Biomedical subjects

K R Jones

Publications and source records attributed to K R Jones.

At least 91 records · Page 5Linked to original sources

PubMed1992

Purified HLA class II peptide complexes can induce adherence and activation of peptide-specific human T cell clones.

An initial event in T cell activation is the specific adherence of T cells via their T cell receptor to the MHC peptide complex. We have studied this adherence by incubating T cells with preformed HLA DR4Dw4 peptide complexes attached to a solid support. Adherence of sodium 51Cr-labeled T cell clones specific for the influenza hemagglutinin peptide, HA 307-319, was maximal after 15 min and was specific for the HLA DR4Dw4-HA 307-319 complex. The binding was temperature dependent and could be blocked with azide or protein kinase C inhibitors, indicating that for adherence the T cells need to be metabolically active and have a functioning protein kinase C pathway. The adherence could be blocked with CD4- or CD3-reactive murine mAb, suggesting that the TCR and CD4 molecules work in concert to induce strong adherence to the HLA DR4Dw4-HA 307-319 complex. A subsequent event in T cell activation is proliferation, which is thought to need additional proteins such as IL-1 or other adhesion molecules. MHC peptide complexes coated on microtiter plates also induced proliferation in the human T cell clones. Removal of any monocytes by treatment of human T cell clones with anti-CD14 in conjunction with C, followed by purification over a nylon wool column, did not abrogate proliferation. After prolonged culture of the T cell clones in plates coated with peptide-pulsed HLA DR4Dw4 in the presence of IL-2, the T cell clones continued to proliferate in response to peptide. These results suggest that human T cell clones do not require a second signal from a monocyte or other APC to proliferate.

Antibodies, Monoclonal↗

PubMed1992

Prognostic factors in the recurrence of stage I and II squamous cell cancer of the oral cavity.

Stage I and II squamous cell cancers of the oral cavity have a high recurrence rate given their size and relative amenability to surgical resection. It has been suggested that one way to decrease this recurrence rate is to augment the surgical resection of these tumors with either elective neck dissection or radiation therapy. However, this would expose a significant number of patients to the unnecessary morbidity associated with either of these modalities. In an attempt to identify those patients most at risk for recurrence, we retrospectively determined the clinical and histologic factors that were associated with recurrence in 49 patients with stage I and II oral cavity cancer. Multiple regression analysis revealed that when various interactions between variables were controlled for, only the presence of a positive surgical margin or a tumor depth greater than 5 mm was significantly associated with recurrence. Each individually increased the likelihood of recurrence almost threefold.

Adult↗

PubMed1992

A method for rapid screening of recombinant proteins for recognition by T lymphocytes.

A simple, cost-effective method is described that allows rapid screening of recombinant protein sequences for their ability to stimulate T cells. Individual microcultures of E. coli each expressing a gene product or peptide sequence fused to protein A are grown in 96-well plates. Following lysis of the bacteria, the fusion peptide is readily captured with immobilized immunoglobulin in tissue culture wells. No further purification is required. T lymphocytes plus appropriate antigen-presenting cells are added directly to the wells and assayed for proliferation. The DNA in bacteria from wells stimulating T cell proliferation is then sequenced. The technique allows rapid mapping of T cell epitopes by facilitating screening of truncation mutants without extensive purification. Described here is a further application of the technique to study monosubstituted analogues of a known T cell epitope.

Animals↗

PubMed1992

Risk of hospitalization for chronic hemodialysis patients.

This study used primary data to analyze the incidence, causes and total days of hospitalization over a six-month period for a sample of chronic hemodialysis patients in one geographic area of the country. Patients were hospitalized most frequently for access-related and cardiovascular problems. Logistic regression analysis indicated that patients were more likely to be hospitalized if they had lower Karnofsky functional status scores, lower serum phosphate and protein levels, repeat access procedures, a negative hepatitis antigen, arthritis, psychiatric disorders, ischemic peripheral vascular disease or other cardiovascular conditions or were from larger households. Risk of hospitalization was not influenced by hemodialysis treatment characteristics. Recommendations for improved management of these high-cost patients were made, which could enhance quality of life and lower hospital-related costs.

Aged↗

PubMed1992

Variations in the hemodialysis treatment process.

The Medicare end-stage renal disease (ESRD) program costs more than $2 billion a year. Costs per treatment vary significantly across hemodialysis facilities, yet the relationship of these cost differentials to case mix and outcomes is uncertain. This study analyzed treatment variations in 527 chronic hemodialysis patients dialyzing in four freestanding and three hospital-based facilities. Results indicated that patients receiving care in the hospital-based units received a more costly routine dialysis treatment as well as more intensive nursing care during the treatment process than did patients in freestanding units. Policy and clinical implications of the findings are discussed.

Aged↗

PubMed1992

The dissonance mutation at the no-on-transient-A locus of D. melanogaster: genetic control of courtship song and visual behaviors by a protein with putative RNA-binding motifs.

Genetic and molecular results are here presented revealing that the dissonance (diss) courtship song mutation is an allele of the no-on-transient-A (nonA) locus of Drosophila melanogaster. diss (now called nonAdiss) was originally isolated as a mutant with aberrant pulse song, although it was then noted to exhibit defects in responses to visual stimuli as well. The lack of transient spikes in the electroretinogram (ERG) and optomotor blindness associated with nonAdiss are shown to be similar to the visual abnormalities caused by the original nonA mutations. nonAdiss failed to complement either the ERG or optomotor defects associated with four other nonA mutations. However, all four of these nonA mutants--which were isolated on visual criteria alone--sang a normal courtship song. nonAdiss complemented at least three of the nonA mutations with regard to the singing phenotype, as assessed by a new method for temporal analysis of the male's pulse song. Both visual and song abnormalities caused by nonAdiss were rescued by P-element-mediated transformation with overlapping 11 and 16 kilobase (kb) fragments of genomic DNA (originally cloned from the nonA locus by Jones and Rubin, 1990). Analysis of behavioral phenotypes in transformed flies carrying mutagenized versions of the 11 kb genomic fragment (in a nonAdiss genomic background) localized the rescuing DNA to a region containing an open reading frame that encodes a polypeptide (NONA) with similarity to a family of RNA-binding proteins. Immunohistochemical determination of NONA's spatial and temporal expression revealed that it is localized to the nuclei of cells in many neural and non-neural tissues, at all stages of the life cycle after very early in development. Genetic connections between the control of two quite different behaviors--reproductive and visual--are discussed, along with precedences for generally expressed gene products playing roles in specific behaviors.

Alleles↗

PubMed1991

The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.

trkB is a tyrosine protein kinase gene highly related to trk, a proto-oncogene that encodes a receptor for nerve growth factor (NGF) and neurotrophin-3 (NT-3). trkB expression is confined to structures of the central and peripheral nervous systems, suggesting it also encodes a receptor for neurotrophic factors. Here we show that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on tyrosine of gp145trkB, one of the receptors encoded by trkB. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells that express gp145trkB. Cotransfection of plasmids encoding gp145trkB and BDNF or NT-3 leads to transformation of recipient NIH 3T3 cells. In these assays, BDNF elicits a response at least two orders of magnitude higher than NT-3. Finally, 125I-NT-3 binds to NIH 3T3 cells expressing gp145trkB; binding can be competed by NT-3 and BDNF but not by NGF. These findings indicate that gp145trkB may function as a neurotrophic receptor for BDNF and NT-3.

Animals↗

PubMed1991

The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3.

The product of the trk proto-oncogene encodes a receptor for nerve growth factor (NGF). Here we show that NGF is a powerful mitogen that can induce resting NIH 3T3 cells to enter S phase, grow in semisolid medium, and become morphologically transformed. These mitogenic effects are absolutely dependent on expression of gp140trk receptors, but do not require the presence of the previously described low affinity NGF receptor. gp140trk also serves as a receptor for the related factor neurotrophin-3 (NT-3), but not for brain-derived neurotrophic factor. Both NGF and NT-3 induce the rapid phosphorylation of gp140trk receptors and the transient expression of c-Fos proteins. However, NT-3 appears to elicit more limited mitogenic responses than NGF. These results indicate that the product of the trk proto-oncogene is sufficient to mediate signal transduction processes induced by NGF and NT-3, at least in proliferating cells.

Animals↗

PubMed1991

Repeated DNA sequence involved in mutations affecting transport of sucrose into Streptococcus mutans V403 via the phosphoenolpyruvate phosphotransferase system.

Mutants of Streptococcus mutans V403 defective in the intracellular sucrose-6-phosphate hydrolase (product of the scrB gene) are sensitive to sucrose because of the intracellular accumulation of the phosphorylated sugar. Using a scrB mutant prepared by allelic exchange, we have isolated and characterized a number of sucrose-resistant revertants. One such mutant was found to lack the ability to transport sucrose into the cell via the phosphoenolpyruvate-dependent sucrose phosphotransferase system (PTS). Genetic analysis of this strain revealed this lesion to be linked to the scrB gene. This was corroborated by the physical demonstration of an insertion mutation very near scrB. Taken together with DNA sequence information (Y. Sato, F. Poy, G. R. Jacobson, and H. K. Kuramitsu, J. Bacteriol. 171:263-271, 1989), our results indicated that all of the mutations characterized were located in the adjoining scrA gene which encodes the membrane-associated, sugar-specific enzyme II (EIIsucrose) component of the sucrose PTS in S. mutans. Biochemically, such a genetic lesion disables the sucrose PTS and prevents sucrose from entering the cell by this system. In this paper, we detail the nature of two independent insertion mutations and conclude them to be the result of duplicative transposition events into the scrA gene. This region of the chromosome was amplified and purified in large quantities by using the polymerase chain reaction. Examination of the amplified DNA revealed that the two independent insertion mutations were composed of sequences that were indistinguishable by size and by restriction site endonuclease maps. Their insertion points in the scrA gene were approximately 200 bp apart. The amplified DNA fragment was also used as a probe to demonstrate the presence of five copies of this element on the S. mutans V403 chromosome. A second strain, S. mutans V310, also was found to carry similarly arranged, multiple copies of this sequence on its chromosome, suggesting a clonal origin of V403 and V310. The small size of this sequence, its presence in multiple copies on the V403 chromosome, and its ability to duplicate itself semiconservatively into remote sites argue compellingly that it is an insertion sequence element. One such insertion mutant, with a defective sucrose PTS, was tested for virulence in rats and was found to cause caries at levels similar to those of the wild-type strain.

Animals↗

PubMed1991

Factors associated with hospitalization in a sample of chronic hemodialysis patients.

This study examines the hospitalization experience of a sample of chronic hemodialysis patients, using primary data sources. There were multiple causes of hospitalization over the six-month tracking period, with stays extending from 1 to 87 days. Patients were more likely to be hospitalized if they had a negative hepatitis antigen, lower functional status scores, lower phosphate and protein levels, repeated access procedures, other cardiovascular conditions, arthritis, psychiatric disorders, ischemic peripheral vascular disease, lung disease, or larger households. Hospitalization for access-related problems was associated with arthritis, previous access procedures, and blood pressure levels. Sociodemographic and treatment characteristics did not have a significant influence on the risk of hospitalization. Improved management in these clinical areas may improve the quality of life of chronic hemodialysis patients and reduce the high level of expenditures associated with delivering inpatient services to this segment of the Medicare population.

Adult↗

PubMed1990

Blood transfusion and other risk factors for recurrence of cancer of the head and neck.

To determine whether perioperative blood transfusion affected the recurrence rate of squamous cell cancer of the head and neck, we performed a retrospective study of all patients with stage III and IV disease treated surgically at the University of North Carolina, Chapel Hill, between 1983 and 1986. Those who recurred were compared with those who did not in regard to 16 prognostic variables, including whether or not they had received a perioperative blood transfusion. Analyzing each variable separately, five were significantly related to recurrence. These were (1) surgical margin status, (2) stage, (3) presence of pathologically positive nodes, (4) blood transfusion status, and (5) type of treatment. However, because several of these variables were clearly interrelated, the same data were subjected to a multivariate regression analysis specifically designed to identify significant prognostic variables independent of their association with other variables. By this analysis, only margin status and the presence or absence of a blood transfusion were statistically significant predictors of recurrence.

Carcinoma, Squamous Cell↗

PubMed1990

Cellulose fiber diet pills. A new cause of esophageal obstruction.

Cellulose fiber diet pills have recently become a popular form of weight control. In the past 2 months, we have seen two patients in whom ingestion of these pills has resulted in complete distal esophageal obstruction. Further studies revealed that each patient had a previously undiagnosed anatomical abnormality of the distal esophagus; in one case a Schatzki's ring, and in the other a stricture probably secondary to chronic reflux. We conclude that patients with known esophageal narrowing, or with a history of reflux and/or dysphagia, should use cellulose fiber diet pills only with extreme caution.

Adult↗

PubMed1990

Polyclonal in vitro proliferative responses from nonimmune donors to Plasmodium falciparum malaria antigens require UCHL1+ (memory) T cells.

The in vitro polyclonal proliferative responses of peripheral blood mononuclear cells to whole blood stage parasites or fractionated antigens from the human malaria parasite Plasmodium falciparum were studied. Cells from healthy laboratory donors who had never been exposed to malaria antigens in vivo consistently proliferated to P. falciparum antigens, as did cord blood mononuclear cells. This response was only observed in sheep rosette-positive cells in the presence of adherent cells and was inhibited by NH4Cl, indicating a requirement for antigen processing. The proliferative response was strongest at day 6 and was dependent on the presence of cells expressing high levels of CD45 180-kD isomer (UCHL1 monoclonal antibody), a marker for activated or memory cells, but not for CD45R (SN130 monoclonal antibody) a marker for naive or unprimed T cells. This suggests a similarity to the recall response to tuberculin antigen. These results suggest that the proliferative response to malaria antigens observed previously and described as a nonspecific mitogenic response may be a cross-reactive response to epitopes shared between P. falciparum and other common immunogens. This would explain the establishment of T cell clones to malaria antigens from such donors, but might suggest that the epitopes to which such clones are specific may be of questionable protective or diagnostic use.

Adult↗

PubMed1990

Molecular analysis of no-on-transient A, a gene required for normal vision in Drosophila.

Mutation of the Drosophila melanogaster gene no-on-transient A (nonA) results in reduced visual acuity, behavior abnormalities, and an electrophysiological defect for which the mutant is named. We mapped the nonA gene genetically to a 20 kb interval within the 14C1,2 region of the X chromosome, isolated this chromosomal region, and used P element-mediated transformation to delimit the nonA gene to a 9 kb region. Analysis of cDNA clones indicates that this region encodes alternatively spliced transcripts encoding protein products of approximately 77 kd that differ only in their C-terminal 35 amino acids. Analysis of mutations generated in vitro in this transcription unit confirm that these transcripts are the products of the nonA gene.

Amino Acid Sequence↗

PubMed1990

Molecular cloning of a human gene that is a member of the nerve growth factor family.

Cell death within the developing vertebrate nervous system is regulated in part by interactions between neurons and their innervation targets that are mediated by neurotrophic factors. These factors also appear to have a role in the maintenance of the adult nervous system. Two neurotrophic factors, nerve growth factor and brain-derived neurotrophic factor, share substantial amino acid sequence identity. We have used a screen that combines polymerase chain reaction amplification of genomic DNA and low-stringency hybridization with degenerate oligonucleotides to isolate human BDNF and a human gene, neurotrophin-3, that is closely related to both nerve growth factor and brain-derived neurotrophic factor. mRNA products of the brain-derived neurotrophic factor and neurotrophin-3 genes were detected in the adult human brain, suggesting that these proteins are involved in the maintenance of the adult nervous system. Neurotrophin-3 is also expected to function in embryonic neural development.

Amino Acid Sequence↗

PubMed1990

Genetic approaches to the study of oral microflora: a review.

As the study of oral microorganisms intensified almost 2 decades ago, the application of genetic techniques resulted in important contributions to the understanding of this clinically and ecologically important group of bacteria. The isolation and characterization of mutants of cariogenic streptococci helped to focus attention on traits that were important in colonization and virulence. Such classic genetic approaches gave way to molecular genetic techniques, including recombinant DNA methodology in the late 1970s. Gene cloning systems and methods to move DNA into cells have been developed for oral streptococci. Many streptococcal genes thought to be important in colonization and virulence have since been cloned and their nucleotide sequence determined. Mutant strains have been constructed using defective copies of cloned genes in order to create specific genetic lesions on the bacterial chromosome. By testing such mutants in animal models, a picture of the cellular and molecular basis of dental caries is beginning to emerge. These modern genetic methodologies also are being employed to develop novel and efficacious cell-free or whole cell vaccines against this infection. Genetic approaches and analyses are now being used to dissect microorganisms important in periodontal disease as well. Such systems should be able to exploit advances made in genetically manipulating related anaerobes, such as the intestinal Bacteroides. Gene cloning techniques in oral anaerobes, Actinomyces and Actinobacillus, are already beginning to pay dividends in helping understand gene structure and expression. Additional effort is needed to develop facile systems for genetic manipulation of these important groups of microorganisms.

Bacteria↗

PubMed1990

Feasibility analysis of preferred provider organizations.

Hospital management frequently considers diversification into Preferred Provider Organizations (PPOs) as a strategy for responding to intense competition for patients. The author presents a feasibility analysis framework for determining the potential success of such an action. Knowledge of this technique allows nursing executives to significantly contribute to the work of committees overseeing these analyses.

Decision Making↗

PubMed1989

Real-time patient weight monitoring system for chair based renal dialysis.

A system is described for monitoring weight changes in patients undergoing renal dialysis. Relatively fit patients dialyse in easy chairs rather than in bed but no commercial system is currently available to monitor weight changes under these conditions. The authors have considered basic requirements and have developed a cost effective system based on a Single Point Off-Centre load cell, all components being mounted under a platform on which the easy chair is located. There is an electrical output signal which may be used to drive a display or be sampled by a computer system.

Body Weight↗