Conserved features in papillomavirus and polyomavirus capsids

Capsids of papilloma and polyoma viruses (papovavirus family) are composed of 72 pentameric capsomeres arranged on a skewed icosahedral lattice (triangulation number of seven, T = 7). Cottontail rabbit papillomavirus (CRPV) was reported previously to be a T = 7laevo (left-handed) structure, whereas human wart virus, simian virus 40, and murine polyomavirus were shown to be T = 7dextro (right-handed). The CRPV structure determined by cryoelectron microscopy and image reconstruction was similar to previously determined structures of bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 1 (HPV-1). CRPV capsids were observed in closed (compact) and open (swollen) forms. Both forms have star-shaped capsomeres, as do BPV-1 and HPV-1, but the open CRPV capsids are approximately 2 nm larger in radius. The lattice hands of all papillomaviruses examined in this study were found to be T = 7dextro. In the region of maximum contact, papillomavirus capsomeres interact in a manner similar to that found in polyomaviruses. Although papilloma and polyoma viruses have differences in capsid size (approximately 60 versus approximately 50 nm), capsomere morphology (11 to 12 nm star-shaped versus 8 nm barrel-shaped), and intercapsomere interactions (slightly different contacts between capsomeres), papovavirus capsids have a conserved, 72-pentamer, T = 7dextro structure. These features are conserved despite significant differences in amino acid sequences of the major capsid proteins. The conserved features may be a consequence of stable contacts that occur within capsomeres and flexible links that form among capsomeres.     

Woody hands in a patient with pancreatic carcinoma: a variant of cancer-associated fasciitis--panniculitis syndrome

We report an elderly woman with rapidly progressive painless, woody induration of the hands. Mild diabetes mellitus was demonstrated. Skin biopsy features included broad fibrous bands extending deeply into subcutaneous fat, a mild mononuclear cell infiltrate, and post-thrombotic recanalization of a deep vessel in one specimen. The patient developed uncontrolled haematemesis and was demonstrated at laparotomy to have disseminated pancreatic carcinoma. The unusual clinical features and temporal relationship between the skin changes and the tumour suggest a paraneoplastic eruption. Which appears best classified as an example of cancer-associated fasciitis-panniculitis syndrome.     

Fine structural specificity differences of trimethoprim allergenic determinants

BACKGROUND: Adverse reactions, including immediate hypersensitivity, to the widely used antibacterial agent trimethoprim occur quite frequently. In recent years some progress has been made in developing an immunoassay to aid diagnosis of type 1 allergic reactions to trimethoprim and to define the basis of IgE antibody recognition of the drug. OBJECTIVES: The molecular basis of IgE binding to trimethoprim was examined more closely with a view to defining the fine structural recognition differences between patient's sera. Utilization of such information may lead to immunoassays that are more specific and sensitive and of greater diagnostic value. METHODS: Immunoassays for specific IgE antibodies and quantitative hapten inhibition studies with trimethoprim and selected structural analogues were employed, together with sera from eight subjects clearly defined clinically as allergic to trimethoprim. RESULTS: Three different allergenic determinant structures have been identified on the trimethoprim molecule. Identification of the 3,4-dimethoxybenzyl group as a determinant was achieved on the basis of inhibitory activities of diaveridine, 3,4-dimethoxyphenylethylamine, 3,4-dimethoxybenzoic acid and 3,4,5-trimethoxycinnamic acid. Evidence that the opposite end of the trimethoprim molecule was not being recognized was obtained from results with some pyrimidine derivatives, each of which showed no activity. Identification of the second determinant, the 2,4-diamino-5-(3',4'-dimethoxybenzyl) pyrimidine group, rested mainly on the superior inhibitory potency of diaveridine, which differs from trimethoprim by just one methoxy group. With sera from some trimethoprim-allergic subjects, only trimethoprim was active, suggesting that the entire molecule was a third IgE-binding determinant structure. CONCLUSION: As with other drug allergenic determinants defined so far, heterogeneity of trimethoprim IgE-binding determinants exists, and fine structural differences between determinants may be as small as a single methoxy group. Identification of the 2,4-diamino-5-(3',4'-dimethoxybenzyl) pyrimidine group as an allergenic determinant increases the number of known trimethoprim determinants to three, and suggests that the number and heterogeneity of determinants will be a reflection of the number of allergic subjects studied.     

Urinary assays for desmosine and hydroxylysylpyridinoline in the detection of cirrhosis

BACKGROUND/AIMS: Non-invasive markers of liver fibrosis have great potential for both the diagnosis and therapy of liver disease and cirrhosis. The aim of this study was to evaluate the potential of urinary amino acids desmosine (DES) and isodesmosine (IDES) derived from the breakdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) derived from fibrillar collagen in diagnosing chronic liver disease. METHODS: We studied 48 patients with chronic liver disease who had varying degrees of liver fibrosis, graded 0-6 using a modified Knodell score, and 20 control subjects without liver disease. Urinary DES (microg/g creatinine) and HP (nmol/mmol creatinine) were measured by an isotope dilution, high performance liquid chromatography method. For liver disease patients, aminoterminal propeptide of type III procollagen (PIIINP) and alanine aminotransferase were determined. The urine and serum markers were correlated to degree of fibrosis and inflammation on liver biopsies. Differences between groups were analyzed by ANOVA and multiple linear regression was applied to determine independence of variables. Sensitivity, specificity and receiver operating curves were derived for each marker. RESULTS: In the 17 patients with liver fibrosis score of 5-6, mean urinary DES, IDES, HP and LP were all significantly greater than in the control group (p<0.05). Urinary DES and IDES correlated best with fibrosis score, r=0.61 for both markers. The correlation coefficient between serum PIIINP and fibrosis score was 0.47. Urinary DES and HP each had an overall diagnostic accuracy of 77% for fibrosis. Combining markers improved accuracy to over 80%. No correlation was seen between the urinary markers and inflammation scores. CONCLUSIONS: Urinary DES and HP are potentially useful clinical markers for liver fibrosis, especially when used in combination or in association with PIIINP.     

The response of asthmatic subjects to isoproterenol inhaled at differing lung volumes

Asthmatics are usually instructed to use pressurized bronchodilator aerosols by delivering a bolus of drug at the beginning of a full inspiration. Because airways are better dilated near total lung capacity, the delivery of the drug near the end of a full breath might allow better penetration of particles into the lung and greater bronchodilatation. To test this hypothesis, 13 asthmatic subjects inhaled 400 mug of isoproterenol at 20 per cent (low) and at 80 per cent (high) vital capacity. The studies were done on 2 separate days when the severity of asthma was the same. Forced vital capacity, 1-sec forced expiratory volume, specific airway conductance and maximal flow at 50 per cent of viral capacity were measured at frequent intervals after drug administration. Ten min after drug delivery, there was a significantly greater (P less than 0.05) improvement in 1-sec forced expiratory volume after the drug was inhaled at the high lung volume compared to the response after delivery at the low lung volume. The differences in forced vital capacity, specific conductance, and maximal flow at 50 per cent of vital capacity were not significant. We concluded that inhaling a bronchodilator drug at the end of a full inspiration causes relatively greater bronchodilatation than inhaling the same dose at the beginning of inspiration.     

Malignant mesothelioma in Pilbara Aborigines

Malignant mesothelioma occurred in a female Aborigine after environmental exposure to asbestos. All known cases of the disease in Aborigines in Western Australia were reviewed; all occurred in Pilbara residents. Most were exposed while involved in the transport of asbestos from the Wittenoom crocidolite operation. Based on recent estimates of the size of the Aboriginal population in the Pilbara region, their incidence of this disease (250 per million for ages 15 and over) is one of the highest population-based rates recorded.     

Electrocardiograph monitor artifacts in a neonatal intensive care unit

A wide variety of artifacts may be found when monitoring the ECG in a neonatal intensive care unit. Many of the artifacts resemble arrhythmias, and unless they are recognized as artifacts they may lead to serious errors of diagnosis and therapy. Many of the artifacts are caused by patient movement such as seizures, tremulousness, or hiccups. Others may be introduced by the monitor itself or be caused by electrical equipment in the vicinity. A group of ECG tracings is presented to illustrate the various artifacts encountered. Features that distinguish the artifacts from the arrhythmias they mimic are described, as are suggestions for elimination of the artifacts.     

Evaluation of drug formulations using LD50 testing in mice

The LD50 values were utilized to assess the relative rate of absorption of two very poorly soluble drugs. Formulations of these drugs were studied by micronization; addition of surfactant, alkaline or buffering agents, and/or bile salts; coprecipitation; melt or fusion techniques; or granulation with hydrophilic agents. Differences in toxicities were demonstrated from formulations compared to pure drugs by the LD50 method. This study shows that the LD50 is a practical, rapid method of achieving comparative evaluations of drug formulations.     

A radioimmunoassay for serum calcitonin in the rat

Persisting primitive papilla epithelialis is described in a 22-year-old woman. The papilla has blurred borders, a central papilla eminence and a yellowish colour. In addition pigmentary pseudoretinopathy with perivascular pigment deposits and hypermetropia with aplasia maculae occurred. This picture can be confused classically with pappilloedema.