Biomedical subjects
J Morrissey
Publications and source records attributed to J Morrissey.
Modern Healthcare celebrates the 25th anniversary of the magazine's ownership by Crain Communications.
In many ways it's been a quarter-century of change. But in some ways it's been just the opposite. To mark Modern Healthcare's silver anniversary under its current ownership, the magazine's staff took a trip through time, looking at pivotal events in healthcare during the past 25 years and the people who helped shape the industry.
S.C. docs sue feds on privacy regs.
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One small step on privacy. HHS action addresses some provider concerns.
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Wanting more from information technology. But smaller budgets force providers to revise their expectations.
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Outlook 2001. Depending on whom you work for, there's good news and bad news.
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Linking clients to clinical and social services.
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CD antigens 2001.
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p21(WAF1) and transforming growth factor-alpha mediate dietary phosphate regulation of parathyroid cell growth.
BACKGROUND: The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P reduces while low P enhances serum 1,25-dihydroxyvitamin D, whose potent antiproliferative properties result from the induction of p21. In addition to reducing p21, high P-induced PT growth could result from increased PT expression of the growth promoter transforming growth factor-alpha (TGF-alpha), known to be elevated in hyperplastic and adenomatous human PT glands. METHODS: The time course for dietary P regulation of PT expression of TGF-alpha and p21 was assessed for seven days after 5/6 nephrectomy in rats and correlated with the degree of PT hyperplasia and secondary hyperparathyroidism. RESULTS: In P-restricted 5/6 nephrectomized rats, PT-p21 mRNA and protein increased by day 2, independent of changes in serum 1,25-dihydroxyvitamin D, and remained higher than in the high P counterparts for up to seven days. The PT hyperplasia of the high P group could not be attributed to a reduction of PT-p21 expression from normal control values. Instead, PT-TGF-alpha protein was higher in uremic rats compared with normal controls and increased further with high dietary P intake. PT levels of proliferating cell nuclear antigen (PCNA), an index of cell mitoses, correlated inversely with p21 and directly with TGF-alpha. Consistent with these findings, PT gland size and serum PT hormone levels, similar in both dietary groups at day 2, were higher in the high P group by day 5. Induction of p21 by low P and of TGF-alpha by high P was specific for the PT glands. Dietary P had no effect either on intestinal growth or p21 or TGF-alpha protein content. CONCLUSIONS: These findings suggest that low P induction of p21 could prevent PT hyperplasia in early uremia, whereas high P enhancement of TGF-alpha may function as an autocrine signal to stimulate growth further.
Susceptibility testing of Aspergillus flavus: inoculum dependence with itraconazole and lack of correlation between susceptibility to amphotericin B in vitro and outcome in vivo.
We have attempted to validate in Aspergillus flavus the main in vitro methodologies that have been used to detect resistance in Aspergillus fumigatus. We developed a murine model with two A. flavus isolates, one that was apparently resistant in vitro to amphotericin B (AFL5) and another that was resistant to itraconazole (AFL8). No correlation was found for amphotericin B in AFL5, since the in vivo response was compatible with a susceptible isolate. Modification of the in vitro susceptibility test methodology for amphotericin B was unsuccessful. Although AFL8 was apparently resistant to itraconazole in vitro, it was found to be susceptible in vivo. Additional in vitro work has detected weaknesses in the in vitro susceptibility methodology validated for A. fumigatus when applied to A. flavus. The principal problems are that changes in the inoculum have a large effect on the MICs of itraconazole for some A. flavus strains and that a trailing end point and spore sediment often appear when an inoculum with a higher colony count is used. We propose a modified method using a final inoculum of 2.5 x 10(4) CFU per ml of RPMI 1640 medium with 2% glucose buffered to pH 7.0 in a microtiter format, incubated for 48 h with no growth end point. Validation of this methodology requires one or more itraconazole-resistant A. flavus isolates, which have yet to be identified.
agr expression precedes escape of internalized Staphylococcus aureus from the host endosome.
Staphylococcus aureus is a versatile pathogen capable of causing life-threatening infections. Many of its cell wall and exoproduct virulence determinants are controlled via the accessory gene regulator (agr). Although considered primarily as an extracellular pathogen, it is now recognized that S. aureus can be internalized by epithelial and endothelial cells. Traditional experimental approaches to investigate bacterial internalization are extremely time-consuming and notoriously irreproducible. We present here a new reporter gene method to assess intracellular growth of S. aureus in MAC-T cells that utilizes a gfp-luxABCDE reporter operon under the control of the Bacillus megaterium xylA promoter, which in S. aureus is expressed in a growth-dependent manner. This facilitates assessment of the growth of internalized bacteria in a nondestructive assay. The dual gfp-lux reporter cassette was also evaluated as a reporter of agr expression and used to monitor the temporal induction of agr during the MAC-T internalization process. The data obtained suggest that agr induction occurs prior to endosomal lysis and that agr-regulated exoproteins appear to be required prior to the release and replication of S. aureus within the infected MAC-T cells.
Contributions of angiotensin II and tumor necrosis factor-alpha to the development of renal fibrosis.
Angiotensin II upregulates tumor necrosis factor-alpha (TNF-alpha) in the rat kidney with unilateral ureteral obstruction (UUO). In a mouse model of UUO, we found that tubulointerstitial fibrosis is blunted when the TNF-alpha receptor, TNFR1, is functionally knocked out. In this study, we used mutant mice with UUO in which the angiotensin II receptor AT(1a) or the TNF-alpha receptors TNFR1 and TNFR2 were knocked out to elucidate interactions between the two systems. The contribution of both systems to renal fibrosis was assessed by treating TNFR1/TNFR2-double knockout (KO) mice with an angiotensin-converting enzyme inhibitor, enalapril. The increased interstitial volume (Vv(int)) in the C57BI/6 wild-type mouse was decreased in the AT(1a) KO from 32.8 +/- 4.0 to 21.0 +/- 3.7% (P < 0.005) or in the TNFR1/TNFR2 KO to 22.3 +/- 2.1% (P < 0.005). The Vv(int) of the TNFR1/TNFR2 KO was further decreased to 15.2 +/- 3.7% (P < 0.01) by enalapril compared with no treatment. The induction of TNF-alpha mRNA and transforming growth factor-beta1 (TGF-beta1) mRNA in the kidney with UUO was significantly blunted in the AT(1a) or TNFR1/TNFR2 KO mice compared with the wild-type mice. Treatment of the TNFR1/TNFR2 KO mouse with enalapril reduced both TNF-alpha and TGF-beta1 mRNA and their proteins to near normal levels. Also, alpha-smooth muscle actin expression and myofibroblast proliferation were significantly inhibited in the AT(1a) or TNFR1/TNFR2 KO mice, and they were further inhibited in enalapril-treated TNFR1/TNFR2 KO mice. Incapacitating the angiotensin II or the TNF-alpha systems individually leads to partial blunting of fibrosis. Incapacitating both systems, by using a combination of genetic and pharmacological means, further inhibited interstitial fibrosis and tubule atrophy in obstructive nephropathy.
CD antigens 2001: aims and results of HLDA Workshops.
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Service delivery and community: social capital, service systems integration, and outcomes among homeless persons with severe mental illness.
OBJECTIVES: This study evaluated the influence of features of community social environment and service system integration on service use, housing, and clinical outcomes among homeless people with serious mental illness. STUDY SETTING: A one-year observational outcome study was conducted of homeless people with serious mental illness at 18 sites. DATA SOURCES: Measures of community social environment (e.g., social capital) were based on local surveys and voting records. Housing affordability was assessed with housing survey data. Service system integration was assessed through interviews with key informants at each site to document interorganizational transactions. Standardized clinical measures were used to assess clinical and housing outcomes in face-to-face interviews. RESEARCH DESIGN: Structural equation modeling was used to determine the relationship between (1) characteristics of the social environment (social capital, housing affordability); (2) the level of integration of the service system for persons who are homeless in each community; (3) access to and use of services by individual clients; and (4) successful exit from homelessness or clinical improvement. PRINCIPAL FINDINGS: Social capital was associated with greater service systems integration, which was associated in turn with greater access to assistance from a public housing agency and to a greater probability of exiting from homelessness at 12 months. Housing affordability also predicted exit from homelessness. Neither environmental factors nor systems integration predicted outcomes for psychiatric problems, substance abuse, employment, physical health, or income support. CONCLUSION: Community social capital and service system integration are related through a series of direct and indirect pathways with better housing outcomes but not with superior clinical outcomes for homeless people with mental illness. Implications for designing improved service systems are discussed.
CD antigens 2001.
This paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of "blind" antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed.
A job for the top dogs. HIPAA compliance being driven by senior healthcare managers, new survey finds.
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