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Biomedical subjects

R Wallace

Publications and source records attributed to R Wallace.

At least 19 recordsLinked to original sources
PubMed1996

Lack of association of trinucleotide repeat polymorphisms in very-low-density lipoprotein receptor gene with Alzheimer's disease.

Inheritance of the apolipoprotein E epsilon 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very-low-density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very-low-density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very-low-density lipoprotein receptor gene is strongly associated with AD.

Alleles↗
PubMed1996

Apolipoprotein E and cognitive change in an elderly population.

The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE E4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impair- ment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.

Aged↗
PubMed1996

Engelmann's disease: a 45-year follow-up.

We report a 45-year follow-up of a patient with Engelmann's disease previously described in 1950, showing progression of the disease with unique involvement of the femoral capital epiphyses. The case is compared with others to add some information about the later stages of a disease which is not fully understood.

Aged↗
PubMed1995

Fixing human factor IX (fIX): correction of a cryptic RNA splice enables the production of biologically active fIX in the mammary gland of transgenic mice.

Transgenic mice and sheep secrete only low levels of human factor IX in their milk because of an aberrant splicing of the transgene RNA in the mammary gland. Removal of the cryptic 3' splice site prevents this splicing and leads to the production of relatively high levels of factor IX. The purified protein is fully active showing that the mammary gland is capable of the efficient post-translational modification of this protein and that transgenic animals are a suitable means of its production.

Animals↗
PubMed1995

Microscopic computation in human brain evolution.

When human psychological performance is viewed in terms of cognitive modules, our species displays remarkable differences in computational power. Algorithmically simple computations are generally difficult to perform, whereas optimal routing or "Traveling Salesman" Problems (TSP) of far greater complexity are solved on an everyday basis. It is argued that even "simple" instances of TSP are not purely Euclidian problems in human computations, but involve emotional, autonomic, and cognitive constraints. They therefore require a level of parallel processing not possible in a macroscopic system to complete the algorithm within a brief period of time. A microscopic neurobiological model emphasizing the computational power of excited atoms within the neuronal membrane is presented as an alternative to classical connectionist approaches. The evolution of the system is viewed in terms of specific natural selection pressures driving satisfying computations toward global optimization. The relationship of microscopic computation to the nature of consciousness is examined, and possible mathematical models as a basis for simulation studies are briefly discussed.

Algorithms↗
PubMed1995

Epithelial proliferation and differentiation in the mammary gland do not correlate with cFABP gene expression during early pregnancy.

Cardiac fatty acid binding protein (cFABP) is abundantly expressed in the nondividing, functionally differentiated mammary epithelium. It is very closely related, if not identical to, a previously described protein termed mammary derived growth inhibitor (MDGI). In vitro studies suggest that low concentrations of diffusible cFABP/MDGI may play a hormone-like role in limiting proliferative activity and promoting functional differentiation of this tissue, but no in vivo data to support this idea have been published. To test this hypothesis, we compared the levels of cFABP mRNA with both the epithelial DNA labelling index and levels of beta-casein mRNA in wild-type mice. We also investigated the effect of a precocious experimental increase of cFABP levels in the mammary gland of transgenic mice on the labelling index and beta-casein mRNA levels. This was accomplished by expressing a bovine cFABP cDNA under the control of the ovine beta-lactoglobulin (BLG) gene promoter. We found that although both the DNA labelling index, beta-casein mRNA levels, and cFABP mRNA levels in wild-type mice are developmentally regulated, they do not correlate with each other during early pregnancy in individual mice. Moreover, a three- to fourfold increase of total cFABP mRNA in two transgenic lines did not affect the DNA labelling index or the levels of beta-casein mRNA, an established marker of differentiation of the mammary epithelium, at this developmental stage. These data suggest that epithelial DNA synthesis, beta-casein gene expression, and expression of the cFABP gene are regulated independently in the proliferatively active mammary gland and that the rapidly dividing mammary epithelial cells are not susceptible to the action of cFABP during early pregnancy.

Animals↗
PubMed1995

U.S. apartheid and the spread of AIDS to the suburbs: a multi-city analysis of the political economy of spatial epidemic threshold.

We compare mechanisms of AIDS diffusion at the county level from five U.S. central city epicenters into their associated metropolitan regions. Four of the five show an expanding 'hollowed out' center of physically and socially devastated, politically and economically abandoned high density minority neighborhoods, surrounded by rings of relatively affluent majority suburban populations. From these centers AIDS diffuses into the suburbs as a single, spatially extended disease ecosystem. The exception, San Francisco, has not yet experienced the 'hollowing out' process and is, we conclude, a major AIDS epicenter markedly less coupled to its suburbs because of that fact. This may constitute one of the few empirical observations of spatial threshold in epidemiology. Our empirical results contradict the conclusions of a recent National Research Council report that AIDS will be largely confined within marginalized urban populations. In reality U.S. urban apartheid, particularly its continuing disruption of minority social structures, has markedly accelerated the diffusion of AIDS into suburban communities. A widespread program of reform, which rebuilds minority physical and social community structures within both city and suburb, is an essential, but largely unrecognized, component to any serious strategy for the control of AIDS in the United States.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Description of two new species of Halomonas: Halomonas israelensis sp.nov. and Halomonas canadensis sp.nov.

Six well-known strains of halotolerant bacteria, including two strains previously identified only as NRCC 41227 and Ba1, have been compared using 125 phenotypic characters and DNA-DNA hybridization. Although these strains represent some of the most heavily studied salt-tolerant bacteria, they have never been taxonomically compared. The data presented show that these bacteria form a relatively homogeneous group related at the genus level. The taxonomic comparison showed that these six organisms represented four distinct species all related above the 65% Jaccard coefficient level. In addition to two previously identified bacterial species, Halomonas elongata (ATCC 33173T) and Halomonas halodurans (ATCC 29686T), the strains included in this study represent two previously unnamed Halomonas species. These two new taxa have been assigned the names Halomonas israelensis (ATCC 43985T) and Halomonas canadensis (NRCC 41227T = ATCC 43984). DNA-DNA hybridization show that these two species are related to the type species H. elongata at 54.9 and 48.9%, respectively.

Culture Media↗
PubMed1995

Impact of access and social context on breast cancer stage at diagnosis.

This study examined the impact of individual demographic characteristics (age, race/ethnicity, and type of reporting hospital), together with measures of social context, including area of residence socioeconomic status (SES), change in SES, and access to screening (area mammography capacity), on breast cancer stage at diagnosis among New York City residents diagnosed between 1980 and 1985. Three logistic regression models evaluated the impact of individual variables, social context variables, and both classes of variables combined on the outcome of having late-stage (regional or distant) compared to early-stage (local) cancer. The logistic regression models indicated that women aged 50 to 64 years were independently more likely to have late-stage cancer than those younger or older. Controlling for individual and social context variables, African American women were 25 percent more likely than White women to have late-stage breast cancer (p < 0.0001); higher odds seen in the individual model for Hispanic women disappeared after controlling for area SES. In the combined model, women diagnosed from public hospitals were 44 percent more likely to have late-stage disease than those diagnosed in nonpublic settings (p < 0.0001). In both the social context and combined models, area mammography capacity was a significant independent predictor of stage (p = 0.016); area-level SES, but not change in SES, was independently related to late-stage disease (p = 0.002). These data suggest that breast cancer control activities should more actively ensure adequate access to screening, particularly for minorities, populations living in socioeconomically disadvantaged areas, and those cared for in the public sector.

Adult↗
PubMed1995

Expression of the v-Mos oncogene in male meiotic germ cells of transgenic mice results in metaphase arrest.

To explore the role of pp39mos in male germ cell meiosis, we have constructed transgenic mice carrying either the c-Mos or v-Mos genes linked to the human male germ cell-specific phosphoglycerate kinase-2 promoter. All male transgenic mice bearing the v-Mos but not the c-Mos construct were sterile due to arrest of germ cells at metaphase I. Immunocytochemistry performed on sections from control and c-Mos transgenic testes with eight different monoclonal and polyclonal antisera against either alpha-, beta- or gamma-tubulins demonstrated that all could recognize MI spermatocyte spindles from control and c-Mos transgenics, but only one monoclonal anti-microtubule sera decorated the spindles of v-Mos-arrested meiotic figures. Western blot analyses with this one serum revealed a change in proteins in the v-Mos samples. Immunocytochemistry with the MPM-2 monoclonal antibody, which is specific for epitopes phosphorylated during mitosis, demonstrated an increase in cytoplasmic and spindle-associated phosphoproteins in arrested v-Mos spermatocytes. Western analysis with MPM-2 showed an increase in a M(r) 50,000-55,000 and a M(r) 25,000-29,000 protein in Mos transgenic testes when compared to controls. An anti-MAP kinase antibody demonstrated an increase in all four MAP kinases in testes of transgenic mice. Thus, overexpression of pp39v-mos during male germ cell meiosis resulted in an alteration of various cell cycle related kinases and cytostatic factor-like arrest at MI.

Animals↗
PubMed1994

Will AIDS be contained within U.S. minority urban populations?

Recent empirical research, and a simple stochastic modeling exercise, suggest that affluent suburban communities are at increased risk for the diffusion of HIV from present inner city epicenters, while the 'core group' construct of sexually transmitted disease theory suggests, somewhat counter-intuitively, that the hypercongregated and strongly self-interacting nature of affluent heterosexual elites in the U.S. places them at significant and increasing risk as well. In turn, a growing body of work strongly associates high HIV prevalence in minority urban populations with the processes of coupled physical and social disintegration which have produced the now-common and politically-generated 'hollowed out' pattern of U.S. cities. We conclude that a return to the principles of the Great Reform Movement, which first brought public health and public order to U.S. urban areas, is a necessary, but at present largely unrecognized, component to any successful national program to control AIDS in the United States, and particularly to stem the diffusion of HIV into heterosexual populations outside present diseases epicenters.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Association of education with incidence of cognitive impairment in three established populations for epidemiologic studies of the elderly.

We analyzed the association of education, occupation, and sex with incidence of cognitive impairment using data from three communities in the Established Populations for Epidemiologic Studies of the Elderly (EPESE) projects (New Haven, East Boston, and Iowa). Participants were initially interviewed in 1981-1983, with follow-up 3 and 6 years later. Incident cognitive impairment was defined on the basis of either: (1) increase in the number of errors in Short Portable Mental Status Questionnaire (SPMSQ) (i.e. from a baseline level below the cutoff value to a score above the cutoff), or (2) inability to respond to interview questions at a follow-up contact (requiring a proxy informant), or (3) death with a recorded diagnosis of a dementing illness. In multiple logistic regression models, the major factors predicting the development of cognitive impairment were advanced age, any errors on baseline SPMSQ, 8 or fewer years of education, and occupation. Education and occupation remained significant predictors after controlling for age, site, sex, stroke, and baseline SPMSQ score.

Aged↗
PubMed1994

Chromosomal position effects and the modulation of transgene expression.

Chromosomal position effects can influence strongly the transcription of foreign genes in transgenic animals. This results in low frequencies and levels of gene expression and, in some cases, in aberrant patterns of expression. Strategies for overcoming these effects are described with particular reference to their application in embryonic stem cells.

Animals↗
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

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↗