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Biomedical subjects

A Moskovitz

Publications and source records attributed to A Moskovitz.

16 recordsLinked to original sources
PubMed2000

Changing epidemiology of dengue fever in travelers to Thailand.

A study was conducted to evaluate the incidence and seasonal pattern of dengue fever occurring among Israeli travelers to Southeast Asia. The illness was diagnosed by Israeli physicians stationed abroad and by serological methods carried out in Israel. Between 1994 and 1998 dengue fever was confirmed in 103 travelers, 80 of whom were diagnosed in Israel. A sharp increase in the incidence was noted in 1998 as compared with the previous 4 years. The attack rate during 1998 in a defined group of travelers was 3.4/1,000 and reached a peak of 5/1,000 during the dry season of 1998.

Dengue↗
PubMed1999

Quantitative analysis of T-cell receptor beta variable-gene usage in cutaneous late-phase reactions: implications for T-lymphocyte recruitment in cutaneous inflammation.

To determine if functionally distinct T-lymphocyte (T cell) subsets accumulate in late-phase immunoglobulin E-mediated reactions (LPR), we quantitatively analyzed the immunophenotype and the T-cell receptor beta variable-gene (Vbeta) repertoire of T cells in cutaneous LPR. Peripheral blood and skin biopsies were obtained 6 or 24 h after sensitive subjects were challenged with intradermal injections of grass pollen allergen (Ag) and control (C) solution. The frequency of cells expressing CD3, CD4, CD8, CD45RO, and CD25/mm2 was determined by immunohistochemistry in nine subjects. Vbeta usage was assessed by reverse transcription-PCR in five of nine subjects. A significantly greater frequency of CD3(+) and CD45RO+ (memory) T cells was detected in Ag sites than in C sites at 24 h after challenge but not at 6 h. The frequency of activated (CD25(+)) and helper (CD4(+)) T cells appeared to be increased in Ag sites as well, though not significantly. Vbeta6 was the most commonly expressed Vbeta detected in Ag sites, but it was also detected in accompanying C sites. Vbeta2 was the most commonly expressed Vbeta detected in C sites. Sequence analysis in one case revealed Vbeta expression in a 6-h Ag site to be essentially polyclonal. Our findings suggest that memory T cells with Vbeta expression similar to that in normal skin accumulate in developing cutaneous LPR. The limited usage of Vbeta suggests a preferential recruitment or retention of reactive T cells from an endogenous subset of skin-homing T cells with its own skewed Vbeta repertoire.

Adult↗
PubMed1997

Inaccurate projection of rat soleus motoneurons: a comparison of nerve repair techniques.

The objectives of this study were 1) to determine the degree to which soleus motoneurons find their appropriate target following crush and transection injuries to the sciatic nerve, and 2) to determine whether repair of a transected nerve with a silicone tube leads to greater specificity of reinnervation and recovery of muscle function than the standard epineurial suture repair method. Sixty adult female Sprague-Dawley rats were randomly assigned to one of three sciatic nerve injury groups: crush injury, transection with epineurial suture repair, or transection with a silicone tube repair. The degree to which soleus motoneurons were able to find their appropriate target following a sciatic nerve injury was examined using a double labeling dye technique in which the original soleus motor pool was labeled with fast blue and reinnervating motoneurons were labeled with Dil. Soleus motoneurons were able to find their appropriate target following a crush injury. The accuracy of reinnervation following a transection injury and repair, however, was relatively poor. Only 14% of the original soleus motoneurons found the correct target following a transection injury. Repair of a lesioned nerve with a silicone tube and a 5-mm gap as opposed to epineurial sutures did not increase the specificity of reinnervation or the degree of muscle recovery.

Animals↗
PubMed1997

Cellular inflammatory responses during immediate, developing, and established late-phase allergic cutaneous reactions: effects of cetirizine.

BACKGROUND: In some previous studies, the antihistamine cetirizine has inhibited both developing (at 6 hours) and established (at 24 hours) gross late-phase skin reactions (LPR) to pollen antigens, possibly relevant to clinical drug effects. However, the effects of cetirizine at the histologic level require further definition. OBJECTIVE: To characterize cetirizine effects on gross and histologic inflammatory events from 20 minutes to 24 hours after intradermal antigen challenge in sensitive patients. METHODS: Gross and histologic responses to intradermal pollen antigen, codeine, histamine, and buffer diluent were assessed during randomized 7-day treatments with cetirizine and placebo. Accumulated neutrophils, eosinophils, activated (EG2+) eosinophils, and T lymphocytes were quantitated. The degrees of extracellular deposition of lactoferrin from neutrophils and eosinophilic cationic protein (ECP) from eosinophils were also assessed. RESULTS: During placebo treatment, wheal-and-flare responses were significantly greater to antigen at 20 minutes (p < 0.01) and induration at 6 hours (p < 0.01) at antigen challenge sites than at buffer diluent sites. During cetirizine treatment, these wheal-and-flare responses to antigen were inhibited significantly (p < 0.01) but gross LPRs were not affected. During placebo treatment, significantly more cells per high-power field were found in antigen sites than in buffer sites of neutrophils at 20 minutes (p < 0.01) and 24 hours; than in eosinophils at 20 minutes, 6 hours, and 24 hours (p < 0.01 for each); than in EG2+ cells at 20 minutes (p = 0.004), 6 hours (p = 0.001), and 24 hours (p = 0.02); and at T lymphocyte sites at 24 hours (p = 0.001). Extracellular deposition of lactoferrin and ECP was significantly greater at antigen sites than at buffer sites at 6 and 24 hours. Cetirizine treatment had no significant effect on these responses. CONCLUSION: Neutrophils, eosinophils, and T lymphocytes were persistently more common at antigen sites than at buffer sites through 24 hours. Many of these neutrophils and eosinophils were activated, releasing more lactoferrin and ECP into the extracellular dermis for at least 24 hours after antigen challenge. Cetirizine inhibited gross immediate responses to antigen, but not the gross LPR nor the cellular inflammatory responses seen in such LPR sites.

Administration, Cutaneous↗
PubMed1997

Cellular inflammatory responses and mediator release during early developing late-phase allergic cutaneous inflammatory responses: effects of cetirizine.

BACKGROUND: Events in developing cutaneous late-phase allergic reactions can be characterized by a combination of skin chamber and biopsy approaches. In some previous studies, cetirizine reportedly inhibited mediator release and/or inflammatory cell responses in late-phase reactions. OBJECTIVE: This study was carried out to determine the effects of cetirizine on early late-phase reactions by using skin chamber and skin biopsy specimens. METHODS: Skin chamber responses during a 6-hour challenge with pollen antigens were assessed in 15 sensitive subjects during randomized, crossover treatment with cetirizine (20 mg/day) or placebo for 7-day periods with measurements of humoral and cellular components. Biopsy specimens of the underlying dermis were obtained. RESULTS: During cetirizine treatment, there was significant (p < 0.01) inhibition of immediate wheal and flare reactions to pollen antigens (34, 46%), codeine (41, 65%), and histamine (38, 68%). However, gross late-phase reactions at 6 hours were unaffected. During both cetirizine and placebo treatment, there was significantly greater accumulation at antigen sites in: (1) skin chamber levels of histamine, total cells, lactoferrin, and eosinophil cationic protein; (2) eosinophils (total and activated) on appended cover glasses; (3) deposition of lactoferrin and eosinophil cationic protein in the underlying dermis. However, these responses were not significantly different during cetirizine treatment compared with placebo treatment periods. CONCLUSION: A persistent pattern of inflammatory cell accumulation with release of granule proteins during early late-phase reactions was unaffected by cetirizine treatment.

Antigens↗
PubMed1995

Products of arachidonic acid metabolism and the effects of cyclooxygenase inhibition on ongoing cutaneous allergic reactions in human beings.

BACKGROUND: There have been conflicting reports about the effects of inhibition of arachidonic acid metabolism on early- and late-phase cutaneous reactions. We re-examined this question with a unique nonsteroidal antiinflammatory drug, tenidap sodium. Tenidap sodium has been demonstrated in in vitro studies to inhibit cyclooxygenase, lipoxygenase, and cytokine production (interleukin-1, interleukin-6, tumor necrosis factor-alpha). METHODS: In a double-blind, randomized, crossover study, seven pollen-sensitive subjects ingested tenidap (120 mg, by mouth, daily) and placebo for 9 days with a 3-week washout period between treatments. On the eighth day they underwent allergen skin testing, measurable for up to 12 hours, and on the ninth day they underwent 5-hour skin chamber exposures to allergen and buffer. Chamber fluids were analyzed for cellular content, neutrophil granule protein release, cyclooxygenase and lipoxygenase arachidonic acid metabolites, histamine, and tryptase. RESULTS: Tenidap did significantly inhibit cyclooxygenase metabolites at both antigen and buffer sites but had no effect on histamine, tryptase, lipoxygenase metabolites, or granulocyte infiltration. Neutrophil granule release of lactoferrin was lower at the antigen site during tenidap administration, but there was no reduction of elastase release. Prostaglandin E2 and leukotriene E4 increased significantly at antigen sites compared with buffer sites during placebo administration and were the most prominent arachidonic acid metabolites detected. CONCLUSION: Tenidap, despite inhibiting cyclooxygenase release at antigen sites, had no effect on skin test responses to antigen or on antigen-induced mediator release or granulocyte infiltration. We conclude that cyclooxygenase metabolites are not important in the development of an allergic cutaneous inflammatory response.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Comparison of cytosolic calcium shifts, superoxide generation, and lactoferrin secretion in the neutrophils of atopics and nonatopics.

We previously found that platelet-activating factor (PAF) stimulated greater lactoferrin secretion by neutrophils of atopics than nonatopics. To help understand underlying mechanisms, we compared agonist-stimulated lactoferrin secretion with another response, superoxide generation, to determine whether there is a global alteration in the reactivity of atopic neutrophils to these stimuli. We also determined Ca2+ mobilization in such neutrophils because such mobilization is a signaling pathway for both superoxide generation and granule content exocytosis. Although PAF again stimulated greater lactoferrin secretion in atopic than in nonatopic neutrophils, the peak superoxide secretion and cytosolic Ca2+ mobilization were not significantly different in atopics and nonatopics. Leukotriene B4-induced superoxide secretion and cytosolic Ca2+ shifts were also similar in atopics and nonatopics. These findings suggest that (1) the enhanced PAF-induced lactoferrin secretion in atopic neutrophils is not a reflection of greater PAF binding or broad-based cell hyperreactivity and (2) a selective signaling pathway in atopic neutrophils may be responsible for the enhanced lactoferrin secretion. These findings may be relevant to in vivo events because we have found increased PAF and lactoferrin release in skin chambers overlying immunoglobulin E-mediated human skin reactions.

Calcium↗
PubMed1993

Fibrin formation during ongoing cutaneous allergic reactions: comparison of responses to antigen and codeine.

BACKGROUND: Fibrin formation, assessed by fibrinopeptide A levels, was evaluated over a 5-hour period at skin chamber sites challenged continuously with pollen antigen or codeine in 10 reactive individuals. METHODS: The levels of fibrinopeptide A at antigen sites were compared with those at sites challenged with buffer diluent alone or with codeine for the first 3 hours, followed by antigen challenge during the subsequent 2 hours. RESULTS: Findings showed: (1) fibrinopeptide A levels were higher at antigen challenge sites than at codeine challenge sites by the third hour, with these levels at both sites greater than those at buffer sites; (2) antigen challenge of the previous codeine sites during the third to fifth hours led to a further increase in fibrinopeptide A levels; (3) fibrinopeptide A levels correlated with chamber fluid immunoglobulin G levels but not with chamber fluid histamine levels. CONCLUSIONS: Because antigen and codeine both activate mast cells prominently, these findings suggest that other factors play a role in the persistent fibrin formation at allergic skin reaction sites. Because antigen activates both basophils and mast cells and codeine only activates mast cells, we conclude that both basophils and mast cells contribute to the persistent fibrin formation at sites of allergic reactions.

Antigens↗
PubMed1992

Activation of the coagulation pathway during ongoing allergic cutaneous reactions in humans.

The levels of histamine, fibrinopeptide A (FPA), and IgG were determined in chamber fluids overlying sites of antigen versus buffer incubation for up to 7 hours in seven atopic and four antigen-nonreactive subjects. Significant increases in histamine were observed at antigen versus buffer sites in the atopic subjects throughout the 7-hour period. FPA and IgG levels were higher in antigen than in buffer sites from 0 to 5 hours in the atopic subjects. Furthermore, FPA levels correlated with the magnitude of induration at 6 hours after antigen injection in atopic subjects. There were no differences in the levels of histamine, FPA, or IgG at antigen versus buffer sites in the skin test-negative subjects. We suggest that the combination of vascular leakage of proteins, induced by vasoactive mediator release, and activation of these proteins during ongoing cutaneous reactions is responsible for fibrin formation that contributes to the pathophysiology of late-phase allergic responses in the skin.

Adult↗
PubMed1990

Release of lactoferrin and elastase in human allergic skin reactions.

Our previous skin chamber studies have shown prominent accumulation of viable neutrophils in human allergic skin reaction sites. To determine whether such neutrophils release components that may be pathogenic in allergic reactions, we have compared the patterns of release of five components: 1) lactoferrin, present in specific granules; 2) and 3) elastase and myeloperoxidase, present mainly in azurophilic granules; 4) lactic dehydrogenase, a cytosolic component generally released during cell damage; 5) histamine, present in mast cells and basophils but not in neutrophils. In 13 pollen-sensitive subjects we found that continuous antigen challenge for 5 h lead to a peak of histamine release into overlying skin chambers during the 1st h, followed by a plateau of low level histamine release over the succeeding 4 h. In contrast, there was no significantly increased released of lactoferrin or elastase during the first h, but significantly increased accumulation of these components at Ag challenge sites over the next 4 h. There was no significant difference at Ag vs buffer control sites in the levels of either myeloperoxidase or lactic dehydrogenase. The increased levels of lactoferrin and elastase at antigen challenge sites in the 2nd to 5th h were not simply a reflection of the greater numbers of neutrophils present in such sites because the levels of these components did not correlate significantly with the number of neutrophils in chamber fluids obtained from individual sites. However, such lactoferrin levels did correlate significantly with the amount of histamine released earlier during the 1st h of Ag challenge at individual sites. These findings suggest a selective in vivo release of neutrophil components in IgE-mediated human allergic skin reactions, possibly related in degree to earlier mast cell activation. Inasmuch as lactoferrin likely plays a role in reactive oxidants effects and elastase is a potent nonspecific protease, release of these agents could play a pathogenic role in late phase allergic reactions.

Adult↗
PubMed1984

Recovery of myelin basic protein reactive T cells from spinal cords of Lewis rats with autoimmune encephalomyelitis.

Mononuclear cells were isolated from the spinal cords of 13 Lewis rats with clinical EAE induced by immunization with MBP in complete Freund's adjuvant. MBP-reactive lymphocytes were recovered from nine of these 13 SC-MNC populations by in vitro culture with MBP, followed by propagation of responding lymphocytes in IL 2-containing medium. T cell subset phenotype determination indicated a predominance of helper phenotype T cells in each of the two cultures examined. Clinical EAE was induced in naive Lewis rats by adoptive transfer of MBP-reactive lymphocytes recovered from three of these cultures.

Animals↗
PubMed1983

In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood mononuclear cells of patients with myasthenia gravis.

We studied the in vitro synthesis of antibodies to acetylcholine receptor (anti-AChR) by peripheral blood mononuclear cells (PBM) of patients with myasthenia gravis (MG) and normal subjects (NS). PBM from three of eight patients with generalized MG (MG-G) synthesized anti-AChR in vitro in the absence of pokeweed mitogen (PWM), and seven of eight did so in the presence of PWM. In individual subjects with MG-G, the levels of anti-AChR secreted in vitro by PBM correlated with serum anti-AChR antibody levels (r = 0.77) but not with the amount of IgG secreted in vitro (r = 0.44). No anti-AChR secretion was seen in culture of PBM from a patient with ocular MG, a patient with thymoma without MG, or six NS.

Adult↗
PubMed1976

Cytotoxicity reactions during immunotherapy of melanoma with neuraminidase altered autologous tumor cells.

Lymphocyte cytotoxicity, serum cytotoxicity, and the ability of the serum to inhibit lymphocyte cytotoxicity (blocking effect) were studied in a melanoma patient treated with six monthly injections of her own (autologous) tumor cells incubated with neuraminidase to increase their antigenicity. The same tumor cells grown in tissue culture were used as target cells for the cytotoxicity test. Large fluctuations of blocking effect in the serum were found, which correlated with the clinical course of tumor removal, recurrence, and regression. After the fifth injection of autologous tumor cells, the blocking effect disappeared from the serum (unblocking). In general, changes in serum cytotoxicity corresponded with changes in the amount of blocking effect produced by the serum. The results suggest that active immunotherapy may play a role in the prevention of metastases and, that when used within the autologous system, the cytotoxicity test is valuable in studying response to this type of therapy.

Antigens, Neoplasm↗
PubMed1976

Neuraminidase immunotherapy: serum potentiation of lymphocyte cytotoxicity related to immunoglobulin levels.

Seven patients completed couses of immunotherapy using neuraminidase-altered autochthonous cells. Their response to therapy was monitored by a cytotoxicity assay using 3H-proline-tagged tumor cells from the patient's own cultured tumor in a strictly autologous system. Serum effects were measured by exposing the tumor target cells to serum to see whether this impeded (blocked) or augmented (potentiated) lymphocyte cytotoxicity. Three of the seven patients developed increasing degrees of serum blocking effect and all died within six months of completing therapy. Four of the seven showed rapidly decreasing blocking and three eventual potentiation. Three patients are living, improved, and free of evidence of tumor. There was an increase in average serum immunoglobulins in patients developing potentiation, and a decrease in those showing blocking. In any immunotherapy program attention must be given to in vitro monitoring studies, and such studies should include attention to the serum factors influencing host response.

Adult↗