p49/STRAP, a Serum Response Factor Binding Protein (SRFBP1), Is Involved in the Redistribution of Cytoskeletal F-Actin Proteins during Glucose Deprivation.

The functional decline that usually accompanies adult aging also encompasses cellular changes including cytoplasmic architecture. In addition to their role in cytoskeletal structure, actin microfilaments have important roles in various cellular processes, including cell-to-cell communication and intracellular signaling. Age-related diseases and late-stage cellular morphological appearances often correlate with altered f-actin structure, which has been observed most notably in cancer. What remains less clear are the molecular pathways that may be involved in normal and premature aging-induced f-actin changes. We report herein that p49/STRAP, a serum response factor binding protein (SRFBP1), is increased with normal aging and appears to be sensitive to low glucose-exposure. Our study results suggest that increased levels of p49/STRAP expression tend to correlate with f-actin redistribution genes, particularly cofilin, while siRNA-mediated knockdown of p49/STRAP resulted in a reduction of thymosin-ß4. Furthermore, with the redistribution of f-actin, we observed an increase in the intermediate filament vimentin, compatible with the notion that vimentin may be increased due to its greater role in cytoskeletal dynamics during advancing population doubling levels (PDLs) and in response to a low-glucose exposure. Taken together, these data suggest that p49/STRAP may play a role in glucose-deprivation associated cytoskeletal changes.

Solubility of cerium in LaCoO3-influence on catalytic activity.

The recent interest in the catalytic properties of lanthanum perovskites for methane combustion and three way catalysis has led to considerable debate as to their structure and defect chemistry. We have investigated the doping of LaCoO3 with the tetravalent cerium cation using atomistic simulation techniques. We have compared three routes for cerium insertion and identified the favoured doping mechanism, which explain experimental observations relating to the effect of cerium on catalytic activity.

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Proximal humeral fractures: a correlation of residual deformity with long-term function.

Twenty-six patients with 27 fractures of the proximal humerus were evaluated by radiographic and clinical examination (Neer rating scale) 13 months to 12 years after injury. Proximal humeral fractures that had healed with less than 55° of angulation and less than 1.5 cm of displacement of the major fracture segments had good or excellent functional results. These fractures were successfully treated with a sling or cuff and collar immobilization. Two- and three-part fractures with greater than 55° of angulation or greater than 1.5 cm of displacement had fair or poor functional results. These fractures should be reduced by closed or open methods if good or excellent results are required. Minimal (0 to 2 mm) displacement of greater tuberosity fractures was often associated with rotator cuff tears. Neither good nor excellent results were obtained in four-part, Group IV fractures treated nonsurgically.

Percutaneous absorption of phenol and methyl alcohol in Magenta Paint B.P.C.

Estimations of phenol and methyl alcohol in the urine of 16 infants with seborrhoeic eczema treated with Magenta (Castellani's) Paint B.P.C. were made to determine the degree of absorption. Phenol was detected in four cases and methyl alcohol in none.

Toxic epidermal necrolysis in two patients with pustular psoriasis.

Two cases of toxic epidermal necrolysis are described in patients suffering from pustular psoriasis. In one of these cases there were no recognized predisposing causes. In the other, although there were alternative possibilities, we consider that the most likely cause of the toxic epidermal necrolysis was pustular psoriasis.

Anencephalus, Spina Bifida, twins, and teratoma.

The twin pairs with spina bifida and or anencephalus collected from the literature by Rogers and Weatherall (1976) form the basis for an argument that the apparent rarity of dizygous twins concordant for these malformations may be due to the breakdown of the interamniotic partition and a subsequent fetus-fetus interaction. It is suggested that this may lead to complete or partial destruction of one twin. When cells survive they may form teratoma or patches of anomalous skin cover. The hypothesis that monozygous twins concordant for these defects may form double monsters is re-stated. The present hypothesis predicts that the incidence of pineal and intraspinal teratoma will vary in time and place with anencephalus and spina bifida, and that the scalp type hairs found over or around spina bifida may prove, in male infants, to have female chromosomes.

A statistical review of controlled trials of imipramine and placebo in the treatment of depressive illnesses.

A method of reviewing a series of clinical trials by extracting the basic data in the form of 2 x 2 tables and analysing these by Fisher's two-tailed Exact Test is described, and illustrated by published imipramine-placebo trials. The results suggest that the benefit of this drug in patients with endogenous depression who have not become institutionalized is indisputable, and that further drug-placebo trials in this condition are not justified. Two of the three trials of imipramine in neurotic depression gave results showing significant improvement. Possible explanations of the apparent failure of this drug in groups of patients with undifferentiated depression are discussed.

Spina bifida and anencephaly: miscarriage as possible cause.

In two retrospective Liverpool surveys the domestic, family, dietary, and medical environments of the mothers of children affected by anencephaly or spina bifida, or both (ASB) were examined. None seemed to be of more than minor importance and the findings of others were therefore examined to see if they suggested a major factor. The most promising lead came from the hypothesis that ASB is usually due to an interaction between twin fetuses or between a fetus and residual trophoblastic material from the previous normal pregnancy, particularly when this is of the opposite sex to the propositus. The sex finding was not confirmed. It was noted that hydatidiform moles, like children with ASB, were usually female and that moles and choriocarcinomas on the one hand and children with ASB on the other occurred in mothers of similar ages, but were to some extent reciprocal in geographical incidence. This suggested that trophoblastic disease might be a factor common to all three and if so then one would expect the frequency of miscarriages to be higher immediately before than immediately after the birth of an ASB child, since mole and choriocarcinoma seldom follow a normal pregnancy. An analysis of published data confirmed that this was almost certainly so. Hence residual pathological trophoblastic material from either a previous miscarriage or a co-twin may interact unfavourably with another fetus to produce ASB and this may be the primary cause of the condition. The hypothesis is consistent with the observed lack of concordance in twins, the high incidence in females, the maternal age effect, and the greater prevalence in social classes IV and V.

Oculodento-digital dysplasia: a rare syndrome.

A rare syndrome that can be diagnosed radiographically has been reviewed. A characteristic physiognomy, variable ophthalmologic anomalies and relatively specific dental and digital defects provide the diagnostic features. No hereditary component was identified and the chromosomal pattern was normal. The history, appearance and characteristic radiographic changes may, as in this case, allow the radiologist to provide a diagnosis not previously appreciated.