env genes of avian retroviruses: nucleotide sequence and molecular recombinants define host range determinants

The env gene of avian sarcoma and leukosis retroviruses is allelic in the virus population permitting the virus to use different host cell receptors. This polymorphism has allowed the classification of these viruses into different subgroups. In order to understand further the role of viral sequences involved in determining this host range phenomenon, we constructed molecular recombinants between subgroup A, B, and E viruses and showed that the host range determinant defining subgroup specificity was located within a 1.1-kb region of the genome that included most of the coding region for the env gene product gp85. We also determined the nucleotide sequence of the region of the env gene encoding gp85 for virus isolates representing subgroup A and B viruses. We compared the predicted amino acid sequences of gp85 to themselves and to the previously published sequences of subgroup B, C, and E env genes. Based on these comparisons, we draw the following conclusions: Within the gp85 coding domain, there are four variable regions (VR-1 to VR-4) ranging in size from 9 to 52 amino acids. The variable regions are located in the same relative positions for each of the env gene alleles compared. The variable regions range in homology from 42% (A compared to B) to 57% (C compared to E) in pairwise comparisons; the flanking conserved domains are on average 95% homologous. The sequences of three different subgroup B virus isolates are highly homologous in both the conserved and variable regions. Secondary structure predictions suggest that gp85 is composed mostly of beta sheet topology. Hydrophilic loops within the variable regions may define sites of receptor interaction and binding sites for subgroup specific neutralizing antibodies.     

Bacillary angiomatosis presenting as a soft-tissue tumor without skin involvement.

A patient with human immunodeficiency virus infection presented with a soft-tissue mass which histologically and clinically mimicked an angiosarcoma. Ultrastructural study, however, revealed bacteria identical to those seen in cutaneous bacillary angiomatosis, but the patient had no skin lesions. To our knowledge, this represents the first report of soft tissue involvement by bacillary angiomatosis without the presence of skin lesions.     

Effects of insulin on hepatic lipid synthesis in alloxan diabetic rats.

In vitro hepatic synthesis of lipids starting from 1-(14)C-acetate was studied in rats made diabetic by subcutaneous alloxan administration (175 mg/kg b.w.). A second group of diabetic rats was treated with lente insulin. In the alloxan-treated rats, a decrese was observed in hepatic incorporation of 1-(14)C-acetate into phospholipids, triglycerides and esterified cholesterol; there was an increased incorporation into nonesterified fatty acids (NEFA) and free cholesterol. Insulin administration restored lipid synthesis values to normal. On histologic examination, an intranuclear glycogenesis was observed in the hepatocytes of the alloxan-treated rats, along with severe hepatic necrosis; the latter however, only in rats sacrified on the 3rd day. Hepatic steatosis with small, medium and large droplets was present in the insulin-treated rats; signs of cellular degeneration were less evident.     

Intracranial capillary hemangiomas: literature review in pediatric and adult population

Neurosurgical Review - Capillary hemangiomas (CHs) of the central nervous system represent a rare diagnosed pathology. CHs are benign vascular tumors whose most common manifestations are dermal and...     

Can Machine Learning Methods Produce Accurate and Easy-to-Use Preoperative Prediction Models of One-Year Improvements in Pain and Functioning After Knee Arthroplasty?

BackgroundApproximately 15%-20% of total knee arthroplasty (TKA) patients do not experience clinically meaningful improvements. We sought to compare the accuracy and parsimony of several machine learning strategies for developing predictive models of failing to experience minimal clinically important differences in patient-reported outcome measures (PROMs) 1 year after TKA.MethodsPatients (N = 587) in 3 large Veteran Health Administration facilities completed PROMs before and 1 year after TKA (92% follow-up). Preoperative PROMs and electronic health record data were used to develop and validate models to predict failing to experience at least a minimal clinically important difference in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total, KOOS JR, and KOOS subscales (Pain, Symptoms, Activities of Daily Living, Quality of Life, and recreation). Several machine learning strategies were used for model development. Ten-fold cross-validation and bootstrapping were used to produce measures of overall accuracy (C-statistic, Brier Score). The sensitivity and specificity of various predicted probability cut-points were examined.ResultsThe most accurate models produced were for the Activities of Daily Living, Pain, Symptoms, and Quality of Life subscales of the KOOS (C-statistics 0.76, 0.72, 0.72, and 0.71, respectively). Strategies varied substantially in terms of the numbers of inputs required to achieve similar accuracy, with none being superior for all outcomes.ConclusionModels produced in this project provide estimates of patient-specific improvements in major outcomes 1 year after TKA. Integrating these models into clinical decision support, informed consent and shared decision making could improve patient selection, education, and satisfaction.Level of EvidenceLevel III, diagnostic study.     

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score

Annals of Surgical Oncology - Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX? (ODX) recurrence scores has been...     

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.     

Autosomal recessive hypermyelinating neuropathy

We studied three patients from two kinships, affected by early onset hereditary motor and sensory neuropathy with probable autosomal recessive inheritance (HMSN type III). Morphological studies of sural nerve biopsies revealed an abnormal myelin proliferation. Two adult patients with long-term follow up, lost ability to walk at 28 and 22 years and showed severe involvement of the cranial nerves. Our observations suggest that hypermyelination neuropathy with early onset is a progressive disease with poor long-term prognosis. In one kinship the occurrence of the disease in two sibs of both sexes but not in parents, is consistent with an autosomal recessive inheritance. Familial cases of hypermyelination neuropathy have not been described in previous reports. Morphological aspects of this condition are compared with other forms of hypermyelination neuropathy.Supported by Telethon-Italy for the project: Chronic inflammatory polyradiculoneuropathy: electrophysiological and immunopathological studies     

Mutagen sensitivity and cancer susceptibility in patients with multiple primary cancers

Thirty-two patients with multiple cancers were evaluated for in vitro sensitivity to mutagens and were compared with normal controls, Mutagen sensitivity was evaluated by exposing lymphocytes to mitomycin-C in vitro and estimating the mitomycin-induced chromosomal gaps and breaks (G/B) and sister chromatid exchanges (SCE) per cell. The results show significant differences between control and patient groups when spontaneous and induced G/B and SCE were evaluated. In addition, establishing the limit of normality for G/B and SCE, among the control group, the examined patients show largely positive levels in respect to both of the parameters used. In this study we discuss the usefulness of mutagen sensitivity as an indirect measure of DNA repair and genetic susceptibility to multiple primary cancers.     

Dynamics of institutionalization of older adults in Belo Horizonte, Brazil

INTRODUCTION: Epidemiological and social changes related to population aging in Brazil will probably increase the need for nursing homes (NH). The study analyses the dynamics of institutionalization in Belo Horizonte, a 3 million inhabitant city of whom 8.0% are aged 60 or more. METHODS: Age and length of stay of 1,128 NH residents (92.5% of the estimated population) was registered and occupancy and institutionalization rates were determined. RESULTS: Among women aged 65+ in Belo Horizonte, 0.88% were living in NH; among men, 0.26%. Occupancy rates were 92%. Women (81%) were older than men (76.4 x 70.4 years; two-tailed t test = 6. 4; p=0.00) and lived there for a longer period (5.6 x 4.5 years; two-tailed t test = 2.6; p=0.01). Almost 1/3 of the men were aged < 65. CONCLUSIONS: High occupancy rates, long waiting lists and hard criteria for admission (half reject demented or dependent individuals) insinuates that these low institutionalization rates are related to scarcity of beds. The preponderance of women reflects the proportion of those widowed or separated in the community (66% of those aged 65-+, versus 76% of married man). The high frequency of institutionalized men aged <65 suggests lower capacity of maintaining themselves after widowhood. High death rates (24% during a 20 month follow-up of a 263 random sample) determines the small median length of stay (3 years). These data unveil the anachronism of a system which is not directed towards the maintenance of the Brazilian older people among their families and homes.