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Biomedical subjects

J Marks

Publications and source records attributed to J Marks.

At least 37 records · Page 2Linked to original sources

Blood will tell (won't it?): a century of molecular discourse in anthropological systematics.

Being derived from the hereditary material, molecular genetic data are often assumed to be a source of sounder inferences about evolution than data from other kinds of investigations. This, however, tends to be taken in the absence of a clear knowledge of the evolutionary processes at work, the technical shortcomings, and the manner of deriving the specific conclusions. The history of biological anthropology shows that, from the beginning of the 20th century, grossly naive conclusions have been promoted simply on the basis that they are derived from genetics, without having been fully thought-out. A balanced consideration of the shortcomings as well as the advantages of genetic data are necessary for its proper integration into the advantages of genetic data are necessary for its proper integration into the field. When molecular and morphological data disagree, both must be re-examined carefully, for genetics has been used irresponsibly as a form of scientific validation, both in American society and in American science. Contemporary data bearing on the molecular relationships of the apes are note-worthy for their diversity in quality, and need to be evaluated in the light of molecular and microevolutionary theory.

Animals

Intraabdominal mesh prosthesis in a canine model.

Laparoscopic inguinal hernia repair is still at an investigational stage, and varying methods have been described in the literature. These include the transabdominal preperitoneal approach, the intraperitoneal onlay mesh procedure, and the extraperitoneal approach. This study evaluates the differences in macroscopic adhesion formation between transabdominal preperitoneal mesh placement, intraperitoneal onlay mesh procedures, and extraperitoneal mesh placement in a canine model. The determination of microscopic tissue ingrowth and mesh incorporation was not a goal of this study. Operative sites utilizing mesh in a reperitonealized fashion resulted in less adhesion formation than did those sites where mesh was placed in an intraperitoneal manner using the onlay technique. Mesh placed in the extraperitoneal space without entering the peritoneal cavity did not exhibit any adhesion formation. Results favor the reperitonealization of intraabdominal mesh or mesh placement by an extraperitoneal approach.

Animals

Loss of chromosome 8p sequences in human breast carcinoma cell lines.

Cytogenetic and molecular analyses of human breast cancer cells have identified consistent losses of specific chromosomal regions in these tumors, suggesting that such regions harbor tumor suppressor genes whose homozygous loss or inactivation directly contributes to tumorigenesis. To date, deletions of chromosome 8 sequences have been described infrequently and only in low percentages of breast carcinomas. We report the identification of a new DNA marker on chromosome 8p that is deleted in 6 (75%) of 8 breast carcinoma cell lines and in 1 primary breast carcinoma examined. No deletion of this marker was detected in any normal or nonbreast carcinoma cell lines analyzed. Southern blot and fluorescence in situ hybridization studies indicate that this clone maps to chromosome 8 between bands p12 and p21. These observations suggest that a new gene, whose loss or inactivation may foster breast carcinoma tumorigenesis, may reside in this chromosome 8p region.

Base Sequence

Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture.

Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study.

Amino Acid Sequence

Brain death in pediatric intensive care unit patients: incidence, primary diagnosis, and the clinical occurrence of Turner's triad.

OBJECTIVES: To determine the incidence and characteristics of children with brain death in the pediatric intensive care unit (ICU), and to assess the incidence of the clinical triad (Turner's triad) of central diabetes insipidus, low glucose demand, and low CO2 production. DESIGN: Retrospective review of medical records. SETTING: Two multidisciplinary pediatric ICUs. PATIENTS: Medical records of pediatric patients declared brain dead and admitted to two multidisciplinary pediatric ICUs. MEASUREMENTS AND MAIN RESULTS: Patient records were reviewed for demographic data, primary diagnosis, severity of illness (Pediatric Risk of Mortality score and calculated risk of mortality), methods by which brain-death diagnosis was determined, presence of central diabetes insipidus, low glucose demand, low CO2 production in the final 24 hrs before the diagnosis was made, and whether organ donation was accomplished. The incidence of brain death among all patients admitted to the pediatric ICUs was 0.9%, accounting for 11% of patients who died during the same period. The most common presentation leading to brain-death diagnoses was trauma, followed by drowning/near drowning, and meningitis. The majority of brain-death diagnoses were made using both clinical criteria and confirmatory tests (66%). The incidence of clinical signs of Turner's triad was 41% for central diabetes insipidus, 49% for low glucose demand, and 53% for low CO2 production. Two of the three features were present in 38% of patients, and 12% of the patients had all three features. CONCLUSIONS: Our series of brain-dead patients in the pediatric ICU showed a 0.9% incidence of brain death. The most common primary diagnosis was trauma, a finding that is similar to other series. We also demonstrated that the clinical triad (Turner's triad) is present in this patient population, although only 12% of study patients demonstrated all three features.

Adolescent

Evidence for structural conservation of Lon and RcsA.

DNA probes specific to the Escherichia coli genes encoding Lon protease and RcsA hybridized to specific DNA sequences in a number of different microorganisms. Antiserum to either E. coli protein Lon or RcsA reacted with specific proteins in these organisms. These results provide structural evidence of the presence of Lon and RcsA in organisms other than E. coli.

ATP-Dependent Proteases

A study of chromium induced allergic contact dermatitis with 54 volunteers: implications for environmental risk assessment.

Over the past 60 years, dose-response patch test studies by various methods have been conducted in an attempt to identify the minimum elicitation threshold (MET) concentration of hexavalent chromium (Cr(VI)) that produces an allergic response in Cr(VI) sensitive subjects. These data are not adequate, however, to provide an accurate estimate of the MET because of the variability in the patch testing techniques and the variability in diagnostic criteria used. Furthermore, the data were not reported in terms of mass of allergen per surface area of skin (mg Cr/cm2-skin), which is necessary for conducting occupational or environmental health risk assessments. Thus the purpose of this study was to determine the MET (mg allergen/cm2) for Cr(VI) and trivalent chromium (Cr(III)) by patch testing techniques. A patch test method that delivers a controlled amount of allergen per surface area of skin was used. A group of 54 Cr(VI) sensitised volunteers were patch tested with serial dilutions of Cr(VI) and Cr(III) to determine the cumulative response rate at several concentrations. The results indicate that the 10% MET for Cr(VI) based on the cumulative response was 0.089 micrograms Cr(VI)/cm2-skin. Only one of the 54 volunteers may have responded to 33 micrograms Cr(III)/cm2-skin, otherwise Cr(III) was unable to produce allergic contact dermatitis in these highly sensitive volunteers. Two supplemental studies were also conducted to assess whether the surface area of the patch and the concentration of Cr(VI) in the patch (related to patch thickness) were likely to influence the results. The data from these studies were used to assess the risk of developing allergic contact dermatitis due to contact with Cr(VI) and Cr(III) in soil. The findings indicated that soil concentrations at least as high as 450 ppm Cr(VI) and 165,000 ppm Cr(III) should not pose an allergic contact dermatitis hazard for at least 99.99% of the people in the community who might be exposed.

Adult

The management of urinary incontinence in the long-term patient.

Urinary incontinence affects 50%-80% of residents in nursing homes, presenting a challenge to the health care team. Assessment of urinary incontinence is crucial to selecting appropriate treatment. This article addresses the scope of the problem, incontinence assessment, and treatment specific to nursing home residents.

Homes for the Aged

A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.

A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons.

Antibodies, Anti-Idiotypic

Hominoid heterochromatin: terminal C-bands as a complex genetic trait linking chimpanzee and gorilla.

The genetic relations of the apes have been the source of contention throughout the last decade. A potentially useful suite of phylogenetic characters is the distribution of darkly staining material (heterochromatin) in the chromosomes of the apes. While the precise etiology of this character suite remains unclear, it appears to be fairly easily reconciled to hominoid phylogeny in general. The distribution of heterochromatin at the tips of the chromosomes of gorillas and chimpanzees suggests a phylogenetic association between those two taxa exclusive of humans.

Animals

The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis?

In the fission yeast Schizosaccharomyces pombe, septum formation and cytokinesis are dependent upon the initiation, though not the completion of mitosis. A number of cell cycle mutants which show phenotypes consistent with a defect in the regulation of septum formation have been isolated. A mutation in the S. pombe cdc16 gene leads to the formation of multiple septa without cytokinesis, suggesting that the normal mechanisms that limit the cell to the formation of a single septum in each cycle do not operate. Mutations in the S. pombe early septation mutants cdc7, cdc11, cdc14 and cdc15 lead to the formation of elongated, multinucleate cells, as a result of S phase and mitosis continuing in the absence of cytokinesis. This suggests that in these cells, the normal mechanisms which initiate cytokinesis are defective and that they are unable to respond to this by preventing further nuclear cycles. Genetic analysis has implied that the products of some of these genes may interact with that of the cdc16 gene. To understand how the processes of septation and cytokinesis are regulated and coordinated with mitosis we are studying the early septation mutants and cdc16. In this paper, we present the cloning and analysis of the cdc16 gene. Deletion of the gene shows that it is essential for cell proliferation: spores lacking a functional cdc16 gene germinate, complete mitosis and form multiple septa without undergoing cell cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

The activity of S.pombe DSC-1-like factor is cell cycle regulated and dependent on the activity of p34cdc2.

In the eukaryotic cell cycle, there are major control points in late G2 to determine the timing of the initiation of mitosis, and in late G1, regulating entry into S phase. In yeasts, this latter control is called start. Traverse of the start control and progression to S phase is accompanied by an increase in the expression of some of the genes whose products are required for DNA synthesis. In Saccharomyces cerevisiae, the coordinate expression of these genes in late G1 is dependent on a cis-acting sequence element called the MluI cell cycle box (MCB). A transcription factor called DSC-1 binds these elements and mediates cell cycle regulated transcription, though it is unclear whether this is by cell cycle-dependent changes in its activity. A DSC-1-like factor has also been identified in the fission yeast S.pombe. This is composed of at least the products of the cdc10 and sct1/res1 genes, and binds to the promoters of genes whose expression increases prior to S phase. We demonstrate that p85cdc10 is a nuclear protein and that the activity of the S.pombe DSC-1 factor varies through the cell cycle; it is high in cells that have passed start, decreases at the time of anaphase, remains low during the pre-start phase of G1 and increases at the time of the next S phase. We also show that the reactivation in late G1 is dependent on the G1 form of p34cdc2.

Anaphase

Mutation of the p53 tumor-suppressor gene is not a feature of endometrial hyperplasias.

OBJECTIVE: Mutation and overexpression of the p53 gene occur in approximately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we examined the p53 gene in endometrial hyperplasias. STUDY DESIGN: Genomic deoxyribonucleic acid was extracted from 117 endometrial hyperplasias (36 simple, 40 complex, 41 atypical) and 30 endometrial cancers. Exons 5 through 8 of the p53 gene were amplified by means of the polymerase chain reaction. Mutations in the p53 gene were sought with single-stranded conformation polymorphism analysis and confirmed by direct deoxyribonucleic acid sequencing. RESULTS: None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in three of 30 (10%) endometrial cancers (p < 0.02). The p53 mutations seen in three cancers were confirmed by direct sequencing (codons 157, 180, 272). CONCLUSION: Because it does not appear to be a feature of endometrial hyperplasias, mutation of the p53 gene may represent a relatively late event in endometrial carcinogenesis.

Base Sequence

Arteriovenous reversal for limb salvage in unreconstructible upper extremity arterial occlusive disease.

PURPOSE: Peripheral vascular disease of the upper extremity as a result of atherosclerotic disease or systemic vascular disorders presents a difficult management problem to the vascular surgeon. When extensive distal disease is present bypass procedures with standard arterial reconstruction techniques may not be possible. The use of retrograde perfusion to deliver oxygenated blood to the capillary bed by means of a normal venous system is not new. Flow reversal has been attempted in the myocardial, cerebral, and distal extremity circulations. Arteriovenous reversal (AVR) has been described for limb salvage in patients with upper extremity ischemia, with variable results. METHODS: We performed six AVR procedures on five patients with diffuse distal arterial disease and limb-threatening upper extremity ischemia. Two patients had insulin-dependent diabetes, one had systemic lupus erythematosus (two extremities), one had rheumatoid arthritis with vasculitis, and the remaining patient had CRST (calcinosis, Raynaud's disease, sclerodactyly, telangiectasia) syndrome. The two patients with diabetes had systemic manifestations of atherosclerotic vascular disease and lower extremity ischemia; the remaining three patients had no evidence of atherosclerosis. In all patients the AVR was performed at the most distal site of nondiseased artery. RESULTS: Limb salvage was obtained in all cases; one patient had a healed minor digital amputation, and another patient had a healed major amputation. Clinical improvement with resolution of pain was achieved in five of six cases. The remaining patient had a significant diabetic neuropathy that was believed to contribute to her persistent pain. CONCLUSIONS: In patients with severe upper extremity ischemia not amenable to standard revascularization techniques, AVR should be considered to provide limb salvage and maximize hand function.

Adult

Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults.

Major depression has been associated with mortality from ischemic heart disease (IHD). In addition, a symptom of depression--hopelessness--has been suggested as a determinant of health status. We studied the relation of both depressed affect and hopelessness to IHD incidence using data from a cohort of 2,832 U.S. adults age 45-77 years who participated in the National Health Examination Follow-up Study (mean follow-up = 12.4 years) and had no history of IHD or serious illness at baseline. We used the depression subscale of the General Well-Being Schedule to define depressed affect and a single item from the scale to define hopelessness. At baseline, 11.1% of the cohort had depressed affect; 10.8% reported moderate hopelessness, and 2.9% reported severe hopelessness. Depressed affect and hopelessness were more common among women, blacks, and persons who were less educated, unmarried, smokers, or physically inactive. There were 189 cases of fatal IHD during the follow-up period. After we adjusted for demographic and risk factors, depressed affect was related to fatal IHD [relative risk = 1.5; 95% confidence interval (CI) = 1.0-2.3]; the relative risks of fatal IHD for moderate and severe levels of hopelessness were 1.6 (95% CI = 1.0-2.5) and 2.1 (95% CI = 1.1-3.9), respectively. Depressed affect and hopelessness were also associated with an increased risk of nonfatal IHD. These data indicate that depressed affect and hopelessness may play a causal role in the occurrence of both fatal and nonfatal IHD.

Aged

The effect of short-term low-dose cyclosporin on renal function and blood pressure in patients with psoriasis.

The effect of short-term (mean 2.4 months), low-dose (5 mg/kg) cyclosporin A (CyA) on renal function and blood pressure was studied in eight patients with psoriasis. Studies were undertaken before, during and after treatment. Glomerular filtration rate (GFR) post-treatment was significantly higher than pretreatment or during treatment (pre, 119 +/- 7; during, 113 +/- 9; post, 133 +/- 11 ml/min per 1.73 m2; pre vs. during, NS; during vs. post, P < 0.01; pre vs. post, P < 0.05); effective renal plasma flow (ERPF) was unchanged (pre, 515 +/- 38; during, 485 +/- 49; post, 560 +/- 45 ml/min per 1.73 m2). There was no change in the urinary excretion of either albumin or the enzymes N-acetyl-glucosaminidase, lactate dehydrogenase, alanine aminopeptidase and alkaline phosphatase. There was a decrease in exchangeable sodium which persisted post-treatment (pre, 56 +/- 3; during, 49 +/- 3; post, 49 +/- 3 mmol/kg LBM; pre vs. during, P = 0.07; during vs. post, NS; pre vs. post, P = 0.06). Blood pressure assessed as either a single reading, or the mean of a 24 h ambulatory recording, increased during treatment (single reading: pre, 113/73; during, 126/83; post, 114/70 mmHg; mean 24 h: pre, 114/71; during, 123/76; post, 120/72 mmHg). Thus, short-term use of CyA at a dose of 5 mg/kg for the treatment of psoriasis is associated with a significant increase in blood pressure, but only a transient mild reduction in GFR, which did not reach significance.

Adult