Virilism as a late manifestation in the Bardet-Biedl syndrome

The second case of virilism as a late manifestation of Bardet-Biedl syndrome (BBS) is described, with endocrine and histological evaluation. Both cases manifested ovulatory cycles and developed virilism in adulthood. Elevated plasma testosterone and 17-OH-progesterone were not suppressed by dexamethasone but were suppressed by medroxyprogesterone acetate. Peripheral and ovarian venous blood obtained at the time of surgery demonstrated a marked gradient for testosterone in both ovaries and for progesterone in the ovary bearing the corpus luteum. Histological evaluation of the ovaries demonstrated bilateral ovarian stromal hyperplasia with focal hyperthecosis. Bilateral ovariectomy resulted in complete correction of the endocrine abnormality, although the established hirsutism remains a mark of previous androgen excess.     

Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation of recent human parainfluenza virus type 2 isolates.

A panel of fourteen neutralizing anti-HN monoclonal antibodies (mAbs) to the prototype Greer strain of human parainfluenza virus type 2 (PI2) was used to determine the extent of antigenic variation in recent virus isolates. Competitive binding analysis with the mAbs indicated the presence of at least five distinct antigenic sites (I to V) on the HN glycoprotein molecule. MAbs recognizing different antigenic sites were found to be associated with the hemagglutinin (sites I, IV and V), hemagglutinin and neuraminidase (site II), or neuraminidase (site III) activities. The location of two distinct epitopes identifying the neuraminidase sites (II and III) was further verified from the generation of escape mutants. Antibodies directed to sites I and III failed to show any detectable binding or neutralizing activity against a number of natural PI2 virus isolates collected in Texas between 1986 and 1987. Interestingly, these natural variants, unlike the prototype virus, did not show any detectable neuraminidase activity with fetuin as a substrate and the enzyme activity was only detected with N-acetylneuramin-lactose as an alternative substrate. Despite the observed variation in the antigenic sites, primary infection with the prototype virus or the natural variants generated a protective immune response against challenge infection with the other virus strains.     

Effects of placentation on selected type A behaviors in adult males in the national heart,lung, and blood institute (NHLBI) twin study

A dermatoglyphic index derived from monozygotic (MZ) twins of known placental type was used to estimate placentation retrospectively in a sample of adult male MZ twins. Examination of behavioral test scores with respect to placentation showed that the within-pair difference of most measures of type A behavior was smaller in presumed monochorionic than presumed dichorionic pairs. Measures of cognitive function and hostility were not related to placental type. Intraclass correlations in the monochorionic subgroup of MZ twins were greater than the correlations reported for the full sample of MZ twins. The trends were strongest for the Adjective Check List scales taken at two different exams 5 years apart and, to a lesser extent, for the Framingham type A scale. Our results are most consistent with greater intrauterine environmental covariance in monochorionic MZ twins as an explanation for inflation of the MZ twin correlation relative to dizygotic (DZ) correlation reported for some type A measures.     

Molecular cloning and sequence analysis of the fusion glycoprotein gene of human parainfluenza virus type 2

A cDNA clone containing a 2.0-kb insert was identified as the human parainfluenza virus type 2 (PI2) fusion glycoprotein gene by hybridizing with a viral RNA probe and a synthetic oligonucleotide derived from a conserved sequence found in other paramyxovirus fusion protein genes. The complete nucleotide sequence of the glycoprotein gene was determined by the dideoxynucleotide sequencing procedure and found to contain a single, large open reading frame encoding a protein of 551 amino acids with a calculated molecular weight of 59,664. Comparison of the P12 fusion protein with those of other paramyxoviruses indicated similarities in overall length, N-terminal signal peptide sequence (amino acids 7 to 25), C-terminal membrane-spanning region (amino acids 486 to 513), and a highly conserved fusion sequence region at the N-terminus of the F1 subunit (amino acids 107 to 132).     

Frequent deletions in nine newly immortal human cell lines.

Nine newly immortal lines of human fibroblasts transfected with SV40 T antigen were examined for recurrent chromosome losses. In order of decreasing frequency, all nine lines had three or more of the following minimal deletions specifically associated with the immortalization event: del(6)(q21), del(3)(p24), del(1)(p34), del(4)(p25), del(5)(p14), del(11)(p11), del(11)(q14), del(12)(p12), and del(14)(p?). Many other chromosome changes were not clearly associated with immortalization, but were acquired during other stages of this multistep model of neoplastic transformation. We propose that these chromosome loci associated with immortalization are candidates for the location of genes involved in cellular senescence.     

Biodegradation studies on periodate oxidized cellulose

Sodium periodate oxidized cellulose was found to degrade into small molecules when implanted subcutaneously in rats. Thus the potentiality of using oxidized cellulose as a biodegradable drug carrier is envisaged.     

Replacing the academic medical center's teaching hospital.

Addressing the need for updated teaching hospital facilities is one of the most significant issues that an academic medical center faces. The authors describe the process they underwent in deciding to build a new facility at the Medical University of South Carolina (MUSC). Initial issues included whether or not the teaching hospital would continue to play a role in clinical education and whether to replace or renovate the existing facility. Once the decision to build was reached, MUSC had to choose between an on-campus or distant site for the new hospital and determine what the function of the old hospital would be. The authors examine these questions and discuss the factors involved in different stages of decision making, in order to provide the academic medicine community guidance in negotiating similar situations. Open communication within MUSC and with the greater community was a key component of the success of the enterprise to date. The authors argue that decisions concerning site, size, and focus of the hospital must be made by developing university-wide and community consensus among many different constituencies. The most important elements in the success at MUSC were having unified leadership, incorporating constituent input, engaging an external consultant, remaining unfazed by unanticipated challenges, and adhering to a realistic, aggressive timetable. The authors share their strategies for identifying and successfully managing these complex and potentially divisive aspects of building a new teaching hospital.     

Scanning electron microscopic characterization of healing and normal rat ligament microstructure under slack and loaded conditions

The objective of this study was to observe and compare behavior of the collagen fiber microstructure in normal and healing ligaments, both in situ and ex vivo, in order to add insight into the structure-function relationship in normal and healing ligaments. Fifty-two ligaments from 26 male rats were investigated. Eleven animals underwent surgical transection of both medial collateral ligaments (MCLs) (22 ligaments), which were allowed to heal for a period of 2 weeks. An additional 15 animals (30 ligaments) were used as normals. Ligaments were placed into six groups: Slack (n = 6 control, n = 6 healing), Reference (n = 4 control, n = 4 healing), Loaded (n = 4 control, n = 4 healing), 15 degrees Flexion (n = 4 control, n = 4 healing), 120 degrees Flexion (n = 4 control, n = 4 healing), and Tissue Strain vs. Flexion Angle (n = 8 normals). All ligaments, except those in the Tissue Strain vs. Flexion Angle group, were prepared for scanning electron microscopy. Tissues were harvested, mounted in a load frame, and chemically fixed in one of five states: (1). slack, (2). reference (onset of loading), (3). loaded, (4). 15 degrees knee flexion, or (5). 120 degrees knee flexion. After fixation the tissues were prepared for electron microscopy (SEM). The micrographs from the slack, reference, and loaded groups show fiber straightening with loading in normal ligaments as well as in both scar and "retracted" regions of healing ligaments. Collagen fibers' diameter and crimp patterns were dramatically changed in the scar region of healing ligaments: Width decreased from 19.4 +/- 1.7 microm to 6.5 +/- 2.1 microm (p <.000001), period from 51.4 +/- 15.1 microm to 11.0 +/- 2.4 microm (p <.000001), and amplitude from 9.8 +/- 0.8 microm to 3.9 +/- 0.8 microm (p <.000001). Normal ligaments fixed in situ show wavy regions at 120 degrees but less so at 15 degrees flexion. Healing ligaments fixed in situ show regions of fiber waviness in the scar region at 120 degrees and also at 15 degrees flexion, indicating ligament laxity persists toward both extremes of the range of motion. The data suggest that straightening of crimped fibers is a functionally relevant phenomenon, not only in normal but also in healing ligaments.     

Hepatitis C virus core protein modulates the interferon-induced transacting factors of Jak/Stat signaling pathway but does not affect the activation of downstream IRF-1 or 561 gene

Hepatitis C virus (HCV) has a propensity to cause chronic infection, with a low proportion of patients exhibiting a sustained response to interferon-alpha (IFNalpha) therapy. An earlier report suggested that HCV inhibits IFNalpha-induced signal transduction through the Jak/Stat pathway by preventing the formation of the transacting factor ISGF3 complex, although the effect on downstream pathway and the specific viral protein responsible for inhibition of IFNalpha-mediated signal transduction were not elucidated. HCV core protein displays a number of intriguing functional properties and has been implicated in virus-mediated pathogenesis. In this study, we have analyzed the effect of core protein upon IFNalpha- or IFNgamma-induced regulation of the Jak/Stat signaling pathway. HCV core protein expression exhibited a reduced Stat1 expression in IFN-treated mammalian cells. A gel retardation assay suggested a reduced level of formation of the transacting factors, GAF and ISGF3, in IFN-treated cells. Further studies from protein expression and RNase protection assay revealed that the reduced level of GAF or ISGF3 formation could be attributed to modulation of Stat1 protein expression, an important player for innate immunity in host defense mechanism. However, these modulatory effects did not interfere with the activation of the downstream effector genes, IRF-1 and 561, in IFN-treated cells. Stable transfectants of cells after introduction of a plasmid DNA encoding both the structural and the nonstructural proteins of HCV also exhibited a similar effect. Taken together, these results suggest that although expression of the core protein alone or with other HCV proteins modulate transacting factors of Jak/Stat signaling pathway, expression of the downstream effector genes IRF-1 and 561 remains unaffected upon IFN treatment and may contribute to host defense mechanism.