Biomedical subjects
Publications and source records attributed to S Becker.
The article provides a concise review of the critical business and legal characteristics of recent health care-driven initial public offerings. In that regard, the article examines three recent provider-driven companies that have effectuated initial public offerings, and reviews certain of their business fundamentals and the manner in which each handled various legal disclosure issues.
To evaluate the completeness of registration of infant and child deaths in Egypt, reinterviews were conducted with families who had reported a death of a child under age 5 in the five years before the survey for two national surveys recently conducted in Egypt: the United Nations PAPCHILD survey of 1990-1991 and the Egyptian Demographic and Health Survey (EDHS) of 1992. The survey instrument included questions regarding notification of the death at the local health bureau. If the family said the death had been notified, separate employees searched the health bureau records for the registration. Overall 57% of infant deaths were reported as notified and 68% of those death reports were found; the corresponding figures for child death were 89% and 74%. Using the percentage reported as notified as an estimate for completeness of registration, we adjusted upward the national infant and child mortality rates from registration data, giving values of 73 per 1,000 for infant mortality and 99 for 5qo for the period 1987-1990. These values are approximately 20% above the corresponding direct estimates from the PAPCHILD and EDHS surveys.
Hospitals are increasingly attempting to integrate their operations with physician constituents through the development of hospital-physician joint ventures and acquisition of physician practices. This article provides an overview of valuation-related issues that result with respect to such affiliation efforts and guidance to assist the health care financial and legal professional in resolving such issues consistent with the business objectives of the transaction parties.
The glycoprotein gene of Ebola virus contains a translational stop codon in the middle, thus preventing synthesis of full-length glycoprotein. Twenty percent of the mRNA isolated from Ebola virus-infected cells was shown to be edited, containing one additional nontemplate A in a stretch of seven consecutive A residues. Only the edited mRNA species encoded full-length glycoprotein, whereas the exact copies of the viral template coded for a smaller secreted glycoprotein. Expression of the glycoprotein by an in vitro transcription/translation system, by the vaccinia virus/T7 polymerase system, and by recombinant vaccinia virus revealed that full-length glycoprotein was synthesized not only when the edited glycoprotein gene (8A's) was used as a template for T7 and vaccinia virus polymerases, but also when the nonedited (genomic) glycoprotein gene was used. Analysis of mRNA produced by T7 and vaccinia virus polymerase from the 7A's construct revealed that 1-5% contained alterations at the same site that was also edited by the Ebola virus polymerase. Our data indicate that the editing site in the Ebola virus glycoprotein gene is recognized not only by Ebola virus polymerase but also by DNA-dependent RNA polymerases of different origin.
The glucose 1-phosphate (Glc-1-P) analog alpha-D-glucose 1-methylenephosphonate (Glc-1-MeP) inhibits competitively Escherichia coli maltodextrin phosphorylases against Glc-1-P (Ki = 0.20 mM) but also Pi (Ki = 0.36 mM). Exchange of the active site residue Glu637 to Asp by site-directed mutagenesis abolishes inhibition only in the synthesis direction (S-mode), while the degradative direction (P-mode) was not affected. Structural and conformational differences of the S-mode versus P-mode were also revealed by 31P-NMR spectroscopy by comparing chemical shifts of the cofactor pyridoxal-P in binary complexes formed either in the presence of Glc-1-MeP or of arsenate. In contrast the apparent pK of pyridoxal-P in both binary complexes was closely similar. Again, the total chemical shift of pyridoxal-P in the synthesis mode respectively degradative mode was differently affected in the binary complexes of the Glu637Asp mutant enzyme. This supports the contention that differential binding of the substrates in the synthesis or the degradative mode changes the arrangement and mutual interactions of cofactor phosphate and substrate phosphates.
The surface protein of Marburg virus (GP) is modified by acylation, as shown by labeling with [3H]myristic and [3H]palmitic acid. Acylation of GP also occurred when it was expressed in insect cells with the baculovirus expression system. Gas chromatographic analyses of the bound fatty acids indicated that exogenously added [3H]myristic acid was partly metabolized to palmitic and stearic acid. To elucidate the nature of the fatty acid bond, [3H]palmitic acid-labeled GP was treated with mercaptoethanol. Since the fatty acids were removed by this treatment, it is concluded that the linkage is of the thioester type. A putative attachment site for thioester-linked fatty acids consisting of two cysteine residues located between the transmembrane anchor and the carboxy-terminal cytoplasmic tail of GP (Cys671 and Cys673) could be identified. Site-directed mutagenesis of these two amino acids to alanine residues clearly demonstrated that both cysteines could serve as acylation sites.
OBJECTIVE: In recent years we have treated 4 rheumatoid arthritis (RA) patients who developed gold-induced enterocolitis, a well-recognized, although rare, complication of chrysotherapy. The aim of the present study was to seek any genetic predisposition for this complication. METHODS: HLA DNA typing was done on fresh white blood cells from the 4 patients. RESULTS: Three of the 4 patients (75%) exhibited the DRB1*0404 allele, whereas the prevalence of this allele among the Ashkenazi Jewish population of RA patients without colitis was 9.2% and 10.2% in 2 different studies. CONCLUSION: The results indicate that the DRB1*0404 may be associated with risk for the development of gold-induced enterocolitis in this population and suggest that HLA DNA typing should be considered in Jews who may be undergoing chrysotherapy.
Proteins expressed specifically in neurons and transported to synaptic terminals are likely to constitute important molecular elements of nervous system function. In an effort to characterize synapse-associated proteins (SAPs) of Drosophila, we have isolated from a hybridoma library several monoclonal antibodies (MABs) that selectively stain synaptic terminals in immunohistochemical preparations. MAB nc46 binds to most but not all synaptic terminals of the Drosophila nervous system, it also recognizes a protein with homologous distribution in other dipteran flies and binds to large parts of fish CNS. In Western blots the antibody labels a Drosophila brain protein of 47 kDa and cross-reacts with brain proteins from several species including insects, fish, mouse and man. From these data we conclude that the corresponding gene has been conserved in evolution at least among diptera. Using MAB nc46 and expression cloning we have identified the 'sap47' gene coding for the 'synapse-associated protein of 47 kDa' of Drosophila melanogaster. Sequence analysis of genomic and cDNA clones reveals the intron-exon structure of the gene and characterizes the complete open reading frames of two alternatively spliced transcripts. The sap47 gene is located in 89A8-B3 on chromosome 3R and codes for two almost identical inferred polypeptides of 347 and 351 amino acids with no significant sequence homology to known proteins.
Factor (F) VIII inhibitor development remains one of the most serious complications in the treatment of hemophilia A. Former and recent studies on inhibitor development revealed that patients with severe hemophilia A and positive inhibitor family history are at highest risk of developing an inhibitor. Comparison of recent inhibitor incidence studies on previously untreated patients indicate that the risk of inhibitor development under treatment with recombinant FVIII concentrates is comparable to the inhibitor incidence under FVIII substitution by plasma-derived concentrates. However, longer observation periods are necessary to draw final conclusions. Since inhibitor development may result in inefficacy of FVIII concentrates in the treatment of severe bleedings, the induction of immune tolerance (IT) is still of main concern. Various regimens to induce IT by application of FVIII concentrates have been conducted up to now. Success rate appears to be influenced by low to high responder status, number of exposure days before onset of treatment, and dosage of therapeutic regimen. Especially, discontinuation of IT therapy seems to be associated with failure of therapy. Taking into account available data on IT therapy, we recommend early onset of a high dosage regimen in high responder patients as soon as possible after inhibitor detection, as this is associated with higher success rate and shorter elimination time.
Children in a day care center underwent serial nasal lavages in order to assess nasal cytokine expression during acute upper respiratory infections (URI). Interleukin (IL)-1 beta, IL-8, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were markedly elevated in nasal lavage fluid during acute URI compared to baseline, and all except TNF-alpha decreased significantly by 2-4 weeks later. Cytokine patterns in respiratory syncytial virus-positive and -negative illnesses did not differ significantly. A subgroup of children also underwent superficial mucosal biopsy under the inferior nasal turbinate. During acute URI, biopsy cells (90%-95% epithelial) showed increased transcripts for IL-1 beta, IL-8, and IL-6 in 7 of 9 subjects, suggesting that epithelial cells may be one source of cytokines during acute URI. The results show that inflammatory cytokines are elevated in nasal secretions during acute URI in preschool children. Thus, cytokines are likely to participate in regulation of respiratory virus-induced inflammation.
We evaluated the efficacy of an oral formulation of 5-amino-salicylic acid in lowering the relapse rate after remission of Crohn's disease. Included were 59 patients who had proven Crohn's disease of at least 1 year's duration, and who had been in continuous remission for at least 6 months, while taking only 5-aminosalicylic acid or no therapy at all. Remission was defined as a Harvey Bradshaw index score (Softley-Clamp modification) of < 4. Patients were given coded mesalzaine 250 mg or placebo tablets (2 x 2 day). They were seen at 0, 1, and 2 months, and then every 2 months until the end of the study. Trial endpoints were 1 year of follow-up, or clinical relapse results. After randomization, 31 patients were included in the placebo arm, and 28 in the treatment arm. There were no significant differences between the two groups at entry. Ten patients were withdrawn from the trial because of noncompliance, loss of follow-up, or headache. There were more clinical relapses in the placebo arm (15 patients, 55%) than in the treatment arm (6 patients, 27%) (p < 0.05). Mesalazine had a significant advantage over placebo (p < 0.05) only in the subgroups of patients with ileal Crohn's disease and in those older than 30 years. We conclude that mesalazine has a moderate but significant benefit in preventing relapse in Crohn's disease in remission; this occurred only in patients with small-bowel involvement or in those older than 30 years.
Markers of bone formation determined in serum include alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin [bone gamma-carboxyglutamic acid peptide (BGP) and procollagen type I carboxyterminal propeptide. Recently, advances have been made in the immunoassay of bone-specific alkaline phosphatase. This is a marker for osteoblastic activity; it is very stable and is not primarily dependent on kidney function because it is degraded in the liver. BGP is not specific for bone formation because it increases in serum during bed rest (which involves increased bone resorption), and it is not stable. Furthermore, the elimination of BGP is dependent on glomerular filtration rate. Procollagen type I carboxyterminal propeptide is not as sensitive as bone-specific alkaline phosphatase because it increases less in women after the menopause. Urinary pyridinoline and deoxypyridinoline determined by high-performance liquid chromatography are regarded as the best methods for measuring bone resorption. These might be replaced by type I collagen crosslinked N-telopeptide or CrossLaps in the future in laboratories not equipped with a high-performance liquid chromatography system. Serum markers of bone resorption are currently under investigation. An immunoassay for the tartrate-resistant acid phosphatase in serum should be a very promising tool for the quantification of bone resorption.
The liver is one of the main target organs of Marburg virus (MBG), a filovirus causing severe haemorrhagic fever with a high fatality rate in humans and non-human primates. MBG grown in certain cells does not contain neuraminic acid, but has terminal galactose on its surface glycoprotein. This observation indicated that the asialoglycoprotein receptor (ASGP-R) of hepatocytes may serve as a receptor for MBG in the liver. Binding studies revealed that the attachment of MBG to ASGP-R-expressing HepG2 cells, but not to ASGP-R-negative E6 Vero cells, has the characteristics of ligand binding to the ASGP-R: binding is dependent on calcium and is inhibited by excess asialofetuin and by anti-ASGP-R antiserum. Asialofetuin and the specific antiserum also inhibited MBG infection of HepG2 cells. In addition, it was shown that expression of ASGP-R cDNA in NIH 3T3 cells enhanced the susceptibility of these cells to MBG infection 4.5-fold. Interaction of MBG with the hepatic ASGP-R could thus explain the marked hepatotropism of the virus.
The cdc25 gene product is a tyrosine phosphatase that acts as an initiator of M-phase in eukaryotic cell cycles by activating p34cdc2. Here we describe the cloning and characterization of the developmental expression pattern of two mouse cdc25 homologs. Sequence comparison of the mouse genes with human CDC25 genes reveal that they are most likely the mouse homologs of human CDC25A and CDC25B respectively. Mouse cdc25a, which has not been described previously, shares 84% sequence identity with human CDC25A and has a highly conserved phosphatase domain characteristic of all cdc25 genes. A glutathione-S-transferase-cdc25a fusion protein can hydrolyze para-nitro-phenylphosphate confirming that cdc25a is a phosphatase. In adult mice, cdc25a transcripts are expressed at high levels in the testis and at lower levels in the ovary, particularly in germ cells; a pattern similar to that of twn, a Drosophila homolog of cdc25. Lower levels of transcript are also observed in kidney, liver, heart and muscle, a transcription pattern that partially overlaps, but is distinct from that of cdc25b. Similarly, in the postimplantation embryo cdc25a transcripts are expressed in a pattern that differs from that of cdc25b. cdc25a expression is observed in most developing embryonic organs while cdc25b expression is more restricted. An extended analysis of cdc25a and cdc25b expression in preimplantation embryos has also been carried out. These studies reveal that cdc25b transcripts are expressed in the one-cell embryo, decline at the two-cell stage and are re-expressed at the four-cell stage, following the switch from maternal to zygotic transcription which mirrors the expression of string, another Drosophila homolog of cdc25. In comparison, cdc25a is not expressed in the preimplantation embryo until the late blastocyst stage of development, correlating with the establishment of a more typical G1 phase in the embryonic cell cycles. Both cdc25a and cdc25b transcripts are expressed at high levels in the inner cell mass and the trophectoderm, which proliferate rapidly prior to implantation. These data suggest the cdc25 genes may have distinct roles in regulating the pattern of cell division during mouse embryogensis and gametogenesis.
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This article provides a review of factors that influence a managed care entity's choice of a provider of outpatient surgical services. In reviewing issues, this article also provides practical guidance to the outpatient surgery center with respect to the pricing and marketing of its services. Finally, the article provides an overview of both business and legal issues relating to managed care contracting choices.
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Studies of in vivo inhalation of nitrogen dioxide (NO2) have demonstrated a transient pulmonary inflammation. This study was done to determine the contribution of airway epithelial cells to the release of inflammatory mediators following NO2 exposure. Confluent cultures of the human bronchial epithelial cell line BEAS-2B on Transwell-Col filters were exposed for 1 h to air or NO2 up to 1.5 ppm with the apical fluids removed with 5% CO2 at 37 degrees C. The cells were hydrated with Hanks' Balanced Salt Solution (HBSS) in the basolateral compartment. Sequential reverse transcription and quantitative cDNA amplification (RT-PCR) was used to measure inflammatory mediator mRNA abundance in BEAS-2B cultures. When compared to air-exposed cells, NO2 induced increases in IL-6 (23.4-fold) and IL-8 (30.9-fold) mRNA abundance. The NO2-dependent increases in mRNA expression reached a maximum between 0 and 1 h post exposure and returned to baseline levels within 24 h. IL-6 and IL-8 proteins as measured by enzyme-linked immunosorbent assays (ELISA) were also elevated in supernatants recovered from NO2-exposed BEAS-2B cells. These studies suggest that exposure to NO2 induces the synthesis and release of inflammatory mediators from airway epithelial cells that may participate in the pathogenesis of airway disease.