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Biomedical subjects

J S Klein

Publications and source records attributed to J S Klein.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interleukin 4 in inflammatory bowel disease and mucosal immune reactivity.

BACKGROUND & AIMS: Interleukin (IL) 4 has immunoregulatory and anti-inflammatory activities, but little is known about IL-4 in the human gut. We investigated production of IL-4 by isolated lamina propria mononuclear cells (LPMCs) from normal and inflamed intestine and its capacity to modulate local immune responses. METHODS: IL-4 levels were measured by enzyme-linked immunosorbent assay in cultures of control and inflammatory bowel disease LPMCs, and the effect of IL-4 on LPMC proliferation and interaction with IL-2, IL-1 beta, lipopolysaccharide, bacterial antigens, superantigen, and antibodies to various T-cell receptors was investigated. RESULTS: Various stimuli induced LPMCs to produce IL-4, but inflammatory bowel disease cells expressed IL-4 messenger RNA and secreted protein in significantly lower amounts than control cells. IL-4 failed to stimulate proliferation by fresh LPMCs, but a vigorous dose-dependent response was observed after preactivation by phytohemagglutinin, IL-2, or IL-4. When added to fresh LPMCs, IL-4 inhibited IL-2-induced proliferation. IL-4 amplified proliferation to IL-1 beta, lipopolysaccharide, peptidoglycan-polysaccharide complexes, staphylococcus enterotoxin A, and antibodies to the CD3 and CD28 receptors but not to tetanus toxoid. CONCLUSIONS: Decreased production of IL-4 in inflammatory bowel disease may cause defective immunosuppressive and anti-inflammatory mechanisms and may contribute to disease pathogenesis. The ability of IL-4 to differentially modulate LPMC reactivity probably influences mucosal immune homeostasis.

Adolescent↗
PubMed1996

Transthoracic needle biopsy with a coaxially placed 20-gauge automated cutting needle: results in 122 patients.

PURPOSE: To determine the utility of coaxial transthoracic needle biopsy (TNB) with use of a 20-gauge automated cutting biopsy needle in the diagnosis of thoracic lesions. MATERIALS AND METHODS: A retrospective review was performed in 122 patients. Computed tomography was used to guide coaxial TNB, which was performed with aspirating (n = 87) and automated cutting (n = 99) needles. The sensitivities for malignant and benign lesions were determined, with a comparison of the relative yields from the two techniques. RESULTS: The overall diagnostic yield for coaxial TNB was 88%. For malignancy the sensitivity was 95%, whereas a specific benign diagnosis was obtained in 91%. Although no difference was found for fine-needle aspiration versus core biopsy of malignant lesions (92% vs 86%), a statistically significant difference was found for benign lesions (44% vs 100%, P<.05). Pneumothorax occurred in 54%. CONCLUSION: Coaxial TNB performed with an automated cutting needle helps provide a diagnosis in the majority of patients with focal chest disease and is particularly useful in the diagnosis of benign lesions.

Adolescent↗
PubMed1996

Hypoproliferative human lamina propria T cells retain the capacity to secrete lymphokines when stimulated via CD2/CD28 pathways.

Human lamina propria (LP) T cells exhibit a reduced proliferative capacity in response to antigen-specific stimulation. To investigate the functional state of such hypoproliferative T cells, we determined the capacity of LP T cells to produce lymphokines when stimulated by monoclonal antibodies that crosslink either the TCR/CD3 complex or accessory pathway molecules (CD2,CD28). We found that TCR/CD3-mediated proliferative responses of LP T cells were greatly diminished when compared to peripheral blood (PB) T cells, but were largely restored when cells were preincubated in IL-2. Despite their proliferative hyporesponsiveness, LP T cells (as compared to PB T cells) secreted equal amounts of IL-2 and increased amounts of IFN-gamma, IL-4 and IL-5; these increased cytokine responses were most evident when cells were stimulated via the accessory pathways. In further studies, purified CD4+ LP T cells were compared with purified CD4+/CD45RO+ PB T cells (i.e., the PB T cell subset they most resemble). LP T cells produced significantly more IFN-gamma and IL-5 but less IL-4 than their CD45RO+ PB counterparts. Overall, LP T cells are unresponsive T cells following stimulation via the TCR/CD3 pathway but nevertheless retain the capacity to produce increased levels of TH1 and TH2-type lymphokines following stimulation via the CD2/CD28 accessory pathway; thus, they are best classified as modified "anergic" T cells.

CD2 Antigens↗
PubMed1995

Internal controls as performance monitors and quantitative standards in the detection by polymerase chain reaction of herpes simplex virus and cytomegalovirus in clinical specimens.

Internal controls (IC) were produced and characterized for an HSV and a CMV PCR assay which serve both as test performance monitors and as quantitative standards. In each of the PCR assays the IC and native targets were amplified with equal efficiency and were detected with the same sensitivity, i.e. < 10 target copies. An algorithm was developed for the use of IC as a quantitative standard which entailed coamplifying a test specimen with four two-fold dilutions of the respective IC target (63-500 copies), followed by regression analysis of the relative yield of amplification products. This approach allowed the determination of both the initial virus genome copy number and the variability of the results, which provided a confidence index for the PCR assay. The relative yields of PCR products were determined by Southern blot and probe hybridization and by densitometry of digitized ethidium bromide-stained gels. Both methods produced estimations of the initial target copy numbers within +/- 40% of the expected value. Such a comprehensive analysis of an internal control for a PCR assay provides a rigorous control of test performance and permits reliable quantitative interpretation of a PCR assay result.

AIDS-Related Opportunistic Infections↗
PubMed1995

Bronchogenic carcinoma in 13 patients infected with the human immunodeficiency virus (HIV): clinical and radiographic findings.

Bronchogenic carcinoma is a cause of parenchymal or hilar masses with or without mediastinal adenopathy in HIV-seropositive smokers. Lung cancer can occur earlier than the more commonly recognized opportunistic infections and in patients not known to be HIV seropositive. Tumor cell types do not differ markedly from those expected in HIV-seronegative young lung cancer patients, but are often poorly differentiated; patients with high-grade malignancies fare poorly independent of their degree of immunocompromise at diagnosis. Computed tomography (CT) scans not only add important information with regard to disease distribution and preferred means of diagnosis, but also result in the detection of new sites of disease with respect to the plain radiography in many patients. Because lung cancer often occurs before the diagnosis of AIDS, the association may not be suspected in some cases; poorly differentiated, rapidly growing tumors in young smokers may raise the suspicion of underlying HIV infection.

Adult↗
PubMed1995

Bacillary angiomatosis in patients with AIDS: multiorgan imaging findings.

PURPOSE: To describe the varied clinical manifestations and imaging findings encountered in bacillary angiomatosis, an infectious complication of the acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Clinical, imaging, and histopathologic findings in nine men (aged 26-50 years) with AIDS and bacillary angiomatosis were described. This condition often manifests as vascular skin lesions that resemble those of Kaposi sarcoma, fever, and anemia and is due to infection with Bartonella (Rochalimaea) henselae. RESULTS: Common imaging findings included lung nodules, mediastinal adenopathy, peripheral adenopathy, pleural effusions, ascites, abdominal adenopathy, soft-tissue masses, and low-attenuation lesions in the liver and/or spleen. Most notably, nodes and soft-tissue lesions were dramatically enhanced with injection of contrast material, which is presumably because the lesions are composed to a large extent of well-formed capillaries. CONCLUSION: Bacillary angiomatosis, a treatable infection, should be considered in patients with AIDS, particularly when Kaposi sarcoma is suspected clinically.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Interventional radiology of the chest: image-guided percutaneous drainage of pleural effusions, lung abscess, and pneumothorax.

Percutaneous catheter drainage of intrathoracic collections has developed as a natural extension of similar interventional radiologic procedures in the abdomen. The advent of CT and sonography, which allow detection and characterization of pleural and parenchymal collections, combined with advances in drainage catheter design and interventional techniques, have made imaging-guided management of intrathoracic collections a safe and effective alternative to traditional surgical therapy. This article begins with a review of the etiology, pathophysiology, diagnosis, and treatment of parapneumonic pleural effusion, which remains the most common indication for image-guided percutaneous drainage. Subsequent sections consider issues related to percutaneous drainage of malignant pleural effusion, lung abscess, and pneumothorax.

Drainage↗
PubMed1994

Biochemical properties, activities, and presence in biologic fluids of eosinophil granule major basic protein.

The existence of a proform of MBP is predicted from the sequence of MBP cDNA clones. ProMBP has been purified from the supernatants of CHO cells transfected with cDNA encoding prepro MBP. Purification involved heparin-Sepharose affinity purification followed by two sequential size fractionation steps over Sephadex G-100 and yielded proMBP with a molecular mass of 33 kd. Recombinant proMBP from the heparin-Sepharose column was subjected to isoelectric focusing followed by SDS-PAGE and Western blot analysis. The results indicated that most of the 33 kd form of proMBP focused predominantly between pI 4.2 and 5.1, with a major peak at a pI of approximately 4.9. Analyses of the carbohydrates associated with the purified 33 kd form of recombinant proMBP indicated the addition of 4856 to 5150 Da by carbohydrates characteristic of the complex type. Consistent with the hypothesis that the function of the propiece is to neutralize MBP toxicity during granule processing, proMBP lacked MBP cytostimulatory properties and actually blocked the effect of MBP in two different systems, basophil histamine release and neutrophil activation. In addition, as a measure of toxicity, proMBP did not inhibit protein synthesis, whereas MBP markedly reduced protein synthesis. The mechanisms by which MBP exerts its actions both as a cytostimulant and as a toxin are not known; however, it is known that cationic MBP readily reacts with acidic lipids. Using artificial liposomes as targets, MBP caused a disordering of the lipid bilayer membrane, resulting in fusion and lysis. Therefore, MBP may act both as a cytostimulant and as a toxin because of its marked cationicity and its ability to disorder lipid membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Eosinophils within the healthy or inflamed human intestine produce substance P and vasoactive intestinal peptide.

The purpose of this study was to show if inflammatory cells within healthy or diseased human intestinal mucosa produce some regulatory neuropeptides. First, inflammatory cells were isolated from the intestinal lamina propria of 11 patients with ulcerative colitis or Crohn's disease. Also collected were cells from anatomically normal intestine derived from five patients requiring bowel resection for diseases not related to inflammatory bowel disease. Extracts of these isolated cells contained authentic substance P (SP) and vasoactive intestinal peptide (VIP) as shown by RIA and their elution profiles on HPLC. Immunostaining of cells from nine of 13 additional patients localized immunoreactive SP and VIP to secretory granules within most mucosal eosinophils. No other cell types stained positive. Messenger RNA encoding SP and VIP was localized to lamina propria eosinophils by in situ hybridization. Mucosa inflammatory cells, from eight of nine more patients, cultured in vitro, released detectable amounts of VIP, but not SP. It is concluded that intestinal eosinophils produce SP and VIP. Since the eosinophils store and release more VIP than SP, it is possible that VIP is the preferred secretory product.

Adolescent↗
PubMed1993

Immune activation genes in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with enhanced activation of T cells, but the genes responsible for this state are not well characterized. METHODS: T-cell activation genes were studied in peripheral blood and intestinal mucosal mononuclear cells of control, Crohn's disease, and ulcerative colitis patients. RESULTS: In all groups the expression of interleukin-2 (IL-2), IL-2 receptor alpha (IL-2R alpha), and IL-2R beta messenger RNA (mRNA) was significantly higher in intestinal than circulating cells, and it correlated well with protein levels. Both IL-2R alpha and IL-2R beta mRNA were abundant in mucosal cells, suggesting that a substantial number of them displays high affinity IL-2R. This would explain why intestinal cells proliferate more, express more IL-2 transcripts, and secrete more IL-2 than peripheral cells. Inflammatory bowel disease cells produced similar or higher IL-2R alpha and IL-2R beta mRNA than controls but generated significantly lower IL-2 mRNA. Thus, the reported defect of IL-2 activity in Crohn's disease and ulcerative colitis is probably related to decreased IL-2 transcription. Crohn's disease intestinal cells had the highest expression of IL-2R gene products. This provides a mechanism for their increased response to IL-2 and supports claims that elevated soluble IL-2R alpha serum levels reflect gut T-cell hyperactivity in this disease. CONCLUSIONS: These findings underscore the importance of T cells in mucosal immunity and indicate that abnormal T-cell activation is intimately associated to the pathogenesis of inflammatory bowel disease.

Adolescent↗
PubMed1993

Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells.

BACKGROUND: Interleukin 1 (IL-1) is a key mediator of bowel inflammation, but there is limited knowledge about the amount and site of production of this cytokine in the gastrointestinal tract under physiological or pathological conditions. METHODS: Epithelial and lamina propria mononuclear cells were isolated from control, and Crohn's disease- and ulcerative colitis-involved mucosa to investigate the capacity of these cells to generate IL-1 bioactivity, IL-1 alpha and IL-1 beta immunoreactivity, and gene expression. RESULTS: Control lamina propria mononuclear cells produced substantial amounts of IL-1 alpha and IL-1 beta, which increased dramatically when inflammatory bowel disease cells were used. Epithelial cells from control, Crohn's disease, and ulcerative colitis intestine displayed no IL-1 bioactivity or immunoreactivity. Lamina propria mononuclear cells contained moderate to large quantities of IL-1 alpha and IL-1 beta messenger RNA (mRNA), respectively, whereas epithelial cells had none. The absence of IL-1 transcripts in epithelial cells was selective, because mRNA for HLA-DR antigens was present in control and inflammatory bowel disease cells. CONCLUSIONS: In normal and inflamed human intestine there is a distinct compartmentalization of IL-1, as mononuclear but not epithelial cells generate this cytokine. The high levels of IL-1 in inflammatory bowel disease may explain several of its local and systemic manifestations, and blockade by specific antagonists could have important therapeutic effects.

Adolescent↗
PubMed1993

Percutaneous transthoracic needle biopsy in AIDS: analysis in 32 patients.

PURPOSE: A retrospective study was performed to determine the success of percutaneous transthoracic needle biopsy (TNB) as an aid in diagnosing focal chest and mediastinal disease in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: The study group was composed of 32 patients seropositive for HIV; 31 of these patients had known AIDS. The subjects underwent chest radiography, computed tomography, and TNB. RESULTS: In 27 of the 32 patients a specific diagnosis was enabled by TNB. Bronchogenic carcinoma was diagnosed most frequently, although infectious agents were isolated in most patients. CONCLUSION: TNB is a safe and effective procedure for evaluation of focal thoracic disease in this patient population and provides information that is often unavailable from alternative diagnostic procedures.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease.

Serum levels of soluble interleukin 2 receptor (sIL-2R) have been proposed as a clinical marker of inflammatory bowel disease. The source of sIL-2R in patients with Crohn's disease and ulcerative colitis is unknown, and other soluble receptors have not been investigated. In the present study, sIL-2R and soluble CD8 and CD4 levels were measured in plasma and culture supernatants of peripheral blood and intestinal mucosal mononuclear cells from patients with inflammatory bowel disease, surgical controls, and healthy subjects. Level of plasma sIL-2R was significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy volunteers. Intestinal cells always produced more sIL-2R than peripheral cells. Spontaneous sIL-2R production by mucosal cells was significantly elevated in Crohn's disease but not in ulcerative colitis supernatants compared with levels of surgical controls. Soluble CD8 and CD4 were poor indicators of systemic or mucosal immunity. A positive correlation was found between plasma sIL-2R and spontaneous production by intestinal cells of patients with Crohn's disease and surgical control patients, whereas ulcerative colitis plasma sIL-2R correlated with spontaneous production by peripheral cells. The association of plasma or spontaneous sIL-2R levels with the degree of intestinal inflammation was weak, and there was a wide overlap with control values. Therefore, caution should be used before considering sIL-2R an accurate marker of inflammatory bowel disease activity.

Aged↗
PubMed1992

High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity.

To determine the prevalence of "nonobstructive" (impairment of gas transfer) emphysema in a select population of smokers with dyspnea, a retrospective study of patients with emphysema evident at high-resolution computed tomography (HRCT) was undertaken. Four hundred seventy HRCT studies were reviewed. In 47 cases, centrilobular emphysema was the dominant or sole parenchymal abnormality. Concomitant chest radiographs were available in 41 of these cases; 16 of the 41 lacked radiographic findings of emphysema. Among these 16 patients, pulmonary function testing revealed 10 to have normal flow rates (ratio of forced expiratory volume in 1 second to forced vital capacity and forced expiratory volume in 1 second greater than 80% predicted) and impaired gas transfer (single-breath carbon monoxide diffusing capacity [DLCOSB] less than 80% predicted). With the exclusion of one patient with congestive heart failure from the group of 10, the severity of emphysema at HRCT correlated inversely with DLCOSB (r = -.643). These results indicate that HRCT allows detection of emphysema in symptomatic patients when chest radiographs and pulmonary function tests are nondiagnostic.

Female↗
PubMed1992

Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia.

To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.

AIDS-Related Opportunistic Infections↗