PubMed Health⌕ Search

Biomedical subjects

P Fishman

Publications and source records attributed to P Fishman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Superoxide anion production by neutrophils derived from peripheral blood of schizophrenic patients.

Evidence indicates that excess free radicals formation may occur in patients with schizophrenia. A study comparing the production of superoxide anion by peripheral blood neutrophils of 29 schizophrenic patients with that of 17 healthy volunteers detected a significant statistical increase in superoxide anion production in schizophrenic patients compared to the healthy control group. Despite the fact that oxidative mechanisms may play a role in schizophrenia, further studies are needed to define their involvement. Such studies would shed light on the etiology and pathogenesis of schizophrenia and may lead to new therapeutic approaches using antioxidants, which might partially alleviate or prevent the symptoms of schizophrenia.

Adolescent↗
PubMed1998

Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin-3 and granulocyte-macrophage colony-stimulating factor expression.

OBJECTIVE: To evaluate the immunomodulatory potential of ciprofloxacin in mice with experimental antiphospholipid syndrome (APS). METHODS: Ciprofloxacin or ceftazidime (control antibiotic) was given to mice with experimentally induced APS. The titers of autoantibodies, levels of cytokines, and number of cytokine-producing cells were determined by enzyme-linked immunosorbent assay. Myeloid progenitor cells were determined by granulocyte-macrophage colony-forming unit, and interleukin-3 (IL-3) messenger RNA (mRNA) was tested by Northern analysis. RESULTS: A decrease in the incidence of pregnancy loss and an improvement in the clinical manifestations of APS were noted in the mice treated with ciprofloxacin, compared with the mice given ceftazidime. The effect of ciprofloxacin was found to be associated with increased serum levels of IL-3 and with increased IL-3 mRNA transcription in the splenocytes. Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was documented by elevated titers in the sera and elevated numbers of colony-forming cells in the bone marrow. CONCLUSION: Ciprofloxacin prevents the manifestations of experimental APS. This effect may be associated with increased IL-3 levels and GM-CSF expression.

Adjuvants, Immunologic↗
PubMed1998

The clinical significance of antityrosinase antibodies in melanoma and related hypopigmentary lesions.

Antityrosinase antibody is a newly detected antibody in the sera of patients with melanoma or vitiligo. The serum level of the antibody is measured by enzyme-linked immunosorbent assay (ELISA). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells Antityrosinase IgG antibodies were found to be present in high titers in sera of patients with vitiligo in comparison to patients with melanoma or healthy volunteers. The level of antityrosinase antibodies in patients with metastatic melanoma was significantly higher than the level in healthy subjects, but insignificantly higher than the level in patients with no evidence of disease. Patients with melanoma and MAH (melanoma-associated hypopigmentation; vitiligo-like) had the same level of antityrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of antityrosinase antibodies by melanoma antigens, and pointed to the participation of the antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease. The most interesting observation was the high level of antityrosinase antibodies in patients with vitiligo in comparison with the low level in patients with melanoma, patients with MAH, and patients with NED. Although the cutaneous manifestations of vitiligo and MAH are similar and result from destruction of melanocytes by specific antibodies, the two situations are immunologically different. The serum level of free antityrosinase antibodies could not serve as marker for the state of the disease or disease progression or relapse, as no significant difference could be detected between the levels in patients without evidence of disease to those with metastatic melanoma; nor could the levels of antityrosinase antibodies differentiate between the different sites of the primary lesion. However, we have shown that antityrosinase antibodies could be used for monitoring the response to active specific immunotherapy by injection of anti-idiotypic antibodies mimicking the HMW-MAA. In the future, antityrosinase antibodies may be incorporated into immunotherapy for malignant melanoma.

Antibodies, Neoplasm↗
PubMed1998

Relationship between routine hematological parameters, serum IL-3, IL-6 and erythropoietin and mild anemia and degree of function in the elderly.

To investigate the influence of functioning on unexplained senile anemia, we measured commonly used hematological parameters (serum iron, transferrin, iron saturation and ferritin) in addition to specific erythropoietic factors, such as interleukin-3 (IL-3), interleukin-6 (IL-6), and erythropoietin (EPO) in 48 elderly subjects aged 65-90 years. The subjects were divided into 3 groups: 1) 17 patients with unexplained mild anemia; 2) 17 non-anemic patients with newly acquired stroke and who previously were functionally active; 3) 14 functionally active patients with no major disease who served as controls. Anemia was defined as hemoglobin (Hb) values under 12.0 g/dL. The degree of functional ability was defined and scored by the "functional independence measure" (FIM) test. Data are presented as mean values +/- SD. The results revealed a correlation between the functional state and levels of Hb, iron and transferrin with unchanged iron saturation. Patients in the mild anemia group were found to be functionally declined (FIM = 57 +/- 19.4) with the relatively lowest mean iron (75.1 +/- 17 micrograms/dL) and transferrin levels (243 +/- 42.6 micrograms/dL). The stroke group (FIM = 62 +/- 17.7) had intermediate levels of iron (85.4 +/- 20.3 micrograms/dL) and transferrin (245 +/- 45.2), and with the continuation of the declined functional state the Hb level decreased significantly (13.7 +/- 0.9 to 12.0 +/- 1.0 g/dL, p < 0.001). The highest mean values of iron (102 +/- 27.9 micrograms/dL) and transferrin (322 +/- 42.7 micrograms/dL) were found in the control group (FIM = 122.7 +/- 5.8). The ferritin levels showed an opposite trend. IL-3 values were undetectable in the anemic and control groups, and were elevated in some patients in the stroke group. The lowest IL-6 level was observed in the anemic group, and the highest in the control group. Serial IL-6 assays in the stroke group showed an upward trend. Erythropoietin levels in all groups showed no difference.

Activities of Daily Living↗
PubMed1998

Interleukin-3 and pregnancy loss in antiphospholipid syndrome.

Cytokines play an important role in the progression of autoimmune diseases, and therefore it is not surprising that their levels may be altered in some of these diseases. Interleukin-3 (IL-3), which is an hematopoietic growth factor as well as an important factor that aids in embryo implantation and placental development, was found to be decreased both in pregnant women with antiphospholipid syndrome (APS) compared with a control group, and in animal models of APS. Treatment of animals having APS with IL-3 succeeded in prevention of disease manifestations. In this communication we review IL-3 and APS interrelationship, and discuss the role of aspirin and other commonly used drugs, with respect to IL-3 levels in APS.

Abortion, Spontaneous↗
PubMed1998

Cost implications of initial antidepressant selection in primary care.

While fluoxetine is considerably more expensive than tricyclic antidepressants (TCAs), some previous studies have suggested that general medical expenditures are lower among patients treated with fluoxetine. In this study, computerised pharmacy and cost-accounting records of a large health plan were used to examine overall treatment costs for 5169 primary-care patients beginning antidepressant treatment with fluoxetine or one of 2 TCAs, imipramine or desipramine. Comparison was based on initial medication prescribed, regardless of subsequent switches or discontinuation. Patients treated with fluoxetine were older, with a higher burden of medical illness and higher overall health-service costs before starting antidepressant treatment, compared with patients receiving the other 2 drugs. Initial choice of fluoxetine was associated with approximately $US140 higher mean antidepressant costs and approximately $US300 higher mean costs for all other health services (1995 costs). Alternative methods of accounting for baseline differences (age, medical comorbidity, prior costs) indicated that adjusted 'non-antidepressant' costs (total costs minus costs of antidepressant therapy) in the fluoxetine group were $US75 to $US300 lower than in either of the TCA groups, but these differences were not statistically significant. Subgroup analyses suggested that the use of fluoxetine was associated with lower overall costs only among those incurring high costs in the pretreatment period. These findings support earlier studies suggesting that the use of fluoxetine as a first-line antidepressant in primary care will increase antidepressant drug costs, but will not significantly increase total treatment costs.

Adult↗
PubMed1998

Mononuclear cells release low molecular weight factors with anti-cancer activity: A lower level of production by cells of cancer patients.

Following the clinical observations that tumor metastases are extremely rare in striated muscles we defined recently a low molecular weight factor which is released by muscle cells (muscle factor, MF) and possesses specific anti-proliferative activity against tumor cells. we demonstrate that peripheral blood mononuclear cells constitutively release low molecular weight factor (LMF) similar to the MF which is capable of inhibiting in vitro the proliferation of carcinoma, melanoma, leukemia and lymphoma cell lines. The proliferation of normal cells such as bone marrow or fibroblasts was not inhibited but slightly stimulated following incubation with the LMF. Biochemical purification of this factor by several HPLC steps revealed that the inhibitory activity against tumor cells was concentrated within two definitive peaks. The LMF affects tumor cell growth by arresting them in the G0/G1 of the cell cycle and its activity is species and tumor non-specific. In vivo studies in melanoma- bearing mice revealed that the LMF inhibited melanoma growth when given either intraperitoneally or orally. Mononuclear cells from cancer patients with different malignancies (non-Hodgkin lymphoma, malignant melanoma, colon carcinoma and carcinoma of the rectum) secreted lower level of LMF in comparison to healthy subjects. The capability of the LMF to inhibit tumor cell growth and promote normal cell proliferation combined with its bioavailability in vivo may lead to its potential therapeutic and diagnostic use.

Animals↗
PubMed1997

Autoantibodies to tyrosinase: the bridge between melanoma and vitiligo.

BACKGROUND: Tyrosinase is an enzyme that participates in the process of melanin production in normal melanocytes and melanoma cells. Enzymes are known to be autoantigens in various autoimmune disorders; thus, after the detection of antityrosinase antibodies in patients with vitiligo and melanoma, tyrosinase was defined as an autoantigen in these conditions. In some patients with melanoma the disease is associated with the appearance of "vitiligo-like" white patches on the skin, called melanoma-associated hypopigmentation (MAH). In this article, the authors summarize the recent data related to antityrosinase antibodies and expand on their role in the pathogenesis of vitiligo, melanoma, and MAH. In addition, the beneficial clinical applications of antityrosinase antibodies are presented. METHODS: An enzyme-linked immunoadsorbent assay to detect the antityrosinase antibodies in the serum of patients and healthy volunteers was established using mushroom tyrosinase. Employing this method, antityrosinase antibodies were analyzed in a diverse group of patients with melanoma and vitiligo and in mice immunized with tyrosinase. RESULTS: In patients with melanoma, those with metastatic disease had a higher titer of antityrosinase antibodies compared with healthy subjects, whereas patients with MAH and those with no evidence of disease had similar titers to the control group. The titer of antityrosinase antibodies in patients with metastatic melanoma treated by vaccination with antiidiotypic antibodies mimicking the high molecular weight melanoma-associated antigen (HMW MAA) initially increased after the vaccination and then decreased. High titers of antityrosinase antibodies were detected in patients with diffuse vitiligo compared with patients with localized disease and with the healthy control group. Mice immunized with tyrosinase generated a high titer of antityrosinase antibodies and after the inoculation of melanoma cells developed a lower number of lung metastases compared with an unvaccinated control group. CONCLUSIONS: The appearance of antityrosinase autoantibodies in the serum of patients with metastatic melanoma and diffuse vitiligo is characterized by these two pathologies. The changes in the serum level of these autoantibodies in patients with melanoma after immunization with another antigen (HMW MAA) may have diagnostic and therapeutic implications.

Animals↗
PubMed1997

Health care utilization and cost among children with asthma who were enrolled in a health maintenance organization.

OBJECTIVE: To measure the impact of asthma on the use and cost of health care by children in a managed care organization. DESIGN: Population-based historical cohort study. SETTING: A medium-sized staff model health maintenance organization in western Washington state. SUBJECTS: All 71 818 children, between age 1 to 17 years, who were enrolled and used services during 1992. OUTCOME MEASURES: Children were identified with one or more asthma diagnoses during 1992 using automated encounter data. Nonurgent outpatient visits, pharmacy fills, urgent care visits, and hospital days, as well as associated costs were measured. All services were categorized as asthma care or nonasthma care. Multivariate regression analysis was used to compute marginal cost for asthma (difference in total cost between children with asthma and other children using services, adjusted for covariates). RESULTS: Treated prevalence of asthma was 4.9%. Children with asthma incurred 88% more costs ($1060.32 vs $563. 81/yr), filled 2.77 times as many prescriptions (11.59 vs 4.19/yr), made 65% more nonurgent outpatient visits (5.75 vs 3.48/yr), and had twice as many inpatient days (.23 vs .11/yr) compared with the general population of children using services. Asthma care represented 37% of all health care received by children with asthma, while the remaining 63% were for nonasthma services. Almost two-thirds of asthma-related costs were attributable to nonurgent outpatient care and prescriptions; only one third was attributable to urgent care and hospitalizations. Controlling for age, sex, and comorbidities, the marginal cost of asthma was $615.17/yr (95% confidence interval $502.73, $727.61), which includes asthma as well as nonasthma services. This marginal cost represents 58% of all health care costs for children with asthma. CONCLUSIONS: Children with asthma use significantly more health services (and incur significantly more costs) than other children using services, attributable largely to asthma care. The majority of all health care costs for children with asthma were for nonasthma services. Urgent care visits and hospitalizations are less important components of asthma costs in this managed care organization than has been found in other national studies.

Adolescent↗
PubMed1996

Muscle cells produce a low molecular weight factor with anti-cancer activity.

The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro and in vivo, is highly specific towards tumor cells, and has no observable effect on normal cells' proliferation. What first prompted us to investigate this factor was the observation that tumor metastases are extremely rare in striated muscles. Co-culturing of striated muscle cells with malignant cells led to marked morphological alterations in the latter, in contrast to the same cells when incubated without muscle cells. A conditioned medium of striated muscle cells was prepared and its effect tested on a variety of cells. This conditioned medium (CM) inhibited proliferation of tumor cell lines of murine (B16 melanoma, Madison 109 lung carcinoma, MCA-105 sarcoma, ESB lymphoma), or of human origin (HTB-38 adenocarcinoma, T47D breast carcinoma, CX1 colon carcinoma). The proliferation of normal cells (bone marrow cells, fetal liver erythroid cells) was not affected by the CM. Flow cytometric analysis of B16 melanoma cells following incubation with the CM revealed that 63% +/- 12 of the cells were in the G0/G1 phase of the cell cycle, compared to 47.8% +/- 8 of cells incubated with a medium (not conditioned) only. The activity of the CM and of certain fractions thereof was also demonstrated in vivo: they prevented tumor growth in mice inoculated intraperitoneally with MCA-105 sarcoma cells. Partial purification of the CM revealed that the active component was a non-proteinaceous compound with a molecular weight of about 500 D. The results clearly suggest that muscle cells produce a low molecular weight factor which can selectively inhibit the proliferation of tumor cells in vitro and in vivo. This factor is neither species nor tumor specific.

Animals↗
PubMed1996

Anti-tyrosinase antibodies in malignant melanoma.

Anti-tyrosinase antibodies were measured by enzyme-linked immunosorbent assay in sera of patients with malignant melanoma with either metastatic disease or no evidence of disease, in patients with melanoma and associated hypopigmentation (MAH), in patients with vitiligo and in healthy volunteers. The mean relative absorbance (Arel) was calculated by dividing the absorbance of each sample by the mean value for the control group. Using this method, the Arel of the control group was 1.000(SE 0.083). Arel of patients with metastatic disease (1.516; SE 0.225) was significantly higher (P = 0.03) than the value for the controls, but insignificantly higher than that for patients with no evidence of disease (1.216; SE 0.148). Patients with no evidence of disease, in whom the primary lesion originated in the lower limb, had a significantly higher (P = 0.01) Arel than the healthy volunteers. Patients with metastatic disease showed higher Arel if their primary lesions were confined to the area of the head and neck or to the lower limb. Patients with vitiligo had higher Arel values for their anti-tyrosinase antibody than any of the other groups. However, those with melanoma and MAH (vitiligo-like) had the same Arel of anti-tyrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of anti-tyrosinase antibodies to melanoma antigens, and pointed to the participation of anti-tyrosinase antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease.

Adult↗
PubMed1996

Ascertaining dementia by expert panel in epidemiologic studies of nursing home residents.

A new method for ascertaining dementia in epidemiologic research and the results of a study to evaluate it are described. The method relies on an expert panel of clinicians reviewing clinically relevant information collected by lay evaluators to arrive at a diagnosis based on DSM-III-R criteria. The approach was developed to study dementia in a statewide sample of over 2400 new admissions to 59 nursing homes in Maryland. Expert panel ascertainment of dementia was compared to that obtained by direct clinical evaluation for 100 nursing home residents. Agreement between the panel and direct assessment was 76% (kappa = 0.59) using a three-category classification of dementia, no dementia, and indeterminate. This ascertainment strategy provides an alternative to methods currently in use and is particularly well-suited for populations with a high prevalence, in those dispersed over large geographic areas, and when timely, cost-effective evaluations are required.

Aged↗
PubMed1996

Tyrosinase as an autoantigen in patients with vitiligo.

Vitiligo is considered an autoimmune disorder due to the generation and presence of autoantibodies directed against melanocyte antigens in the patients' sera. In the present study we point towards a newly defined autoantigen in vitiligo, the enzyme tyrosinase, which participates in the process of melanogenesis. Anti-tyrosinase antibodies were detected in the sera of seven patients with diffuse and 11 patients with localized vitiligo. Employing solid-phase ELISA to mushroom tyrosinase, we found that patients with diffuse vitiligo had significantly higher titres of IgG anti-tyrosinase autoantibodies than patients with localized disease or healthy subjects. These anti-tyrosinase autoantibodies have relatively high functional affinity to tyrosinase and can be recovered from vitiligo patients' sera by affinity purification. The anti-tyrosinase antibodies do not cross-react with other enzymes recognized as autoantigens in different autoimmune disorders and the autoantibodies do not block the enzymatic activity of tyrosinase, indicating that they are not reacting with the catalytic site of the enzyme. These data point to tyrosinase as an autoantigen in vitiligo and suggest that anti-tyrosinase titres can serve as a marker for disease activity.

Autoantibodies↗
PubMed1996

Malignant melanoma of the head and neck. Clinical and immunological considerations.

Prolonged exposure to sun for long periods during most of the year has led to an increase in the frequency of malignant melanoma in Israel, especially for head and neck (H&N) melanoma. H & N melanoma is found in males more than in females and diagnosed when already locally advanced. The disease-free interval between treatment of the primary lesion and recurrence of the disease correlated with the patient's age and the depth of invasion according to Breslow. A higher recurrence rate correlated with male gender, location in the scalp, and the stage of the disease. Metastatic disease involved the lungs, liver, and brain and responded poorly to systemic therapy. Improved survival was related to female gender, early stage of the disease, low Breslow thickness, and location of the primary lesion elsewhere than the scalp. Immunologically, we found that the titers of antimelanoma antibodies in patients with metastatic disease originating in the area of the head and neck were higher than the titer in disease-free H & N melanoma patients (p = 0.05). Moreover, patients with metastatic H & N melanoma had a higher titer of antityrosinase antibodies compared with healthy subjects. These two types of antibodies might be used as markers for disease progression in H & N melanoma. The more aggressive character of H & N melanoma was not reflected by different titers of antimelanoma antibodies nor by antityrosinase antibodies in patients with H & N versus non-H & N melanoma.

Adult↗
PubMed1996

Melanoma-associated hypopigmentation: where are the antibodies?

Antibodies to the B16 melanoma cell line and to tyrosinase have been recently defined in our laboratory in sera of patients with vitiligo, melanoma, melanoma-associated hypopigmentation (MAH), and in healthy subjects. The antibody titers in each subject were measured by enzyme-linked immunosorbent assay, were compared with the mean optical density (OD) of the control group, and were expressed as relative OD. The titers of anti-B16 antibodies (relative OD +/- standard error) were 1.000 (0.058) in the controls, 1.025 (0.077) in patients with metastatic melanoma, 0.5862 (0.15) in MAH, 1.377 in surgery-induced MAH, 1.087 in vaccination with anti-idiotypic antibodies, and 2.098 (0.15) in autoimmune vitiligo. The titers in vitiligo were significantly higher (p < 0.0001) than in MAH or in healthy controls. Antityrosinase antibodies were found in titers of 1.000 (0.1024) in the controls, 1.516 (0.225) in metastatic melanoma, 1.027 (0.180) in MAH, 1.075 in surgery-induced MAH, 2.308 in vaccination-induced MAH, and 4.536 in vitiligo. Differences were found between vitiligo and MAH (p = 0.008), surgery-induced MAH (p = 0.009), vaccination-induced MAH (p = 0.059), and healthy subjects (p < 0.0001). The results of this study point to the cross-antigenicity between melanocytes and melanoma cells, and to participation of antibodies against melanoma-associated membrane antigens in the mechanism leading to the development of MAH in patients with melanoma.

Adult↗
PubMed1996

Aspirin-interleukin-3 interrelationships in patients with anti-phospholipid syndrome.

PROBLEM: Previously we reported on the generation of experimental anti-phospholipid syndrome (APS) in mice. These models were employed to evaluate the efficacy of various novel therapeutic modalities including interleukin-3 (IL-3) and low dose aspirin. The efficacy of the latter was found to be interrelated. Low dose aspirin is capable of inhibiting the activity of the enzyme cyclooxygenase which is responsible for the metabolism of arachidonic acid towards the production of prostaglandins. This shifts the metabolism of arachidonic acid to the other pathway and leads to an overproduction of leukotrienes. The leukotrienes act as stimulators of IL-3 production, a positive cytokine in pregnancy which enhances placental and fetal development. In the current study we evaluated the IL-3 levels in pregnant women with APS and expanded our knowledge on the interrelationships between aspirin, arachidonic acid metabolites and IL-3 in the human system. METHODS: IL-3 levels were recorded in the serum of pregnant women with APS and compared to a control pregnant group. In addition peripheral blood mononuclear cells from healthy subjects were incubated with different concentrations of aspirin or with arachidonic acid metabolites (Leukotriene B4, C4 or PGE2), and IL-3 production in the culture fluids was evaluated. RESULTS: Serum level of IL-3 in pregnant patients with primary APS, APS secondary to SLE and SLE was lower in comparison to the control group. The in vitro studies revealed that only low dose aspirin (10 mg/microliters) stimulated IL-3 production while higher doses of the drug failed to induce the cytokine generation. Leukotriene B4 and C4 were stimulatory whereas PGE2 acted as inhibitor of IL-3 production. CONCLUSIONS: The serum level of IL-3 is decreased to pregnant women with primary or secondary APS. Low dose aspirin is capable of stimulating IL-3 production in vitro most probably through an elevation of leukotriene production, which may explain its beneficial activity in preventing the manifestations of APS.

Antiphospholipid Syndrome↗
PubMed1996

Healthy People 2000: what progress toward better nutrition?

At the 1995 status review of the Healthy People 2000 nutrition objectives, progress was reported in several areas. These include dietary fat consumption, calcium intake, use of nutrition label information, incidence of coronary and stroke mortalities and blood pressure and cholesterol levels. However, a lack of progress was reported in the incidence of overweight in both men and women. Physicians can help their older patients achieve better health by providing assessments for under- or over-nutrition and education in age-appropriate dietary practices.

Aged↗