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Biomedical subjects

P Fishman

Publications and source records attributed to P Fishman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity (vitiligo).

Anti-tyrosinase antibodies are found in the sera of patients with diffuse vitiligo, metastatic melanoma and in sera of patients with melanoma and hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells. The production of autoantibodies in both diseases is associated with the development of white patches on the patients' skin. The presence of these autoantibodies in patients with melanoma may suggest a better prognosis. Cross-antigenicity between melanoma cells and normal melanocytes is most probably the key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies are absorbed by melanocytes and by melanoma cells in all the 3 situations (melanoma, vitiligo, MAH). However, since the production of antibodies in vitiligo exceeds that in melanoma or MAH, the antibodies are detected in significantly higher levels only in vitiligo. It is suggested here that anti-tyrosinase antibodies may be responsible, or at least participate in destruction of normal melanocytes during the immune response to melanoma antigens. This mechanism may be responsible for the phenomenon of MAH in patients with melanoma, and for the formation of the autoimmune vitiligo. Anti-tyrosinase antibodies may serve for two clinical applications. One is a marker for monitoring and follow up of patients with melanoma treated by immune therapy. The second is active (or passive) immunotherapy. We have recently shown that C57BL/6J mice immunized with tyrosinase generated a high titer of antityrosinase antibodies, and following the inoculation of melanoma cells developed lower number of lung metastases, compared to the unvaccinated control group.

Autoantibodies↗
PubMed1995

Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice. Pathogenetic role in experimental vasculitis.

OBJECTIVE: To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG). METHODS: BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis. RESULTS: Mice immunized with human ANCA developed anti-human ANCA and anti-anti-human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. CONCLUSION: The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.

Animals↗
PubMed1995

Increased interleukin-1 and interleukin-3 like activity in schizophrenic patients.

1. The interleukins play an important role in the development and maintenance of the immune system 2. Decreased cell mediated immunity measures were found in schizophrenic patients. 3. The purpose of the present study was to study the spontaneous production of interleukin-1 (IL-1) and interleukin-3 like activity (IL-3-LA) by human mononuclear cells from schizophrenic patients in comparison to healthy individuals. 4. Interleukin-1 was increased significant by schizophrenic patients as compared to controls. 5. Interleukin-3 like activity was slightly elevated in schizophrenic patients as compared to controls. 6. These findings support the hypothesis of an autoimmune dysfunction in some schizophrenic patients.

Adult↗
PubMed1995

Interleukin-2 and ovarian hyperstimulation syndrome: a pilot study.

A prospective case-controlled study was conducted to evaluate the association between the concentrations of interleukin-2 (IL-2) in human follicular fluid obtained at the time of oocyte collection for in-vitro fertilization (IVF) and the development of ovarian hyperstimulation syndrome (OHSS). Follicular fluid was obtained at the time of oocyte collection for IVF consecutively from 40 patients at risk of developing OHSS. Among the 40 patients participating in the study, seven subsequently developed OHSS. Their follicular fluid samples, together with those of an additional seven patients matched by age who did not develop OHSS, were tested for osmolality, total protein content and IL-2 concentrations, and mean serum oestradiol concentrations at the time of human chorionic gonadotrophin (HCG) administration and the mean number of aspirated oocytes were also measured. Follicular fluid IL-2 concentrations were significantly higher (P < 0.002) in the OHSS group as compared to the control group. No significant differences were found between the two groups regarding the mean serum oestradiol concentration on the day of HCG administration, or the mean number of aspirated oocytes, follicular fluid osmolality, or total protein concentrations. This study suggests an association between follicular fluid IL-2 concentration and OHSS. IL-2 is known to cause 'vascular leak syndrome', which resembles OHSS. These observations, together with the established interaction between the immune and the reproductive systems, may suggest a pivotal role of IL-2 in the pathogenesis of OHSS.

Case-Control Studies↗
PubMed1995

Anti-tyrosinase antibodies participate in the immune response to vaccination with anti-idiotypic antibodies mimicking the high-molecular-weight melanoma-associated antigen.

Seven patients with metastatic melanoma were vaccinated with anti-idiotypic monoclonal antibody (mAb) MK2-23 which mimics the high-molecular-weight melanoma-associated antigen (HMW MAA). Sera samples were assayed for anti-anti-idiotypic antibodies, by Ab1-Ab2 complex inhibition test, for anti-B16 epitope antibodies, which are a heterogeneous group against various antigens presented on B16 melanoma cells and for anti-tyrosinase antibodies, which are specific against tyrosinase. Our results pointed to the participation of anti-tyrosinase antibodies in the immune response to vaccination by anti-idiotypic antibodies mimicking the HMW MAA. The anti-tyrosinase antibody kinetic curves presented an initial increase in titres in five cases followed by decreasing titres; in two cases a constant decrease was noted. The inhibition assay demonstrated an increasing percentage of inhibition (range 17-100%) within 100-400 days of treatment. The titre of the anti-tyrosinase antibodies increased following the vaccination, then decreased--probably due to absorption of the antibodies to melanoma cells and normal melanocytes. A positive slope in the percentage of inhibition was roughly associated with a negative slope of anti-tyrosinase antibodies. In one case, a long-standing complete clinical response was accompanied by development of melanoma-associated hypopigmentation. Anti-B16 epitope antibodies had no role in the response to vaccination. The development of anti-tyrosinase antibodies in response to vaccination by anti-idiotypic antibodies mimicking another antigen may be explained by induction of non-specific polyclonal B lymphocytes activation, a well-recognized phenomenon in autoimmune disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1995

IL-3-LA production by mononuclear cells of patients with multiple sclerosis: effect of treatment with intravenous immunoglobulins.

IL-3-like activity (IL-3-LA) is a growth factor that stimulates stem cell maturation. We examined the production of IL-3-LA by peripheral blood mononuclear cells of 10 patients with relapsing-remitting multiple sclerosis (MS) following one year of treatment with intravenous immunoglobulins (IVIG). The results were compared with those obtained in 13 age- and sex-matched untreated patients with relapsing-remitting MS and in 14 healthy controls. IL-3-LA was assayed using the IL-3-dependent 32-D-cl-23 murine cell line. IL-3-LA production was 60% higher in untreated MS patients than in healthy controls (134 +/- 19 u/ml and 78.7 +/- 15.9 u/ml, respectively; p < 0.01), and lower in patients treated with IVIG than in untreated patients (101.4 +/- 4.9 u/ml; p < 0.02). IL-3-LA production also decreased after incubation of mononuclear cells with IVIG of both untreated MS patients and controls. This study indicates a possible beneficial effect of IVIG on the immunological status of MS patients.

Adolescent↗
PubMed1995

Hypertension: special concerns in managing the older patient.

In most populations, average diastolic BP increases with age until the sixth decade and then remains constant, whereas average systolic BP continues to rise. Many studies have shown an increase in cardiac and stroke risk with increasing BP, even in elderly populations. Antihypertensive therapy in the elderly has been shown to reduce the risk of nonfatal and fatal stroke, nonfatal and fatal coronary heart disease, and all-cause mortality. The right combination of diet and lifestyle changes can help to control hypertension and reduce cardiovascular risk. For optimal results, give the patient as much informed choice as possible in the selection of therapies and setting of goals. Proceed cautiously when it is necessary to add pharmacologic therapy, whatever agent is chosen.

Aged↗
PubMed1995

Aspirin modulates interleukin-3 production: additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome.

OBJECTIVE: The granulocyte macrophage colony stimulating factors (GMCSF) and interleukin-3 (IL-3) are defined as positive signals for pregnancy, since they support the process of trophoblast invasion and expansion and induce placental growth and development. Aspirin and IL-3 were shown to be effective in preventing the manifestations of experimental antiphospholipid antibody syndrome (APS). Aspirin inhibits the activity of the enzyme cyclooxygenase in macrophages, which leads to a shift in the arachidonic acid metabolism toward the lipoxygenase pathway, and results in overproduction of leukotrienes. Our data indicated that leukotrienes are capable of stimulating IL-3 production in vitro. Our aim was to examine whether aspirin may exert its beneficial effect in APS not only by its ability to prevent thromboxane A2 production and prostaglandin I2 (PGI2) formation, but also by stimulating IL-3 production. METHODS: Splenocytes and macrophages from naive mice were cultured in vitro with low dose aspirin. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, was added to mixed cultures of splenocytes and macrophages containing low dose aspirin. IL-3 production was observed. RESULTS: When splenocytes and macrophages were cultured in vitro with low dose aspirin (10 micrograms/ml), a marked stimulation of IL-3 production was noted. When NDGA was added to mixed cultures of splenocytes and macrophages containing low dose aspirin, it decreased the IL-3 production. Higher dose of aspirin did not affect the cytokine production. When splenocytes were incubated without the addition of exogenous macrophages, no stimulation of IL-3 production was noted. However, when purified leukotriene B4 or leukotriene C4 was added, there was an increase of 71 and 261%, respectively, in the stimulation of IL-3 production (p < 0/01). These results were supported by in vivo studies, in which a higher serum IL-3 level was detected in mice fed low dose aspirin, compared to the control group and to mice fed a higher dose of aspirin. CONCLUSION: Aspirin acts as a potent stimulator of IL-3 through its ability to raise leukotriene production, which induces production of IL-3 both in vitro and in vivo.

Animals↗
PubMed1994

Vitiligo- and melanoma-associated hypopigmentation: a similar appearance but a different mechanism.

The significance of the association between the appearance of hypopigmentation in patients with melanoma and the prognosis is still not clear. It was postulated that, in melanoma, an immune response is responsible for the destruction of the malignant as well as the normal pigmented cells, and that the eventual development of vitiligo-like patches in melanoma patients improves their prognosis. We studied the level of anti-melanoma antibodies in the sera of patients with melanoma with hypopigmentation and compared it to the titer in patients with melanoma only, to the titer of patients with vitiligo, and to that of healthy subjects. Only IgG-type antibodies were found in the sera of patients with vitiligo, with melanoma, or with melanoma with hypopigmentation. No significant differences in the titer of anti-melanoma antibodies could be found between the patients with melanoma when subgrouped according to the initial stage and the status of the disease at the time when the test was carried out. Statistically significantly (P < 0.001) higher titers of antibodies were detected in the sera of patients with vitiligo in comparison to the lower titers in the other groups. Our results point to a similar immunobiological status, which probably does not give any advantage to patients with melanoma with hypopigmentation compared to patients without it. The appearance of hypopigmentary plaques in melanoma patients should be regarded, in our opinion, as a concomitant immunological phenomenon of the disease.

Adolescent↗
PubMed1994

Antigens and antibodies in malignant melanoma.

Antigens, antibodies and immune complexes seem to play a major role in the course of malignant melanoma, in detection of the disease progression, in treatment planning and monitoring. Of particular interest are cell and matrix adhesion molecules, growth factors and cytokines, proteases, gangliosides and major histocompatibility complex class I and II molecules. Antigens expressed on melanoma cells, but not on mature melanocytes, may be used as markers for the degree of the differentiation of the melanoma cells. The more the melanoma cells are dedifferentiated, the smaller is the antigenic similarity to normal melanocytes. Also, different antigens may be identified in various stages of the disease and may be used as tumor markers for disease recurrence or progression. Certain melanoma-associated antigens (MAA) such as epidermal growth factor receptor and adhesium molecules can be modulated by cytokines. Early melanoma evokes an antigen-derived T cell response, which becomes attenuated with the progression of the disease. A variety of cell adhesion molecules present on melanoma cell surfaces may play a role in regulation of cellular cytotoxicity. Free antimelanoma antibodies are usually not detectable in the sera of patients with melanoma, possibly due to their binding to shed antigens and formation of immune complexes or to tissue antigens. When bound to normal melanocytes, they cause the appearance of associated hypopigmentation. The identification of melanoma surface antigens led to generation of monoclonal antimelanoma antibodies (MAb) by laboratories. Strategies utilizing MAb based on immunologic approaches have been developed. MAb to tumor-associated antigens of melanoma cells may be used for therapeutic purposes in man. Sera of patients with vitiligo were capable of causing regression of melanoma metastases in mice due to the presence of a high titer of naturally occurring antimelanoma antibodies. Immunization of melanoma patients with vaccines containing treated melanoma cells or specific melanoma antigens or anti-idiotypic antibodies resulted in an increasing titer of antimelanoma antibodies and regression of the tumor to some extent. The appearance of hypopigmentation in patients with melanoma serves as proof for the activity of antimelanoma antibodies, although its association with the prognosis is still not clear. The thorough investigation in the field of MAA and related antibodies is aimed at improving specific antimelanoma immunotherapy, such as antigenic targeting or enhancement of production of autoantibodies, as well as better understanding of the process of metastasis and the melanoma-immune system interaction.

Animals↗
PubMed1994

Role of IL-3 in the antiphospholipid syndrome.

Antiphospholipid syndrome (APLS) is characterized by recurrent thromboembolic phenomena, thrombocytopenia and fetal loss. We describe various methods of induction of experimental APLS. These models were employed to study a variety of therapeutic agents including low dose aspirin, low molecular weight heparin, IVIG and thromboxane receptor antagonist. Because interleukin-3 (IL-3) is a multilineage cytokine affecting also megakaryocytes, is regarded as a 'good' cytokine in various stages of pregnancy and as low levels of IL-3 were recorded in APLS, it was logical to employ IL-3 as a therapy for APLS. Indeed, this treatment completely abrogated all the manifestations of experimental APLS. Furthermore, it was found that low dose aspirin most probably affect positively APLS via inducing an increased production of IL-3 by monocytes.

Animals↗
PubMed1994

Detecting malnutrition's warning signs with simple screening tools.

Nutrition problems of aging adults can be prevented, controlled, or treated, but the warning signs of malnutrition are often overlooked. Untreated malnutrition can lead to a spiral of infection, further malnutrition, and death. Simple assessment tools developed and distributed by the Nutrition Screening Initiative (NSI) can be used during an office visit to identify risk factors for poor nutritional status. These include advanced age, depression, social isolation, physical or cognitive impairment, and low income. Patients who are identified as being at high risk require immediate intervention, including medical and psychological evaluations. Often, an older adult without cognitive impairment can resume independent function when proper support is provided to correct the causes of malnutrition.

Aged↗
PubMed1993

Vitiligo autoantibodies are effective against melanoma.

BACKGROUND: Vitiligo is a dermatologic disease characterized by local, dispersed, or diffuse white patches on the skin. The disease is defined as an autoimmune disorder because autoantibodies against membranal components of melanocytes are found in the patients' sera. The current study examined whether the autoantibodies reacting with the normal melanocytes could be a potent therapy against melanoma cells. METHODS: The three in vitro assays used to determine the antibody reactivities using a mouse melanoma cell line B-16-F10 and M-14 human melanoma cells as targets are as follows: enzyme-linked immunosorbent assay (ELISA), proliferation assay, and morphologic examination in the presence of antibodies purified from sera of patients with vitiligo. In the in vivo studies, experimental melanoma was intravenously induced in C57BL/6J mice, and the mice were treated by daily intraperitoneal injections with purified immunoglobulin G (IgG) fraction derived either from patients with vitiligo or from healthy subjects. RESULTS: The binding of IgG derived from patients with vitiligo was demonstrated by ELISA: Exposure of melanoma cells to the vitiligo autoantibodies was followed by inhibition of their proliferation capacity. In addition, morphologic alterations exemplified by detachment of the cells from their solid support associated with melanin release were observed in the B-16-F10 cells. Less metastatic foci developed in the lungs of the mice treated with the purified IgG fraction from the sera of patients with vitiligo compared with those treated with purified IgG fraction from healthy subjects. CONCLUSIONS: The results of this study point to the presence of anti-melanoma autoantibodies in the sera of patients with localized and diffuse vitiligo. These antibodies have a destructive effect on melanoma cells in vitro and in vivo.

Animals↗
PubMed1993

The effect of alpha-interferon on thymidine, uridine, and leucine uptake and ultrastructure of peripheral blood mononuclear cells from multiple myeloma patients.

The effect of IFN alpha-2b on thymidine, uridine, and leucine uptake was examined on peripheral blood mononuclear cells (PBMC) of healthy donors and 15 patients with multiple myeloma (MM). In addition, the surface ultrastructure of the cells incubated without or with IFN alpha-2b was examined with a scanning electron microscope. The results showed that IFN had no effect on thymidine, uridine, or leucine uptake of unstimulated MM and control PBMC. On the other hand IFN inhibited thymidine, and uridine uptake of PWM-stimulated MM PBMC, but had no effect on healthy donor stimulated PBMC. IFN inhibited also thymidine and uridine uptake in PHA-stimulated healthy donors and MM patients' PBMC. The cellular surface ultrastructure of MM lymphocytes incubated with 100 u/ml IFN showed disappearance of the microvilli and formation of cellular pits, whereas in healthy donor lymphocytes IFN caused flattening of microvilli.

Aged↗
PubMed1993

Who enrolled in a state program for the uninsured: was there adverse selection?

Managed care plans may hesitate to participate in programs for uninsured persons because they fear adverse selection, whereby only the sickest people or highest users would choose to join the program. We studied this issue in Washington State's Basic Health Plan, a demonstration program that provides subsidized health insurance for families earning less than 200% of the poverty level. We interviewed people in three counties who enrolled in the program, and compared them to people in the same counties who were eligible but did not enroll. There were substantial differences between enrollees and eligibles in education, age, income, employment, race, and insurance status. In spite of these demographic and access differences, health status was remarkably similar for enrollees and eligibles, with the few significant differences favoring the enrollees. In addition, previous and subsequent use of health services was similar or lower for enrollees. The results for health status and utilization were similar across the three counties, even though the counties and the providers were quite different. We conclude that there is no evidence of adverse selection. This is welcome news for the health plans, but suggests that the BHP may not have reached those most in need of insurance.

Age Factors↗