Properties of a filamentous virus of the honey bee (Apis mellifera)

An ellipsoidal particle, measuring 450 x 150 nm, from honey bees comprises a nucleocapsid measuring 3000 x 40 nm, containing double-stranded DNA with a molecular weight of approximately 12 x 10(6), which is coiled within a membrane. The buoyant densities in CsCl of the whole particle, nucleocapsid, DNA and DNA with ethidium bromide are 1.28, 1.36, 1.71 and 1.61 g/ml, respectively. The particle contains about 12 proteins, with molecular weights ranging from 13,000 to 70,000, which are distributed approximately equally between the membrane and the nucleocapsid.     

Features associated with suicide attempts in recurrent major depression

Sixty-seven individuals with recurrent major depression and a history of suicide attempts are compared with 163 individuals with recurrent major depression and no history of suicide attempts. The groups are contrasted on demographic features, clinical course, severity of depression, co-morbidity, and acute symptom profiles. Patients with a history of attempts are distinguished from non-attempters by suicidal ideation, marital isolation, neurovegetative signs, feelings of failure, and co-morbid alcoholism or bipolar II disorder. Logistic regression analysis using a model which included a portion of the significant variables correctly classified 77% of the cases. These findings are discussed with reference to prediction of suicide attempts in individuals with major affective disorder.     

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.     

Epidemiologic modeling using a microcomputer spreadsheet package

Epidemiologic modeling has provided both researchers and students with a means of studying complex disease processes as well as making intervention recommendations to decision makers. To develop more than the most elementary model, however, it has become necessary to be well versed in a computer programming language. While this has deterred many modelers in the past, with microcomputers it is now possible to develop even complex models without significant investment of time spent in learning a computer language. In addition to being affordable, many microcomputers offer "canned" spreadsheet packages which are readily adapted for epidemiologic modeling. To demonstrate this, two models were developed and run using a microcomputer spreadsheet package: 1) the classic Reed-Frost model, and 2) a modified Reed-Frost model with two intermixing subpopulations.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Timebanking and the co-production of preventive social care with adults; what can we learn from the challenges of implementing person-to-person timebanks in England?

This paper explores the potential contribution of timebanking, an innovative volunteering scheme, to the co-production of preventive social care with adults in England. Interest in volunteering in social care has increased as one proposed solution to the international crisis of a rising demand for services in juxtaposition with decreased resources. Volunteering has been particularly promoted in preventive services that prevent or delay care needs arising. Despite sustained interest in volunteering and co-production in social care, little is known about how theory translates into practice. Reporting implementation data from a Realistic Evaluation of six case studies in England, this paper explores one volunteering scheme, timebanking. The research explores how timebanks were working, what contribution they can make to adult social care, and whether they are an example of co-production. Data collected included interviews, focus groups or open question responses on surveys from 84 timebank members, and semi-structured interviews with 13 timebank staff. Each timebank was visited at least twice, and all timebank activity was analysed for a period of 12 months. Data were triangulated to improve reliability. The research found that in practice, timebanks were not working as described in theory, there were small numbers of person-to-person exchanges and some timebanks had abandoned this exchange model. Timebanks faced significant implementation challenges including managing risk and safeguarding and the associated bureaucracy, a paternalistic professional culture and the complexity of the timebank mechanism which required adequate resources. Lessons for timebanks are identified, as well as transferable lessons about co-production and volunteering in social care if such schemes are to be successful in the future.     

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.     

Preliminary evaluation of a fixed dose of zwitterionic piperazine (TVZ-7) in clinical cancer

One of the zwitterion buffers that has shown significant therapeutic value in the treatment of pain due to cancer, immunologically mediated diseases, and the pain associated with these conditions is in the class of N-substituted amino-sulfonic acids known as "Good Buffers." Zwitterion molecules have neither a negative nor a positive charge; thus, they are neutral. 4-(2 Hydroxyethyl)-1-piperazine ethane sulfonic acid has been used for several decades in artificial biological systems (tissue culture) as a buffer. We have been exploring the therapeutic value of these zwitterionic buffers. Pilot animal studies have demonstrated that zwitterionic piperazine increases bone marrow hypercellularity and induces extramedullary hematopoiesis. We report the initial human use to explore dose toxic and physiologic effects of a fixed dose of the zwitterionic piperazine molecule. There appears to be potential therapeutic value in the treatment of pain due to cancer, and there are preliminary indications that tumor activity and tumor size are reduced. Immunologically mediated diseases may also be affected. Toxicity is low and there appear to be minimal side effects.     

Pilot ascending dose tolerance study of parenterally administered 4-(2 hydroxyethyl)-1-piperazine ethane sulfonic acid (TVZ-7) in dogs

We report a pilot toxicity study in healthy beagle dogs which revealed no significant adverse events for TVZ-7 given at i.v. doses up to 520 mg/kg/day. All treated dogs displayed calm behavior and maintained normal clinical laboratory values throughout the study. Increased bone marrow hypercellularity and extramedullary hematopoiesis was also noted in these dogs. Three other dogs with advanced spontaneously occurring tumors have also been dosed. No serious adverse events were reported in any of the dogs. This pilot study suggests that 4-(2 Hydroxyethyl)-1-piperazine ethane sulfonic acid may be used safely in planned human clinical trials.