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Biomedical subjects

K Kelleher

Publications and source records attributed to K Kelleher.

At least 55 records · Page 3Linked to original sources
PubMed1992

Psychosocial interventions in adult patients with coronary heart disease and cancer. A literature review.

A growing body of evidence suggests that chronic medical illness is associated with an increased prevalence and incidence of psychiatric and psychological disturbances. The present literature review is based on two theses: first, that chronic illness is viewed as a stressor and is associated with increased psychological distress, and secondly, that interventions can minimize the distress. A review of the studies conducted with adult patients diagnosed either with coronary heart disease or cancer suggests that psychosocial interventions are, in general, efficacious in relieving self-reported psychological distress. The review also recommends psychosocial interventions for high-risk patients rather than all patients, and that researchers need to identify other outcomes such as health care costs, disability, days in hospital, morbidity, and mortality in order to convince policy makers that these interventions are worthwhile. Recommendations for future research are also discussed.

Adaptation, Psychological↗
PubMed1992

Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5.

IL12 (formerly NKSF or CLMF) is a unique cytokine composed of two unrelated disulfide-linked subunits. The larger 40-kDa subunit (p40) is a member of the cytokine receptor family, and the smaller 35-kDa subunit (p35) is related to IL6 and GCSF. The chromosomal localization of these two subunits was determined by PCR analysis of DNA from rodent-human hybrids. More refined mapping was obtained by PCR analysis of hybrids containing translocation chromosomes and for p40, by analysis of radiation hybrids. The subunits map to different chromosomes: p40 (IL12B) to 5q31-q33 and p35 (IL12A) to 3p12-3q13.2.

Animals↗
PubMed1992

High level expression on a chimeric anti-ganglioside GD2 antibody: genomic kappa sequences improve expression in COS and CHO cells.

We report a flexible strategy for the high level expression of a recombinant human monoclonal antibody (mAb) in Chinese hamster ovary (CHO) cells, initially using COS monkey kidney cell transfections to evaluate rapidly modifications to immunoglobulin (Ig) DNA constructs. Using sequential transfections with two amplifiable markers, we generated CHO cell lines and clones that secrete 80-110 micrograms/10(6) cells/24 hours of a mouse-human chimeric IgG1 kappa mAb. This cellular productivity is considerably greater than most murine hybridomas and transfected myelomas. Our data also demonstrate that genomic kappa sequences can improve mAb expression in COS and CHO cells. As a paradigm, we focused our expression studies on a human chimeric form of 3F8, a murine mAb that binds to ganglioside GD2 on neuroblastoma and melanoma tumor cells.

Animals↗
PubMed1992

Intensive short course chemotherapy for tuberculous meningitis.

This nonrandomized, open clinical investigation of tuberculous meningitis evaluated 53 children with Stage I (n = 8), Stage II (n = 29) and Stage III (n = 16) disease. The overall mortality was 20.8% (11 of 53) with a rate of sequelae of 35.7% (15 of 42) in survivors reflecting the advanced stages of children at diagnosis. Various combinations of standard antituberculous drugs including isoniazid, rifampin, pyrazinamide, streptomycin and ethambutol were given. Three treatment durations used during various time periods were evaluated: 12, 9 and 6 months with only the 6-month regimen receiving pyrazinamide (PZA). This prospective evaluation demonstrated that: (1) severe disease at presentation is highly associated with early mortality (P less than 0.05), regardless of drug regimen; and (2) intensive short course chemotherapy (6 months) with PZA, regardless of stage of disease at presentation, is more efficacious than longer course therapy (9 or 12 months) without PZA in preventing total negative outcomes and sequelae (P less than 0.05). This study demonstrates that a 6-month regimen containing PZA can be used in treating children with tuberculous meningitis.

Antitubercular Agents↗
PubMed1991

Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells.

We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-I-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31-32, a region found to be deleted in a number of patients with acquired 5q- abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5'-flanking region of the human IL-9 gene that may play an important role in the control of IL-9 gene expression. The 5'-regulatory region of the human IL-9 gene also contains sequences identified in the 5'-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-I-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O-tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5'-flanking region of IL-9 gene upstream from the firefly luciferase ciferase report gene indicated that the 0.9-kb Smal-Sacl fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL-9 gene in HTLV-I-transformed cells. These results will now allow us to study the regulatory mechanism of IL-9 gene expression in normal and leukemic human T cells.

Amino Acid Sequence↗
PubMed1991

Molecular cloning and characterization of a complete Chinese hamster provirus related to intracisternal A particle genomes.

We report here the nucleotide sequence of a full-length Chinese hamster genomic proviral element, CHIAP34. CHIAP34 is 6,403 bp long with long terminal repeats of 311 bp at each end. The genetic organization of CHIAP34 was determined by comparison with intracisternal A particle (IAP) genetic elements from the mouse and Syrian hamster. Extensive homology at the nucleotide and deduced amino acid sequence levels was observed between CHIAP34 and the mouse and Syrian hamster IAP elements. CHIAP34 may represent a defective Chinese hamster IAP genetic element. The gag gene consists of 837 codons, of which 558 codons are in a single long open reading frame followed by several frameshifts. The pol gene begins with a -1 frameshift and consists of a long open reading frame of 753 codons followed by a short open reading frame of 103 codons. The putative env region contains multiple termination codons in all reading frames. CHIAP34 is representative of the predominant retroviral elements in the Chinese hamster ovary cell genome present at around 80 copies per haploid genome.

Amino Acid Sequence↗
PubMed1991

Prescribing exercise for the adult with diabetes.

Exercise is a useful tool in the management of diabetes, contributing to cardiovascular and psychosocial well-being, weight control, and, in noninsulin-dependent diabetes, improvement of blood glucose levels. An optimal exercise program should be based on a comprehensive assessment and include a written prescription for the type, frequency, duration, and intensity of exercise. This article includes guidelines for writing exercise prescriptions as well as techniques for monitoring its effects. A discussion of risks related to diabetes provides safety guidelines.

Diabetes Mellitus↗
PubMed1990

Expression of functional alpha beta T cell receptor gene rearrangements in suppressor T cell hybridomas correlates with antigen binding, but not with suppressor cell function.

We have examined the expression of TCR genes in 4-hydroxy-3-nitrophenyl-acetyl (NP)-specific Ts cell hybridomas. Each of three independently isolated hybridomas expressed in-frame TCR alpha-chain rearrangements derived from the original suppressor Ts cell. Different V alpha and J alpha gene segments were rearranged and expressed in each Ts cell line. The only TCR beta-chain expressed in these cells was derived from the BW5147 fusion partner. Expression of the BW5147 beta-chain was found to correlate with cell surface Ag binding, inasmuch as subclones derived from one of the original Ts lines expressed greatly reduced levels of beta-chain mRNA and no longer bound to NP-coupled RBC. Subclones that continued to express beta-chain mRNA did bind to NP-coupled RBC. This suggests that the Ag receptor on Ts hybridomas is a TCR-alpha beta dimer composed of a unique alpha-chain and the BW5147 beta-chain. Ag binding could be modulated by preincubation of Ts hybridoma cells with anti-TCR-alpha beta antibody, thereby supporting this conclusion. Suppressor factor activity was measured in the conditioned media of Ts subclones that differed by 250-fold in levels of beta-chain mRNA expression. No difference in suppressor factor activity was found; conditioned media from these subclones suppressed both plaque-forming cell responses and delayed-type hypersensitivity responses at approximately equivalent dilutions. Suppressor factor activity in the conditioned media of both a beta-chain negative subclone and a beta-chain positive subclone could be absorbed with an antibody that recognizes the TCR alpha-chain, but not with an antibody that recognizes the TCR beta-chain. We conclude that suppressor factor activity in the conditioned media of these Ts hybridomas is not derived from surface TCR-alpha beta receptors, although it does share TCR alpha-chain determinants.

Amino Acid Sequence↗
PubMed1990

Cloning and expression of eukaryotic initiation factor 4B cDNA: sequence determination identifies a common RNA recognition motif.

Eukaryotic protein synthesis initiation factor 4B (eIF-4B) is an 80,000 dalton polypeptide which is essential for the binding of mRNA to ribosomes. A highly purified preparation of eIF-4B from HeLa cells was subjected to enzymatic cleavage and amino-terminal amino acid sequence analysis. Degenerate oligonucleotide probes were used to isolate a 3851 bp cDNA encoding eIF-4B from a human cDNA library. The DNA encodes a protein comprising 611 residues with a mass of 69,843 daltons. The amino-terminal domain of eIF-4B contains a consensus RNA binding domain present in a number of other RNA binding proteins. Expression of eIF-4B in transfected COS-1 cells yielded a polypeptide which reacted with anti-eIF-4B antiserum and comigrated with purified eIF-4B. Expression of eIF-4B in COS-1 cells resulted in a general inhibition of translation, possibly due to a 50-fold eIF-4B overproduction.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine.

Hematopoiesis occurs in close association with a complex network of cells loosely termed the hematopoietic microenvironment. Analysis of the mechanisms of microenvironmental regulation of hematopoiesis has been hindered by the complexity of the microenvironment as well as the heterogeneity of hematopoietic stem cells and early progenitor cells. We have established immortalized primate bone marrow-derived stromal cell lines to facilitate analysis of the interactions of hematopoietic cells with the microenvironment in a large animal species. One such line, PU-34, was found to produce a variety of growth factors, including an activity that stimulates the proliferation of an interleukin 6-dependent murine plasmacytoma cell line. A cDNA encoding the plasmacytoma stimulatory activity was isolated through functional expression cloning in mammalian cells. The nucleotide sequence contained a single long reading frame of 597 nucleotides encoding a predicted 199-amino acid polypeptide. The amino acid sequence of this cytokine, designated interleukin 11 (IL-11), did not display significant similarity with any other sequence in the GenBank data base. Preliminary biological characterization indicates that in addition to stimulating plasmacytoma proliferation, IL-11 stimulates the T-cell-dependent development of immunoglobulin-producing B cells and synergizes with IL-3 in supporting murine megakaryocyte colony formation. These properties implicate IL-11 as an additional multifunctional regulator in the hematopoietic microenvironment.

Amino Acid Sequence↗
PubMed1990

Health care use by children receiving mental health services.

Reduction in medical care utilization is one criteria for assessing the impact of mental health treatment for children with psychosocial problems. This reduction has been termed the "offset" effect. Almost all published research concerning offset after mental health treatment concerns adults, and the few studies in pediatric populations are limited by methodologic problems. A study of health care utilization after mental health treatment for children was conducted. Mental health treatment for psychosocial problems was significantly associated with decreased use of medical care only for older children, after potentially confounding variables were controlled for. Furthermore, this decreased use was found only for nonmental health specialty care visits. No reduction in primary care visits occurred. Other factors such as previous patterns of use and the presence of other morbidity were stronger predictors of subsequent primary health care use than was mental health treatment. Mental health treatment does not have a major impact on the high utilization of most children with psychosocial problems in pediatric settings. Because the reasons for this may be particular morbidity patterns in these children, future studies should include some measure of case mix as a potentially important variable in assessment of mental health treatment effects.

Child↗
PubMed1989

Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40.

We used functional expression cloning in mammalian cells to identify a cDNA clone encoding a hematopoietic growth factor that is mitogenic for the factor-dependent human megakaryoblastic leukemic cell line, MO7E. Analysis of the sequence of this cDNA revealed striking similarity to that of a recently reported novel murine growth factor for helper T-cell clones designated T-cell growth factor P40. The mRNA for the human P40 protein is expressed by several different human T-cell lines and by mitogen-stimulated peripheral blood lymphocytes. The recombinant protein displays substantial size heterogeneity typical of other glycoprotein cytokines. These properties plus the observation that this cytokine may well act within both the lymphoid and myeloid lineages warrant the designation of P40 as interleukin-9.

Amino Acid Sequence↗
PubMed1987

The nucleotide sequence encoding the hamster 78-kDa glucose-regulated protein (GRP78) and its conservation between hamster and rat.

The complete nucleotide (nt) sequence encoding the hamster 78-kDa glucose-regulated protein has been determined using a cDNA plasmid p3C5. Comparison of the nucleotide sequences from rat and hamster showed a strong conservation in the coding region as well as 5'- and 3'-untranslated regions (UTRs). The relatively long (206 nt for rat) 5'UTR shares 72% sequence homology between rat and hamster in the 142 nt upstream from the ATG start codon. This conserved region contained an imperfect inverted-repeat sequence. The long 5'UTR region is capable of forming stable dyad structures. The homology within the rat and hamster protein-coding region is 93.7%, with most of the differences resulting in silent site mutations. Out of the 654 amino acids, only four changes are detected, two of which are located in the signal peptide. While the sizes of the 3'UTR are different between the two species compared, strong sequence homologies (95%) were observed throughout the entire UTRs. Also, the 3'UTR was not rich in A + T residues as found in other eukaryotic mRNAs.

Animals↗
PubMedDate not supplied

Clinical predictors of treatment reduction in hypertensive patients.

OBJECTIVE: To demonstrate that some hypertensive patients under good blood pressure (BP) control can reduce medications, and to identify predictors of successful reduction. DESIGN: Observational study with 11-month follow-up. SETTING: Outpatient hypertension clinic at the Seattle Veterans Administration Hospital. PATIENTS: 59 males (51% of those eligible) with diastolic BP less than 95 mm Hg for greater than or equal to 6 months; 57 patients (97%) completed the study. INTERVENTION: Gradual reduction of medications unless diastolic BP rose above 95 mm Hg. MEASUREMENTS AND MAIN RESULTS: Intensity of treatment with BP medications was assessed using a scale of their comparative "vigors." 35 patients (59%) reduced medications successfully. By the end of the study, systolic BP had risen by 8.2 +/- 12.3 mm Hg (mean +/- SD) in successful patients, while diastolic BP did not change significantly. Two predictors of treatment reduction were statistically significant in both univariate and multivariate analyses: successful patients had been treated more intensively (2.7 +/- 1.7 vs. 1.3 +/- 0.5 "vigor units," p = 0.0001), and they had been enrolled in the clinic longer (5.5 +/- 3.0 vs. 3.1 +/- 2.3 years, p = 0.003). Lower systolic BP, higher urinary sodium excretion, lower compliance, and younger age were significant predictors of treatment reduction on univariate analysis only. Age less than or equal to 65 years had the highest sensitivity (86%) for treatment reduction, while treatment with two or more "vigor units" had the highest specificity (79%) and likelihood ratio (3.3). CONCLUSIONS: Treatment reduction is feasible in many well-controlled hypertensives, though systolic BP rises. Patients with high intensity and long duration of treatment are most likely to reduce medications successfully.

Antihypertensive Agents↗
PubMedDate not supplied

Smoking, occupancy and staffing levels in a selection of Dublin pubs pre and post a national smoking ban, lessons for all.

BACKGROUND: On the 29th March 2004 the Irish government introduced a comprehensive workplace smoking ban to protect the health of workers. This study evaluates the impact the ban had on staffing levels, customer numbers and smoking rates in a sample of 38 public houses in Dublin. METHODS: A total of 38 public houses were visited prior to the introduction of the ban, each visit lasted at least three hours, and the number of staff, customers and the number of people smoking was recorded each hour. Follow-up visits were conducted exactly one year later, on the same day of the week and at the same time of day, allowing controlling for seasonal and weekday effects. RESULTS: There was a decrease (8.82%) in average staff levels while customer numbers increased by 11% and there was a dramatic reduction in numbers smoking on a visit to a pub (77.8%). CONCLUSIONS: The hospitality industry predicted major job losses as a consequence of the introduction of the smoking ban; this work has shown that there was no significant decrease in the number of staff employed or in customer numbers. There was full compliance, with no customers smoking inside the public houses following the introduction of the ban. The ban has been good for the industry, staff, and customers.

Humans↗