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Biomedical subjects

B Johnston

Publications and source records attributed to B Johnston.

At least 19 recordsLinked to original sources
PubMed2001

Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential.

Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell-dependent upregulation, while IL-4 inhibits it. In blood, 35-56% of Bonzo+ CD4 T cells are Th1 cells, and 60-65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases.

Arthritis↗
PubMed2000

Pentosan polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA): a prospective multicenter clinical trial.

OBJECTIVES: Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) has clinical and perhaps etiologic characteristics similar to interstitial cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the treatment of interstitial cystitis, has shown moderate benefit in reducing chronic pelvic pain and voiding symptoms in patients with interstitial cystitis. We undertook a prospective open-label, multicenter Phase II pilot study to examine the potential efficacy of PPS in the treatment of CPPS in men, using outcome tools validated for CPPS in men. METHODS: Patients with a diagnosis consistent with National Institutes of Health (NIH) CPPS category IIIA (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global assessment. RESULTS: Thirty-two patients (mean age 45.5 +/- 11 years; duration of symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were available for evaluation. Seven patients experienced drug-related side effects, including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to 36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to 9.2) symptom scores at 6 months compared with baseline was significant. The decrease was associated with a significant improvement in patients' quality of life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients had a greater than 50% improvement in the Symptom Frequency Questionnaire, Symptom Severity Index, and NIH-CPSI (rated as clinically significant improvement). At 6 months, mild, moderate, and marked improvement was noted (subjective global assessment) by 33%, 19%, and 15% of the patients, respectively. CONCLUSIONS: PPS is well tolerated and appears to have efficacy in reducing the severity and frequency of general symptoms, reducing specific pain symptoms, and improving the quality of life in many male patients with CPPS. The results of this study justify the initiation of a randomized controlled trial comparing the safety and efficacy of PPS to placebo.

Adult↗
PubMed2000

Alpha 4 integrin-dependent leukocyte recruitment does not require VCAM-1 in a chronic model of inflammation.

Rats immunized with Mycobacterium butyricum in Freund's adjuvant develop a chronic vasculitis, with large increases in leukocyte rolling and adhesion in mesenteric postcapillary venules that are significantly inhibited with an alpha 4 integrin Ab. Using intravital microscopy to visualize chronically inflamed microvessels, we demonstrated that alpha 4 integrin-dependent leukocyte rolling and adhesion was inhibited with a beta 1 integrin, but not a beta 7 integrin Ab. To date, VCAM-1 has been presumed to be the primary ligand for alpha 4 beta 1 integrin in the vasculature. However, alpha 4 beta 1 integrin-dependent interactions were not reduced by monoclonal or polyclonal VCAM-1 Abs or a VCAM-1 antisense oligonucleotide despite increased VCAM-1 expression in the mesenteric vasculature. To ensure that the VCAM-1 Abs were functional and used at saturating concentrations, blood from Ab-treated rats was perfused over monolayers of CHO cells transfected with rat VCAM-1. Sufficient alpha 4 integrin or VCAM-1 Ab was present to inhibit leukocyte interactions with rat VCAM-1 by 95-100%. Under in vitro flow conditions, only mononuclear leukocytes were recruited from blood of control rats onto purified VCAM-1. However, neutrophils were also recruited onto VCAM-1 from whole blood of adjuvant-immunized animals via alpha 4 integrin. Another ligand for alpha 4 beta 1 integrin is the connecting segment-1 (CS-1) region of fibronectin. An Ab to the CS-1 portion of fibronectin, which did not reduce rolling and adhesion in adjuvant arthritis animals, completely inhibited leukocyte adhesion to CS-1 under static conditions. These findings provide the first evidence that alpha 4 beta 1 integrin-dependent leukocyte rolling and adhesion can occur in vivo via a mechanism other than VCAM-1.

Adjuvants, Immunologic↗
PubMed2000

Outcomes of the Kaiser Permanente Tele-Home Health Research Project.

CONTEXT: Level of acuity and number of referrals for home health care have been escalating exponentially. As referrals continue to increase, health care organizations are encouraged to find more effective methods for providing high-quality patient care with cost savings. OBJECTIVE: To evaluate the use of remote video technology in the home health care setting as well as the quality, use, patient satisfaction, and cost savings from this technology. DESIGN: Quasi-experimental study conducted from May 1996 to October 1997. SETTING: Home health department in the Sacramento, Calif, facility of a large health maintenance organization. PARTICIPANTS: Newly referred patients diagnosed as having congestive heart failure, chronic obstructive pulmonary disease, cerebral vascular accident, cancer, diabetes, anxiety, or need for wound care were eligible for random assignment to intervention (n = 102) or control (n = 110) groups. INTERVENTION: The control and intervention groups received routine home health care (home visits and telephone contact). The intervention group also had access to a remote video system that allowed nurses and patients to interact in real time. The video system included peripheral equipment for assessing cardiopulmonary status. MAIN OUTCOME MEASURES: Three quality indicators (medication compliance, knowledge of disease, and ability for self-care); extent of use of services; degree of patient satisfaction as reported on a 3-part scale; and direct and indirect costs of using the remote video technology. RESULTS: No differences in the quality indicators, patient satisfaction, or use were seen. Although the average direct cost for home health services was $1830 in the intervention group and $1167 in the control group, the total mean costs of care, excluding home health care costs, were $1948 in the intervention group and $2674 in the control group. CONCLUSIONS: Remote video technology in the home health care setting was shown to be effective, well received by patients, capable of maintaining quality of care, and to have the potential for cost savings. Patients seemed pleased with the equipment and the ability to access a home health care provider 24 hours a day. Remote technology has the potential to effect cost savings when used to substitute some in-person visits and can also improve access to home health care staff for patients and caregivers. This technology can thus be an asset for patients and providers.

Aged↗
PubMed2000

A biodialysis system for liver support tested in a porcine hepatic failure model.

BACKGROUND: A practical liver support system for patients in fulminant hepatic failure (FHF) remains a needed therapeutic modality. A new method of bioartificial liver support, the liver biodialysis system (LBDS), is described. METHODS: Porcine hepatocytes, removed from direct contact with the treated subject's circulation, are in culture in a bioreactor which is combined in a dialysis circuit for patient treatment. The LBDS was tested in a porcine ischaemic hepatic failure model. RESULTS: The viable hepatocyte content of the bioreactor was 2.49 +/- 0.72 x 10(10). Cells remained viable in culture throughout the experiments (30 +/- 3 h) without evidence of immunological damage. A decrease in the degree of accumulation in the blood of ammonia (P < 0.02) and of 14 amino acids (P < 0.001) was achieved by the LBDS. Cerebral perfusion pressure was maintained at significantly higher levels in LBDS-treated animals (P < 0.05). CONCLUSIONS: In the LBDS, hepatocytes in large numbers and satisfactory culture conditions in a bioreactor have sustained viability and function. When combined in a dialysis circuit for the treatment of FHF pigs, immune reactions between the blood and hepatocytes were prevented and beneficial metabolic effects were observed.

Amino Acids↗
PubMed2000

Increased sensitivity to the C-X-C chemokine CINC/gro in a model of chronic inflammation.

OBJECTIVE: The C-C chemokine MCP-1 elicits significant neutrophil emigration in rats with chronic adjuvant-induced inflammation, but not in naive animals. We examined responses to the C-X-C chemokine CINC/gro to determine whether this class of chemokine elicits altered neutrophil responses during chronic inflammation. METHODS: CINC/gro was superfused over mesenteric venules of naive rats or animals with chronic adjuvant-induced vasculitis. Antibodies were used to characterize adhesive mechanisms. RESULTS: CINC/gro elicited leukocyte transendothelial migration in adjuvant-immunized rats at 100-fold lower concentrations than required to elicit transmigration in naive animals. In both groups, neutrophils constituted > 95% of the leukocytes recruited by CINC/gro. Using in vitro chemotaxis assays, neutrophils from control and adjuvant-immunized rats responded equally to CINC/gro, suggesting differences in migration were not related to neutrophil phenotype. Differences in adhesion molecule usage were noted in vivo. In control animals, CD18 antibodies blocked CINC/gro-induced neutrophil adhesion and emigration. In adjuvant-immunized animals, an alpha 4-integrin antibody reduced adhesion and emigration, while a CD18 antibody selectively inhibited emigration. CONCLUSIONS: This study demonstrates increased sensitivity to a C-X-C chemokine in a model of chronic inflammation, implicates the alpha 4-integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion.

Animals↗
PubMed2000

Exploring the new frontier: home care gets wired.

The driving forces toward adoption of TeleCare into the non-acute care setting are more compelling than ever before. The dramatic increase in our elderly population, which provides an endless consumer base, availability of functional and affordable technologies, and a national mandate to control costs of health care are forcing even the most skeptical health care decisionmakers to accept TeleCare as a standard model of care. Add to this the most severe nursing shortage to date and the formula is complete.

Aged↗
PubMed2000

Improving patient satisfaction with time spent in an orthopedic outpatient clinic.

OBJECTIVE: To determine if patient satisfaction can be improved by changing patients' expectations of the clinic visit and by decreasing the total time spent in the clinic. DESIGN: A prospective comparative analysis carried out in 4 phases. SETTING: An university-affiliated orthopedic outpatient clinic. PATIENTS: All patients seen in the orthopedic outpatient clinic were eligible. Phase 1 determined the total clinic time required by patient type; phase 2 assessed baseline satisfaction; phase 3 altered patients' expectations; and phase 4 altered patients' expectations and scheduled visits by patient type. INTERVENTION: Patient questionnaires. MAIN OUTCOME MEASURE: Patient satisfaction with time spent in the clinic. RESULTS: Of 708 distributed questionnaires, 622 (88%) were completed (547 totally complete, 75 partially complete). Total time spent in the clinic decreased across phases 2, 3 and 4 (mean 99.2, 94.7 and 85.2 minutes, respectively, but was significantly different only between phases 3 and 4; p = 0.05, Duncan's multiple range test). The percentage of patients who rated their waiting time as "excellent" increased across phases 2, 3 and 4 (14.6%, 18.8% and 31.1%, respectively; p = 0.0004, chi 2 test). CONCLUSION: Patient satisfaction can be improved by altering patient expectations and by decreasing the total time spent in clinic.

Female↗
PubMed1999

Role of prolactin in regulating the onset of winter fur growth in mink (Mustela vison): A reconsideration.

The objectives of this study were to determine: (1) if the onset of winter hair growth (anagen) in mink could be delayed or inhibited by elevating endogenous PRL concentrations; (2) if bilaterally adrenalectomy (ADX)-induced winter anagen occurs concomitantly with a reduction in serum PRL concentrations, and (3) if exogenous dehydroepiandrosterone (DHEA), an adrenal steroid or Delta(5)-DIOL (a peripherally produced metabolite of DHEA), would delay or inhibit the onset of winter anagen. During early July, while in the resting (telogen) stage of the hair growth cycle, mink were treated with slow release implants containing haloperidol (HAL, a dopaminergic antagonist), melatonin (MEL), deoxycorticosterone (DOC), DHEA and Delta(5)-DIOL. In addition, mink were ADX'd and supplemented with DOC and DHEA. MEL reduced PRL levels to basal levels and induced winter anagen 7 weeks earlier than controls. Surprisingly, HAL initiated winter anagen 7 weeks earlier than controls (P < 0.05), although serum PRL levels were not different between the two groups. Mink that were ADX'd or ADX + DHEA-treated exhibited winter anagen 6 weeks earlier than controls (P < 0.05), but serum PRL concentrations were not different between the three groups. The administration of DHEA or Delta(5)-DIOL to mink with intact adrenals had no effect on the time of onset of winter anagen or serum PRL levels. Our findings suggest that a reduction in circulating PRL levels is not essential for onset of winter anagen in the mink and that the apparent inhibitory effects of the adrenal glands on initiation of winter anagen is not mediated through DHEA or its metabolite Delta(5)-DIOL. J. Exp. Zool. 284:437-444, 1999.

Adrenalectomy↗
PubMed1999

Endothelin-1 causes P-selectin-dependent leukocyte rolling and adhesion within rat mesenteric microvessels.

Endothelin-1 (ET-1) is a potent vasoconstrictor postulated to play a role in hypertension, ischemia-reperfusion, and atherosclerosis. In addition to these contributions, it has been also proposed to induce leukocyte-endothelial cell interactions. The aim of the present study was to assess the mechanisms of action of ET-1 on leukocyte recruitment in vivo. Intravital microscopy of the rat mesenteric postcapillary venules was used. Ten minutes after 1 nM ET-1 superfusion, a significant increase in leukocyte rolling (77.5 +/- 22.6 vs. 20.5 +/- 4.5 cells/min) and adhesion (15.5 +/- 2.9 vs. 3.0 +/- 0.8 cells/100 micrometer) but not emigration was observed. These effects were found not to be mediated by mast cell activation. No platelet-endothelial cell interactions were detected in this in vivo system and furthermore, flow cytometry analysis revealed no increase of P-selectin expression in rat platelets on ET-1 stimulation. Pretreatment of animals with an anti-rat P-selectin monoclonal antibody (mAb) dramatically reduced leukocyte rolling and adhesion by 100 and 94% respectively when compared with control mAb-treated animals. At this dose of ET-1, a very transient decrease in shear rate was detected, arteriolar diameter was significantly reduced but venular diameter remained unchanged. A similar mechanical reduction in blood flow did not induce leukocyte recruitment. Thus this study demonstrates that ET-1 can directly cause significant leukocyte rolling and adhesion adding to its potential pathophysiological role in the development of disease states of the cardiovascular system.

Animals↗
PubMed1999

Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1.

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals. However, the function of this chemokine in models with preexisting inflammation is not known. Therefore, MCP-1 was superfused over the mesentery of naive rats or rats with chronic adjuvant-induced vasculitis. MCP-1 elicited increased leukocyte transendothelial migration in adjuvant-immunized rats compared with naive animals. Surprisingly, histology revealed that neutrophils constituted the majority of leukocytes recruited in adjuvant-immunized animals. In vitro, MCP-1 was also able to induce chemotaxis of neutrophils isolated from adjuvant-immunized rats but not from naive rats. Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals. In naive animals, an antibody against CD18 blocked leukocyte adhesion and emigration in response to MCP-1. In adjuvant-immunized animals, leukocyte adhesion was reduced by antibodies against the alpha4-integrin but not by antibodies against CD18. However, the CD18 antibody did block emigration. To our knowledge, this study is the first to show increased sensitivity to a CC chemokine in a model with preexisting inflammation, and altered leukocyte recruitment profiles in response to MCP-1. It also demonstrates that CD18 is required for chemokine-induced leukocyte transendothelial migration, independent of its known role in mediating firm adhesion. J. Clin. Invest. 103:1269-1276 (1999).

Animals↗
PubMed1999

Observer variability in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis.

We examined (1) the observer variability (both interobserver and intraobserver) in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis (NEC), (2) the interobserver variability for individual radiologic signs used to diagnose NEC, and (3) the influence of experience in determining the extent of observer variability. Our hypotheses were (1) there would be considerable observer variability in interpretation of abdominal radiographs of infants with suspected NEC; (2) the extent of observer variability would differ for individual radiologic signs of NEC; and (3) the extent of observer variability would be determined by the observer's experience. The participants included 12 observers: two pediatric radiologists, four attending neonatologists, three neonatal fellows, and three pediatric residents. The participating observers under similar interpretation conditions, twice independently, interpreted the same 40 pairs of abdominal radiographs from infants with suspected NEC. The interval between the two interpretations was 3 to 6 months. Intraobserver and interobserver variability was assessed by applying the Kappa statistic to the radiologic signs of NEC for the two separate interpretations. The observers were blinded to patient's identity and the clinical course. Each observer recorded the absence, suspicion, or presence of (1) intestinal distention, (2) air fluid levels, (3) bowel wall thickening, (4) pneumatosis intestinalis, (5) portal venous gas, (6) pneumoperitoneum, and (7) NEC. We found low intraobserver and interobserver agreements. There was considerable variation in observer variability for individual radiologic signs. Trained observers performed better than intraining observers. We conclude that the radiologic signs in isolation should not be considered reliable. We recommend studies to formulate more objective criteria for many of the radiographic features of NEC. Standardization and periodic enforcement of these criteria among observers could reduce observer variability. We suggest that, to decrease both false-negative and false-positive interpretation, an experienced observer should always review the radiographs of infants with suspected NEC.

Diagnosis, Differential↗
PubMed1999

Nitric oxide inhibits microvascular protein leakage induced by leukocyte adhesion-independent and adhesion-dependent inflammatory mediators.

OBJECTIVE: The purpose of this study was to determine whether exogenous nitric oxide could block permeability alterations induced by neutrophil-independent (histamine) and neutrophil-dependent (CINC/gro) inflammatory mediators. METHODS: Intravital microscopy was used in the rat mesentery to examine leukocyte adhesion, transvascular FITC-albumin leakage, and perivascular mast cell activation (ruthenium red uptake) in response to local superfusion with histamine or the chemokine CINC/gro. The effects of the nitric oxide donor spermine-NO, or the cGMP analog 8-Br-cGMP were examined. RESULTS: Histamine superfusion increased vascular protein leakage within minutes, but did not increase firm adhesion above that seen in control preparations. The increase in albumin leakage could be prevented by co-administration of spermine-NO, but was not affected by 8-Br-cGMP. CINC/gro elicited a linear increase in vascular protein leakage and a profound increase in leukocyte adhesion. Treatment with spermine-NO or 8-Br-cGMP significantly attenuated increases in both adhesion and albumin leakage. The actions of spermine-NO and 8-Br-cGMP were not due to mast cell stabilization as neither histamine nor CINC/gro elicited mast cell activation. CONCLUSIONS: This study demonstrates that exogenous nitric oxide and 8-Br-cGMP could block adhesion dependent alterations in vascular permeability induced by CINC/gro, while adhesion-independent alterations in permeability induced by histamine could be blocked by exogenous NO but not 8-Br-cGMP. This suggests that different NO-dependent signalling pathways are important in modulating these two types of vascular protein leakage.

Animals↗