Reduction of morbidity and mortality rates for neonatal group B streptococcal disease through early diagnosis and chemoprophylaxis.

Pregnant women, part of the term service population at Orlando Regional Medical Center, were screened for group B streptococci (GBS), using Lim Group B Strep Broth (GIBCO Laboratories, Madison, Wis.) and the Phadebact Strep B Test (Pharmacia Diagnostics, Piscataway, N.J.). Of the 803 women screened, 173 were confirmed as colonized with GBS at the time of admission in labor. Eighty of these women were treated with ampicillin at least 6 h prior to delivery. The remaining 93 women received no ampicillin. None of the infants born to the treated women was colonized with GBS at surface culture sites. Forty-three of the infants born to untreated women were colonized. Rapid identification of GBS colonization in women, combined with ampicillin chemoprophylaxis, significantly reduced vertical transmission of GBS.     

Dysferlin is a plasma membrane protein and is expressed early in human development

Recently, a single gene, DYSF, has been identified which is mutated in patients with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy (MM). This is of interest because these diseases have been considered as two distinct clinical conditions since different muscle groups are the initial targets. Dysferlin, the protein product of the gene, is a novel molecule without homology to any known mammalian protein. We have now raised a monoclonal antibody to dysferlin and report on the expression of this new protein: immunolabelling with the antibody (designated NCL-hamlet) demonstrated a polypeptide of approximately 230 kDa on western blots of skeletal muscle, with localization to the muscle fibre membrane by microscopy at both the light and electron microscopic level. A specific loss of dysferlin labelling was observed in patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two different frameshifting mutations demonstrated very low levels of immunoreactive protein in a manner reminiscent of the dystrophin expressed in many Duchenne patients. Analysis of human fetal tissue showed that dysferlin was expressed at the earliest stages of development examined, at Carnegie stage 15 or 16 (embryonic age 5-6 weeks). Dysferlin is present, therefore, at a time when the limbs start to show regional differentiation. Lack of dysferlin at this critical time may contribute to the pattern of muscle involvement that develops later, with the onset of a muscular dystrophy primarily affecting proximal or distal muscles.     

Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection.

The serum antibody response of 50 infants and children infected with respiratory syncytial virus (RSV) was determined by a glycoprotein-specific enzyme-linked immunosorbent assay, and the effects of age and preexisting antibody titer at the time of RSV infection on response to the G and F glycoproteins of RSV were examined. The immune response to the G and F glycoproteins was assessed with anti-human immunoglobulin A to permit measurement of the response of young infants in the presence of maternally derived immunoglobulin G. The findings suggested that age primarily affects the response to the F glycoprotein and that preexisting antibody titer affects the response to the G glycoprotein.     

Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.     

Routes to transplant tolerance versus rejection; the role of cytokines

The alloimmune response can be divided into specific junctures where critical decisions between tolerance and immunity are made which define the outcome of the transplant. At these "decision nodes" various cytokines direct alloresponsive T cells to develop either a proinflammatory response aimed at graft destruction or an immunoregulatory response facilitating graft acceptance. This review will focus on the role of these cytokines in influencing the progression of an alloimmune response leading ultimately to either allograft survival or rejection.     

Suppression of charge movement by calcium antagonists is not related to calcium channel block

The calcium channel-inhibiting drugs nitrendipine and diltiazem represent two important classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents and charge displacement currents in bullfrog semitendinosus muscle fibers was examined using a vaseline gap voltage clamp. Nitrendipine (10 M) reduced the quantity of charge that moved both during the ON phase (Q_ON) and the OFF phase (Q_OFF) of charge movement. This action appeared to be most selective for Q_ON. However, at this same concentration, nitrendipine had no blocking action on inward calcium currents. In contrast to these findings, diltiazem blocked calcium currents in a concentration-dependent manner, while slightly increasing the quantity of charge moved during Q_ON and Q_OFF. The enhancement of charge movement by diltiazem resulted from two actions. First, diltiazem shifted the voltage-dependence of charge movement to more negative potentials. Second, diltiazem increased the maximum amount of charge moved. (Supported by NIH NS 03178 and HL 07382.)     

Supraependymal cells in the third ventricle of the neonatal rat

Supraependymal cells in the third ventricle of neonatal male and female rats were examined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Supraependymal cells in the third ventrical of adult male rats were also studied with SEM. Many neonate supraependymal cells were round to oval in shape and exhibited varying degrees of surface irregularity. Small finger-like processes or narrow pseudopodia projected from the cell bodies over the underlying ependymal cells. Some neonatal supraependymal cells exhibited flattened cell bodies with broad pseudopodia and few surface irregularities. TEM revealed a variety of cell profiles. Prominent within the cytoplasm of many supraependymal cells were lysosomes, smooth and coated vesicles suggesting pinocytosis, subplasmalemma vacuoles, and occasional lipid droplets. The morphological characteristics of neonatal supraependymal cells suggested they were mononuclear phagocytes. Adult supraependymal cells exhibited more pleomorphic cell shapes with numerous cell processes, varying widely in size and shape, and often extending over the ventricular surface for considerable distances. These observations, in combination with previous studies by other investigators, suggest that some adult supraependymal cells may also be phagocytic in nature. The differences in morphology between adult and neonatal supraependymal phagocytes may relate to the differing third ventricle environment between adult and neonates and/or differences in the origin of the phagocytes with age.     

In situ characterization of T lymphocyte subpopulations in leprosy in the mangabey monkey.

Leprosy in the mangabey monkey is an experimental model which is similar both clinically and histologically to human lepromatous leprosy. The immunopathology of these diseases was compared using monoclonal antibodies against T lymphocyte subpopulations in frozen tissue sections with an immunoperoxidase technique. In both mangabey and human lepromatous granulomas OKT4 (or Leu 3a) and Leu 2a cells were scattered among macrophages with greater numbers of Leu 2a as compared with OKT4 (or Leu 3a) cells. The results suggest that from an immunopathological standpoint experimental leprosy in mangabeys will provide a suitable model for the investigation of the pathogenesis of human lepromatous leprosy and for the evaluation of new antileprosy vaccines.     

Immunocytochemical localization of a granuliberin-like peptide in Rana pipiens brain

The histamine-releasing peptide “granuliberin”, originally isolated from the skin of Rana rugosa, was localized by immunofluorescence within nerve cell bodies and fibers in the brain of Rana pipiens. The granuliberin-positive neurons were characterized ultrastructurally by electron microscopic observation of ultrathin sections stained either with immunoperoxidase or with conventional stains. Granuliberin-positive nerve cell bodies were seen throughout the hypothalamus, from the suprachiasmatic area rostrally to the full length of the periinfundibular grey matter caudally. Similarly positive nerve fibers were localized in the hypothalamus radiating upwards to the optic vesicles in the midbrain, extending through the preoptic area into the subpallium in the forebrain, and throughout the white matter surrounding the floor and lateral walls of the fourth ventricle in the brainstem. The granuliberin-positive nerve cells showed the presence of variable numbers of small cytoplasmic neurosecretory granules. Possessing an electron dense elongated core, and measuring 250–350 nm in their largest diameter. The functional significance of a granuliberin-like peptide in neurons of the frog brain is not known.