Immunological characterization of an early cytomegalovirus single-strand DNA-binding protein with similarities to the HSV major DNA-binding protein

Monospecific polyclonal antisera were prepared against the 129-kDa, early, single-strand DNA-binding protein (DB129) of strain Colburn cytomegalovirus (CMV), and used to study its distribution in infected cells and its relatedness to a proposed human CMV (HCMV) counterpart (DB140). Indirect immunofluorescence of fixed, infected human fibroblasts showed DB129 to be localized within the intranuclear inclusions characteristic of replicating CMV. Treatment of infected cells with 50 to 100 micrograms phosphonoformic acid per milliliter resulted in the overproduction of DB129 and its accumulation within nuclei, both inside the inclusions and in surrounding areas of the nucleoplasm, whereas treatment with 500 micrograms/ml prevented inclusion formation, and DB129 was localized at discrete points throughout the infected-cell nuclei. The sera cross-reacted an estimated 10% with HCMV DB140 in an indirect immunoassay, and their use in immunofluorescence localized DB140 to the nuclear inclusions of HCMV-infected cells. Their immunological cross-reactivity, as well as their similar biochemical properties and intracellular distribution, support the likelihood that DB129 and DB140 are the protein products of homologous genes. The relationship of these proteins to the herpes simplex major DNA-binding protein is discussed.     

Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease.

We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain.     

Homozygosity by descent for a rare mutation in the myophosphorylase gene is associated with variable phenotypes in a Druze family with McArdle disease.

We examined a large consanguineous Druze family with McArdle disease for mutations in the glycogen myophosphorylase (PYGM) gene. All affected subjects were autozygous for a single G to A transition that abolishes the 5' consensus splice site in the first nucleotide of intron 14. The G to A transition is a rare mutation, with only one previous report in a single white subject heterozygous for this mutation and another, more common, mutation at codon 49. The kindred in our study is the first family reported in which disease is caused by homozygosity for this rare mutation. This kindred was originally reported as the first familial case of McArdle disease in the Druze.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

HIV prevalence among IDUs in Australia: a methodological review

A review was carried out of Australian studies which have measured the prevalence of HIV infection among injecting drug users (IDUs). The review considered published studies which had reported on serologically-determined HIV prevalence. There were five studies reported from specialized sexually-transmissible disease of HIV clinics, five studies reported from health services aimed at IDUs, three studies reported from other health services and one multi-centre behavioural study. The main findings from the studies were that HIV prevalence in IDUs has been low in Australia, apart from in male IDUs who also had homosexual contact. HIV prevalence ranged from 20 to 24% in male IDUs reporting homosexual contact and from 0 to 5% in other IDUs.

The studies, while reflecting a range of research methodologies, are subject to a number of limitations. Most of the studies did not provide detailed analyses of HIV prevalence by age and sex or behavioural factors, and several studies used sampling frames which were not clearly defined. There is little available information on temporal trends in seroprevalence and geographical comparisons are rendered difficult by differences in the study methodology. Adoption of standardized, continuing seroprevalence surveys on IDUs would provide a better means of monitoring the occurrence of HIV infection in this group, which has been a key determinant of the course of the HIV epidemic in a number of Western countries.     

A comprehensive educational approach to improving patient isolation practice

OBJECTIVE: To describe a workable plan for the successful education of a large, diverse group of healthcare workers in a university hospital setting. DESIGN: A prospective, nonrandomized study of compliance with infection control isolation practice following various educational interventions. SETTING: 300-bed tertiary-care, academic medical center with out-patient clinics. PARTICIPANTS: Hospital employees and contract workers. INTERVENTIONS: The infection control department introduced a plan to implement the Centers for Disease Control and Prevention's new isolation guidelines. A comprehensive proposal was presented to administration. It included a time line for institution and a comprehensive educational and performance-improvement plan, including standard lectures and a video that explained Standard and Transmission-Based Precautions. Follow-up consisted of customized in-services and one-on-one continued education tailored to the individual units. RESULTS: Compliance with isolation procedure after standardized lectures and video alone was poor. Compliance improved after institution of smaller, more intensive in-services tailored to individual departments and given during all shifts. CONCLUSIONS: Intensive, individualized education is the key to compliance. This requires sufficient infection control staffing and administrative support.     

Reduced femoral geometry but normal biomechanics in the dorsomedial hypothalamic nucleus-lesioned rat.

Bone geometry, structure, and biomechanical properties were investigated in a model of growth retardation, the dorsomedial hypothalamic nucleus-lesioned (DMNL) weanling rat. Male weanling Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nucleus (DMN) at age 27 days. Sham-operated rats served as controls. All rats were maintained postoperatively for 40 days. Upon sacrifice, DMNL rats weighed less (p < 0.01), were shorter (p < 0.01), and ate less (p < 0.01) when compared to controls, but their body composition was normal. The femora in DMNL were shorter (p < 0.01), had a smaller outer anteroposterior (AP) diameter (p < 0.04), polar moment of the area (p < 0.02), and maximal (p < 0.02) and minimal (p < 0.03) principal moment of the area when compared with sham-operated rats. Notably, mean torque at failure, torsional energy, stiffness, and maximal stress did not demonstrate statistically significant differences between the two groups. These data clearly show that despite the reduced size and bone growth, DMNL rats responded normally to the mechanical challenges applied to test bone biomechanical properties. The data, therefore, add to previous evidence and strengthen the hypothesis that DMNL rats are governed by an "organismic" set point.     

Spatz-Lindenberg disease: a rare cause of vascular dementia

BACKGROUND: Isolated cerebral thromboangiitis obliterans (Spatz-Lindenberg disease) is not well recognized as a cause of vascular dementia. CASE DESCRIPTION: A 58-year-old woman presented with dementia and pyramidal signs. Neuroimaging showed multiple areas of white matter change. Brain biopsy showed intimal thickening of the walls of leptomeningeal and intraparenchymal arteries, almost to complete occlusion, with an intact internal elastic lamina and media and without inflammation or infiltration. The cortex showed only moderate gliosis. CONCLUSIONS: Spatz-Lindenberg disease should be considered in the differential diagnosis of vascular dementia. Additional studies of its pathogenesis are required to determine appropriate treatment.