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D R Johnson

Publications and source records attributed to D R Johnson.

At least 19 recordsLinked to original sources

Up-regulated expression of the alpha7 nicotinic acetylcholine receptor subunit on inflammatory infiltrates during Dictyocaulus viviparus infection.

Cholinergic signalling is known to affect immune cell function, but few studies have addressed its relevance during nematode infection. We therefore analysed the anatomical distribution and expression pattern of the nicotinic acetylcholine receptor (nAChR) alpha7 subunit in lungs obtained from Dictyocaulus viviparus-infected and uninfected control cattle. The analysis was performed on trachea and lung parenchyma from uninfected animals and animals necropsied at 15, 22 and 43 days post-infection (DPI). Localization of the alpha7 nAChR was evaluated by immunohistology and mRNA expression analysed by gene-specific reverse transcription-polymerase chain reaction (RT-PCR). In uninfected animals, tracheal, bronchial and bronchiolar epithelium and smooth muscle cells constitutively expressed the alpha7 nAChR, as did type I and II alveolar epithelial cells and alveolar macrophages and a few infiltrating leucocytes. By 15 DPI, immunohistology revealed a massive influx of alpha7 nAChR+ inflammatory cells into the lung parenchyma and tracheal wall. This was reflected in the RT-PCR results. At later time points, both parenchyma and tracheal wall contained large numbers of alpha7 nAChR+ leucocytes, but detection of transcript was restricted to the trachea. Recruitment of nAChR-containing leucocytes to the lungs of D. viviparus-infected cattle suggests that these cells may represent possible downstream targets for parasite-secreted acetylcholinesterases.

Acetylcholinesterase↗

Local cytokine responses in Dictyocaulus viviparus infection.

The high degree of immunity induced by the bovine lungworm, Dictyocaulus viviparus, makes it an ideal model in which to study nematode-induced protective immune responses. Here, cytokine responses were measured over the course of an experimental infection of D. viviparus. Local cytokine messenger RNA (mRNA) transcripts were measured in lung parenchyma, tracheal rings and draining lymph nodes using semi-quantitative reverse transcriptase-polymerase chain reaction. Responses were measured in animals necropsied at 15, 22 and 43 days post-infection (DPI). The responses elicited at these time points were compared with cytokine levels observed in uninfected animals. Interleukin (IL)-4, IL-5, IL-10, IL-12p35, IL-13 and interferon gamma (IFNgamma) mRNA levels were measured in duplicate at each site. By 42 DPI, very few parasites were recovered, either from faeces or lungs. Transcripts of all cytokines increased in the lung parenchyma, tracheal rings and caudal mesenteric lymph nodes by 15 DPI. The response was rapid and peaked during the time of larval migration through the lungs. By 42 DPI, expression levels of most cytokines were reduced to levels similar to, or below, base line values measured in uninfected animals. Highest levels of IL-10, IL-12p35, IL-13 and IFNgamma transcript were measured in the bronchial lymph nodes of uninfected animals. IgG1 levels were negatively correlated with expression levels of all cytokines. The results demonstrate that a mixed cytokine response occurs over the course of a primary infection during which the parasites were eliminated by day 43 DPI. These results agree with those obtained for other helminths in cattle and challenge the hypothesis that polarised Th2 responses are essential for protection against nematodes in this species. These observations are important in the development of recombinant vaccines, particularly when considering adjuvant choice.

Animals↗

Clinical response augments NK cell activity independent of treatment modality: a randomized double-blind placebo controlled antidepressant trial.

BACKGROUND: Major depressive disorder (MDD) has been associated with alterations in immune function. Suppression of natural killer (NK) cell activity (NKCA) reliably characterizes immunological alterations observed in MDD. Antidepressant pharmacotherapy has been associated with modulation of NKCA. Previous investigations into antidepressant modulation of NKCA have not employed randomized double-blind placebo controlled designs. Thus, it is unknown whether treatment-associated changes in immune function are due to drug, placebo, or spontaneous remission effects. The present investigation examined the effect of antidepressant treatment on NKCA utilizing a randomized double-blind placebo controlled experimental design. METHOD: Patients (N = 16) met DSM-IV criteria for MDD and were randomly assigned to drug (N = 8; citalopram, 20 mg/day) or placebo (N = 8) under double-blind conditions. Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS). NK cell function was measured using a standard chromium-release assay and NK cell number assessed by flow cytometry. HDRS scores, NK cell function, and NK cell numbers were collected at 0, 1, 2 and 4 weeks of treatment. RESULTS: Clinical response was associated with augmented NKCA independent of treatment condition. Failure to respond to treatment resulted in significantly reduced NKCA over treatment interval. CONCLUSIONS: The present results suggest that alterations in the depressive syndrome, regardless of therapeutic modality, may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD.

Adult↗

A prospective randomized multi-center study for the treatment of lumbar spinal stenosis with the X STOP interspinous implant: 1-year results.

Patients suffering from neurogenic intermittent claudication secondary to lumbar spinal stenosis have historically been limited to a choice between a decompressive laminectomy with or without fusion or a regimen of non-operative therapies. The X STOP Interspinous Process Distraction System (St. Francis Medical Technologies, Concord, Calif.), a new interspinous implant for patients whose symptoms are exacerbated in extension and relieved in flexion, has been available in Europe since June 2002. This study reports the results from a prospective, randomized trial of the X STOP conducted at nine centers in the U.S. Two hundred patients were enrolled in the study and 191 were treated; 100 received the X STOP and 91 received non-operative therapy (NON OP) as a control. The Zurich Claudication Questionnaire (ZCQ) was the primary outcomes measurement. Validated for lumbar spinal stenosis patients, the ZCQ measures physical function, symptom severity, and patient satisfaction. Patients completed the ZCQ upon enrollment and at follow-up periods of 6 weeks, 6 months, and 1 year. Using the ZCQ criteria, at 6 weeks the success rate was 52% for X STOP patients and 10% for NON OP patients. At 6 months, the success rates were 52 and 9%, respectively, and at 1 year, 59 and 12%. The results of this prospective study indicate that the X STOP offers a significant improvement over non-operative therapies at 1 year with a success rate comparable to published reports for decompressive laminectomy, but with considerably lower morbidity.

Aged↗

Group a streptococcal serotypes isolated from healthy schoolchildren in iran.

Serotypes of group A streptococci are still a major cause of pharyngitis and some post-infectious sequelae such as rheumatic fever. As part of the worldwide effort to clarify the epidemiological pattern of group A streptococci in different countries, the present study was conducted to assess the prevalence of Streptococcus pyogenes serotypes in Iran. A total of 1588 throat swabs were taken from healthy school children in the city of Gorgan during February and March 1999. Of those isolates, 175 resulted positive for group A streptococci. The distribution pattern was similar for girls and boys, with 10.8% and 11.2%, respectively. Urban school children showed a higher rate of colonization compared to those in rural areas. Serotyping was performed on 65 of the positive isolates using standard techniques, and only 21 (32%) were M-type isolates. Their profiles fell into four types with M1 predominating, which could reflect the presence of rheumatic fever in the region. However, when isolates were challenged for T-antigen types, nearly all were positive (94%). The pattern of T types was diverse (18 types), with the most common T types being T1 (26%), TB3264 (15%), TB\1-19 & B\25\1-19 (9.2%) and T2 & 2\28 (7.7%). When isolates were tested for opacity factor, only 23 (35%) were positive while 34 (52%) responded to the serum opacity reaction test. Although the number of isolates in this study was not sufficient to make any epidemiological conclusions, the scarcity of serotyping studies in Iran could render these data useful for future attempts to develop a streptococcal vaccine.

Adolescent↗

Epidemiologic analysis of invasive and noninvasive group a streptococcal isolates in Hong Kong.

Since the mid-1980s, there has been a resurgence of severe forms of invasive group A streptococcal (GAS) disease in many Western countries. In Hong Kong, a similar increase has also been observed in recent years. One hundred seven GAS isolates collected from 1995 to 1998 from individuals with necrotizing fasciitis, toxic shock syndrome, meningitis, or other type of bacteremic sepsis (invasive group, n = 24) as well as from individuals with minor skin and throat infections (noninvasive group, n = 83) were characterized through serologic and/or emm sequence typing. Thirty-two M protein gene sequence types were identified. Types M1, M4, and M12 were the most prevalent in both the invasive group and the noninvasive group; together they accounted for 70.8 and 37.3% of the isolates, respectively. No clear pattern of skin and throat infection M types was observed. Type M1 was overrepresented in the invasive and pharyngeal isolates. The same pulsed-field gel electrophoresis pattern was shared by most invasive and all pharyngeal M1 isolates. Overall, resistance to erythromycin (32%) and tetracycline (53%) was high, but M1 isolates were significantly less likely to have resistance to either antimicrobial agent than non-M1 isolates. One novel emm sequence type, stHK, was identified in an isolate from a patient with necrotizing fasciitis. Minor emm gene sequence alterations were noted for 31 isolates, and for 13 of these isolates, deletion, insertion, or point mutations were seen in the hypervariable 50 N-terminal residues.

Amino Acid Sequence↗

Dynamic epidemiology of group A streptococcal serotypes associated with pharyngitis.

BACKGROUND: Despite the past 15 years of heightened awareness of the disease-causing potential of group A streptococci, the possible epidemiological influence of rapid changes in prevalent serotypes has not been fully appreciated. METHODS: We analysed throat cultures collected as part of routine medical care in a semi-closed community of nearly 500 children and adults between January, 1999, and April, 2000. beta-haemolytic streptococci from all positive cultures were characterised by serological grouping, T-agglutination pattern, and serotyping for M protein or opacity factor. FINDINGS: We saw an increase in the number of symptomatic individuals with pharyngitis beginning in mid-1999. Between July 1 and Dec 31, 1999, 111 (29%) of 378 throat cultures yielded group A streptococci, 102 (92%) of which were serotype M1. Between Jan 1 and Mar 31, 2000, 126 (45%) of 277 throat cultures yielded group A streptococci. Unexpectedly, 106 (84%) of these throat isolates were serotype M6, and only 16 (13%) were M1. 20 (28%) of the 71 individuals with M1 infection subsequently acquired infection with M6. INTERPRETATION: This rapid and almost complete shift in predominance of group A streptococcal serotype in this community draws attention to the dynamic epidemiology of these organisms. This change has important implications for further understanding the epidemiology of group A streptococcal infections, and for the development and use of a vaccine.

Adolescent↗

Endemic infection of a cat colony with a feline calicivirus closely related to an isolate used in live attenuated vaccines.

We have typed three feline calicivirus (FCV) isolates obtained over a 5-month-period from an endemically infected cat colony. Sequence analysis from variable region E of the capsid gene from these isolates strongly suggests they are minor variants of a single FCV strain, and that this strain is closely related to the one used in many live-attenuated FCV vaccines. Such a vaccine was last used approximately 2 months before the first of the isolates in this study was obtained. Sequence differences between the 'colony isolate' and the vaccine virus suggest that the colony virus has evolved from the vaccine virus and was persisting in the colony. The extent to which vaccine virus may contribute to the continued high prevalence of FCV needs to be determined.

Animals↗

Transport of fluorescein in MDCKII-MRP1 transfected cells and mrp1-knockout mice.

The multidrug resistant-associated protein 1 (MRP1) is a membrane-bound transport protein that is involved in the efflux of organic anions and has been implicated in multidrug resistance in cancer. MRP1 has also been reported to be ubiquitously expressed in normal tissues, including the brain. The presence of functional organic anion transporters in the blood-brain and blood-CSF barriers that influence the distribution of various compounds to the brain has long been known. The purpose of this study was to examine the role of MRP1 in the brain distribution of a model organic anion, fluorescein. The substrate specificity of MRP1 for fluorescein was initially determined by examining the accumulation of fluorescein in MDCKII MRP1-transfected cells. The distribution of fluorescein in the brain was then examined in wild-type and mrp1 gene knockout mice. The results show that in MDCKII MRP1-transfected cells, the accumulation of fluorescein was significantly lower (about 40% lower) than that in wild-type MDCKII cells. MRP1 inhibitors such as probenecid, MK-571, and LY402913 enhanced fluorescein accumulation in MDCKII MRP1-transfected cells to a greater extent than in wild-type MDCKII cells. In an in vivo study, after intravenous injection of fluorescein, the fluorescein brain-to-plasma concentration ratio in mrp1 knockout mice was not significantly different than that in wild-type mice. However, when probenecid was co-administered with fluorescein in wild-type mice, the fluorescein brain-to-plasma ratio was significantly increased (1.5-fold). These findings suggest that fluorescein is a substrate for MRP1. Furthermore, the in vivo study also suggests that MRP1 has a limited role in the transport and distribution of fluorescein in the brain. Therefore, other organic anion transport proteins, including the various isoforms of the MRP family, may be responsible for the accumulation and transport of organic anions in the brain.

ATP-Binding Cassette Transporters↗

Human vascular endothelial cells stimulate a lower frequency of alloreactive CD8+ pre-CTL and induce less clonal expansion than matching B lymphoblastoid cells: development of a novel limiting dilution analysis method based on CFSE labeling of lymphocytes.

We have previously shown that human endothelial cells (EC) are less efficient than professional APC, e.g., B lymphoblastoid cells (BLC), at stimulating allogeneic CD8(+) T cells to develop into CTL. In this study we describe FACS-based limiting dilution analyses using the dilution of the intracellular dye CFSE as an indicator of CD8(+) T cell alloactivation and expansion with significantly increased sensitivity compared with conventional, cytotoxicity-based assays. In addition, this assay permits the relative size of clonal CTL populations that are generated in individual CD8(+) T cell cultures to be determined (clonal burst size). We have applied this method to quantitatively compare the generation of CTL at the clonal level following stimulation of allogeneic CD8(+) T cells by either BLC or HUVEC derived from the same donor. CD8(+) T cells expanded by allostimulation were identified as CD8(+), CFSE(low) cells and were categorized as CTL by the expression of intracellular perforin and IFN-gamma. Precursor frequencies for EC-stimulated CTL were 5- to 40-fold (mean, 7.5-fold) lower compared with BLC-stimulated CTL (p < 0.01). Concomitantly, the average clonal burst sizes in EC-stimulated CTL cultures were significantly smaller than those in conventional CTL cultures, primarily due to the occurrence of some very large clone sizes exclusively with BLC stimulation. Although EC-stimulated CTL were generated only from the memory subset of CD8(+) T cells, BLC-stimulated very large burst sizes of CTL were observed from both naive and memory CD8(+) T cell precursors. These data establish that both a lower frequency of reactive precursors and more limited clonal expansion, but not regulatory T cells, contribute to the reduced capacity of EC to promote alloreactive CTL differentiation compared with that of professional APC.

Antigens, CD↗

False-positive rapid antigen detection test results: reduced specificity in the absence of group A streptococci in the upper respiratory tract.

Rapid antigen detection tests (ADTs) are promoted for identification of group A streptococci (GAS) in the upper respiratory tract. Although debate persists about their sensitivity, most investigators consider ADTs to be highly specific. Nevertheless, reports continue to describe false-positive ADT results (positive ADT result, negative culture result). This study examined culture results from 522 adult patients with acute pharyngitis and a positive ADT result; unexpectedly, 15% had throat culture results negative for GAS. Normal bacterial flora from 30% of these "negative" culture results produced a positive ADT result. An ADT-reactive organism belonging to the Streptococcus milleri group was isolated from 1 culture; it carried group A carbohydrate antigen. Although S. milleri previously has been associated with false-positive ADT reactions, the frequency of this phenomenon is unknown. The present, large study suggests that false-positive ADT reactions may be more common than previously reported, an observation that must be precisely explained and epidemiologically and clinically defined.

Adult↗

The pharmacological phenotype of combined multidrug-resistance mdr1a/1b- and mrp1-deficient mice.

Two major classes of plasma membrane proteins that actively extrude a wide range of structurally diverse hydrophobic amphipathic antineoplastic agents from cells, with different mechanisms of action, lead to multidrug resistance. To study the importance of these ATP-binding cassette transporters to the toxicity of cancer chemotherapy agents, we have used mice genetically deficient in both the mdr1a and mdr1b genes [mdr1a/1b(-/-) mice], the mrp1 gene [mrp1(-/-) mice], and the combined genes mdr1a/1b and mrp1 [mdr1a/1b(-/-), mrp1(-/-) mice] and embryonic fibroblasts derived from wild-type mice and from the three gene knockout animals. The consequences of export pump deficiencies were evaluated primarily using vincristine and etoposide. Mice deficient in the three genes, mdr1a/1b and mrp1, exhibited a 128-fold increase in toxicity to vincristine and a 3-5-fold increase in toxicity to etoposide; increased toxicity to embryonic fibroblast cells from triple knockout mice also occurred with vincristine and etoposide. Vincristine, which normally does not express toxicity to the bone marrow and to the gastrointestinal mucosa when used at therapeutic doses, caused extensive damage to these tissues in mdr1a/1b(-/-), mrp1(-/-) mice. The findings indicate that the P-glycoprotein and mrpl are compensatory transporters for vincristine and etoposide in the bone marrow and the gastrointestinal mucosa and emphasize the potential for increased toxicities by the combined inhibition of these efflux pumps.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Monocyte 5-HT1A receptors mediate pindobind suppression of natural killer cell activity: modulation by catalase.

Serotonin (5-hydroxytryptamine; 5-HT) modulates constituents of the immune system. 5-HT1A receptor antagonists potently suppress lymphocyte function. NK cell activity (NKCA) was measured after exposure of mononuclear cells to the 5-HT1A receptor antagonist pindobind and the 5-HT(1C/2) receptor antagonist ketanserin. Elutriated monocytes were exposed to pindobind, incubated with peripheral blood lymphocytes (PBL) in the presence or absence of an H2O2 scavenger catalase, and NKCA measured. Pindobind, but not ketanserin, suppressed NKCA in vitro. Pindobind-treated monocytes suppressed NKCA, whereas pindobind treatment of PBL did not affect NKCA. Catalase inhibited pindobind-induced suppression of NKCA. These data are consistent with previous results that 5-HT modulates NKCA via 5-HT1A receptors on monocytes and suggest that 5-HT may abrogate monocyte suppression of NKCA by inhibiting monocyte signals such as H2O2.

Catalase↗

Radiation protection in interventional radiology.

There is growing concern regarding the radiation dose delivered during interventional procedures, particularly in view of the increasing frequency and complexity of these techniques. This paper reviews the radiation dose levels currently encountered in interventional procedures, the consequent risks to operators and patients and the dose reduction that may be achieved by employing a rigorous approach to radiation protection.

Fluoroscopy↗

Substance use, need, and demand for substance user treatment services in patients treated for sexually transmitted diseases in michigan.

The association between substance use and communicable diseases, and the need for substance user treatment services for patients treated for communicable diseases, is well documented. This study builds upon this knowledge in that it quantifies the need and demand for substance user treatment services in a large population of patients treated for communicable diseases, specifically, sexually transmitted diseases (STDs), an area in which there is insufficient research published in the literature, but which is essential for policy development. More than 1700 patients treated for STDs in publicly funded clinics in Michigan between 1994-1995 were interviewed about their substance use, consequences of use and demand for substance user treatment services. Results indicated that the rates of substance use and demand for substance user treatment services were significantly higher among persons encountered in the STD clinics compared to the Michigan general adult population; however, a large proportion of STD patients determined to need substance user treatment services according to DSM-III-R criteria for "substance dependence" and "abuse" did not report ever receiving it. These results are followed by a discussion of possible policy implications for planning for substance user treatment services for patients treated for STDs in publicly funded clinics and suggestions for further research.

Adolescent↗

Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic.

Recent work shows that long-term exposure to low levels of arsenite induces malignant transformation in a rat liver epithelial cell line. Importantly, these chronic arsenic-exposed (CAsE) cells also develop self-tolerance to acute arsenic exposure. Tolerance is accompanied by reduced cellular arsenic accumulation, suggesting a mechanistic basis for reduced arsenic sensitivity. The present study examined the role of xenobiotic export pumps in acquired arsenic tolerance. Microarray analysis of CAsE cells showed increased expression of the genes encoding for glutathione S-transferase Pi (GST-Pi), multidrug resistance-associated protein genes (MRP1/MRP2, which encode for the efflux transporter Mrp1/Mrp2) and the multidrug resistance gene (MDR1, which encodes for the efflux transporter P-glycoprotein). These findings were confirmed at the transcription level by reverse transcription-polymerase chain reaction and at the translation level by Western-blot analysis. Acquired arsenic tolerance was abolished when cells were exposed to ethacrynic acid (an inhibitor of GST-Pi), buthionine sulfoximine (a glutathione synthesis inhibitor), MK571 (a specific inhibitor for Mrps), and PSC833 (a specific inhibitor for P-glycoprotein) in dose-dependent fashions. MK571, PSC833, and buthionine sulfoximine markedly increased cellular arsenic accumulation. Consistent with a role for multidrug resistance efflux pumps in arsenic resistance, CAsE cells were found to be cross-resistant to cytotoxicity of several anticancer drugs, such as vinblastine, doxorubicin, actinomycin-D, and cisplatin, that are also substrates for Mrps and P-glycoprotein. Thus, acquired tolerance to arsenic is associated with increased expression GST-Pi, Mrp1/Mrp2 and P-glycoprotein, which function together to reduce cellular arsenic accumulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Treatment of sclerosing mesenteritis with corticosteroids and azathioprine.

Sclerosing (idiopathic) mesenteritis is a rare disease that may present with abdominal pain or bowel obstruction. A 21-year-old man was diagnosed with sclerosing mesenteritis, and treated with a partial ileal resection and defunctioning ileostomy. He was subsequently started on corticosteroids and azathioprine. Five months later, at the time of ileostomy reversal, he was disease-free. The diagnosis and management of this disease are discussed.

Adrenal Cortex Hormones↗

Levels of monocyte reactive oxygen species are associated with reduced natural killer cell activity in major depressive disorder.

Major depressive disorder (MDD) is associated with reductions in natural killer cell activity (NKCA), however the mechanism(s) mediating reduced NKCA in MDD has yet to be determined. In light of evidence that MDD is associated with an inflammatory immune response, we propose that reactive oxygen species (ROS), generated by inflammatory leukocytes (monocytes and/or neutrophils), may mediate the suppression of NKCA in MDD. Intracellular levels of monocyte ROS were significantly associated with reductions in NKCA in outpatients (n = 15) diagnosed with MDD. Sleep disturbance was also significantly correlated with reductions in NKCA. Elevated levels of ROS may be an additional characteristic of a subset of depressed patients in whom an inflammatory response persists and elevations in ROS may, in part, mediate the associations observed between MDD, cardiovascular disease, and cancer.

Adult↗