A periodically active pulsar giving insight into magnetospheric physics.

PSR B1931+24 (J1933+2421) behaves as an ordinary isolated radio pulsar during active phases that are 5 to 10 days long. However, when the radio emission ceases, it switches off in less than 10 seconds and remains undetectable for the next 25 to 35 days, then switches on again. This pattern repeats quasi-periodically. The origin of this behavior is unclear. Even more remarkably, the pulsar rotation slows down 50% faster when it is on than when it is off. This indicates a massive increase in magnetospheric currents when the pulsar switches on, proving that pulsar wind plays a substantial role in pulsar spin-down. This allows us, for the first time, to estimate the magnetospheric currents in a pulsar magnetosphere during the occurrence of radio emission.

Fumonisin B1 influenced the effects of arachidonic acid, prostaglandins E2 and A2 on cell cycle progression, apoptosis induction, tyrosine- and CDC2-kinase activity in oesophageal cancer cells.

In a previous study, we showed that, of a group of lipids including arachidonic acid (AA), prostaglandins E2 (PGE2) and A2 (PGA2), PGA2 had the most marked effect on the inhibition of cell growth, activation of tyrosine kinase activity, lowering of the number of G1-phase cells, and induction of p53 levels in oesophageal carcinoma (WHCO3) cells. No significant effects by the three lipids were seen in normal monkey kidney cells. In the present study, the effects of the inhibitor of ceramide synthesis, fumonisin B1 (FB1), a metabolite of Fusarium verticillioides (= F. moniliforme) which is implicated in the high incidence of oesophageal cancer, were determined on AA, PGE2 and PGA2 WHCO3 treated cells. In the presence of FB1, the lipid-enhanced tyrosine kinase activity was lowered. Flow cytometric and morphological studies showed that FB1 lowered the marked apoptosis induced by especially PGA2. FB1, however, in combination with AA, PGE2 or PGA2 increased the number of G2/M cells. AA>PGE2>PGA2 alone decreased CDC2-kinase activity, but, in the presence of FB1, CDC2-kinase activity was significantly increased. The PGA2- and AA-induced p53 levels were lowered in the presence of FB1. We concluded that FB1 diminished the cytotoxic effects of the lipids on oesophageal tumour cells.

Chronic fungal vaginitis: the value of cultures.

OBJECTIVE: Our purpose was to examine the importance of fungal cultures in evaluating patients with symptoms of chronic vaginitis by assessing the relative contribution of various yeast species and by comparing infections caused by Candida albicans with those caused by other species. STUDY DESIGN: A prospective observational study of patients referred with chronic vaginal symptoms was undertaken. In addition to a standard evaluation of symptoms, cultures for yeast were performed on modified Sabouraud agar plates. RESULTS: Seventy-seven isolates were obtained from 74 patients. A total of 68% were Candida albicans; 32% were other species. The clinical syndromes caused by non-Candida albicans isolates were indistinguishable from Candida albicans infections. Fluconazole gave a short-term mycologic cure in all Candida albicans but only 25% of non-Candida albicans cases (p < 0.001). In non-Candida albicans infections, boric acid suppositories achieved the best mycologic cure rate (85%). CONCLUSION: Because non-Candida albicans species are responsible for a significant number of chronic fungal vaginal infections and are more resistant to therapy with fluconazole, fungal cultures are a valuable aid in confirming the diagnosis and selecting appropriate therapy.

Malassezia furfur folliculitis of the vulva: olive oil solves the mystery.

BACKGROUND: In treating women with chronic fungal infections, it is important to know which organism is responsible for the infection. In the past, organisms thought to cause vaginitis and vulvitis could all be cultured on modified Sabouraud agar. CASE: We describe a case of a woman whose chronic fungal vulvar folliculitis masqueraded as squamous epithelial hyperplasia. The 46-year-old woman, taking immunosuppressive therapy for rheumatoid arthritis, was referred with an 8-month history of vulvar vesicles, itching, and burning. Her examination revealed a vulvar folliculitis. When fungal cultures were initially negative, a vulvar biopsy revealed a squamous epithelial hyperplasia. However, a fungal culture covered with sterile olive oil eventually grew Malassezia furfur, a yeast with peculiar growth requirements. She was cured with a 2-week course of fluconazole. CONCLUSION: Malassezia furfur, an organism rarely described in the vaginitis literature, can cause vulvar folliculitis in a patient on immunosuppressive therapy.

Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.

In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro.

Differential exon expression in myelin basic protein transcripts during central nervous system (CNS) remyelination.

1. In order to characterize some of the molecular events leading to repair of myelin in the adult central nervous system (CNS), we examined the expression of transcripts for myelin basic protein (MBP) during remyelination in the mouse. C57B1/6 mice develop a demyelinating disease when glial cells are selectively infected by the A59 strain of mouse coronavirus. The virus is spontaneously cleared from the mice by 4 weeks postinfection (WPI), a time when remyelination is starting. 2. At 3 WPI total MBP transcripts are decreased by 75% in demyelinating lesions compared to control white matter. Using RNase protection assays and in situ hybridization with probes for particular MBP exons, we detected an increase in MBP transcripts containing exon 2 information, coincident with the earliest histological signs of remyelination. 3. The expression of MBP transcripts containing exon 2 information was first seen clustered in the perinuclear cytoplasm of oligodendrocytes scattered within the lesions. This is reminiscent of the increased levels and perinuclear clustering of MBP transcripts containing exon 2 seen during early developmental myelination. The peak abundance of exon 2-containing transcripts in the lesions was 13-fold that seen in control white matter. At later stages of remyelination, additional forms of MBP transcripts (without exon 2) increased and their distribution was more diffuse. 4. Thus, during remyelination, preforms of MBP transcripts, which are normally present at low levels in the adult CNS, are abundantly expressed and regulated in a manner similar to that observed in developmental myelination.

Expression of viral and myelin gene transcripts in a murine CNS demyelinating disease caused by a coronavirus.

C57BI/6N mice develop a CNS demyelinating disease when inoculated intracranially at 4 weeks of age with the A59 strain of mouse hepatitis virus (MHV-A59). In order to explore the virus-host interactions, the histological features of the demyelinating disease were correlated with the spatial and temporal distribution of viral transcripts and the expression of oligodendrocyte-specific genes (myelin basic protein, proteolipid protein, myelin-associated glycoprotein, and 2',3' cyclic nucleotide 3'-phosphohydrolase) in the spinal cord of diseased mice. Three distinct phases in the disease were identified. In the first phase, 1 week postinfection (1 WPI), virus replication was widespread in both gray and white matter but was preferentially occurring in glial cells. In the ventral and dorsal root zones where viral transcripts were most abundant, all myelin gene transcripts were decreased before demyelination was seen. During the second phase of the disease (2-3 WPI), viral transcripts decreased in abundance and became restricted to the white matter. Numerous demyelinating lesions were observed and were characterized by inflammatory cells, paucity of oligodendrocytes, and a profound decrease of all myelin gene transcripts. In the third phase of the disease (4-6 WPI) no viral transcripts were detected, and remyelination began. In the lesions and the tissue surrounding them, transcripts of all myelin genes increased to levels above normal. The increased expression of myelin gene transcripts occurred in a synchronized manner and with a cellular distribution reminiscent of that seen in developmental myelination. These molecular events correlated with efficient remyelination and clinical recovery in this murine demyelinating disease.

Morphological changes occurring during thrombogenesis and embolization on biomaterials in a canine ex-vivo series shunt.

An acute canine ex-vivo femoral A-V shunt technique was used to study thrombus formation and embolization on a number of porous and non-porous polymer surfaces over a one-hour blood contact period. The technique allows for simultaneous exposure of all the surfaces under similar physiological and hematological conditions. This makes comparisons between surfaces more reliable. SEM was used to study changes in the morphology of platelets and thrombi present on the polymer surfaces. Quantitative information was obtained using radiolabeled platelets. In general, platelet deposition, activation, and aggregation was followed by thrombus formation which peaked at about 15-30 minutes of blood contact. Thrombi were composed mainly of platelets with few leukocytes present. Embolization was observed on Silastic (SIL), polyvinylchoride (PVC), polyethylene (PE), and oxidized polyethylene (OX-PE) surfaces between 20 and 60 minutes of blood contact. The mechanism for embolization involved clot retraction under the influence of a shear field. Leukocytes did not appear to be necessary for the initiation of embolization but were present during the embolization phase on OX-PE, possibly due to chemotactic factors. Although extensive thrombus formation was observed on the porous PTFE materials (GORE-TEX and IMPRA), the thrombi formed were flat and did not significantly block the lumen. By 60 minutes of blood contact, only minimal embolization had occurred on the PTFE surfaces. SEM examination of the sequence of thrombus formation and embolization was found to correlate well with trends in platelet deposition measured using radiolabeling techniques.

A radiographic and histologic study of fracture healing in osteopetrotic rats.

Repair of tibial fractures in osteopetrotic rats was delayed in comparison to that of normal littermates, due to reduced remodeling. Reduced bone resorption, known to be the cause of the disease in this mutation, is expressed in both skeletal development and fracture repair. The possible implications for human juvenile osteopetrosis are discussed.