal ulcer healing could be shown. We conclude that effective anti-ulcer therapy, such as ranitidine, is required to heal a duodenal ulcer which presents with haemorrhage.     

beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones

Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with β1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of β1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify β1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.     

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.