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Biomedical subjects

R Wallace

Publications and source records attributed to R Wallace.

At least 91 records · Page 5Linked to original sources
PubMed1994

Mycobacterium abscessus pseudoinfection traced to an automated endoscope washer: utility of epidemiologic and laboratory investigation.

After 15 patients had positive cultures for Mycobacterium abscessus without evidence of infection (i.e., pseudoinfection) following endoscopy, retrospective cohort studies of patients undergoing endoscopy and microbiologic sampling of the environment were done to examine potential nosocomial transmission and to identify the source and risk factors for M. abscessus pseudoinfection. In the epidemic period, M. abscessus-positive cultures were significantly more likely to be obtained during bronchoscopy than gastroendoscopy (16/149 vs. 1/860, P < .001) and during procedures using bronchoscopes disinfected in an automated washer rather than by other methods (16/54 vs. 0/95, P < .001). M. abscessus was recovered from the automated washer, the inlet water feeding the washer, and a flexible bronchoscope. Environmental and case-patient isolates had identical large restriction fragment (LRF) patterns of genomic DNA separated by pulsed-field gel electrophoresis. Molecular typing using LRF analysis supported the epidemiologic results and demonstrate the utility of combined epidemiologic and laboratory investigations in nosocomial outbreaks of nontuberculous mycobacteria.

Adult↗
PubMed1994

Contracting for emergency room coverage by rural hospitals.

Obtaining adequate physician availability remains a challenge to many rural communities. To ensure 24-hour emergency room physician coverage, many rural hospitals contracted for emergency room services from out-of-area and/or local physician. Survey findings for 99 rural and rural referral Iowa hospitals addressing the nature, extent, and cost of contracting physician coverage of the emergency room are presented. While nearly two-thirds of the hospitals reported contracting for at least some emergency room coverage, the extent and costs of contracts vary widely. Advantages and disadvantages of contracting for emergency room services are discussed.

Contract Services↗
PubMed1994

Regulation of the sheep beta-lactoglobulin gene by lactogenic hormones is mediated by a transcription factor that binds an interferon-gamma activation site-related element.

Polypeptide and steroid hormones regulate the transcription of milk protein genes in the mammary gland. The promoter sequence motifs and factors through which these hormones mediate their effects in vivo are not clearly defined. Milk protein binding factor (MPBF) is a factor that has recognition sites in the promoters of many milk protein genes including three sites in the promoter of the sheep beta-lactoglobulin (BLG) gene. Mutagenesis of these sites reduced expression of the BLG gene in lactating mammary glands of transgenic mice but did not affect the tissue specificity of the transgene. Furthermore, mutation of all three sites abolished the response of the BLG gene to lactogenic hormones in HC11 mammary cells. Together these results indicate that MPBF mediates the effects of lactogenic hormones in the mammary gland but does not play a role in determining mammary specificity. The similarity between the MPBF binding site and the gamma-interferon activating site suggests that MPBF is related to the STAT family of cytokine-induced transcription factors.

Animals↗
PubMed1993

Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics.

The calicheamicin family of antitumor antibiotics are capable of producing double-stranded DNA breaks at sub-picomolar concentrations. Their potency suggested that the calicheamicins would be excellent candidates for targeted delivery and a hydrazide prepared from the most potent and abundant of the naturally occurring derivative, gamma 1I, was linked to oxidized sugars on CT-M-01, an internalizing anti-polyepithelial mucin antibody. The conjugates retained the immunoreactivity of the unmodified antibody and were specifically cytotoxic toward antigen positive tumor cells in vitro and in vivo. Hydrazide analogues of less potent calicheamicin derivatives were also prepared and conjugated to CT-M-01. Comparison of the therapeutic efficacy of the conjugates against the MX-1 xenograft tumor implanted s.c. in nude mice showed that conjugates of derivatives missing the rhamnose, a sugar residue that is part of the DNA binding region of the drug, were not as promising as antitumor therapies. However, conjugates of two derivatives, alpha 3I and N-acetyl-gamma 1I, in which the rhamnose residue is present but the amino sugar residue of the parent drug is either missing or modified, significantly inhibited tumor growth over a 4-fold dose range and produced long-term tumor-free survivors. Sterically hindering methyl groups adjacent to the disulfide in the linker further increased the therapeutic window of these potent conjugates.

Aminoglycosides↗
PubMed1993

Enhancing the efficiency of transgene expression.

Two strategies for enhancing gene expression in transgenic animals are described with particular reference to targeting expression to the mammary gland. Gene constructs in which the protein-encoding DNA sequences are contained within a genomic segment (comprising most or all of the natural introns of the corresponding gene) are shown to be expressed more efficiently than their intronless counterparts. Secondly, co-integrating an otherwise poorly expressed transgene in the vicinity of an actively expressed transgene can dramatically improve its efficiency of expression.

Animals↗
PubMed1993

Social disintegration and the spread of AIDS--II. Meltdown of sociogeographic structure in urban minority neighborhoods.

An elementary model of sociogeographic network structure in an urban minority community suggests externally applied stress, particularly that which triggers frequent individual or family moves of increasing distance, may cause a sudden 'phase change' resulting in disconnection of previously integrated subgroups from the community. Such 'community meltdown' would seriously disrupt mechanisms for social control, economic opportunity and socialization of youth, while intensifying substance abuse and indiscriminate and frequent sexual activity, particularly among the very young. 'Phase change' of this nature would seem to preclude success of programs to control spread of HIV infection, particularly in heterosexual populations. The possibility is explored that programs of 'community recrystalization' in disintegrated urban area might likewise need to exceed some threshold of investment and organizing activity before becoming effective. However, if supported to levels above threshold, this work implies such programs might have very great impact in a very short time. The possibility of interaction between behavioral pathologies resulting from the initial meltdown and further consequent deterioration in sociogeographic network structure leads to speculation that the threshold for recrystalization may become significantly and progressively greater than for meltdown. Implications of these matters for diffusion of HIV into the general population are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A fractal model of HIV transmission on complex sociogeographic networks: towards analysis of large data sets.

"A paradigm of HIV (human immunodeficiency virus) transmission along very large 'sociogeographic' networks--spatially focused nets of social interaction--is extended to include fractal (dilationally self-similar) structures upon which a metric of 'sociogeographic' distance can be defined.... Techniques are sketched for determining the sociogeographic structure of a large, geographically centered social network, providing a possible empirical basis for predicting forms and rates of spread of the initial, rapid stages of an HIV outbreak for networks not yet infected, and perhaps greatly expanding the utility of routinely collected small-area administrative data sets in the design of mutually reinforcing, multifactorial disease-control strategies."

Communicable Diseases↗
PubMed1993

The coming crisis of public health in the suburbs.

A process of urban decay, coupled with forced displacement and behavioral problems, affecting an increasing number of neighborhoods in large U.S. cities. The resulting social disintegration has intensified a nexus of deviant behaviors and conditions, including substance abuse, that are related to transmission of HIV and resurgence of other contagious diseases. These diseases will diffuse, or are already diffusing, along the transportation hierarchy from larger into smaller central cities, and radially from the central cities into the surrounding areas. A widespread program of urban reform is a critical precondition for the control of contagious disease in the United States. It also is important for housing, social services, housing-related public services, and public health across urban and suburban jurisdictions.

Communicable Disease Control↗
PubMed1992

Rescuing transgene expression by co-integration.

To test whether foreign gene expression can be improved in transgenic mice by manipulating the site of integration, we co-integrated the efficiently expressed sheep beta-lactoglobulin gene with two poorly expressed beta-lactoglobulin-derived hybrid genes encoding human proteins. In each case, we observed a significant improvement in the frequency and level of expression of the hybrid gene. "Rescuing" transgene expression by co-integration may provide a general solution for improving the efficiency of heterologous gene expression in transgenic animals.

Animals↗
PubMed1992

Progressive hind limb paralysis in mice carrying a v-Mos transgene.

To study the function of the protooncogene Mos in mouse brain development we have created a transgenic mouse model system in which an activated form of the gene, the murine retroviral v-Mos gene, is highly overexpressed in the brain. Six transgenic founder animals and mice of one established transgenic line (line TG66) displayed a progressive hind limb paralysis with onset between 18 days and 9 months. The severity of the neurological phenotype correlated with pathological alterations and the degree of v-Mos expression in the brain which varied between individual animals of line TG66. The most striking feature of the brain pathology was the presence of large, abnormal astrocytes in the cerebellum, medulla, thalamus and in the dorsal horn of the spinal cord. These areas also contained shrunken and basophilic neurons whose cytoplasm was abnormally immunoreactive for phosphorylated epitopes of neurofilaments. In addition to neuropathologic changes, these mice also displayed aberrant eye lens differentiation and absence of hair cells in the inner ear. These results establish v-Mos transgenic mice as a model system to study progressive neurodegenerative disease and provide further evidence that the Mos protein-serine/threonine kinase has a function in brain development.

Animals↗
PubMed1992

Vascular endothelial cell antibodies in diabetic patients. Association with diabetic retinopathy.

OBJECTIVE: To determine the incidence of antiendothelial cell antibodies in diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS: The study consisted of 70 insulin-dependent diabetic (IDDM) subjects, 36 non-insulin-dependent diabetic (NIDDM) subjects, and 40 nondiabetic control subjects. Blood samples were obtained from diabetic patients and control subjects and patients with background and proliferative retinopathy were identified. RESULTS: Vascular endothelial cell (VEC) antibodies were examined in the sera of 36 NIDDM subjects, 70 IDDM subjects, and 40 nondiabetic control subjects by indirect immunofluorescence. VEC antibodies were present in 5 of 40 (12%) control subjects, 7 of 23 (30%) newly diagnosed IDDM patients, 6 of 17 (35%) IDDM patients without retinopathy, 12 of 18 (67%) IDDM patients with background retinopathy (P less than 0.05), and 9 of 12 (75%) IDDM patients with proliferative retinopathy (P less than 0.01). Three of 13 (23%) NIDDM patients with retinopathy and 6 of 23 (26%) without retinopathy were VEC antibody positive. No associations were observed between the presence of VEC antibodies and either the quality of glycemic control or the duration of diabetes. A significant association between VEC antibodies and large-vessel disease was found in IDDM patients with retinopathy (P less than 0.05). CONCLUSIONS: Antibodies directed against vascular endothelial cells may play a role in the development of microvascular, and possibly macrovascular, disease in diabetes.

Adult↗
PubMed1991

Prospective study of radial bone mineral density in a geographically defined population of postmenopausal Caucasian women.

The radial bone mineral density (BMD) mass of 324 Caucasian women, aged 55-80 years, from geographically defined areas was evaluated in 1983 using single photon absorptiometry; 271 of these women (86%) were reexamined 5 years later in 1988. More than 65% of women lost radial BMD in excess of 1%/year in the 5-year follow-up. Thirty percent of women lost at least 2%/year. Baseline radial BMD measures taken in 1983 were highly predictive of the 1988 radial BMD values, explaining approximately 82% of the variability. The rate of bone change, expressed as percent change or 5-year difference (g/cm2), was not associated with baseline radial BMD value. Rate of change was not strongly associated with chronologic age or years since menopause, even when data were restricted to those women who reported no previous use of perimenopausal estrogen or thiazide medication. We conclude that BMD loss in a general population may be more substantial than previously believed.

Absorptiometry, Photon↗
PubMed1991

Social disintegration and the spread of AIDS: thresholds for propagation along 'sociogeographic' networks.

Previous work on the asymptotic spread of HIV infection along a low dimensional 'sociogeographic' network--a social network characteristically embedded within a limited geographic area--is extended to explore threshold conditions under which the infection extends widely beyond an initial set of infected individuals or communities. Results for one dimension suggest that threshold behavior is analogous to a chain reaction with criticality determined conjointly by the susceptibility of individuals within a community to a nexus of behavior conducive to rapid HIV spread and by the probability of transmission between susceptible communities. Once threshold is exceeded, a stochastic reformulation finds the asymptotic rate of transmission between communities may be markedly raised by positive correlation between susceptibility to rapid disease spread within a community and the transmissibility between communities, for example outmigration driven by social disintegration or residential instability arising from inherent structural factors associated with community susceptibility, as with male prostitution. Examination of threshold conditions for higher dimensional sociogeographic networks most likely characteristic of disease spread beyond the 'deep ghettos' now suffering the highest burden of infection suggests it is at least as, and likely more, effective to decrease the fraction of population susceptible to the high risk behavioral nexus as it is to lower the probability of disease transmission between susceptible individuals or communities.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Traveling waves of HIV infection on a low dimensional 'socio-geographic' network.

Observation of an essentially linear growth in time of U.S. and New York City AIDS cases, from about 1984 through early 1988, is shown to imply a relatively constant rate of transmission of HIV infection in its early stages, as has been observed for limited times in cohorts of male homosexuals in San Francisco and New York City. Observation by Potterat et al. of an exceptionally close intertwining of spatial and social patterns of endemic gonorrhea within a minority population, coupled with a percolation process model of HIV transmission within geographically constrained social networks, leads to inference that a constant rate of HIV transmission, in turn, implies a 'surface growth' phenomenon resulting in a traveling wave of infection advancing at a fixed 'velocity' along a 'one dimensional socio-geographic network.' Implications of this view are discussed for both data collection and analysis, and for intervention. Differences for the processes of disease transmission and control, based on the relative stability of socio-geographic networks, are postulated between the ghettoes of the middle-class male homosexual community and the physically devastated and socially distintegrated ghettoes of the minority urban poor.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Utility of the polymerase chain reaction (PCR) for prenatal diagnosis of genetic disease.

Gene amplification by the polymerase chain reaction (PCR) has been applied to prenatal diagnosis for alpha and beta thalassemias (1 and 5 cases respectively), Hemoglobin (Hb) Lepore/beta thalassemia (1 case) and cystic fibrosis (14 cases). Chorionic villus samples were obtained in the tenth week of pregnancy and DNA analysed in parallel with conventional gene mapping. Direct diagnosis of the common Mediterranean beta-thalassemia mutations (IVS-1-110 and codon 39), Hb Lepore, and the delta F508 mutation causing cystic fibrosis was achieved by hybridization of amplified material with pairs of allele-specific oligonucleotide (ASO) probes or by restriction enzyme digestion of PCR products. Results were confirmed by DNA mapping. Definitive diagnosis or exclusion of an affected fetus was possible in 17 of 21 cases thus examined. PCR reduces the time required for prenatal diagnosis. DNA contamination is a potential source of error.

Alleles↗