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Biomedical subjects

R M Vetto

Publications and source records attributed to R M Vetto.

At least 55 records · Page 3Linked to original sources
PubMed1979

Assessment of the mechanism of the leukocyte adherence inhibition test.

This study was designed to elucidate the mechanism of the leukocyte adherence inhibition (LAI) test in man. To identify the reactive cell types, enriched leukocyte populations (dextran-separated leukocytes and Hypaque-Ficoll-isolated mononuclear cells and neutrophils, as well as rosette-isolated B- and T-lymphocytes) were tested for leukocyte adherence in the absence of serum to tumor-specific antigens. LAI reactivity was not restricted to any of the enriched populations, suggesting the involvement of multiple cell types. Attempts to demonstrate soluble lymphocyte factors in the LAI mechanism have been uniformly negative. In contrast, factors in serum of immune donors were able to arm naive cells to be specifically responsive. This suggests a role for serum factors in the mechanism of LAI reactivity and partially explains the participation of multiple cell types in the responses observed. In additional studies, we could not document a correlation between the magnitude of the dermal test (delayed cutaneous hypersensitivity) and the magnitude of the LAI response in patients with squamous cell carcinoma of the head and neck. In 34 of 54 of these patients, there was agreement between the two tests (both positive, 27 of 54; both negative, 7 of 54). In the remaining 20 patients, the dermal test was greater than 5 mm while the LAI test was negative (less than 30% inhibition).

Antibodies, Neoplasm↗
PubMed1979

Human transfer factors: structural properties suggested by HPRP chromatography and enzymatic sensitivities.

Leukocyte extracts containing human transfer factor (TF) were fractionated by exclusion chromatography, and the active fraction (Sephadex G25, Fraction IIIa) was subjected to high pressure, reverse phase (HPRP) chromatography and enzymatic degradation. TF activity was assessed by the systemic transfer of dermal skin test reactivity from KLH-immunized donors to naive recipients. Preparative HPRP chromatography resolved Fraction IIIa into multiple chromophoric regions, two of which demonstrated transfer of KLH reactivity. Alkaline phosphatase treatment of Fraction IIIa converted the major ultraviolet-absorbing component, 5'-inosine monophosphate, to inosine and resulted in TF activity being restricted to one region. This HPRP region (R1A) contained less than 1% of the UV254 active material in Fraction IIIa but greater than 90% of the reactivity. The sensitivity of TF to pronase, proteinase K, phosphodiesterase I, and phosphodiesterase II was evaluated by inhibition of systemic transfer of KLH reactivity. Pronase and proteinase K destroyed systemic transfer activity and the pronase destruction could be inhibited with traysylol. Phosphodiesterase I, a 3' exonuclease, destroyed activity, whereas phosphodiesterase II, a 5' exonuclease, did not. The data are consistent with a phosphodiester-containing polypeptide in the structure of human TF for KLH reactivity.

Alkaline Phosphatase↗
PubMed1979

Association of melanoma tumor antigen activity with beta2-microglobulin.

The majority of melanoma tumor antigen activity present in melanoma extracts derived from fresh tumor tissue binds to a Sepharose-anti-beta2-microglobulin adsorbent. Removal of HLA antigens from the extracts of melanoma tissue by using a KBr flotation technique did not reduce either the tumor antigen activity of the extracts or the binding of melanoma tumor antigen (MTA) activity to the Sepharose-anti-beta2-microglobulin adsorbent. The complete blocking of MTA activity by pretreating the anti-beta2-microglobulin adsorbent with beta2-microglobulin and the lack of detectable MTA binding to a Sepharose anti-normal human serum adsorbent demonstrated the specificity of the binding of MTA to the anti-beta2-microglobulin adsorbent.

Antigens, Neoplasm↗
PubMed1978

Changes in tumor immunity during therapy determined by leukocyte adherence inhibition and dermal testing.

Leukocyte adherence inhibition (LAI) is an easily carried out in vitro test for tumor reactivity which is based on the prevention of adherence of leukocytes incubated with antigen to which the donor is immune. In this study a comparison is made with dermal response to tumor antigen. A total of 234 patients were tested, 74 of whom had melanoma, 111 of whom had squamous cell carcinoma of the head and neck, 18 of whom had neuroblastoma and 31 of whom had other tumors. Forty-two persons without tumors acted as controls for the LAI test. A high degree of correlation was found between LAI and dermal response. Furthermore, LAI exhibited marked tumor specificity and showed a ten-fold greater sensitivity than dermal response. LAI may be used to monitor serial changes in tumor reactivity in cancer patients.

Adolescent↗
PubMed1978

Transference of cell mediated immunity in patients with head and neck cancer.

A group of 67 patients with head and neck cancer has been studied of which 40 have received immunologic transfer factor from a normal donor pool. Examination of these patients revealed that lymphocyte reactivity to nonspecific mitogrens is depressed in patients who have head and neck cancer to a much greater extent than is seen in patients with other types of tumors. Furthermore, the depression is more prevalent among patients who have been treated with radiation. Patients in the head and neck group who have received transfer factor show an initial decreased response to PHA stimulation in culture. This is not seen in a control group of head and neck cancer patients or in patients with nonsquamous cander. Thymus-derived lymphocytes are depressed in patients with head and neck cancer, irrespective of whether they have received radiation. Th T-lymphocyte levels increased in eight of 38 patients who received nonimmune transfer factor, but 7 of these were in the group who had not received radiation. The leukocyte adherence inhibition (LAI) test has been used to determine tumor immunity in the patient test group. Changes in tumor immunity did not occur in those patients who received normal nonimmune transfer factor. Studies are presently in progress which provide for treatment of patients with head and neck cancer with specific squamous carcinoma immune transfer factor.

Antibody Specificity↗
PubMed1977

Human transfer factor: fractionation by electrofocusing and high pressure, reverse phase chromatography.

The biologically active fraction of human transfer factor (Sephadex G-25, fraction III) has been separated by exclusion chromatography into two component fractions (IIIa and IIIb). Fraction IIIa transferred donor reactivities to PPD or KLH into 9 of 9 recipients. Fraction IIIb did not transfer donor reactivities (0 of 8 transfers) but did produce both antigen-independent and antigen-dependent dermal reactions in recipients. Fractionation by electrofocusing and high pressure reverse phase chromatography revealed that IIIa has a major UV254 absorbing component and that fraction IIIb has at least three major and three minor UV absorbing components. The major component of IIIa was isolated by preparative electrofocusing, had an isoelectric point of 1.6, and transferred KLH reactivity to four of five recipients.

Chemical Fractionation↗
PubMed1976

Transfer factor therapy in patients with cancer.

The objective of this study was to utilize transfer factor to stimulate cell-mediated immunity to specific tumor antigens in cancer patients. Thirty-five selected patients with advanced recurrent cancer, who were not suitable for further conventional therapy, were treated with transfer factor. Transfer factor was prepared from cohabitants of the patients and administered at 2-week intervals. This immunotherapeutic approach produced a clinical effect in 13 patients in terms of regression of tumor (1), arrest of metastatic disease (14), or pain relief (14). Conversion of dermal reactivity to specific tumor antigens was observed during periods of clinical improvement. Despite continued immunotherapy, the duration of clinical improvement was short (2 weeks to 12 months). Seven of the 11 patients not responding to therapy exhibited serum blocking of lymphocyte responsiveness. In 11 patients there is insufficient data to evaluate the clinical effectiveness of this therapy. The results suggest that transfer factor can stimulate specific cell-mediated immunity in cancer patients and produce a clinical effect on tumor under certain circumstances.

Antigens, Neoplasm↗
PubMed1976

Automated counting of T cell rosettes.

Human T cell rosettes were enumerated using an automated particle counter, the Bio/Physics Cytograf 6300A. An electronic oscilloscope representation of particle absorbance and scatter of a focused laser beam allows the separation and enumeration of both rosetted and non-rosetted lymphocytes. Repeated Cytograf sampling of a single rosette preparation gave highly reproducible results, and sampling from replicate tubes produced the same degree of variation as microscopic analysis. T cell rosettes prepared from 27 volunteers and compared by both methods of quantitation showed a high degree of correlation. This method can objectively measure at least 100 times as many cells for their rosette-forming capability as the tedious microscopic technique.

Blood Cell Count↗
PubMed1976

Human transfer factor: fractionation and biologic activity.

Human transfer factor (TF) was fractionated by exclusion chromatography and the fractions were tested for biologic activity in vivo and in vitro. Specific TF activity in vivo was found to reside in the major UV-absorbing peak (Fraction III). Fraction III eluted at 2.7 X V(O) and transferred tuberculin, candida, or KLH-reactivity to previously negative recipients. Fraction III from nonreactive donors was ineffective. When the fractions were tested in vitro, we found that both the mitogenic activity of whole TF and the suppressive activity to mitogen activation when present in TF was found in Fraction I. Fraction III contained components responsible for augmentation of PHA and PWM responses. In addition, Fraction III contained the component responsible for antigen-dependent augmentation of lymphocyte transformation. Fraction IV was suppressive to antigen-induced lymphocyte transformation. These data suggest that TF preparations contain components which can affect immune reactions in both specific and nonspecific ways.

Antigens↗
PubMed1976

Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor.

The component in human transfer factor (TF) (Fraction IV, from exclusion chromatography on Sephadex G-25) responsible for suppression of antigen-induced lymphocyte transformation was previously identified as nicotinamide. Commercially available nicotinamide was subsequently shown to produce suppression of antigen-induced responses in vitro previously observed with TF Fraction IV. Nicotinamide was found to be nontoxic at the highest concentrations employed (10(-2)M) and suppressive over a relatively broad range (10(-5) to 10(-2)M. The suppression appeared to be related to the magnitude of antigen- or mitogen-induced transformation and was apparent even when nicotinamide was added as late as 48 hr after stimulant addition.

Antigens↗
PubMed1976

Human transfer factor: effects on lymphocyte transformation.

Transfer factor preparations from 57 different donors have been compared for effects on mitogen- and antigen-induced lymphocyte transformation. Nine of the preparations were mitogenic when added to cultured lymphocytes although the magnitude of this activity was relatively low. The majority of the preparations (48/57) did not affect PHA-induced lymphocyte transformation although augmentation (6 of 57) and suppression (3 of 57) was observed with some. In addition we observed that most of the preparations tested suppressed ConA stimulation and augmented the PWM response. When selected preparations were evaluated on antigen-responsive cells, there was a correlation between the magnitude of antigen responsiveness and the magnitude of TF augmentation of antigen-induced lymphocyte transformation (p less than 0.005). Cultures that were not responsive to antigen (KLH-negative or BUdR-treated) could not be stimulated by TF from immune donors and antigen. These data suggest that TF preparations contain either stimulatory or inhibitory components and that TF is not capable of activating naive lymphocytes to undergo transformation in response to antigen.

Antigens↗
PubMed1975

Influence of serum blocking factors on cancer patients undergoing immunotherapy.

Blocking factors are small polypeptide molecules that may appear in the serum of patients with cancer. These factors block the transformation of lymphocytes in culture to nonspecific mitogens such as phytohemagglutinin or concanavalin A and, therefore, may reflect changes in the immunocompetence of the patient. Blocking factors were monitored during the clinical course of thirty-five patients with cancer. These factors did not develop in patients with response to therapy whereas they did develop in patients without response. A third group of patients without response to therapy after a previous remission showed an absence of lymphocyte responsiveness in culture that was not due to blocking factors, suggesting that immune clone consumption had occurred. Dermal responsiveness to tumor antigen correlated with a favorable clinical course and was usually absent when serum blocking factors were present.

Antibody Formation↗