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Biomedical subjects

K Harrison

Publications and source records attributed to K Harrison.

At least 19 recordsLinked to original sources

Medical eligibility, comprehension of the consent process, and retention of injection drug users recruited for an HIV vaccine trial.

Injection drug users (IDUs) at high risk for human immunodeficiency virus (HIV) infection are being identified as a population for HIV vaccine trials. We studied willingness of drug users to enroll and their comprehension of consent procedures in the context of a Phase II trial at one site. Of 175 people screened for enrollment and whose data sets were complete, 119 (68%) were IDUs. Of the 71 who were eligible, 39 (55%) were IDUs. Exclusion of IDUs was usually for medical reasons. Using a 17-item true/false test, comprehension of the informed consent procedure was high (median score, 16 of 17 for IDUs and non-IDUs); only three subjects (all of whom were IDUs) were excluded from enrollment due to lack of comprehension. Follow-up rates were similar for IDUs and non-IDUs. These data suggest that recruitment of IDUs into HIV vaccine trials is feasible, that IDUs can comprehend and complete the informed consent procedures, and that they return for follow-up visits.

AIDS Vaccines

Clinical trial of fermented maize-based oral rehydration solution in the management of acute diarrhoea in children.

In an effort to identify appropriate fluids available in the home for oral rehydration therapy in Ghana, a study was designed to investigate the efficacy of fermented maize gruel, a popular Ghanaian traditional food, in the management of acute diarrhoea. Altogether 108 children aged between 4 and 27 months presenting with acute diarrhoea at the Princess Marie Louise Children's Hospital in Accra, with mild to moderately severe dehydration, were randomly assigned to treatment with either WHO/UNICEF oral rehydration solution (ORS) or fermented and unfermented maize solutions. About 35 children were admitted to each of the three treatment groups. Treatment with the rehydration fluid was maintained for 24 h. Efficacy of the various treatments, assessed in terms of fluid intake, stool output, stool frequency, weight gain and duration of diarrhoea, showed no significant variation among the three groups. The results indicate that the maize solutions were as effective as WHO/UNICEF ORS for oral rehydration therapy. However, the fermented maize was more readily accepted by the children than the unfermented solution. Because fermented maize gruel is widely consumed, inexpensive, readily available, and culturally acceptable to most communities in Ghana, it may be recommended as an appropriate home-available fluid for the management of acute diarrhoea in children at the community level.

Acute Disease

Germinal transpositions of the maize element Dissociation from T-DNA loci in tomato.

We have analyzed the pattern of germinal transpositions of artificial Dissociation (Ds) transposons in tomato. T-DNA constructs carrying Ds were transformed into tomato, and the elements were trans-activated by crossing to lines transformed with a stabilized Activator (sAc) that expressed the transposase gene. The sAc T-DNA carried a GUS gene to monitor its segregation. The Ds elements were inserted in a marker gene so that excision from the T-DNA could be monitored. The Ds elements also carried a genetic marker that was intended to be used for reinsertion selection of the elements after excision. Unfortunately, this gene was irreversibly inactivated on crossing to sAc. Germinal excision frequencies of Ds averaged 15-40%, but there was large variation between and within plants. Southern hybridization analysis of stable transposed Ds elements indicated that although unique transpositions predominate, early transposition events can lead to large clonal sectors in the germline of developing plants and to sibling offspring carrying the same transposition event. Multiple germinal transpositions from three different loci were examined for uniqueness, and 15 different transpositions were identified from each of three T-DNA loci that carried a single independent Ds. These were mapped relative to the donor T-DNA loci, and for each locus 70-80% of the transposed elements were closely linked to the donor site.

Base Sequence

Oral cavity and pharyngeal cancer among Department of Veterans Affairs hospital discharges.

OBJECTIVES: The purpose of this study is to determine the number of oral cavity and pharyngeal cancers among hospital discharges at Department of Veterans Affairs (VA) medical centers in one 12-month period. METHODS: A SAS file was created from the patient treatment file (PTF) with all discharges during fiscal 1990 having ICD-9-CM codes for oral cavity and pharyngeal cancer. Up to 10 discharge diagnoses from the most recent discharge summary were included in the data set. ICD-9-CM codes for alcohol dependence syndrome, drug dependence, and nondependent abuse of drugs also were included. ICD-9-CM codes for salivary and nasopharyngeal cancers were excluded. RESULTS: There were 3,733 unique individuals discharged with a diagnosis of oral cavity and pharyngeal cancer. The majority of cases (62%) were found in the oral cavity. The age distribution of oral cavity and pharyngeal cancer did not parallel the age distribution of veterans discharged during this year. Race and ethnicity of those discharged with the disease does not differ from that of all VA hospital discharges for 1990. CONCLUSIONS: VA data provide descriptive statistics of oral cavity and pharyngeal cancer among VA hospital discharges. VA data sets such as the PTF may offer the opportunity to examine hospital management issues, length of stay, and co-morbid diagnoses associated with oral cavity and pharyngeal cancer.

Adult

Developmentally regulated cell death on expression of the fungal avirulence gene Avr9 in tomato seedlings carrying the disease-resistance gene Cf-9.

Plant defense responses are induced when the products of disease-resistance genes and pathogen avirulence genes interact. We report here the effects of expressing the Cladosporium fulvum avirulence Avr9 gene product in a tomato line containing the Cf-9 disease-resistance gene. A synthetic Avr9 gene was constructed to produce constitutive high-level expression of AVR9 peptide in the plant apoplast. Avr9 expression in Cf-9-containing tomato lines is lethal, but cell death is developmentally regulated, in that necrosis is not visible until 10 days after planting seed. Plant lines lacking Cf-9 and expressing Avr9 remain healthy. The synthetic Avr9 gene exhibited the same specificity of action as the authentic C. fulvum Avr9 gene. Our results have significant implications for strategies using the gene combination Avr9/Cf-9 to engineer plants with enhanced disease resistance.

Amino Acid Sequence

Chloroplast targeting of spectinomycin adenyltransferase provides a cell-autonomous marker for monitoring transposon excision in tomato and tobacco.

Antibiotic resistance genes can act as either cell autonomous or non-cell autonomous genetic markers with which to monitor the excision of plant transposons. To convert spectinomycin resistance from a non-cell autonomous resistance to cell autonomous resistance, a transit peptide for chloroplast localization from a petunia ribulose bisphosphate carboxylase (rbcS) gene was fused in-frame to the aadA gene, which confers spectinomycin and streptomycin resistance. Constructs were generated in which the expression of this chimeric gene was prevented by the presence, in the 5' untranslated leader, of the maize transposons Activator (Ac) or Dissociation (Ds). When progeny of tobacco or tomato plants transformed with these constructs were germinated on spectinomycin-containing medium, germinally revertant and somatically variegated individuals could be distinguished.

Base Sequence

Tetrasomy 12p (Pallister-Killian syndrome): ultrasound indicators and confirmation by interphase fish.

Tetrasomy 12p (Pallister-Killian syndrome) is a mosaic aneuploidy syndrome in which the isochromosome is present in amniocytes with a much greater percentage than fetal lymphocytes. Two new cases identified by prenatal diagnosis are reported. Indications for prenatal diagnosis were advanced maternal age and fetal anomalies. The most consistent reported prenatal ultrasound findings for tetrasomy 12p include polyhydramnios with short femurs and a diaphragmatic hernia. Recognition of congenital malformation patterns prenatally may allow appropriate selection of tissue for chromosome analysis. Molecular cytogenetic analysis using fluorescence in situ hybridization was used retrospectively to confirm the presence of the isochromosome 12p in various formalin-fixed fetal tissues. The levels of mosaicism detected in fetal and placental tissues were lower than those detected prenatally.

Abnormalities, Multiple

Analysis of the chromosomal distribution of transposon-carrying T-DNAs in tomato using the inverse polymerase chain reaction.

We are developing a system for isolating tomato genes by transposon mutagenesis. In maize and tobacco, the transposon Activator (Ac) transposes preferentially to genetically linked sites. To identify transposons linked to various target genes, we have determined the RFLP map locations of Ac- and Dissociation (Ds)-carrying T-DNAs in a number of transformants. T-DNA flanking sequences were isolated using the inverse polymerase chain reaction (IPCR) and located on the RFLP map of tomato. The authenticity of IPCR reaction products was tested by several criteria including nested primer amplification, DNA sequence analysis and PCR amplification of the corresponding insertion target sequences. We report the RFLP map locations of 37 transposon-carrying T-DNAs. We also report the map locations of nine transposed Ds elements. T-DNAs were identified on all chromosomes except chromosome 6. Our data revealed no apparent chromosomal preference for T-DNA integration events. Lines carrying transposons at known map locations have been established which should prove a useful resource for isolating tomato genes by transposon mutagenesis.

Base Sequence

Pain perception in self-injurious patients with borderline personality disorder.

Pain ratings during the cold pressor test were significantly lower in female inpatients with borderline personality disorder who report that they do not experience pain during self-injury (BPD-NP group, n = 11), compared with similar patients who report that they do experience pain during self-injury (BPD-P group, n = 11), and normal female subjects (n = 6). Pain ratings were not significantly different in the BPD-P and normal control groups. Self-report ratings of depression, anger, anxiety, and confusion were significantly lower, and ratings of vigor significantly higher following the cold pressor test in the BPD-NP group, but not in the BPD-P group. Only anxiety was significantly lower in the normal control group following the cold pressor test. The implications and limitations of these preliminary findings are discussed.

Adolescent

Factors affecting the separation and loading capacity of proteins in preparative gradient elution high-performance liquid chromatography.

The optimum conditions for the purification of proteins by gradient elution in reversed-phase liquid chromatography were studied, with emphasis on the column length. Because of the strong dependence of the retention of proteins on the mobile phase composition, very short columns can be used successfully to perform analytical separations. A similar conclusion is extended to preparative separations. Columns with different lengths and diameters were used. The dependence of the loading capacity for touching band separation on the column length, diameter and volume was studied, in addition to the regeneration time between successive runs, the starting mobile phase composition and the necessary column efficiency.

Animals

Effective vectors for transformation, expression of heterologous genes, and assaying transposon excision in transgenic plants.

Progress in plant molecular biology has depended heavily on the availability of effective vectors for plant cell transformation and heterologous expression. In this paper we describe the structures of a wide array of plasmids which have proved extremely effective in (a) plant transformation, (b) expression of heterologous genes and (c) assaying the activity of transposons in transgenic plants. Constructs that confer resistance to kanamycin, hygromycin, streptomycin, spectinomycin and phosphinotricin, or that confer beta-glucuronidase (GUS) gene expression are presented. Binary vector constructs that carry polylinkers of the pUC and Bluescript types are also described. Plasmids that permit the expression of any heterologous reading frame from either nopaline synthase (nos) or octopine synthase (ocs) promoters, as well as the cauliflower mosaic virus 35S promoter, using either the nopaline synthase or octopine synthase 3' polyadenylation sequences, are presented. These constructs permit a choice of orientation of the resulting transgene of interest, relative to the orientation of the selection marker gene. Most of the plasmids described here are publicly available.

Amino Acid Oxidoreductases

Reduced erythrocyte and leukocyte magnesium is associated with cyclosporin treatment and hypertension in renal transplant patients.

Plasma, urine, erythrocyte and leukocyte magnesium were measured in normotensive and hypertensive renal transplant patients who were being treated with either azathioprine or cyclosporin. These were compared with essential hypertensive patients and normal subjects. Erythrocyte and leukocyte magnesium were reduced in renal transplant patients in independent association (ANOVA) with both cyclosporin treatment (P = 0.03, P = 0.016 respectively) and hypertension (P less than 0.001 for both). Therefore, hypertensive transplant patients on cyclosporin had the lowest magnesium content of both erythrocytes (1.22 +/- 0.09 mmol/l cells) and leukocytes (2.68 +/- 0.2 nmol/10(6) cells) compared to normal subjects (1.96 +/- 0.17 and 4.11 +/- 0.58 respectively) whereas normotensive transplant patients on azathioprine had normal values (2.12 +/- 0.16 and 5.13 +/- 1.0 respectively). Plasma magnesium was also reduced with cyclosporin treatment. Urine magnesium was not significantly different between any of the groups. Therefore, magnesium depletion may have a role in hypertension in renal transplant patients. Since cyclosporin treatment is also associated with magnesium depletion, this could explain the increased occurrence of hypertension in these patients.

Adult

Promoter fusions to the Activator transposase gene cause distinct patterns of Dissociation excision in tobacco cotyledons.

To explore the effects of altering the level of Activator (Ac) transposase (TPase) expression, a series of plasmids was constructed in which heterologous promoters were fused to the TPase gene. Promoters for the cauliflower mosaic virus (CaMV) 35S transcript and the octopine synthase (ocs) and nopaline synthase (nos) genes were tested. These fusions, and constructs expressing TPase from the wild-type Ac promoter, were introduced into tobacco, and their activity was monitored by crossing to a line carrying Dissociation (Ds) in a streptomycin phosphotransferase gene (Ds::SPT). The SPT marker provides a record of somatic excisions of Ds that occur during embryo development. The patterns of somatic variegation that resulted from transactivation by each fusion were distinct and strikingly different from the pattern triggered by the wild-type Ac constructs. Unlike wild-type Ac, which caused transposition throughout embryo development, each fusion gave rise to sectors of discrete size. Sectors triggered by the CaMV 35S fusion were largest, ocs sectors were intermediate, and nos were smallest. These patterns appear to indicate differential timing of the activation of these promoters during embryogeny. Measurement of transcript abundance for each transformant indicated that the CaMV 35S-transformed plants accumulated approximately 1000-fold more TPase mRNA than plants containing wild-type Ac, whereas ocs- and nos-transformed lines accumulated about 100-fold and 20-fold higher levels, respectively. Measurements of germinal excision frequencies driven by the chimeric TPase fusions, however, indicated that increasing transcription does not necessarily result in an increase in germinal excision. These measurements showed that the ocs and nos fusions have very low rates of germinal excision. Only the CaMV 35S fusion transformants were found to have higher rates than the Ac constructs, although significant pod-to-pod variation was observed. Gel blot analysis of DNA from progeny carrying germinal excision events resulting from the CaMV 35S fusion showed that excision is associated with reinsertion and that siblings sometimes carry the same transposition events. These findings suggest that in tobacco there is no direct proportionality between TPase expression and Ac-Ds transposition activity. This possibility has important implications for understanding the regulation of Ac transposition and for designing efficient gene tagging systems.

Base Sequence

Painful sensory symptoms in neuroleptic-induced extrapyramidal syndromes.

OBJECTIVE: The authors tested the hypothesis that neuroleptic-induced extrapyramidal syndromes are associated with painful sensations objectively conforming to the characteristics of primary sensory symptoms as reported in idiopathic and postencephalitic parkinsonism. METHOD: The frequency of subjective painful sensory symptoms and their relation to neuroleptic-induced extrapyramidal syndromes were examined in a consecutive series of 107 psychiatric patients newly admitted to acute care units at a teaching hospital. Patients without illnesses or conditions likely to be associated with pain were included in the study if they had a diagnosis other than organic mental syndromes and were receiving psychotropic medications as prescribed by their treating physicians. Structured interviews with a modified version of the McGill Pain Questionnaire to assess sensory complaints and neurological examinations for neuroleptic-induced extrapyramidal syndromes (parkinsonism and akathisia) were conducted independently by two raters blind to each other's findings and patients' medication status. RESULTS: Fourteen (23%) of 60 patients receiving neuroleptics reported experiences of spontaneous pain subjectively attributed to pharmacological treatment, compared with only one (2%) of 47 patients receiving psychotropic medications other than neuroleptics. There was no difference between these two groups in subjective complaints of paresthesia (8% versus 9%). Twelve (55%) of the 22 patients with neuroleptic-induced extrapyramidal syndromes reported pain, compared with only two (5%) of the 38 patients who received neuroleptics but did not experience extrapyramidal syndromes. CONCLUSIONS: Although consonant with the study hypothesis, these results should be regarded as preliminary and interpreted conservatively in the light of the methodological limitations of the study.

Adult

Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization.

The purposes of this study were to determine the prevalence of angiographically significant renal artery stenosis in a patient population referred for diagnostic cardiac catheterization and to develop a model that predicts the highest-risk subset of patients who have significant renal artery narrowing. A prospective validation cohort study was undertaken in a referral-based university hospital. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery disease. A convenience sample of 1,302 of 1,651 consecutive patients undergoing diagnostic cardiac catheterization were enrolled in the study. Of the 1,302 abdominal aortograms performed, 1,235 (95%) were deemed of adequate quality for the evaluation of renal artery anatomy. Renal artery disease was identified in 30% of the patients. Insignificant renal artery stenosis was found in 187 (15%) and significant (greater than or equal to 50% diameter narrowing) stenosis was found in 188 (15%). Significant unilateral disease was present in 11%, and bilateral disease was present in 4%. By univariable and multivariable logistic regression analysis, the association of both clinically and catheterization-derived variables with renal artery disease was assessed. Multivariable predictors included age, severity of coronary artery disease, congestive heart failure, female gender, and peripheral vascular disease. Hypertension was not an associated variable. These data reveal the previously undetected high prevalence of renal artery disease in patients undergoing cardiac catheterization and provide clinical and angiographic features that assist in predicting its presence.

Aged

The predictive value of idiopathic failure to fertilize on the first in vitro fertilization attempt.

OBJECTIVE: To investigate the subsequent performance of patients with idiopathic fertilization failure on the first in vitro fertilization (IVF) cycle. DESIGN: A retrospective study of 2,322 consecutive patients undergoing their initial IVF cycle. SETTING: Advanced infertility treatment in an IVF/general infertility clinic. PATIENTS: In 5 years, 94 couples with unexplained failed oocyte fertilization had 270 cycles of treatment. Each couple's performance was tracked through subsequent cycles of treatment. INTERVENTIONS: In vitro fertilization with husband and donor sperm. MAIN OUTCOME MEASURE(S): Investigated retrospectively after 5 years of data collection. RESULTS: Sixty-five couples of the original 94 had a second IVF attempt. Fifty of these successfully fertilized oocytes with husband's sperm and 4 with donor sperm. Nineteen of the 65 couples who continued treatment achieved a pregnancy, and only one couple had continuing fertilization failure. CONCLUSIONS: The prognosis in the study group was surprisingly favorable despite the initial failed IVF treatment cycle.

Adult

In vitro susceptibility of Brucella melitensis to antibiotics.

The in vitro susceptibilities of 86 recent clinical isolates of Brucella melitensis to minocycline, streptomycin, co-trimoxazole, rifampin, and six fluoroquinolones were determined. Minocycline exhibited the lowest MIC and was followed by rifampin and streptomycin. Among the quinolones, WIN 57273 and ciprofloxacin were the most active agents. No antibiotic combination of these agents exhibited synergy against 15 selected isolates. In killing rate experiments, streptomycin exhibited the most rapid kill (less than 12 h), while a complete kill with minocycline, rifampin, and ciprofloxacin was delayed up to 48 h. The combinations of streptomycin with each of minocycline, rifampin, or ciprofloxacin exhibited the fastest kills (within 2 h), while with the other combinations, a complete kill was delayed up to 96 h. These results demonstrate the discrepancy between the results of various in vitro methods in evaluating the antibiotic susceptibility of B. melitensis.

Anti-Bacterial Agents