cDNA Sequencing of the 5′ Noncoding Region (5′ NCR) to Determine Hepatitis C Genotypes in Patients with Chronic Hepatitis C

Reports suggest that response tointerferon-alpha therapy is influenced by both hepatitisC viral genotype and titer. Our aim was to determine ifdirect, automated, cycle sequencing of the PCR productfrom an HCV RNA detection assay could be used toreliably determine HCV genotype. In addition, theapproach was used to determine the HCV genotypedistribution in our patient population and to learn ifthere was a correlation between HCV genotype and RNAtiter that could be used to predict response totreatment. In all 143 consecutive patients were testedfor both HCV RNA titer and genotype. Automated, cycle sequencing of PCR product was highly effectiveand failed to yield a genotype in only 3 (2%) patients.The distribution of HCV genotypes was: 1a (40%), 1b(39%), 2a (2%), 2b (6%), 3a (4%). There were significant differences in the median HCV RNA titersbetween genotypes 1, 2, and 3. 6 High HCV RNA titers>4.4 × 10⁶ copies/ml were only seenin genotype 1. However, the HCV RNA level should not beused as a surrogate marker of genotype because of a significantoverlap of titers within the genotypes.     

Protein kinase C agonist and antagonist effects in normal human epidermal keratinocytes

Abstract Several lines of evidence implicate protein kinase C (PKC) in the development of basal cell and squamous cell carcinomas, tumors which originate from epidermal keratinocytes. To examine PKC in a model relevant to human skin, we exposed normal human epidermal keratinocytes (NHEK) in serum-free media to a variety of PKC agonists and antagonists. NHEK PKC activity increased up to 10-fold within the 1st hour of exposure to tetradecanoyl phorbol acetate (TPA), and gradually returned to control values within 72 h. TPA-induced PKC activity was enhanced by pretreatment of cultures with protein and RNA synthesis inhibitors. TPA-induced growth arrest and differentiation was antagonized by staurosporine. Down-regulation by bryostatin pretreatment blocked TPA-stimulated differentiation. Our overall conclusion is that activation of PKC in cultured human keratinocytes is required for differentiation. These results are crucial to the analysis of compounds suspected of promoting or inhibiting epidermal tumors.     

Improved sib-pair linkage test for disease susceptibility loci

An improved sib-pair test for linkage is introduced which is superior to the previously proposed tests. The test is derived from the standard chi-squared goodness of fit statistic by restricting the alternative hypothesis to the genetically possible. Critical values are given and exact power comparisons are made with the previously proposed tests. The new test is shown to be more powerful for finite samples as well as being asymptotically uniformly most powerful. © 1993 Wiley-Liss, Inc.     

Going, going, gone . . . ? Implicit and explicit tests of conceptual knowledge in a longitudinal study of semantic dementia

Patients suffering from semantic dementia provide important constraints on theories of the structure and organisation of semantic memory. In this article we report one such patient, AM, whose progressive deterioration of semantics enables us to address the much-debated issue of whether conceptual structure is hierarchically organised. The hierarchical account predicts that brain damage should impair lower levels of the hierarchy (property information) before affecting higher level (category) information (Warrington and Shallice, Q. J. Exp. Psychol. 1975, 27, 635–657). We evaluate this prediction by repeated testing of AM in two studies—a semantic priming task and a verification task—over an 18 month period, contrasting the progressive deterioration of properties (functional and perceptual) and category relations (category co-ordinates and category labels). Properties were preserved longer than category information, arguing against a hierarchical account of semantic memory. In addition, functional properties were most robust to brain damage, supporting our claim that functional information plays a special role in semantic representations (Durrant-Peatfield et al., Proc. 19th Ann. Conf. of the Cognitive Science Society. Erlbaum, Mahwah, NJ, 1997, pp. 193–198. Tyler et al., Cognitive Neuropsychol. 1997, 14, 511–545).     

Codon usage patterns in chromosomal and retrotransposon genes of the mosquito Anopheles gambiae

Codon usage was compiled for fourteen chromosomal genes and four retrotransposons from the mosquito Anopheles gambiae. Variation exists among chromosomal genes in the degree of bias. The genes showing the highest bias are probably most highly expressed. In these genes, the base composition at the third codon position is much richer in G + C than is the overall coding sequence. Thus, codon usage is biased toward G- or C-ending codons. Codon usage in each retrotransposon is quite different, not only from chromosomal genes but also from the other retrotransposons. Codon usage comparisons among homologous genes from An. gambiae and two other Dipterans, the yellow fever mosquito Aedes aegypti and the fruitfly Drosophila melanogaster, show that while there are similarities, particularly between An. gambiae and D. melanogaster in the preference for G-and C-ending codons, each species has evolved a distinct pattern of codon usage.     

Drug Induced Acute Generalized Exanthematous Pustulosis

A 62-year-old woman with diabetic triopathy developed widespread erythematous macules, numerous pustules, and a high fever after she underwent electric coagulation for vitreous hemorrhage. She was administered several drugs at that time. After discontinuation of the drugs, the eruption disappeared, and the fever returned to normal within two weeks. A positive patch test with isepamicin sulfate highly suggested that the symptoms described above were due to drug allergy. Cadralazine, which was positive in the drug lymphocyte stimulation test (DLST), could not be excluded from the causative drugs. A false-positive DLST with ofloxacin was confirmed by an accidental challenge test. To our knowledge, this is the first report of acute generalized exanthematous pustulosis due to isepamicin sulfate and/or cadralazine.     

Auditory and vestibular system findings in patients with vertebrobasilar dolichoectasia

Impairment of the auditory-vestibular system has been reported in patients with vertebrobasilar dolichoectasia (VBD), but little is known about the underlying cause of the symptoms. Auditory testing (pure tone audiometry, auditory brain stem response and stapedius reflex) and vestibular tests (assessment of nystagmus, eye tracking tests, caloric test and rotational test) were performed in 23 patients with auditory-vestibular symptoms and/or cranial nerve impairment associated with VBD. Specific evidence of auditory and/or vestibular system impairment was observed in 19 cases (83%). Among patients with abnormal test findings, 47% had evidence suggesting peripheral impairment, 16% evidence suggesting central dysfunction, and 37% evidence suggesting both peripheral and central dysfunction. Although compression of the vestibulocochlear nerve plays an important role in the genesis of the auditory-vestibular dysfunction in patients with VBD, mechanism such as brain stem-cerebellar ischemia and impaired blood supply to the vestibular labyrinth may be just as important.     

Heparin–coated circuit during cardiopulmonary bypass

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg^-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg^-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml^-1±1.2 to 27.5 ng ml^-1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml^-1 ± 1.2 to 35.6 ng ml^-1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated.     

Small-dose oral iron absorption test in anaemic and non-anaemic elderly hospitalized patients

Abstract: The small-dose (20 mg) oral iron absorption test (OIAT) was performed in 76 hospitalized elderly patients and 30 healthy adults. Of the elderly patients, 34 were considered as iron deficient (serum ferritin level <20 μg/L) of whom 23 were anaemic and 11 not anaemic, 21 had the anaemia of chronic disorders (ACD) and another 21 were non-anaemic patients with a normal serum ferritin level. There was a significant inverse correlation between the serum ferritin level as a measure of iron store and the maximum increase in serum iron during a 3-h test (C_max), in the elderly as well as in the healthy adult group. A decision limit of 80 μg/dL for C_max is a good discriminant between absent (serum ferritin <20 μg/L) and adequate body iron stores. Sixty-eight per cent of the patients with a serum ferritin level <20 μg/L but virtually none of the ACD patients, non-anaemic elderly inpatients with normal serum ferritin levels and healthy adults had a C_max level >80 μg/L. Although further investigation is needed before the OIAT can be recommended as a valuable test for evaluating iron absorption, predicting mild iron deficiency and differentiating between different categories of anaemia, it seems worthwile that more effort should be done to validate this simple and safe test.