Direct relation of long-term synaptic potentiation to phosphorylation of membrane protein F1, a substrate for membrane protein kinase C

One hour after long-term potentiation (LTP) in the intact hippocampus, a selective increase in protein F₁ in vitro phosphorylation was observed in homogenate prepared from dorsal hippocampus. Protein F₁ phosphorylation was directly related to the magnitude and persistence of potentiation. No other phosphoprotein studied exhibited a relationship with synaptic enhancement. Low-frequency, non-potentiating stimulation did not increase protein F₁ phosphorylation, and phosphorylation of F₁ was not elevated when high-frequency stimulation did not produce potentiation. We also confirmed our earlier demonstration of a similar pattern of results 5 min after LTP. In related work we have previously observed: (1) that protein F₁ is a substrate for protein kinase C (PKC); (2) that membrane PKC activity was increased by translocation from the cytosol following LTP; and (3) that membrane PKC activity was directly related to the persistence of enhancement. We therefore predicted in the present study that protein F₁ phosphorylation in a dorsal hippocampal membrane fraction would be related to LTP. Hippocampal membrane protein F₁ was found to be directly related to both the magnitude and persistence of response enhancement. Thus the molecular events leading to prolonged potentiation may involve increased PKC/protein F₁ association. Persistence of potentiation may be related to synaptic growth processes involving the growth-associated function of protein F₁.     

Portal venous gas in a patient with Crohn's disease

Portal venous gas usually occurs in the setting of an acute abdomen. Several causes for benign portal venous gas (PVG) have been reported. We describe the finding of PVG by computed tomography in a febrile patient with Crohn's disease and discuss the clinical implications of such a finding.     

Head circumference/abdominal circumference ratio, ponderal index and fetal malnutrition. Should head circumference/abdominal circumference ratio be abandoned?

Head circumference/abdominal circumference (HC/AC) ratios of the fetus are accepted as a means of distinguishing different patterns of growth retardation with a high ratio implying malnutrition of the fetus. Ponderal index (birthweight/length3) is used by paediatricians as a measure of neonatal wasting and would therefore be expected to correlate with HC/AC ratios at delivery. Anthropometric data on 999 newborn infants have been collected and analyzed by multiple regression. The results show a poor correlation between ponderal index and HC/AC ratio, worse than that between ponderal index and AC alone. The use of HC/AC ratios antenatally to identify subgroups of intrauterine malnutrition should be abandoned. The prediction of intrauterine malnutrition by weight/length ratios should be investigated further.     

Reversible optic neuropathy associated with low-dose methotrexate therapy.

A 66-year-old woman had progressive bilateral optic neuropathy with dense central scotomas and dyschromatopsia. She had been taking oral methotrexate 2.5 mg three times per week for rheumatoid arthritis for the previous 10 months (total intake 322.5 mg) without folic acid supplementation. She had never smoked or abused alcohol and her diet was healthy. Serum folate was reduced at 1.6 ng/mL (normal >4 ng/mL) and vitamin B12 levels were normal. After stopping methotrexate and after administration of oral folic acid, she experienced complete recovery of vision. Serum folate levels returned to normal during folic acid treatment but decreased to below normal once folic treatment was stopped. The persistently low folate level remains unexplained and may reflect a genetic defect in folate metabolism. Methotrexate can cause toxic side effects resulting from folate inhibition but has not been shown definitively to cause a reversible optic neuropathy associated with low serum folate.     

Future needs for ERCP: incidence of conditions leading to bile duct obstruction and requirements for diagnostic and therapeutic biliary procedures.

Although the development of endoscopic methods of treatment for biliary obstruction has proceeded rapidly in recent years, endoscopic retrograde cholangiopancreatographic (ERCP) services are patchily distributed. A recent survey by the British Society of Gastroenterology has shown that almost half the district general hospitals questioned did not have a sphincterotomy service available locally. To assess the level of provision required, two investigations have been undertaken. Firstly, an epidemiological study of bile duct obstruction has been carried out in the South Western Region. Secondly, the actual surgical and endoscopic workload in treating obstructive jaundice has been analysed in two health districts. Using present incidence and treatment rates at least 50 ERCPs per 100,000 of the population per year are estimated to be required in the future. Surgical treatment rates can be expected to fall as the number of therapeutic ERCPs increases. The implications of this estimate in equipment and staffing terms are discussed.     

Respiratory effects of lowering tar and nicotine levels of cigarettes smoked by young male middle tar smokers. I. Design of a randomised controlled trial.

STUDY OBJECTIVE--The aim was to investigate the effect on respiratory health of male middle tar smokers changing the tar and nicotine levels of the cigarettes they smoke for a six month period. DESIGN--This was a randomised controlled trial. Middle tar smokers were randomly allocated to smoke one of three different types of cigarette (low tar, middle nicotine; middle tar, middle nicotine; and low tar, low nicotine) in place of their usual cigarette for a six month period. Main outcome measures were assessment of respiratory health by documenting respiratory symptoms and peak expiratory flow rates, and of nicotine inhalation by measuring the urinary excretion of nicotine metabolites. SETTING--21 local authority districts of England. SUBJECTS--Participants were male middle tar smokers aged 18-44 years. MAIN RESULTS--Postal questionnaires were sent to 265,016 individuals selected from the electoral registers of 21 local authority districts of England; 64% of questionnaires were returned revealing 7736 men aged 18-44 years who smoked only middle tar cigarettes. Of these, 7029 (90%) were sent a health warning and 707 (10%) were not; the latter acted as a control group to assess the effect of the health warning. Of the 7029 men who had received a health warning and were visited at the recruitment stage, 2666 agreed and were eligible to participate in the trial although only 1541 (58% of those who agreed and were eligible) actually started smoking the study cigarettes; 643 men (24% of those willing to participate at the beginning of the trial and 42% of those who actually started smoking the study cigarettes) completed the trial smoking the study cigarettes. Of these, 213 were in the low tar middle nicotine group, 220 were in the middle tar middle nicotine group, and 210 were in the low tar low nicotine group. CONCLUSIONS--This study shows the feasibility of identifying and recruiting sufficient numbers of male middle tar smokers, with adequate numbers completing the trial, to detect any changes in respiratory health over a six month period.     

Factors Associated with Parental Acceptance of Dental Sealants

Whereas a number of surveys have documented oral disease preventive behaviors and associated factors, little is known about public knowledge and beliefs about dental sealants. In this study, factors associated with the presence of sealants were studied in first and second graders residing in Columbia, SC. From a sample of 1,119 children, 88 were found clinically to have sealants; 508 did not have, but needed them. Parents of the sealant children (n = 87) and of a random sample of the no-sealant children (n = 289) were interviewed by telephone to obtain information regarding (1) factors related to parents' inclination to obtain sealants for their children, (2) ability of the family to obtain oral disease preventive services, and (3) the influence of others in the family's decision-making efforts. Analysis of 16 factors thought to be related to sealant presence revealed that parents were more likely to obtain dental sealants for their children if dentists or their staffs recommended them, if the parents were knowledgeable about dental sealants, if the parents were more highly educated, and if the parents had dental insurance coverage. Parents were less likely to obtain dental sealants for their children if they heard about them from mass media. The latter finding is unexpected and may have been influenced by conflicting or negative opinion expressed by some dental practitioners through mass media or other channels of communication.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activated T and B lymphocytes in peripheral blood of patients with Chagas' disease

Whole blood preparations from patients with either the indeterminate(asymptomatic) or cardiac clinical forms of chronic Trypanosomacruzl infection were analyzed by flow cytometry using double-labelingto identify subsets of circulating lymphocytes. Several significantdifferences were demonstrated between the blood lymphocyte profilesof chagaslc patients and non-chagaslc controls. Clear increasein the percentages and actual numbers of double-positive cellsof the phenotype CD3⁺/HLA-DR⁺, as well as decrease in the percentageof CD45RA⁺/CD4⁺ and CD45RA⁺/CD8⁺ T cells, Indicate greater numbersof activated T cells circulating in the blood of infected patients.Consistent parallel increases were seen also in the B lymphocytesubset which stained double-positive for CD19/CD5. There wereno significant differences in the circulation of these chronicchagaslc patients in the CD4:CD8 ratios. Also, no substantivephenotyplc differences were observed in the lymphocyte populationsbetween the two ends of the clinical spectrum (Indeterminateversus cardiac) in chronic human Chagas' disease. These observationsdemonstrate that increased levels of activated T cells and CD5⁺B cells are present in the circulation of people with chronicChagas' disease. These are cell phenotypes that have been associatedin other conditions with autoimmune, polyclonal, and hyperlmmuneresponses. The specificities of these activated cells and theroles they may play in resistance or pathogenesis during chronicChagas' disease need now to be determined.     

Hemangioendothelioma of the hepatobiliary system: the classic and the unusual

Two children are reported with hemangioendothelioma of the hepatobiliary system. One patient, a 7-month-old girl, presented with classic symptomatology of hepatomegaly and congestive heart failure, but did not have any cutaneous lesions. She was treated with systemic steroids and supportive therapy and did very well. The other patient, a 22-month-old boy, is the first patient reported with exclusive involvement of the extrahepatic biliary tree. His symptoms included hepatomegaly and obstructive jaundice. He was evaluated with an endoscopic retrograde cholangiopancreatogram and a transhepatic cholangiogram. He did very well after resection of the lesion and Roux-en-Y drainage of the proximal biliary tree and remains asymptomatic 2 years after surgery.