Nuclear lamins in cell regulation and disease.

The nuclear lamins are type V intermediate filament proteins that form meshworks at the inner aspect of the nuclear envelope and are also present throughout the nuclear interior. Through these meshwork structures, lamins regulate the shape, size, and mechanical properties of the nucleus. During the last 25 years, the Goldman laboratory has studied the organization and dynamic properties of the lamins in the nucleus. These studies have characterized the role of lamin phosphorylation in nuclear lamina assembly and disassembly during mitosis. Furthermore, our studies have demonstrated a role for the lamins in chromatin modification and epigenetics, transcription, and DNA replication. Recently, the discovery of numerous mutations in the gene encoding A-type lamins causing the collection of diseases known as laminopathies has provided new insights into the roles of lamins in cellular regulation and differentiation.

Virologic, immunologic, and clinical evaluation of human immunodeficiency virus antibody status of symptom-free children born to infected mothers.

STUDY OBJECTIVE: To determine the prevalence of infection by the human immunodeficiency virus (HIV) in a population of symptom-free children who were born to HIV-infected mothers and who subsequently underwent seroreversion from an HIV antibody-positive to an HIV antibody-negative status. DESIGN: Cohort. SETTING: Pediatric HIV program in a community setting. PATIENTS: We used HIV DNA polymerase chain reaction (PCR) and coculture to detect the presence or absence of HIV in peripheral blood mononuclear cells of 134 children aged 6 to 53 months. All children had HIV antibody at birth and underwent a subsequent seroreversion to antibody-negative status. RESULTS: In 134 children with HIV antibody-negative status, 219 of 220 culture results and 242 of 247 HIV-1 DNA PCR assay results were negative. Six positive laboratory results were obtained for six different children, each of whom had negative results on multiple assays. For HIV-infected children, 56 of 62 cultures and 99 of 104 PCR evaluations showed positive results. There was no clinical or laboratory evidence of HIV infection in the group with HIV antibody-negative status. CONCLUSION: We were unable to find evidence of latent HIV type 1 infection in this cohort of symptom-free children who underwent seroreversion to HIV antibody-negative status. The loss of maternal HIV antibody in these children indicates the absence of HIV infection. False-positive PCR and culture results occurred sporadically, indicating that repeated analysis of HIV seropositivity in infants and children is necessary.

Neurosurgical management of single brain metastasis.

A series of 74 consecutive cases undergoing craniotomy for single brain metastasis in the Beilinson Medical Center between October 1975 and October 1981 were reviewed. All patients underwent radiation therapy after craniotomy. The most common metastasis was that of unknown origin (35%), followed by lung (24%) and breast (16%). Overall median survival after craniotomy was 6.6 months. Overall 1- and 2-year survival rates were 30 and 15%, respectively. Operative mortality (30 days) was 15%. For the patients with metastases to the lung, median survival was 7.5 months and 1-year survival rate was 33%. It appears from this report that two dominant factors affect the prognosis of these patients. The first is the long latent interval (time between diagnosis of primary tumor and detection of metastasis). The second is the location of the metastasis; those with lesions in the cerebral hemispheres had a far better outcome than those with cerebellar lesions (p less than 0.0001).