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Biomedical subjects

C L Karp

Publications and source records attributed to C L Karp.

46 records · Page 3Linked to original sources

Mechanism of suppression of cell-mediated immunity by measles virus.

The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for the generation of CMI. Measles virus (MV) infection of primary human monocytes specifically down-regulated IL-12 production. Cross-linking of CD46, a complement regulatory protein that is the cellular receptor for MV, with antibody or with the complement activation product C3b similarly inhibited monocyte IL-12 production, providing a plausible mechanism for MV-induced immunosuppression. CD46 provides a regulatory link between the complement system and cellular immune responses.

Antibodies, Monoclonal↗

Conjunctival intraepithelial neoplasia. A possible marker for human immunodeficiency virus infection?

BACKGROUND: Conjunctival intraepithelial neoplasia has traditionally been found at the limbus in elderly individuals. Recently, this ocular tumor has been observed in younger patients. OBJECTIVE: To investigate the potential association of human immunodeficiency virus infection with the emergence of this atypical presentation of conjunctival intraepithelial neoplasia. DESIGN, SETTING, AND PARTICIPANTS: Records of patients at the Bascom Palmer Eye Institute (Miami, Fla) in whom conjunctival intraepithelial neoplasia was diagnosed between January 1, 1991, and December 31, 1993, were reviewed. Attempts were made to contact those patients younger than 50 years for clinical evaluation and human immunodeficiency virus serologic testing. RESULTS: Conjunctival intraepithelial neoplasia was diagnosed in 73 patients during the study period. Of the nine patients younger than 50 years, six were available for serologic testing. Three (50%) of these individuals were found to be positive for human immunodeficiency virus. CONCLUSION: Human immunodeficiency virus testing and counseling should be considered in patients younger than 50 years in whom conjunctival intraepithelial neoplasia is diagnosed.

Adult↗

Euphorbia sap keratopathy: four cases and a possible pathogenic mechanism.

AIMS: To report four cases of Euphorbia sap causing anterior segment toxicity. METHODS: Medical records of four patients who presented with Euphorbia sap keratoconjunctivitis were reviewed. Clinical findings were compared with previously published reports. RESULTS: All of these patients experienced a similar clinical course. Initial contact with Euphorbia sap caused punctate epitheliopathy; patients noted immediate burning and photophobia, but no visual loss. In all cases, patients experienced epithelial slough with delayed healing, requiring approximately 9 days to heal the epithelial defect. Patients were treated with topical antibiotics, pressure patching or a bandage contact lens, and final visual acuities were excellent in all cases. A review of the literature revealed that Euphorbia sap contains a diterpenoid diester which exhibits antineoplastic activity in rodents. CONCLUSIONS: Individuals who work with Euphorbia plants should be cautioned to wear eye protection. Patients with Euphorbia sap anterior segment toxicity should be informed that their condition may worsen initially, but that visual outcome is generally excellent. The progressive corneal epithelial sloughing and delayed corneal epithelial healing may be secondary to the antineoplastic effects of Euphorbia sap.

Adult↗

Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats.

Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl) should inhibit liver regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated and control rats. Functional assays and Northern blot analysis of a Kupffer cell-specific mRNA confirmed that GdCl depleted Kupffer cells. Despite this, semiquantitative reverse transcription-polymerase chain reaction analysis of total hepatic RNA showed six- to eightfold higher levels of TNF transcripts in GdCl-treated rats. In this group, PH caused 12-to 16-fold greater induction of interleukin-6, a TNF-inducible cytokine, and two- to threefold greater induction of several cytokine-regulated genes (c-jun, C/EBP-beta, and C/EBP-delta). GdCl also amplified regeneration-associated increases in the DNA binding activity of AP-1, a growth regulatory transcription factor. Furthermore, hepatic incorporation of [3H]thymidine, expression of the S-phase antigen, proliferating cell nuclear antigen, and the hepatocyte mitotic index were each significantly greater in GdCl-treated rats. Thus, although GdCl causes Kupffer cell depletion, it does not decrease liver TNF and actually enhances liver regeneration after PH.

Animals↗

T-cell responses to infected autologous monocytes in patients with cutaneous and mucocutaneous leishmaniasis.

Although there is strong evidence that the control and resolution of human leishmanial infections depend primarily on activation of parasite-infected macrophages mediated by lymphokines derived from T cells, less is known about the nature of the responding cell type(s) which is protective or the antigen(s) (Ag[s]) that elicits these cells to respond. Studies using preparations of whole soluble Ag ("dead Ag") show that patients respond to a wide range of leishmanial Ags. The objective of the present study was to characterize the response of T cells from patients with healing or healed cutaneous or mucosal infections to Ag expressed by or derived from actively infected autologous monocytes ("live Ag"). Unfractionated T cells proliferated and produced gamma interferon in response to both live and dead Ags. Depletion of CD4+ T cells resulted in the loss of proliferative and gamma interferon responses to both live and dead Ags. The effect of CD8 depletion, although variable and not limited to the cells stimulated by infected monocytes, was clear for some patients. Expansion of T cells specific for live Ags by using amastigote-infected cells followed by restimulation with fast-protein liquid chromatography-fractionated soluble Ags revealed that a diversity of Ags are associated with infected monocytes. There may, however, be quantitative differences in the expression of certain Ags since prestimulation with live Ag induced higher responses to restimulation in mucocutaneous leishmaniasis patients than in localized cutaneous leishmaniasis patients. Prestimulation with dead Ag induced similar secondary responses in both patient groups.

Animals↗

Adjunctive use of transconjunctival mitomycin-C in ab externo diode laser sclerostomy surgery in rabbits.

This study evaluates the role of transconjunctival mitomycin-C (MMC) in laser sclerostomy surgery. Sixteen albino rabbits underwent ab externo diode laser sclerostomy surgery in one eye (with the fellow eye as a control), with a single, intraoperative, 7-minute transconjunctival application of MMC (MMC group). Ten rabbits had the same sclerostomy surgery without MMC (NOMMC group). Successful filtration, defined as a difference in intraocular pressure less than 4 mm Hg between the operative and control eyes, lasted significantly longer in the MMC group (16.4 +/- 11.0 days) than in the NOMMC group (8.5 +/- 4.5 days) (P = .02). These data suggest that transconjunctival MMC can enhance the success of diode laser sclerostomy surgery in rabbits.

Animals↗

Diode laser surgery. Ab interno and ab externo versus conventional surgery in rabbits.

BACKGROUND: Fibroblastic proliferation of subconjunctival tissues remains a primary mechanism of failure in filtration surgery. Minimizing the surgical manipulation of episcleral tissues may reduce scarring. Laser sclerostomy surgery involves minimal tissue dissection, and is gaining attention as a method of potentially improving filter duration in high-risk cases. METHODS: Twenty-five New Zealand rabbits underwent filtration surgery in one eye, and the fellow eye remained as the unoperated control. Ten rabbits underwent ab externo diode laser sclerostomy surgery, ten underwent ab interno diode sclerostomy surgery, and five had posterior sclerostomy procedures. Filtration failure was defined as a less-than-4-mmHg intraocular pressure (IOP) difference between the operative and control eyes. RESULTS: The mean time to failure for the ab externo, ab interno, and conventional posterior sclerostomy techniques measured 17.4 +/- 11.5, 13.1 +/- 6.7, and 6.0 +/- 3.1 days, respectively. In a comparison of the laser-treated groups with the conventional procedure, the time to failure was significantly longer (P = 0.02) for the ab externo filter. The mean ab interno sclerostomy duration was longer than the posterior lip procedure, but this difference was not statistically significant (P = 0.15). The overall level of IOP reduction was similar in the three groups. CONCLUSIONS: These data suggest that diode laser sclerostomy is a feasible technique in rabbits, and the ab externo approach resulted in longer filter duration than the conventional posterior lip procedure in this model.

Animals↗

In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma.

The immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cytokines. Transcript levels of IL-10 as well as IFN-gamma were significantly elevated in patients with active visceral leishmaniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macrophages that is necessary for the control of leishmanial infection.

Adolescent↗

Lipophosphoglycan masks recognition of the Leishmania donovani promastigote surface by human kala-azar serum.

Markedly elevated titers of anti-leishmanial antibodies are a hallmark of kala-azar. We investigated the role played by the lipophosphoglycan (LPG) in determining the reactivity of kala-azar serum with the surface of Leishmania donovani promastigotes. In assays performed with liver parasites there was negligible agglutination or fluorescent staining of LPG-bearing promastigotes by kala-azar serum, but strong reactivity in both assays with the use of an L. donovani mutant strain (R2D2) that lacks surface expression of LPG. Immunoprecipitation of lysates of 125I surface-labeled promastigotes indicated that kala-azar serum has reactivity with several surface proteins common to both the wild-type and R2D2 strains, and no reactivity with surface proteins unique to R2D2. Although direct ELISA showed that kala-azar serum recognizes purified promastigote LPG, inhibition ELISA suggested that such recognition is based solely upon reactivity with the normally unexposed core-anchor region of the molecule. We conclude that the poor reactivity of kala-azar serum with the surface of L. donovani promastigotes is caused by its lack of recognition of the exposed phosphodisaccharide repeat units of LPG, which in turn effectively mask the surface molecules that are recognized by kala-azar serum antibodies.

Animals↗

Personality differences and stressful life events. Differences between treated periodontal patients with and without maintenance.

The purpose of this study was to determine whether personality differences exist between patients who have had periodontal therapy and continued in maintenance compared with those who have had periodontal therapy and no maintenance. In addition, an attempt was made to determine whether there were differences in reactions to stressful life events among the 2 groups of patients. Patients were evaluated for personality differences using the adjective check list. A background questionnaire was used to gather personal data and information pertinent to stressful life events. The maintained group had a more positive image of themselves. They had higher achievement, endurance and affiliation scores than did the patients without maintenance. The unmaintained group had higher negative aggression scores, a higher incidence of stressful life events, and less stable personal relationships in their lives.

Attitude↗