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Biomedical subjects

M Perry

Publications and source records attributed to M Perry.

At least 73 records · Page 4Linked to original sources
PubMed1995

Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome.

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Venereal Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.

Adult↗
PubMed1995

A phase II study of recombinant interferon-gamma following combination chemotherapy for patients with extensive small cell lung cancer. CALGB.

A total of 71 patients with extensive small cell lung cancer were enrolled in CALGB study 8733. Chemotherapy was administered with cisplatin 33 mg/m2, i.v. infusion days 1-3, doxorubicin 45 mg/m2 i.v. day 1, cyclophosphamide 800 mg/m2 i.v. day 1, and etoposide 80 mg/m2 i.v. infusion days 1-3 (PACE). Following four courses of PACE, patients achieving a CR or PR were started on recombinant interferon-gamma (rINF-gamma) 0.2 mg s.c. daily until grade IV toxicities or progression occurred. Of the 71 patients enrolled, 67 are evaluated (47 males and 20 females), median age 59 years, and median PS1. The response rate to PACE was 48/67, 72%. Grade 3-4 toxicities included granulocytopenia, thrombocytopenia, and five treatment-related deaths (7%). Forty-one patients were started on rINF-gamma. Of these 41 patients, 11 were in CR, 30 in PR. The objective response rate to rINF-gamma was 2/30 or 6.7%. Recombinant rINF-gamma is inactive in small cell lung cancer, even when the tumor burden has been substantially reduced by prior chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Screening for germline mutations of the p53 gene in familial breast cancer patients.

The constitutive DNA from members of four families showing predisposition to breast cancer was amplified by PCR in the region of exons 5, 6, 7 and 8 of the p53 proto-oncogene. Single-strand conformation polymorphism (SSCP) gels were used to compare patient DNA with mutant and wild-type control samples. No cases of anomalous mobility were observed in samples from the susceptible families. The lack of inherited mutations was confirmed for exons 5 and 7 by solid-phase DNA sequencing. The results lend further support to the view that inherited mutations in p53 alleles are not a significant contributor to breast cancer predisposition and it is not, therefore, clinically worthwhile to screen predisposed or potentially predisposed families for germline mutations in the p53 gene.

Adult↗
PubMed1995

Interaction of the CCAAT displacement protein with shared regulatory elements required for transcription of paired histone genes.

The H2A and H2B genes of the Xenopus xlh3 histone gene cluster are transcribed in opposite directions from initiation points located approximately 235 bp apart. The close proximity of these genes to one another suggests that their expression may be controlled by either a single bidirectional promoter or by separate promoters. Our analysis of the transcription of histone gene pairs containing deletions and site-specific mutations of intergenic DNA revealed that both promoters are distinct but that they overlap physically and share multiple regulatory elements, providing a possible basis for the coordinate regulation of their in vivo activities. Using the intergenic DNA fragment as a probe and extracts from mammalian and amphibian cells, we observed the formation of a specific complex containing the CCAAT displacement protein (CDP). The formation of the CDP-containing complex was not strictly dependent on any single element in the intergenic region but instead required the presence of at least two of the three CCAAT motifs. Interestingly, similar CDP-containing complexes were formed on the promoters from the three other histone genes. The binding of CDP to histone gene promoters may contribute to the coordination of their activities during the cell cycle and early development.

Animals↗
PubMed1995

Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281.

PURPOSE: We sought to compare three doxorubicin-based therapies for metastatic breast cancer for response frequency, time to treatment failure (TTF), and survival. MATERIALS AND METHODS: Women with metastatic breast cancer who had measurable disease, required laboratory tests, had received no prior chemotherapy for metastases, had a Cancer and Leukemia Group B (CALGB) performance status < or = 2, and provided informed consent were eligible. Treatment included the following: arm I--cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm II--vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm III--VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity criteria were used. RESULTS: Between August 1982 and February 1987, 497 women were entered and 491 were treated on study. Pretreatment characteristics were well balanced and the median follow-up duration was 79 months. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III. The median TTFs were 8, 8, and 9 months, respectively, in favor of arm III when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respectively. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TTF and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively. Lethal toxicities were seen in four, five, and six women, respectively. Overall, there were more grade > or = 3 toxicities on arm II than I, and most occurred on arm III (P = .02). CONCLUSION: The VATH regimen appears similarly effective to the CAF regimen as initial therapy. Alternating CMFVP with VATH did not improve response rate or survival. After accounting for other variables, treatment arm was not related to outcome. New therapeutic regimens are still needed.

Adult↗
PubMed1995

Mean versus median for the multiple sleep latency test.

Since its introduction in the mid-1970s, the multiple sleep latency test (MSLT) has become the standard method for evaluating hypersomnolence. The mean sleep latency is usually calculated and constitutes the traditional basis for interpretation. Mean and median are both measures of the central tendency of a distribution, but because the trials of the MSLT are limited to 20 minutes, the median may be more appropriate. The objective of this study was to compare the value of the mean versus the median sleep latency in the interpretation of the MSLT. We retrospectively analyzed 100 MSLTs performed for evaluation of excessive daytime sleepiness. Patients' ages ranged from 6 to 84 years (mean 43). Mean and median sleep latencies were calculated according to standard formulas. We classified each record into one of three categories, using both the mean and the median sleep latencies: normal (> 10 minutes), moderate (> or = 5 and < or = 10 minutes), and severe sleepiness (< 5 minutes). Of the 100 MSLTs, 89 remained in the same category (normal, moderate, severe) whether mean or median was used. In 11 cases, the category changed. All shifts were by one category, that is, no shift occurred between normal and severe. This study suggests that, despite valid theoretical arguments for the use of the median, both measures are equally acceptable for clinical purposes.

Adolescent↗
PubMed1994

Homeodomain protein MHox and MADS protein myocyte enhancer-binding factor-2 converge on a common element in the muscle creatine kinase enhancer.

MHox is a mesoderm-specific homeodomain protein that binds an A/T-rich element that is essential for activity of the muscle creatine kinase (MCK) enhancer. The MHox binding site also binds the ubiquitous homeodomain protein Oct-1 as well as myocyte enhancer-binding factor-2 (MEF2), which belongs to the MADS superfamily of transactivators. To determine which of these proteins activates MCK transcription through the A/T element, we mutated this sequence such that it would selectively bind MHox, MEF2, or Oct-1 and tested the activities of the mutant enhancers in skeletal muscle cells. These mutant enhancers revealed that only MEF2 is able to activate the MCK enhancer through the A/T element. The convergence of homeodomain and MADS proteins on the A/T element in the MCK enhancer provides a mechanism through which a single DNA sequence can mediate positive and negative regulation of gene transcription and is reminiscent of the roles of these two classes of transcription factors in the control of other cell-specific genes.

Animals↗
PubMed1994

Activation of Xenopus MyoD transcription by members of the MEF2 protein family.

Members of the MEF2 family of DNA binding proteins interact with a set of AT-rich sequences commonly found in the promoters and enhancers of muscle-specific genes. We have shown that a MEF2 binding site precisely overlaps the TFIID binding site (TATA box) in the Xenopus MyoDa (XMyoDa) promoter and appears to play an important role in muscle-specific activity of this promoter. To further investigate the potential role of MEF2 in the regulation of XMyoDa transcription, we have analyzed the appearance of factors that interact with the XMyoDa TATA/MEF2 site during early amphibian development. Proteins that bind specifically to this site were present at low levels during early development and increased in abundance during gastrulation and neurulation. Two related cDNAs were isolated that encode proteins that recognize the XMyoDa TATA motif. Both proteins are highly homologous to each other, belong to the MADS (MCM1 agamous deficiens SRF) protein family, and are most highly related to the mammalian MEF2A gene products. Xenopus MEF2A (XMEF2A) transcripts accumulated preferentially in forming somites after the appearance of XMyoD transcripts. Ectopic expression of XMEF2A and other members of the MEF2 gene family activated transcription of a reporter gene controlled by the XMyoDa promoter. Transcriptional activation of the XMyoDa promoter required only the conserved DNA binding domain of XMEF2A and was independent of a domain necessary for activity when this factor was bound to multiple upstream sites. These results suggest that the XMyoDa promoter can be activated by binding of MEF2 to the XMyoDa TATA motif and indicate that MEF2-dependent transcriptional activation occurs by different mechanisms depending on the location of the MEF2 binding site. We suggest that XMEF2 expression in myogenic cells contributes to the activation and stabilization of XMyoDa transcription during muscle cell differentiation.

Amino Acid Sequence↗
PubMed1994

Does omeprazole (Prilosec) improve respiratory function in asthmatics with gastroesophageal reflux? A double-blind, placebo-controlled crossover study.

Gastroesophageal reflux (GER) is common among patients with asthma, and it has been speculated that high GER may exacerbate asthma in some. This study was designed to determine if suppression of acid reflux in patients with asthma would improve pulmonary function. A double-blind, placebo-controlled crossover study design was used to determine the effect of GER suppression with omeprazole (20 mg twice daily) on pulmonary function among asthmatic patients with esophagitis. Four of 15 (27%) asthma patients with GER were shown to have a > or = 20% net improvement in pulmonary function (FEV1) after treatment for six weeks with omeprazole. These results indicate that some patients with asthma and GER will have improved pulmonary function when acid GER is treated with omeprazole.

Adult↗
PubMed1994

A plasmid-encoded rfbO:54 gene cluster is required for biosynthesis of the O:54 antigen in Salmonella enterica serovar Borreze.

Previous studies demonstrated that the presence of a 7-8 kb plasmid is correlated with expression of the lipopolysaccharide (LPS) O:54 antigen in several Salmonella enterica serovars. In this study, a 6.7 kb plasmid from a field isolate of S. enterica serovar Borreze was shown to encode enzymes responsible for the synthesis of the O:54 polysaccharide. Curing the plasmid results in simultaneous loss of smooth O-polysaccharide-substituted LPS molecules and O:54 serotype. SDS-PAGE analysis of other O:54 isolates indicated that the O:54 O-polysaccharide can be co-expressed with an additional O-polysaccharide, likely encoded by chromosomal genes. The structure of the O:54 polysaccharide was determined by a combination of chemical and nuclear magnetic resonance (NMR) methods and was found to be an unusual homopolymer of N-acetylmannosamine (D-ManNAc) residues. The polysaccharide contained a disaccharide repeating unit with the structure:-->4)-beta-D-ManpNAc-(1-->3)-beta-D-ManpNAc-(1--> This structure does not resemble other O-polysaccharides in S. enterica. To examine the role played by plasmid functions in synthesis of the O:54 polysaccharide, the 6.7 kb plasmid was cloned to produce a hybrid plasmid (pWQ800) in pGEM-7Zf(+). In Escherichia coli K-12 delta rfb, pWQ800 directed the synthesis of authentic O:54 polysaccharide. Polymerized O:54 polysaccharide was also produced in S. enterica serovar Typhimurium rfb and rfc mutants. From these data, we conclude that pWQ800 carries the rfbO:54 gene cluster and synthesis of the O:54 polysaccharides does not require host chromosomal rfb functions. However, synthesis of the O:54 polysaccharide requires the function of the rfe and rffE genes which are part of the gene cluster encoding enzymes involved in biosynthesis of enterobacterial common antigen. The rffE gene product synthesizes the O:54 precursor, uridine diphospho-N-acetylmannosamine. This is the first description of a plasmid-encoded rfb gene cluster in Salmonella.

Bacterial Proteins↗
PubMed1994

Binding of TFIID and MEF2 to the TATA element activates transcription of the Xenopus MyoDa promoter.

Members of the MyoD family of helix-loop-helix proteins control expression of the muscle phenotype by regulating the activity of subordinate genes. To investigate processes that control the expression of myogenic factors and regulate the establishment and maintenance of the skeletal muscle phenotype, we have analyzed sequences necessary for transcription of the maternally expressed Xenopus MyoD (XMyoD) gene. A 3.5-kb DNA fragment containing the XMyoDa promoter was expressed in a somite-specific manner in injected frog embryos. The XMyoDa promoter was active in oocytes and cultured muscle cells but not in fibroblasts or nonmuscle cell lines. A 58-bp fragment containing the transcription initiation site, a GC-rich region, and overlapping binding sites for the general transcription factor TFIID and the muscle-specific factor MEF2 was sufficient for muscle-specific transcription. Transcription of the minimal XMyoDa promoter in nonmuscle cells was activated by expression of Xenopus MEF2 (XMEF2) and required binding of both MEF2 and TFIID to the TATA motif. These results demonstrate that the XMyoDa TATA motif is a target for a cell-type-specific regulatory factor and suggests that MEF2 stabilizes and amplifies XMyoDa transcription in mesodermal cells committed to the muscle phenotype.

Animals↗
PubMed1994

Localization biopsy for impalpable breast lesions in a district general hospital.

127 patients undergoing localization biopsy for impalpable breast lesions were analysed retrospectively. Patients were included from both the UK Breast Screening Programme and from the symptomatic Breast Clinic. 49.6% of the biopsies were histologically benign, whereas 50.4% were malignant, including in-situ carcinoma. This is a significantly higher cancer rate than previous series. Localization biopsy has an important role in the diagnosis of mammographically suspicious lesions which are impalpable. 80% of the patients originated from the Breast Screening Programme which has important financial implications on surgical workload.

Adult↗
PubMed1993

Interactions among vertebrate helix-loop-helix proteins in yeast using the two-hybrid system.

The helix-loop-helix (HLH) motif is contained in a rapidly growing family of transcription factors and has been shown to mediate dimerization among heterologous HLH-containing proteins. E12 is a widely expressed HLH protein that preferentially forms heterodimers with cell type-specific HLH proteins such as MyoD, myogenin, and the achaete-scute gene products. As a first step toward screening for novel cell type-specific partners of E12, we used a modification of the two-hybrid assay for detection of protein-protein interactions in vivo to determine whether dimerization of HLH proteins with E12 can occur in yeast. Using the GAL4 DNA-binding domain fused to the E12 HLH motif and the GAL4 transcription activation domain fused to MyoD, we show that E12 and MyoD can efficiently dimerize in yeast and reconstruct a hybrid transcription factor that activates reporter genes linked to the GAL4 DNA-binding site. The GAL4 DNA-binding domain fused to E12 was used to screen a mouse T-cell cDNA library in which the cDNA was fused to the GAL4 activation domain. Several cDNA clones encoding proteins that interact with E12 were isolated, one of which corresponded to the HLH protein Id-2. Given the ability of E12 to dimerize preferentially with cell type-specific HLH proteins, this strategy should be useful for cloning novel partners for E12 from a variety of cell types.

Amino Acid Sequence↗
PubMed1993

Taurolin for the prevention of parenteral nutrition related infection: antimicrobial activity and long-term use.

A case is described in which bis (1, 1 dioxoperhydro-1, 2, 4-thiadiazinyl-4-) methane (Taurolin) has saferly been administered on a long term basis to prevent recurrent sepsis in a patient receiving parenteral nutrition. A 26-year-old male with Crohn's disease receiving parenteral nutrition suffered repeated episodes of sepsis and developed an infected intra-atrial thrombus despite repeated courses of antimicrobial chemotherapy and surgical intervention. Continued parenteral nutrition was essential du5e to intestinal failure. Taurolin was administered in the parenteral feed, as a 0.3% solution, to prevent recrudescent and recurrent infection. This concentration was shown, in vitro, to be bactericidal to a variety of pathogenic organisms. No recurrence of sepsis, nor any evidence of side effects was observed throughout the 12 month period of Taurolin administration. After 12 months the taurolin was discontinued and within 2 weeks the patient was re-admitted with recurrent septicaemia. Following re-introduction of Taurolin the infection was controlled and the patient remains well. In our experience the addition of taurolin to the nutritive feeds of a patient at risk of sepsis is a safe and effective method of preventing recurrent sepsis.

Journal Article↗
PubMed1993

Relationships between dialysis quantification and normalized protein catabolic rate in peritoneal dialysis.

Normalized protein catabolic rates (NPCR) and urea clearances (Kt/V urea) correlate significantly in peritoneal dialysis suggesting that the adequacy of dietary protein intake and dialysis dose are interrelated. However, both of these calculated parameters are mathematical functions of the normalized urea appearance rate (GN). NPCR, GN, Kt/V urea, total creatinine clearance, residual renal clearance, and peritoneal urea and creatinine clearances were determined in 29 stable peritoneal dialysis patients with no history of recent peritonitis or other catabolic illness. Multiple linear regression analysis showed that NPCR correlated closely with both GN (r = 0.96; p < 0.0001) and Kt/V urea (r = 0.77; p < 0.0001), whereas GN also correlated with Kt/V urea (r = 0.66; p < 0.0001). Total weekly creatinine clearances rather than Kt/V urea should be utilized in peritoneal dialysis to permit independent estimations of dialysis dose and NPCR, since both Kt/V and NPCR are related closely to GN. Total weekly creatinine clearances correlated with NPCR (r = 0.59; p < 0.0002), which supports the hypothesis that dietary protein intake is dependent on the delivered dialysis dose.

Creatinine↗