Structural studies of the capsular antigen of haemophilus infuenzae type c

The structure of the capsular antigen from Haemophilus influenza type c has been investigated, n.m.r. spectroscopy being the principal method used. It is concluded that the antigen is composed of repeating-units having the following structure:

O-Acetyl groups are present in ～90% of the repeating-units.     

Cell surface component(s) involved in rat hepatocyte intercellular adhesion

Aggregation of rat hepatocytes was effectively inhibited by monovalent antibodies (Fab fragments) directed against hepatocyte plasma membranes, but monovalent antibodies against some distinct, known hepatocyte surface antigens had no effect. Surface antigens, which neutralized the Fab inhibiting effect on cell aggregation, could be solubilized from plasma membranes by limited proteolytic digestion. Thus, hepatocyte intercellular adhesion seems to involve specific cell surface components, which may be proteins or protein derivatives.     

The metabolism of steroids in the fatty liver induced by orotic acid feeding.

1. The metabolism of 4-[4-14C]androstene-3,17-dione, 4-[4-14C]pregnene-3,20-dione, 5alpha-[4-14C]androstane-3alpha,17beta-diol, [4-14C]cholesterol, 7alpha-hydroxy-4-[6beta-3H]cholesten-3-one, 5beta-[7beta-3H]cholestane-3alpha,7alpha-diol and [3H]lithocholic acid was studied in the microsomal fraction of livers from control and orotic acid-treated male rats. 2. As a result of the treatment the orotic acid-fed rats had fatty livers and subnormal concentrations of cholesterol and triglycerides in serum. 3. The 6beta- and 7alpha-hydroxylation of 4-androstene3,17-dione, and the 2alpha-, 2beta- and 18-hydroxylation of 5alpha-androstane-3alpha,17beta-diol, and the 5alpha-reduction of 4-androstene-3,17-dione and 4-pregnene-3,20-dione were decreased by 40--50% in orotic acid-fed rats. Other oxidative and reductive reactions of the steroid hormones were not significantly affected. 4. The 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one was decreased by about 50%, whereas the 7alpha-hydroxylation of cholesterol and the 26-hydroxylation of 5beta-cholestane-3alpha,7alpha-diol were not significantly decreased. The 6beta-hydroxylation of lithocholic acid was stimulated by 40%. 5. The results are discussed in relation to present knowledge of the heapatic drug-metabolizing enzymes and to the recent findings of an abnormal bile acid metabolism in liver disease.     

The structure and properties of 27S and larger iodoproteins in the thyroid gland.

Iodoproteins larger than 19S were isolated from hog and calf thyroid glands using gel filtration on Sepharose 6B and one or two centrifugations in glycerol density gradients. Purified protein fractions were analysed in the analytical ultracentrifuge and characterized by the combined use of electrophoresis in continuous polyacrylamide gel gradients and electron microscopy. Three bands migrating more slowly than 19S could be identified in the polyacrylamide gels. Electron microscopy of the fastest of these species, having a sedimentation constant of 27S, showed pairs of 19S thyroglobulin molecules which had the same size and the same ovoid shape as normal, well-iodinated thyroglobulin molecules. The ovoids were randomly attached side to side, end to end. The more slowly migrating proteins were shown to consist of similar aggregates of three, four or more randomly attached molecules. Iodine and sialic acid determinations in 27S and 19S separated from the same pool of well iodinated protein showed no difference in iodine content but a larger amount of sialic acid in 27S than in 19S.     

Recovery of brain noradrenaline after 5,7-dihydroxytryptamine-induced axonal lesions in the rat

Time-dependent changes in regional CNS noradrenaline (NA) concentration, 3H-NA uptake and fluorescence morphology of CNS NA neurons were analysed in the adult rat up to 6 months after intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT), and compared with the time-course of changes in brain and spinal cord indolamine neurons. Following a substantial depletion of both amines in all CNS regions (telodiencephalon, brainstem and spinal cord) at 10 days after 150 mug 5,7-DHT, brain NA--but not 5-HT--levels recovered to near-normal values in brainstem and forebrain (35% below the age-matched controls) within 4 months. This was accompanied by a total restoration of the initially decreased capacity of the brain tissue to accumulate 3H-NA in vitro. Within 10 days after 5,7-DHT, there was a disappearance of NA terminals from many telencephalic, diencephalic and lower brain stem nuclei, from the cerebral and cerebellar cortices, and the grey matter of the spinal cord, concomitant with the appearance of numerous distorted, highly fluorescent swellings along the non-terminal axons of the major noradrenergic projection pathways. The recovery of the NA levels was paralleled by a re-appearance of fluorescent fibres, signifying an intense sprouting and regrowth of the drug-lesioned axons, which eventually re-innervated some of the previously denervated telodiencephalic regions. Except for a permanent loss of some surface-near perikarya in group A1 (the main source of the bulbospinal projections) there was no evidence of a retrograde degeneration of noradrenergic cell bodies in the rat CNS. The results are compatible with the idea that 5,7-DHT mainly causes a lesion of NA axons at a distance from the cell bodies, and this is followed by sprouting and regrowth of axons from the lisioned neurites, and formation of new terminal-like fibres in some previously denervated telodiencephalic regions. These findings indicate that chemical axotomy of central NA neurons induced by 5,7-DHT is--in contrast to that induced by 6-hydroxydopamine--followed by extensive axonal regeneration.     

Shift Work Disorder in a Random Population Sample – Prevalence and Comorbidities

Few studies have investigated the presence of shift work disorder (SWD) in the general community. We addressed many of the limitations in this literature and present new findings. SWD has been treated as an ‘all or none’ construct but we propose the need to consider the ‘severity’ of the disorder. Using random digit dialling, we randomly recruited 1163 participants. Participants completed an extensive battery of scales and questions concerning work, health and individual differences. Three questions based on the criteria from the International Classification for Sleep Disorders were used to categorise participants with SWD (n = 176). In addition, we asked participants whether SWD interfered with aspects of their life and high ratings were used to define severe shift work disorder (SSWD). The prevalence of SWD was 32.1% among night workers and 10.1% in day workers (p<.001). SSWD was present in 9.1% of night workers and 1.3% of day workers (p<.001). Adjusted logistic regression analyses found significant associations between SWD and night work (OR  = 3.35, CI 2.19-5.12), weekly work hours (OR  = 1.02, CI 1.00–1.04), short sleep (≤6 h; OR  = 2.93, CI 1.94–4.41), languidity (OR  = 1.11, CI 1.06–1.16) and resilience (OR  = 0.56, CI 0.43–0.81). Night work, short sleep, languidity, and hypertension were significantly associated with SSWD. Overall, participants with SSWD slept 0.80 h less than other participants (p<.001). Night work, short sleep and languidity were associated with both SWD and SSWD. Day workers with SWD symptoms reported significantly shorter sleep duration, higher levels of languidity and worked longer working hours compared to day workers without SWD.     

Family studies of hereditary hemochromatosis in Denmark and the Faroe Islands

Summary Pedigree studies were performed based on one Faroese and four Danish probands with overt idiopathic hemochromatosis (IH). The study consisted of HLA typing and determination of biochemical iron status indicators (serum transferrin saturation, serum ferritin). In total, 130 persons were evaluated. The screening identified 6 homozygous (h/h) subjects with preclinical IH, 46 heterozygous (h/n), and 8 normal (n/n) subjects, while 39 subjects were classified as normal or heterozygous (n/h?). One family demonstrated both a homozygous x heterozygous as well as a heterozygous x heterozygous mating. Recombination between the HLA region and IH locus occurred possibly in three subjects in three different families. The significance of detailed screening in families with probands with IH is discussed.