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Biomedical subjects

M E Hughes

Publications and source records attributed to M E Hughes.

8 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↗
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↗