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Biomedical subjects

M E Hughes

Publications and source records attributed to M E Hughes.

18 recordsLinked to original sources
PubMed2026

Tumor genomic landscape of older patients with metastatic breast cancer☆.

BACKGROUND: Metastatic breast cancer (MBC) in older patients has distinct clinical and histologic characteristics. Elucidating the genomic basis of MBC helps identify potential therapeutic targets to improve outcomes for older patients with MBC. PATIENTS AND METHODS: Using a prospective database and targeted DNA sequencing (OncoPanel), we examined MBC's genomic landscape in older patients (age &#x2265;70 years at MBC diagnosis) and compared findings with those in younger (aged <50 years) and middle-aged (aged 50-69 years) patients. After classifying single nucleotide variants (SNVs) and copy number variations (CNVs) as oncogenic (via OncoKB), the frequencies of SNVs and CNVs, tumor mutational burden (TMB), and oncogenic signaling pathways were compared by age group using Fisher's exact tests. We estimated the association between continuous age at MBC diagnosis and mutations via multivariate logistic regression analysis, adjusting for race, stage at initial diagnosis, subtype, histology, and sample tested (primary versus metastatic). RESULTS: Our study included 2379 patients [853 (35%) younger, 1311 (55%) middle-aged, and 215 (9%) older] who underwent OncoPanel testing between 2013 and 2020. The most frequent tumor alterations in older patients were SNVs in PIK3CA (44%), TP53 (33%), CDH1 (22%) and amplifications in CCND1 (18%). After adjustment, older age was associated with higher frequency of SNVs in CDH1 [odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.21-1.68, q < 0.001], MAP3K1 [OR = 1.30, 95% CI 1.10-1.54, q = 0.008], and PIK3CA [OR = 1.21, 95% CI 1.11-1.31, q < 0.001] and fewer SNVs in TP53 [OR = 0.84, 95% CI 0.77-0.91, q < 0.001]. Patients in the older group were more likely to have tumors with &#x2265;10 mutations/megabase than the youngest patients (26% versus 17%, P = 0.003). CONCLUSIONS: In this large cohort of patients with MBC, the tumor genomic landscape differed between older and younger patients even after accounting for tumor subtype. Older patients were more likely to have high-TMB and PIK3CA-mutated tumors, highlighting the importance of genomic testing for treatment applications in this population.

NGS↗
PubMed2003

Profile and activity of the bacterial biota of ground beef held from freshness to spoilage at 5-7 degrees C.

Four samples of fresh ground beef were stored aerobically and held at 5-7 degrees C for up to 28 days. Although one sample initially yielded 21 different genera of bacteria while two others yielded only seven, all four spoiled essentially in the same way as assessed by aerobic, psychrotrophic, and Gram-negative counts, and by extract-release volume (ERV) and pH values. Pseudomonas spp. was dominant in the spoilage of all samples. As to why this group is so consistently associated with the low-temperature aerobic spoilage of fresh meats, it is hypothesized that they possess the capacity to form a biofilm and that quorum sensing is involved in the overall biofilm forming and functioning processes.

Animals↗
PubMed2002

Effect of chronic intermittent immobilization stress on Fos-like immunoreactivity in rat brain and adrenal medulla.

The present study examined the influence of short- and long-term chronic intermittent immobilization stress throughout the brain and on the adrenal medulla of intact rats using Fos-like immunoreactivity (Fos-LI) as a marker of cellular activation. The effect of adreno-medullectomy on the central nervous system (CNS) response to chronic immobilization stress was also examined. It was found that control unoperated, unstressed rats had no Fos-LI cells in the brain or in the adrenal medulla. In intact rats, neither short term (1 week) nor long term (4 weeks) chronic intermittent immobilization stress produced significant increases in Fos-LI in the CNS compared with control animals. However, marked increase in the number of Fos-LI cells was observed in the adrenal medulla of animals stressed for 4 weeks compared with control, unstressed animals or those stressed for 1 or 2 weeks. In adreno-medullectomised rats, 4 weeks, but not 1 week, chronic immobilization stress produced significant increases in numbers of Fos-LI neurons in the paraventricular hypothalamic and supraoptic nuclei and the medial amygdala compared with intact animals stressed for a similar period of time. It is concluded that long term stress produces chronic Fos-LI in the adrenal medulla and that adreno-medullectomy increases the Fos response of the PVN, supraoptic nucleus and medial amygdala to long term stress.

Adrenal Medulla↗
PubMed1999

At risk on the cusp of old age: living arrangements and functional status among black, white and Hispanic adults.

OBJECTIVES: We examine the relationship between living arrangements and multiple measures of physical, cognitive, and emotional functioning in late midlife. METHODS: Using cross-sectional data from the Health and Retirement Study, we first assess the bivariate relationship between living arrangements and functioning; we then take into account demographic characteristics and measures of household resources and demands. RESULTS: We find evidence of differential functioning among individuals in various living arrangements. Married couples living alone or with children show the highest levels of functioning, whereas single adults living in complex households show the lowest levels. Functional deficits for those in complex households are reduced but not eliminated when we take demographic characteristics and household resources and demands into account. We find few differences by gender and race/ethnicity in the relationship between living arrangements and functioning. DISCUSSION: We show a pattern of poorer functioning among those in arguably the most demanding and least supportive household environments. This points to a vulnerable and risk-filled transition from middle to old age for these persons. Because Blacks and Hispanics show lower levels of functioning than Whites and are more likely to live in complex households, they may be particularly disadvantaged.

Activities of Daily Living↗
PubMed1998

A behavioral intervention for improving verbal behaviors of heroin addicts in a treatment clinic.

Positively reinforcing appropriate behaviors improved verbal behaviors of opioid-dependent patients in a buprenorphine treatment clinic. During B phases of an ABAB design, clients received stickers for engaging in appropriate verbal or nonverbal behaviors. Each sticker provided a chance of winning $25. No reinforcement was provided during the A phases. Appropriate verbal behaviors increased during reinforcement periods, and inappropriate verbal behaviors decreased.

Adult↗
PubMed1998

Interacting effects of multiple roles on women's health.

Our study tests several hypotheses concerning the effects of employment, marriage, and motherhood on women's general physical health. These hypotheses predict how the health effect of each role varies, depending on specific role characteristics and the other roles a woman holds. Our analyses utilize longitudinal panel data for 3,331 women from the National Longitudinal Surveys of Young Women (follow-up intervals: 1978-83 and 1983-88). The Role Substitution Hypothesis proposes that employment and marriage provide similar resources (e.g., income and social support), and consequently, employment and marriage can substitute for each other in their beneficial effects on health. As predicted, we found that employment had beneficial effects on health for unmarried women, but little or no effect for married women. Similarly, marriage had beneficial effects on health only for women who were not employed. The Role Combination Strain Hypothesis proposes that employed mothers experience role strain, resulting in harmful effects on health. However, we found very little evidence that the combination of employment and motherhood resulted in harmful health effects. Contrary to the predictions of the Quantitative Demands Role Strain Hypothesis, it appears that neither longer hours of employment nor having more children resulted in harmful effects on health. As predicted by the Age-Related Parental Role Strain Hypothesis, younger age at first birth, particularly a teenage birth, appeared to result in more harmful health effects.

Adolescent↗
PubMed1997

Marital status effects on health: are there differences between never married women and divorced and separated women?

To test whether the effects of marital status on health differ between never married women and divorced and separated women, this study utilizes prospective panel data for a large national sample of non-institutionalized young women in the U.S. (the National Longitudinal Surveys of Young Women). The women were aged 24-34 at the beginning of two successive five-year follow-up intervals (1978-1983 and 1983-1988). The health effects of marital status were evaluated in regressions which assessed the relationships between initial marital status and subsequent health trends in each follow-up interval. In the first follow-up interval, never married women tended to have worse health trends than divorced and separated women for physical impairments and for overall health problems. However, there were no differences between never married women and divorced and separated women in health trends for psychosomatic symptoms in either follow-up interval or for any health measure in the second follow-up interval. Our analyses of cross-sectional data showed few significant differences in health between never married women and divorced and separated women. Taken together, the evidence from our study and previous studies suggests that differences between never married women and divorced and separated women may vary by age and/or cohort. Evidence for the 1970s and 1980s suggests that, among older women, divorced and separated women may have experienced more harmful health effects than never married women; however, among younger women, this difference may have been absent or possibly reversed.

Adult↗
PubMed1996

Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus.

We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (IL1RN*2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of IL1RN*2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of IL1RN*2 and diabetic nephropathy (P<0.001, Pcorrected<0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that IL1RN*2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.

Adult↗
PubMed1996

Marriage protection and marriage selection--prospective evidence for reciprocal effects of marital status and health.

Married adults are generally healthier than unmarried adults. It has been hypothesized that marriage is associated with good health because marriage has beneficial effects on health (marriage protection effects) and/or because healthier individuals are more likely to marry and to stay married (marriage selection effects). To investigate these hypotheses, this study analyzes prospective panel data for a large national sample of women in the U.S. (the National Longitudinal Surveys of Young Women). The women were aged 24-34 yr at the beginning of two successive five-year follow-up intervals. Analyses of the prospective data indicate that there were significant marriage protection effects, but only among women who were not employed. Specifically, for women who were not employed, married women had better health trends than unmarried women in each follow-up interval. It appears that marriage had beneficial effects on health for women who did not have a job which could provide an alternative source of financial resources and social support. In addition, analyses of the prospective data provide limited evidence for marriage selection effects. Specifically, women who had better health initially were more likely to marry and less likely to experience marital dissolution, but only for women who were not employed full-time and only during the first follow-up interval. Thus, the prospective evidence suggests that, for women who were not employed, both marriage protection and marriage selection effects contributed to the marital status differential in health observed in cross-sectional data. In contrast, neither marriage protection nor marriage selection effects were observed for women who were employed full-time. As would be expected, the cross-sectional data show that marital status differentials in health were large and highly significant for women who were not employed, whereas marital status differentials in health were much smaller and often not significant for employed women. Women who were neither married nor employed had particularly poor health. Additional evidence indicates that the women who were neither married nor employed suffered from multiple interacting disadvantages, including poor health, low incomes, and sociodemographic characteristics which contributed to difficulty in obtaining employment.

Adult↗
PubMed1989

Fine structural ribonucleoprotein components of the cell nucleus visualized after spreading and high resolution autoradiography.

The fine structure of the nuclear components was studied following mild lysis of mouse or Drosophila tissue culture cells and spreading of nuclear material. Particular attention was paid to nuclear ribonucleoprotein (RNP) constituents, which were analysed by high resolution autoradiography after [3H]uridine pulse labelling of cells. Comparison with the labelling kinetics of various in situ nuclear RNP constituents described previously suggests strong similarities between in situ constituents and structures observed within spread nuclear components. The present observations suggest that the nucleolar dense fibrillar component, shown previously in ultrathin sections of [3H]uridine-labelled intact cells as carrying rapidly labelled pre-rRNA, in fact consists of highly compacted transcribing ribosomal genes. The growing RNP fibrils appearing in transcription complexes of extranucleolar active genes and the in situ observed perichromatin fibrils also show the same labelling properties. This confirms that the two structures indeed represent the same nucleoplasmic constituents. As for the nuclear structures involved in post-transcriptional events, our observations demonstrate the occurrence of a rapidly labelled RNP fibro-granular network. Its granular elements correspond, in size and perichromatin location, to the perichromatin granules seen in the situ preparations and suggest similarities between the two constituents. The results are discussed in the light of other data providing information on the role of various nuclear structural constituents.

Animals↗
PubMed1988

An easy guide to electronystagmography interpretations.

Although there are numerous text books and long articles written on electronystagmography, there are few comprehensive summary tables to assist in teaching ENG interpretation. The use of such a device, however, is particularly helpful for medical students, residents, audiologists, nurses, and medical specialists who do not interpret electronystagmograms regularly.

Electronystagmography↗
PubMed1979

Visualization of Transcription in early mouse embryos.

Transcriptional activity during early mammalian embryogenesis was examined in 2 cell, 4--8 cell and late morula/early blastocyst mouse embryos. Zona pellucida-free embryos were obtained after pronase digestion followed by a PMSF wash to inhibit proteolytic activity. The embryos were then lysed with NP40 detergent and spread for electron microscopy according to Miller and Bakken (1972). pre-mRNA transcription was observed at all stages. Comparison of growing RNP chain lengths revealed statistically significant differences in the distribution of shorter fibrils between the successive developmental stages examined. The number of shorter fibrils was lower in the 4--8 cell stage than in either of the two other stages. Transcription complexes of ribosomal type were detected only in 4--8 cell and morula/blastocyst embryos. Structures resembling replication loops were observed within chromatin from all stages. Similar loop-like structures as well as individually transcribed RNP fibrils were also occasionally found on fibres emerging from mitotic chromosomes. The results are discussed in the context of recent findings concerning genetic expression in early mouse embryos.

Animals↗
PubMed1977

Extensive exchange of rat liver microsomal phospholipids.

Liver microsomal fractions were prepared from rats injected with a single dose of choline [14C]methylchloride or with single or multiple doses of 32Pi. Exchangeability of microsomal phospholipids was determined by incubation with an excess of mitochondria and phospholipid exchange proteins derived from beef heart, beef liver or rat liver. Labeled phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were found to act as a single pool and were 85--95% exchangeable in 1--2h. High latencies of mannose-6-phosphate phosphohydrolase activities and impermeability of microsomes to EDTA proved that phospholipid exchange proteins did not have access to the intracisternal space. If microsomal membranes are largely composed of phospholipid bilayers, the experiments suggest that one or more of the phospholipid classes in microsomal membranes undergo rapid translocation between the inner and outer portions of the bilayer.

Animals↗
PubMed1976

Meningitis caused by an alkali-producing pseudomonad.

The clinical and microbiological features of a case of meningitis, due to an alkali-producing pseudomonad which closely resembles Pseudomonas pseudoalcaligenes, are described. A respiratory infection and a course of antibiotic therapy before admission to hospital may have been predisposing factors to opportunistic infection by this normally saprophytic organism. The problems of identifying alkali-producing pseudomonads are discussed.

Alkalies↗
PubMed1975

Use of phospholipid exchange protein to measure inside-outside transposition in phosphatidylcholine liposomes.

The exchange of phosphatidylcholine between (32P)phosphatidylcholine lipososomes and unlabeled mitochondria was catalyzed by a purified phospholipid exchange protein from bovine heart cytosol. The loss of (23P)phosphatidylcholine from the liposomes appeared to proceed in two stages: with 100 units of phospholipid exchange protein per ml the half-time of the initial stage was about 10 min and that of the final stage 4 days or greater. Agarose-gel chromatography of the liposomes showed an elution compatible with a homofwnwoua pool od amLL single walled vesicles. Treatment of phosphatidyl (14C) choline liposomes with phospholipase D (phosphatidylcholine phosphantidohydrolase) showed that labeled phospholipid removable during the rapid exchange phase was subject to hydrolysis by the phospholipase, but that the labeled phospholipid left after the rapid exchange was completed cound not by hydrolyzed by phospholipase D. It is proposed that the rapidly exchanging phosphatidylcholine constitutes the outer layer of the liposome bilayer. The long half-lives of 4 days or more probably represent the transposition of phosphatidylcholine from the inner to the outer layer of the liposome bilayer.

Animals↗
PubMedDate not supplied

The impact of an increase in family planning services on the teenage population of Philadelphia.

In an assessment conducted 30 months after a Philadelphia-area project increased the resources that community family planning agencies devoted to teenage services, teenagers in targeted communities showed no generalized improvement in rates of pregnancy and childbearing, in knowledge or use of clinic services, or in attitudes toward contraception compared with those of teenagers in the entire city. Samples of adolescents aged 14-18 from the clinics' catchment areas and from the entire city were interviewed in mid-1988, when the project's activities began, and 2.5 years later. The results suggest that while community family planning clinics may provide effective services to the teenagers who seek them out, they may not be the most effective strategy for decreasing rates of pregnancy and childbearing in the overall teenage population.

Adolescent↗