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Biomedical subjects

T Davis

Publications and source records attributed to T Davis.

At least 19 recordsLinked to original sources
PubMed2007

Congenital linear unilateral basal cell nevus: a case report with patched gene molecular studies.

BACKGROUND: Linear unilateral basal cell nevus represents a linear collection of macules and papules histologically similar to basal cell carcinoma but with benign clinical behavior. We describe a patient who initially presented at the age of 6 months with a unilateral linear basal cell nevus on the right flank. The differential diagnosis included the nevoid basal cell carcinoma syndrome. Constitutional PTCH mutations are causative of the nevoid basal cell carcinoma syndrome, and somatic PTCH mutations are found in the vast majority of basal cell carcinomas. Somatic SMO mutations have also been found in some basal cell carcinomas. METHODS: Histologic examination of the lesions is performed. Short tandem-repeat molecular analysis at the PTCH locus and sequencing of PTCH and SMO genes is performed. RESULTS: Histologic examination revealed features initially indistinguishable from basal cell carcinoma. Short tandem-repeat DNA analysis did not reveal loss of heterozygosity at the PTCH locus. DNA sequencing of both the PTCH and the SMO genes from the patient's lesions revealed neither inactivating mutations of PTCH nor activating mutations of SMO. CONCLUSION: Molecular examination indicates that the PTCH and SMO genes are not involved in the pathogenesis of the patients' congenital linear unilateral basal cell nevus. Furthermore, we discuss the relationship between linear basal cell nevus and basaloid follicular hamartoma.

DNA, Neoplasm↗
PubMed2006

Preimplantation genetic diagnosis of familial adenomatous polyposis.

Familial adenomatous polyposis is a severe autosomal dominant cancer predisposition syndrome. It is characterized by the development of hundreds to thousands of polyps in the gastrointestinal tract, primarily in the colon, at a mean age of 16 years. Without a colectomy, colon cancer is inevitable. FAP is caused by mutations in the adenomatous polyposis coli (APC) gene. A couple was referred to Monash IVF following a request to undertake preimplantation genetic diagnosis for FAP. The female proband had an AGTT deletion mutation in exon 15 of the APC gene. Analysis of the APC-linked marker D5S346 showed that the parental alleles were fully informative. A multiplex polymerase chain reaction (PCR) test was developed involving direct mutation detection and the co-analysis of D5S346 to identify allele drop out and avoid a misdiagnosis. The delAGTT mutation and D5S346 alleles were diagnosed by fluorescent PCR and allele sizing. Following standard hormone stimulation and IVF procedures, 14 oocytes were collected, 11 inseminated and nine embryos were biopsied on day 3. Of the nine embryos that were analysed, five embryos were affected and four were unaffected. Two unaffected embryos were transferred on day 4 resulting in a triplet pregnancy and the birth of three healthy babies.

Adenomatous Polyposis Coli↗
PubMed2006

A case of an anomalous pectoralis major muscle.

We present a case of a right sided accessory head of the pectoralis major muscle located inferior to its abdominal head. This variation was found during a routine anatomy dissection at the American University of the Caribbean School of Medicine. The muscle fibres of the accessory head of the pectoralis major muscle arose from those of the serratus anterior muscle and travelled superolaterally towards the axilla. The accessory muscle terminated by fusing with the tendinous fibres of the pectoralis major muscle as they underwent their normal anatomical rotation before insertion upon the lateral lip of the bicipital groove of the humerus. Although variations in the pectoral muscles are not uncommon, this case appears to be unique in the literature. The possible clinical implications are discussed.

Aged↗
PubMed2005

Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease, partly owing to dyslipidaemia, which can be amenable to fibrate therapy. We designed the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study to assess the effect of fenofibrate on cardiovascular disease events in these patients. METHODS: We did a multinational, randomised controlled trial with 9795 participants aged 50-75 years, with type 2 diabetes mellitus, and not taking statin therapy at study entry. After a placebo and a fenofibrate run-in phase, we randomly assigned patients (2131 with previous cardiovascular disease and 7664 without) with a total-cholesterol concentration of 3.0-6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0-5.0 mmol/L to micronised fenofibrate 200 mg daily (n=4895) or matching placebo (n=4900). Our primary outcome was coronary events (coronary heart disease death or non-fatal myocardial infarction); the outcome for prespecified subgroup analyses was total cardiovascular events (the composite of cardiovascular death, myocardial infarction, stroke, and coronary and carotid revascularisation). Analysis was by intention to treat. The study was prospectively registered (number ISRCTN 64783481). FINDINGS: Vital status was confirmed on all but 22 patients. Averaged over the 5 years' study duration, similar proportions in each group discontinued study medication (10% placebo vs 11% fenofibrate) and more patients allocated placebo (17%) than fenofibrate (8%; p<0.0001) commenced other lipid treatments, predominantly statins. 5.9% (n=288) of patients on placebo and 5.2% (n=256) of those on fenofibrate had a coronary event (relative reduction of 11%; hazard ratio [HR] 0.89, 95% CI 0.75-1.05; p=0.16). This finding corresponds to a significant 24% reduction in non-fatal myocardial infarction (0.76, 0.62-0.94; p=0.010) and a non-significant increase in coronary heart disease mortality (1.19, 0.90-1.57; p=0.22). Total cardiovascular disease events were significantly reduced from 13.9% to 12.5% (0.89, 0.80-0.99; p=0.035). This finding included a 21% reduction in coronary revascularisation (0.79, 0.68-0.93; p=0.003). Total mortality was 6.6% in the placebo group and 7.3% in the fenofibrate group (p=0.18). Fenofibrate was associated with less albuminuria progression (p=0.002), and less retinopathy needing laser treatment (5.2%vs 3.6%, p=0.0003). There was a slight increase in pancreatitis (0.5%vs 0.8%, p=0.031) and pulmonary embolism (0.7%vs 1.1%, p=0.022), but no other significant adverse effects. INTERPRETATION: Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events. It did reduce total cardiovascular events, mainly due to fewer non-fatal myocardial infarctions and revascularisations. The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit.

Aged↗
PubMed2002

Ursodeoxycholic acid enhances fractional calcium absorption in primary biliary cirrhosis.

Bone disease is a frequently reported complication in primary biliary cirrhosis (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is the treatment of choice in PBC, improving survival, but its effect on calcium absorption is unknown. In this study, we have measured fractional calcium absorption, using a single isotope method, in a group of female PBC patients (median age: 60 years, range: 46-78 years) and age-matched female controls (median age: 58 years, range: 36-74). Bone mineral density (BMD) in PBC patients was significantly lower than age-matched controls (g/cm(2) +/- SEM; lumbar spine: controls 1.139+/-0.028, PBC patients 1.004+/-0.026, p = 0.0028; femoral neck: controls 0.944+/-0.034, PBC patients 0.819+/-0.023, p = 0.0032). Twenty two PBC patients, who were not vitamin D-deficient, were off and on UDCA for approximately 1 month and approximately 8 weeks, respectively. Fractional calcium absorption in PBC patients prior to UDCA treatment (mean +/- SEM, 33.8+/-2.6%) was significantly lower than controls (52.0+/-2.4%, p<0.001). Following UDCA therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1+/-2.6%, On UDCA: 36.6+/-2.5%, p<0.0058). Osteocalcin levels were significantly raised in the PBC group (mean +/- SEM, ng/ml, 41.4+/-2.02) compared to controls (31.1+/-2.64, p = 0.002). There were no differences in parathyroid hormone (PTH) or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy. In conclusion, we found that PBC patients display low spinal and femoral neck BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The calcium malabsorption is corrected partially by UDCA therapy. Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC.

Absorptiometry, Photon↗
PubMed2001

Comparative analysis of the Band 4.1/ezrin-related protein tyrosine phosphatase Pez from two Drosophila species: implications for structure and function.

The FERM-PTPs are a group of proteins that have FERM (Band 4.1, ezrin, radixin, moesin homology) domains at or near their N-termini, and PTP (protein tyrosine phosphatase) domains at their C-termini. Their central regions contain either PSD-95, Dlg, ZO-1 homology domains or putative Src homology 3 domain binding sites. The known FERM-PTPs fall into three distinct classes, which we name BAS, MEG, and PEZ, after representative human PTPs. Here we analyze Pez, a novel gene encoding the single PEZ-class protein present in Drosophila. Pez cDNAs were sequenced from the distantly related flies Drosophila melanogaster and Drosophila silvestris, and found to be highly conserved except in the central region, which contains at least 21 insertions and deletions. Comparison of fly and human Pez reveals several short conserved motifs in the central region that are likely protein binding sites and/or phosphorylation sites. We also identified novel invertebrate members of the BAS and MEG classes using genome data, and generated an alignment of vertebrate and invertebrate FERM domains of each class. 'Specialized' residues were identified that are conserved only within a given class of PTPs. These residues highlight surface regions that may bind class-specific ligands; for PEZ, these residues cluster on and near FERM subdomain F1. Finally, the PTP domain of fly Pez was modeled based on known PTP tertiary structures, and we conclude that Pez is likely a functional phosphatase despite some unusual features of the active site cleft sequences. Biochemical confirmation of this hypothesis and genetic analysis of Pez are currently underway.

Amino Acid Sequence↗
PubMed2001

Does centralized intake improve drug abuse treatment outcomes?

This study was designed to assess whether centralized intake and assessment in a drug abuse treatment system would lead to improved outcomes. Clients entering treatment through a centralized intake unit (CIU) or through individual programs (non-CIU) were interviewed at admission, and at 1 month and 1 year postadmission. Interviews included measures of treatment access and satisfaction, psychiatric symptoms, social support, and Addiction Severity Index composite scores. At treatment entry, CIU participants had more employment and psychological problems and lower social support, were more often required to be in treatment, and were more often placed on a waiting list. In analyses controlling for baseline differences between groups, there were main effects of time, but no CIU status effects or CIU status by time interactions. The CIU may have improved access to treatment for a more disabled population; however, clients entering treatment through the CIU did not have better outcomes than those entering treatment directly.

Adult↗
PubMed2001

Clinical trials in a rural population: professional education aspects.

BACKGROUND: While the majority of cancer patients in rural New Hampshire and Vermont are treated in community hospitals, few have entered clinical trials. This report describes a rural hospital consortium as a single Cancer and Leukemia Group B (CALGB) affiliate that used local cancer teams and itinerant oncologists to develop a clinical trials program. METHOD: Grafted onto an existing oncology outreach program, educational programs were developed to help identify patients and recruit them to cooperative group clinical trials. Outcomes included the number of patients accrued to clinical trials, and a comparison of the quality of audited research records with those of affiliated institutions of the CALGB. The consequences of the program were to measure changes in patterns of care of breast, prostate, colorectal, and lung cancers during the study period. These included diagnostic, staging, and treatment changes that occurred over time. RESULTS: 3.3% of incident cases were accrued to clinical trials during the study period, more often for breast and colorectal than for lung and prostate cancers. Reasons that were identified for low accrual were lack of clinical trials for the majority of cases, including the elderly. More than 65% of the patients in the outreach population were older than 65, compared with 50% at the cancer center. Patterns of care did change for breast and prostate cancers, but were similar to national trends.

Adult↗
PubMed2001

Haptoglobin, inflammation, and tumorigenesis in the MIN mouse.

We have determined that the MIN mouse, which is predisposed to adenomas of the small and large intestine, exhibits chronic inflammation characterized by the induction of haptoglobin (HP), as well as other acute phase proteins. Inflammation is initiated at about 40-70 days of age, and is maintained throughout the life of the animal. Delayed onset of inflammation brought on by dietary means is associated with a reduction in tumor number and longer life-span. Knockout mice that lack haptoglobin exhibit an increase in tumor number, indicating that the acute phase reactant suppresses tumorigenesis, perhaps through inhibition of the inflammatory response. The MIN mouse is, therefore, a useful model for studying the roles of HP and inflammation in tumorigenesis in vivo.

Adenoma↗
PubMed2001

Undergraduate environmental health education: preparing for the future.

Attendees indicated that the workshop was beneficial and that the opportunity to communicate with faculty representing 23 programs accredited by EHAC and nine programs not accredited by EHAC was extremely useful. There was general agreement on a number of points: There is a need for undergraduate environmental health programs to collaborate on matters related to distance learning. Topics related to women, gender, diversity, ethics, and international environmental health should be incorporated into the environmental health curriculum. There are no major problems with current EHAC curricular guidelines, but the guidelines should be evaluated on a regular basis. Field experience or internship is an essential component in the academic preparation of undergraduate environmental health students. There is a significant need for increased funding for undergraduate environmental health programs. There is a need to increase the visibility and recognition of environmental health programs. There is a need to solidify ties with traditional partners and to establish new linkages at the local, regional, and national levels in the government, community, and private sector. It is essential that undergraduate faculty communicate with each other on matters relating to the preparation of environment health practitioners. There is a need for an association of undergraduate academic programs to provide leadership and a focal point for identification and resolution of issues common to all. The establishment of an association was viewed as the most practical and effective way to address these issues and to pursue related opportunities.

Accreditation↗
PubMed2000

Distinct distribution of rare us kshv genotypes in south texas. Implications for kshv epidemiology and evolution.

PURPOSE: Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). Although previous studies have assessed the geographic distribution of KSHV genotypes, the molecular epidemiology of KSHV remains largely unknown. The purpose of the present study was to examine the genotypes of KSHV isolates from KS patients in South Texas.METHODS: Eighteen KSHV isolates from 16 KS and 1 PEL patients in South Texas were collected between 1996 and 1998 and analyzed for KSHV subtypes by PCR sequencing of ORFK1 gene and KS330 fragment, and by PCR of ORFK15 gene. DNA sequences were aligned with known sequences and KSHV subtypes were assigned based on sequence variations.RESULTS: Of 18 KSHV isolates, 13 exhibited C subtype, and 5 exhibited A subtype in ORF K1 gene. ORF K15 genotyping showed that 10 of the isolates exhibited M form, of which 9 had C3 subtype. A unique C subtype isolate was found and classified as C6 clade. All of the M form KSHV isolates were found among KS patients over 50 years of age. Conversely, all KS patients under 40 years of age had only the P form KSHV isolates.CONCLUSIONS: In South Texas there is a distinct distribution of C3/M KSHV isolates, which are rarely found in other US regions (1 of 29). The C3/M KSHV genotype is more prevalent in HIV-negative elderly KS patients while the P-form of KSHV is more common among many young AIDS-KS patients.

Journal Article↗
PubMed2000

Changing spectrum of mortality due to human immunodeficiency virus: analysis of 260 deaths during 1995--1999.

We analyzed the deaths in an outpatient human immunodeficiency virus (HIV) care clinic at University Hospitals in Cleveland from January 1995 through December 1999. The number of annual deaths decreased progressively, from 112 in 1995 to 32 in 1999. The median final CD4(+) cell count before death increased progressively from 10 cells/microL in 1995 to 90 cells/microL in 1999 (P<.01); 20%--25% of patients who died from 1997 through 1999 had plasma HIV RNA levels below detection limits. From 1995 through 1998, deaths due to infection, to end-stage acquired immune deficiency syndrome, and to malignancies decreased, whereas the proportion of deaths due to end-organ failures and of uncertain relationship to HIV infection increased. The spectrum of mortality in HIV disease has changed recently; although opportunistic infections cause death less frequently, deaths are occurring in people who have control of HIV replication and with some preservation of immune function. These observations underscore the need to monitor the etiologies of HIV-associated mortality and to better our understanding of the relationships among immune defenses, treatment-related toxicities, and end-organ failure in patients with HIV disease.

Adult↗
PubMed2000

Genomic organisation and characterisation of the neural sex-determination gene fruitless (fru) in the Hawaiian species Drosophila heteroneura.

There are several mechanisms for the determination of sex. Sexual behaviour is part of the sex-determination cascade, and in Drosophila melanogaster male courtship is controlled in part by the fruitless gene. As part of a study of sexual behaviour in Hawaiian Drosophila, we have cloned the neural sex-determination gene fru from the Hawaiian picture-wing species Drosophila heteroneura. The fru gene has at least seven exons covering a region of 18kb and encodes three transcripts, fruA, fruB and fruC. Each transcript encodes a single ORF of 841, 678 and 691aa, respectively. The FRUA and FRUB proteins have a BTB protein-protein-binding domain and two zinc finger-like domains and are well conserved with the D. melanogaster proteins. The FRUC protein has a BTB domain but no zinc finger-like domains. The fru gene is expressed in 1-7 day old adult males as a 5.1kb transcript. This transcript is not seen in adult females, so the fru gene has a different pattern of sex-differential expression in the Hawaiian Drosophila compared with D. melanogaster.

Alternative Splicing↗
PubMed2000

Infective endocarditis in intravenous drug users: does HIV status alter the presenting temperature and white blood cell count?

The intent of this study was to determine if HIV seropositivity alters the maximum temperature (T(max)) and WBC count of febrile intravenous (i.v.) drug users with infective endocarditis (IE). A review of 497 charts of patients with endocarditis provided 228 eligible patient visits (46%), with 158 cases (69.3%) of IE among 126 patients (74 HIV+ and 52 HIV-). Mean T(max) for all patients with IE was 39.1 degrees C (102.4 degrees F). Mean T(max) was similar between the HIV+ (39.1 degrees C, 102.4 degrees F) and HIV- (39.2 degrees C, 102.5 degrees F) groups. There were no differences in mean T(max) among HIV+ patients with CD4 counts > 200 (39.0 degrees C, 102.3 degrees F), those with CD4 < or =200 (39.2 degrees C, 102.5 degrees F), and the HIV- group (39.2 degrees C, 102.5 degrees F). Nearly 8% of i.v. drug users with confirmed IE presented to the ED with a T(max) below 37.8 degrees C (100.0 degrees F). Mean WBC count was significantly lower in HIV+ (11.1 k/mm(3)) than in HIV- patients (15.4 k/mm(3)) and significantly lower in the group with CD4 < or =200 (8.0 k/mm(3)) than in the HIV- group. In conclusion, HIV infection was not associated with lower T(max), but it was associated with decreased WBC count in the general HIV+ group and in the group with CD4 < or =200.

Adult↗
PubMed2000

Elimination of male germ cells in transgenic mice by the diphtheria toxin A chain gene directed by the histone H1t promoter.

Expression of the diphtheria toxin A-chain gene was directed to the male germ line by fusion to 1 kilobase of the 5'-flanking DNA of the rat histone H1t gene. Two independent lines of mice were established that expressed the toxic transgene. Female carriers were fertile; males were sterile although otherwise apparently normal. Adult transgenic males had very small testes that were virtually devoid of germ cells. A developmental study showed that germ cells survived until late fetal life but that testes of 3-day-old transgenic mice were severely depleted of prospermatogonia. During postnatal development of transgenic animals, remaining germ cells progressed to the pachytene stage of meiosis in 10% to 30% of tubular cross sections but degenerated before the completion of meiosis. By 3 mo of age the residual germ cells had almost completely disappeared. These transgenic lines demonstrate the complete tissue specificity of the H1t promoter and reveal a period of its activity just prior to formation of the definitive adult spermatogonial stem cell population. Whereas full expression of H1t occurs only in mid to late pachytene spermatocytes, one or more of the factors that impart tissue specificity to its expression must be transiently activated in the neonatal germ line. This report discusses the possibility that this genetic technique for eliminating germ cells may have practical application in making recipients for spermatogonial stem cell transplantation.

Animals↗
PubMed2000

Genomic organisation of the neural sex determination gene fruitless (fru) in the Hawaiian species Drosophila silvestris and the conservation of the fru BTB protein-protein-binding domain throughout evolution.

We report the cloning and sequencing of the fru gene from the Hawaiian picture-wing species Drosophila silvestris. The fru gene has seven exons spanning 15-kb encoding two transcripts with ORFs of 841 and 695 amino acids. The protein encoded by the fruA transcript is well conserved with the D. melanogaster type A protein, particularly the BTB protein-protein-binding domain, which is encoded by exons I and II and is 100% conserved. The peptide encoded by exon III has several sequence differences but these are confined mostly to regions of repetitive sequence and exons IV to VI are well conserved. The peptide encoded by exon VII is semi-conserved for the 5' end and 100% conserved for the Zinc finger domains; the rest of the peptide is virtually unconserved. The FRUA protein has a BTB domain and two zinc finger domains whereas the FRUC protein only has the BTB domain. The genomic DNA sequence encoding the BTB domain of the fru gene has been cloned from 21 species of Diptera. The protein-coding sequence is highly conserved and the amino acid sequence is identical except for two changes in the Tephritidae. The intron sequences are completely unconserved except between very closely related species such as the Hawaiian Drosophila. The phylogeny produced using the BTB exon sequences suggests that the most closely related mainland Drosophila species to the Hawaiian clade is D. moriwakii of the melanica species group. The phylogeny also shows that the Scaptomyza are closely related to the Hawaiian Drosophila so supporting a Hawaiian origin for the Scaptomyza. The genus Zaprionus is placed in the subgenus Drosophila closely related to D. immigrans along with the genera Samoaia and Liodrosophila.

Amino Acid Sequence↗