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Biomedical subjects

A D Klion

Publications and source records attributed to A D Klion.

15 recordsLinked to original sources
PubMed2006

Platelet-derived growth factor receptor-alpha-associated hypereosinophilic syndrome and lymphomatoid papulosis.

Fip1-like 1/platelet-derived growth factor receptor-alpha (FIP1L1/PDGFRA)-positive hypereosinophilic syndrome is a rare disorder with a poor prognosis if untreated and for which treatment with imatinib mesilate is highly effective. A 33-year-old man presented with recurrent papular skin lesions and marked peripheral eosinophilia. Skin biopsy revealed proliferation of CD30(+) T cells consistent with lymphomatoid papulosis (LyP), whereas molecular analysis of peripheral blood mononuclear cells demonstrated the presence of the FIP1L1/PDGFRA fusion gene. As the presence of this gene has important prognostic and therapeutic implications, this report underscores the importance of molecular testing in the evaluation of patients with LyP and peripheral eosinophilia.

Adult↗
PubMed2006

CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of Fc epsilon RI.

BACKGROUND: Fc epsilon RI expression by monocytes can affect monocyte function via multiple mechanisms, thereby potentially influencing the generation of allergic inflammation. Previous studies on the in vivo regulation of monocyte Fc epsilon RI expression by ambient IgE have yielded conflicting results. OBJECTIVE: We hypothesized that monocyte Fc epsilon RI expression is limited to a specific monocyte subset, and that within that subset Fc epsilon RI surface expression is correlated to serum IgE. METHODS: Study 1: Blood was obtained from non-allergic subjects (n=14) and subjects with allergic asthma (n=18), hypereosinophilic syndrome (n=2), hyper-IgE syndrome (n=6), and helminth infection (n=4). Study 2: Blood was obtained from allergic subjects in a clinical trial of omalizumab before and during study drug treatment. Monocyte surface Fc epsilon RI expression was measured using flow cytometry. RESULTS: Fc epsilon RI expression was significantly greater in the CD2(high) vs. CD2(low) monocyte subsets (31% vs. 1.9% median Fc epsilon RI+, respectively). In asthmatic and non-atopic healthy control subjects, CD2(low) monocytes expressed little or undetectable Fc epsilon RI. In study 1, Fc epsilon RI expression was highly correlated to serum IgE in the CD2(high), but not in the CD2(low) monocyte subpopulation (R values of 0.67 and 0.41, respectively). In study 2, omalizumab, but not placebo, caused a significant and sustained decline in Fc epsilon RI expression within the CD2(high) monocyte subset. CONCLUSIONS: CD2 defines a monocyte subset with high Fc epsilon RI expression, whose magnitude is highly correlated to serum IgE. As such, this new description of CD2(high) monocytes as Fc epsilon RI-bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies.

Adult↗
PubMed2001

"Pseudo-conduction block" in a patient with vasculitic neuropathy.

A 63-year-old man presented with progressive asymmetric weakness and numbness in his hands of 2 weeks duration. Nerve conduction studies showed low amplitude motor evoked potentials of both median nerves. The right ulnar, left tibial and peroneal nerves had normal potentials on distal stimulation with markedly decreased amplitudes proximally, suggestive of "conduction block". Three weeks later, amplitudes were decreased throughout. The patient was diagnosed with vasculitis. The acute ischemic injury presumably resulted in axonal damage between the distal and proximal stimulation sites, with subsequent Wallerian degeneration.

Churg-Strauss Syndrome↗
PubMed2000

Onchocerciasis in a nonendemic population: clinical and immunologic assessment before treatment and at the time of presumed cure.

Although suppressive therapy for onchocerciasis with intermittent ivermectin prevents the development of pathology in endemic populations, the clinical and immunologic effects of therapy in the absence of continued exposure are unknown. To address this question, 14 patients treated with ivermectin for onchocerciasis acquired >10 years ago during temporary residence in Africa were reevaluated. None had evidence of continued infection or pathology at follow-up. Although eosinophilia, serum IgE, and antifilarial antibody levels decreased after ivermectin therapy, none of these parameters was useful in predicting the resolution of symptoms in infected patients. Peripheral blood mononuclear cells isolated from patients at follow-up were more responsive to parasite antigen in vitro, which is as assessed by proliferation and production of interferon-gamma and interleukin (IL)-5. In contrast, antigen-induced levels of IL-10 were significantly decreased at follow-up, consistent with diminished down-regulatory factors rather than a switch from type 2 to type 1 immune responses.

Animals↗
PubMed2000

The relationship between serum IgE and surface levels of FcepsilonR on human leukocytes in various diseases: correlation of expression with FcepsilonRI on basophils but not on monocytes or eosinophils.

BACKGROUND: Expression of receptors for IgE (FcepsilonR) have been mainly studied on mast cells and blood basophils in the context of allergic disease. Some reports have noted limited expression of FcepsilonR on other leukocytes, including blood monocytes and eosinophils in certain patients. An association between human blood basophil expression of FcepsilonRIalpha and serum IgE has been noted among allergic subjects. OBJECTIVE: Recent evidence supports regulation of FcepsilonRIalpha by free IgE on both mast cells and basophils. We hypothesized that this relationship would exist across an extremely wide range of IgE levels for human basophils, irrespective of underlying disease. We further examined whether a similar relationship existed between serum IgE and FcepsilonRIalpha or FcepsilonRII (CD23) expression on monocytes and eosinophils in these same subjects. METHODS: Blood was obtained from nonallergic subjects (n = 3) and subjects with allergic asthma (n = 5), atopic dermatitis (n = 3), hypereosinophilic syndromes (n = 7), hyper-IgE syndrome (n = 6), helminth infestation (n = 6), or IgE myeloma (n = 1). Levels of serum IgE were determined by using RIA and ranged from 3 to 4.7 mg/mL. Levels of cell surface FcepsilonRIalpha, FcepsilonRII, and IgE were measured by using immunofluorescence and flow cytometry. RESULTS: Basophil surface IgE density and FcepsilonRIalpha expression correlated with serum IgE levels (r = 0. 67 and r = 0.46, respectively; P <.01; n = 31) regardless of the disease state. In contrast, monocyte FcepsilonRIalpha expression did not correlate with serum IgE (r = 0.09, P >.5, n = 29), and low-level eosinophil FcepsilonRIalpha expression was only detected in a single asthmatic subject. CD23 expression was not detected on basophils or eosinophils, except for the eosinophils from the donor with IgE myeloma. CD23 was present on monocytes from some donors but did not correlate with serum IgE levels. CONCLUSIONS: In a variety of disease states, FcepsilonRIalpha expression by basophils, but not monocytes or eosinophils, correlated with serum IgE levels across a 6-log range of IgE. These data support the concept of in vivo regulation of FcepsilonRIalpha on basophils by serum IgE and further demonstrate that this is independent of allergic disease per se.

Adolescent↗
PubMed1999

Albendazole therapy for loiasis refractory to diethylcarbamazine treatment.

Although diethylcarbamazine is curative in approximately 60% of patients who acquire loiasis as long-term visitors to an endemic area, some individuals continue to have signs and symptoms of infection despite multiple courses of diethylcarbamazine. On the basis of a study of albendazole treatment of loiasis in microfilaremic patients that suggested a macrofilaricidal effect of the drug, we treated three patients who had symptomatic loiasis refractory to more than four courses of diethylcarbamazine with albendazole. At the time of treatment, all patients had persistent symptoms despite decreasing titers of antifilarial antibodies and normal eosinophil counts. Symptoms resolved in all three patients following albendazole therapy. In one patient, nonspecific symptoms recurred 2 years later, but unlike her symptoms before albendazole therapy, they were not accompanied by the appearance of subcutaneous nodules containing adult worms. The other two patients have been symptom-free in the 8 years after albendazole treatment. In summary, albendazole may be useful for the treatment of loiasis when diethylcarbamazine is ineffective or cannot be used.

Adult↗
PubMed1998

Lymphatic filariasis in a hyperendemic region: a ten-year, follow-up panel survey.

The present study is a long-term panel survey of a population living in a previously identified Wuchereria bancrofti-endemic area of Benin. Unexpectedly, a marked decrease in the prevalence of microfilaremia (from 9.4% to 0.48%; P < 0.001) occurred over a 10-year period in the absence of chemotherapy or vector control measures. The percentage of patients with chronic pathology remained stable during the study period. The decrease in the prevalence of parasitemia could not be explained by environmental or sociologic changes in the region, or by differences between the two study populations. These data suggest that the epidemiology of lymphatic filariasis in an endemic region may change independently of recognized modulating factors.

Adolescent↗
PubMed1994

Ceftazidime-related nonconvulsive status epilepticus.

The third-generation cephalosporin, ceftazidime, is widely used for the treatment of serious gram-negative infections. As is true of cephalosporins in general, reported adverse effects have been few. We report a case of ceftazidime-induced status epilepticus in a patient with Pseudomonas aeruginosa meningitis and compare the clinical manifestations of this case with those of two previously described cases of ceftazidime-related encephalopathy. This diagnosis should be entertained and an electroencephalogram should be obtained in all patients with myoclonus and/or altered mental status while they are receiving ceftazidime therapy.

Aged↗
PubMed1994

OvGalBP, a filarial antigen with homology to vertebrate galactoside-binding proteins.

The increased incidence of "allergic" symptomatology and clinical complications seen in non-endemic individuals with loiasis, as compared to natives of endemic areas, is thought to reflect a heightened immune response to filarial antigens. To identify antigens involved in this hyperresponsiveness, a cDNA library constructed from adult female RNA from the related filarial parasite, Onchocerca volvulus, was screened with serum from a North American who acquired loiasis in West Africa. Sequence analysis of one of the identified clones, OvGalBP, revealed significant homology to the vertebrate S-type lectins, a family of thiol-dependent, metal-independent galactoside binding lectins, which includes an IgE-binding protein thought to be involved in IgE regulation. The 1100-bp insert of OvGalBP contains the entire protein coding region and has a 3' poly(A) tail. The two amino acid consensus sequences (WGxExR and HFNPRF) found in all of the S-type lectins are present. Purified recombinant protein expressed as a fusion with glutathione-S-transferase (OvGalBP-GST) was recognized by sera from a majority of filaria-infected patients but not by putatively immune individuals from an endemic area or by unexposed endemic and non-endemic controls. Interestingly, OvGalBP-GST specifically bound IgE (and not IgG) in a lactose-inhibitable manner, suggesting a potential role for this protein in the pathophysiology of human filarial infection.

Amino Acid Sequence↗
PubMed1994

Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate visitors to endemic regions: long-term follow-up.

Although successful treatment of loiasis with diethylcarbamazine (DEC) has been reported, little is known about the long-term success rate of therapy or the predisposing factors for treatment failure. To address these questions, 32 patients were followed 2-15 years (median, 4.5) after DEC treatment; all had acquired infection while expatriate visitors to endemic areas of Africa. Using a strict definition of successful treatment, 12 (38%) appeared to be cured after one course of therapy and 5(16%) after two courses. Of the remaining 15 patients, 3 continued to be symptomatic despite more than four courses of treatment. Although 12 of the 17 patients who relapsed did so within 1 year of treatment, several had relatively long asymptomatic periods (2-8 years). There was no predictive difference in clinical or laboratory parameters (including eosinophilia and specific filarial serology) between patients requiring one or more courses of therapy.

Diethylcarbamazine↗
PubMed1993

Albendazole in human loiasis: results of a double-blind, placebo-controlled trial.

To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia.

Adolescent↗
PubMed1992

Pulmonary involvement in loiasis.

A 40-yr-old West African man presented acutely with pleural effusion. Cytologic evaluation of the pleural fluid revealed Loa loa microfilariae. No additional etiology for the pleural effusion could be identified, and antifilarial treatment with diethylcarbamazine led to a rapid resolution of the patient's symptoms and pulmonary abnormalities. Loa loa must be considered as a treatable cause of eosinophilic pleural effusions in persons from endemic areas of West and Central Africa.

Adult↗
PubMed1991

Cloning and characterization of a species-specific repetitive DNA sequence from Loa loa.

A genomic DNA library of Loa loa was constructed in lambda gt11 using EcoRI-digested DNA from microfilariae isolated from two West African patients. Screening with labeled L. loa DNA yielded several potential repetitive DNA clones. An MboI fragment of one of these, LL3M9, was identified and characterized. Sequence analysis of LL3M9 revealed an 839-bp fragment with an unusual 356-bp region containing 37 copies of the hexamer CTTAGG, many of which are arranged in repeated motifs of 12, 27 and 63 bp. This region shares many of the characteristics of eukaryotic satellite DNA. A synthetic oligonucleotide corresponding to the 27-bp repeated motif, LL3M9REP, was found to be both sensitive and species-specific by dot hybridization. Species specificity of LL3M9REP was confirmed by amplification of the repetitive region using genomic DNA as a template in the polymerase chain reaction.

Animals↗
PubMed1991

Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation.

To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis.

Adolescent↗