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C Horvath

Publications and source records attributed to C Horvath.

At least 37 records · Page 2Linked to original sources
PubMed1993

Immunohistochemical localization of Trk receptor protein in pediatric small round blue cell tumors.

Expression of Trk protein has been documented by Northern analysis in neuroblastomas with good prognosis. To localize the expression of this protein at the cellular level within individual tumors, we adapted a recently characterized pan-Trk antibody for use in formalin fixed, paraffin-embedded tissue. We have examined a group of small round blue cell tumors occurring in children, including both high and low stage neuroblastomas, to assess the presence or absence of Trk expression and its cellular localization. Positive staining for Trk protein was observed in four of four low stage (good prognosis) neuroblastomas, five of five primitive neuroectodermal tumors/Ewing's sarcoma, five of five rhabdomyosarcomas, and no lymphomas. Within the neuroblastomas, expression of Trk protein was most striking in ganglion cells, in which positive cytoplasmic staining was demonstrated regardless of tumor stage. The latter observation may lend further insight into the pathobiology of this malignant childhood tumor.

Antibodies↗
PubMed1988

[Teratogenic effect of pyrimethamine in the rat. In vivo prevention by calcium folinate].

In vivo prevention of malformations induced by pyrimethamine was studied in the rat. The administration of calcium folinate had an almost complete antiteratogenic effect on external, visceral and skeletal malformations, provided that the vitamin was administered together with the pyrimethamine and that the treatment was continued for the following two days.

Abnormalities, Drug-Induced↗
PubMed1988

Pathogenesis of limb and facial malformations induced by pyrimethamine in the rat.

The temporal sequence of morphological events resulting in limb and face malformations was studied in pyrimethamine (PY) treated female rats, 30 mg/kg of PY in a 10 ml/kg suspension of 0.9% NaCl were administered i.p. on days 12, 13 and 14 of gestation. Controls received only 0.9% NaCl solution. The females were killed at different stages of gestation (between 14 and 21 days). Early PY treated embryos showed mainly haematomas in the extremities and the mandibulo-maxillary areas. During the course of gestation, fewer haematomas and more malformations were observed. At term, malformations were observed in the same localisations where haematomas were previously seen.

Animals↗
PubMed1987

Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation.

The Pgp-1 glycoprotein was identified on a minor (27%) subset of peripheral Lyt-2+ or L3T4+ T cells. In contrast, mature medullary-type thymocytes (Lyt-2+ L3T4-, Lyt-2- L3T4+) were nearly devoid of cells expressing detectable surface Pgp-1. The appearance of peripheral Pgp-1- T cells was found to be thymus dependent, as demonstrated by the diminished proportion of Pgp-1- T cells after thymectomy and their virtual absence in athymic nude mice. The subsequent acquisition of surface Pgp-1 was found to be a stable differentiation event occurring concomitantly with primary antigenic stimulation; selected Pgp-1- mature T cells from thymus or periphery acquired constitutive expression of Pgp-1 after stimulation in vitro with alloantigen or mitogens. These observations were extended by studies in vivo showing that immunization with various antigens augmented the percentage of Pgp-1+ spleen cells within the Lyt-2+ subset. Furthermore, the frequencies of antigen-specific CTLp, after immunization by any of three different antigens tested, were greatly enriched in the Pgp-1+ compared with the Pgp-1- subpopulations. Peritoneal exudate Lyt-2+ cells, after a localized allograft rejection, demonstrated a particularly prominent Pgp-1+ subpopulation (78%) that contained virtually all the allospecific cytolytic activity. A model consistent with all of these data proposes that mature thymocytes lacking surface Pgp-1 upon emigration to the periphery acquire its expression at the time of primary antigenic stimulation. Hence, expression of Pgp-1 among peripheral T cells is an important differentiation marker for identifying antigen-stimulated memory T cells.

Animals↗
PubMed1987

Functional activity in vivo of effector T cell populations. III. Protection against Moloney murine sarcoma virus (M-MSV)-induced tumors in T cell deficient mice by the adoptive transfer of a M-MSV-specific cytolytic T lymphocyte clone.

The functional activity of Moloney murine sarcoma virus (M-MSV)-specific T lymphocytes in vivo was assayed by the i.v. injection of virus-specific T lymphocytes into T cell-deficient "B mice". Virus-specific T lymphocytes generated in mixed lymphocyte tumor cell cultures were transferred i.v. into syngeneic "B mice" injected simultaneously at a distant site with the virus. These experiments indicated that a low dose (1 X 10(6) cultured cells) of infused lymphocytes can afford protection. To define the T lymphocyte subpopulation which was active, Lyt-2+ lymphocytes were selected by "panning" on plastic petri dishes coated with anti-Lyt-2 monoclonal antibody, and Lyt-2- lymphocytes selected by treatment with anti-Lyt-2 monoclonal antibody and complement. The results indicated that a Lyt-2+ lymphocyte-enriched population was more efficient in conferring protection against M-MSV-induced tumors. To investigate if cytolytic T lymphocytes (CTL) alone had a protective effect, a M-MSV-specific CTL clone was transferred in the same model system. The results demonstrated that a M-MSV-specific CTL clone prevented M-MSV-induced tumor growth and also induced the destruction of syngeneic Moloney murine leukemia virus (M-MuLV)-induced MBL-2 leukemic cells in the peritoneal cavity. However, the cell dose required to obtain protection using a CTL clone was higher than that which was effective when mixed lymphocyte tumor cell culture cells were used. To assess the ability of the transferred cells to home and to repopulate the lymphoid organs of the "B mice", the frequency of virus-specific CTL precursors in the spleen was evaluated by limiting dilution analysis. The results indicated that lymphocytes from mixed lymphocyte tumor cell cultures can be recovered from the spleens of "B mice" injected i.v. 25 days earlier. On the contrary, following the transfer of an active CTL clone, a very low frequency (less than 1/200,000 cells) of virus-specific CTL precursors was present in the spleens of recipient animals. The same M-MSV-specific CTL clone did not yield protection against M-MSV-induced tumors or MBL-2 leukemic cells when injected i.v. into M-MuLV tolerant mice.

Animals↗
PubMed1987

Circadian time dependence of murine tolerance for the alkylating agent peptichemio.

Since the extent of host toxicity of cytostatics is considerably affected by dosing time, a chronopharmacologic approach was undertaken for optimizing the therapeutic index of the alkylating agent, peptichemio (PTC). In 4 studies involving a total of 463 male B6D2F1 mice, a highly statistically significant circadian rhythm characterized murine tolerance for PTC (8 or 10 mg/kg/day i.v. X 3 days). Six circadian stages were explored (3, 7, 11, 15, 19 and 23 Hours After Light Onset--HALO). Day-40 survival rate varied between 20% (PTC at 3 HALO) and 55% (PTC at 15 HALO) (chi 2 = 16.7; P less than 0.01). In each study, body weight loss was maximal in mice injected with PTC at 3 HALO and minimal in those treated at 15 HALO (P less than 0.01). In a further study involving 96 male B6D2F1 mice, the toxicity of PTC on several target tissues (bone marrow, spleen, small bowel, colon, liver, kidney and lungs) was investigated by histology and leukocyte count as a function of drug dosing time. A circadian rhythm in the susceptibility of the bone marrow, the spleen and the intestinal tract was demonstrated. Optimal murine tolerance for PTC resulted from dosing it at 15 HALO, e.g. in the first half of the activity span.

Animals↗
PubMed1987

Extracorporeal enzyme reactors for depletion of phenylalanine in phenylketonuria.

Multitubular enzyme reactors with immobilized enzymes were developed to achieve depletion of circulating substrate by extracorporeal means. To act as prototypes, reactors were prepared with immobilized L-phenylalanine ammonia-lyase, an enzyme that metabolizes phenylalanine to trans-cinnamic acid and ammonia without the need for a coenzyme. We report the first application of phenylalanine ammonia-lyase reactors in an extracorporeal circulation system in a patient with phenylketonuria. A phenylalanine level of 1.82 mmol/L (for the last 6 years) decreased to 1.24 mmol/L after 5.5. hours of treatment, without the enzyme entering the circulation. Total phenylalanine depletion from blood and tissue stores was estimated at 1800 mg. The hemodialysis-like procedure proved to be without side effects, specific for phenylalanine, and suitable in the management of pregnant women with phenylketonuria and late-onset hyperphenylalaninemia. The extracorporeal use of enzyme reactors for temporary enzyme replacement represents a new, safe, and effective therapeutic modality.

Adult↗
PubMed1986

Calcitonin secretion in streak gonad syndrome (Turner's syndrome).

Osteoporosis in one of the most common complications of streak gonad syndrome (SGS), however, its pathogenesis is still unclear. To test whether SGS is associated with calcitonin (CT) deficiency, 11 affected individuals and 8 age-matched healthy women were studied. Calcium, 3.6 mg/kg b.w. as a 10% solution of calcium chloride, was given intravenously for 3 minutes. Serum levels of CT and calcium were measured before and at 5, 30, 60, and 120 minutes after the injection. There was a statistically significant rise in serum calcium levels both in the control subjects and patients with SGS, with significantly lower levels prior to and at 30, 60, and 120 minutes following calcium load in the control group. The CT rise following calcium load was also significant at 5, 30, and 60 minutes in the controls and at 5 and 30 minutes in patients with SGS, with a significantly lower baseline and 30, 60, and 120 minutes levels in the latter group. Maximum levels of calcium and CT occurred 5 minutes after the calcium load and were statistically indistinguishable. There were no significant differences in either the calcium or the CT incremental changes between the two groups. These findings are consistent with decreased basal (and 30-120 minute) CT levels in SGS and suggest that CT deficiency may be involved in the development of osteoporosis in patients with SGS. The possible causal relationship of estrogen deficiency to the reduced CT levels in SGS is discussed.

Adolescent↗
PubMed1985

Production and characterization of monoclonal anti-Thy-1 antibodies that stimulate lymphokine production by cytolytic T cell clones.

In an effort to derive monoclonal antibodies (mAb) which can induce production of macrophage-activating factor (MAF) by cloned murine cytolytic T lymphocyte (CTL) lines, we have fused spleen cells from a rat immunized with a CTL clone with the nonsecreting mouse myeloma X63-Ag8.653. Three mAb (designated I-22, III-5 and V-8) were found to stimulate MAF production by the immunizing CTL clone and (with a single exception) two other unrelated CTL clones. However, none of these mAb inhibited the cytolytic activity of the clones. Immunoprecipitation studies indicated that the three mAb reacted primarily with a 25-30-kDa protein which could not be distinguished from that precipitated by either a reference anti-Thy-1.2 mAb or a polyclonal rabbit anti-Thy-1 antiserum. Moreover, competition binding experiments demonstrated that the three mAb competed with each other and with the reference anti-Thy-1.2 mAb. Flow cytofluorometric analysis of the strain distribution of the molecules defined by the mAb revealed that two of the antibodies (I-22 and III-5) were directed against nonpolymorphic determinants of Thy-1, whereas V-8 mAb reacted only with Thy-1.2+ lymphocytes. One of the mAb (III-5) was also able to stimulate proliferation and interleukin 2 secretion by normal splenic T cells. Since mAb directed against a number of other surface structures on CTL clones did not stimulate MAF production, it thus appears that Thy-1 (or molecules associated with Thy-1) may play a functional role in T lymphocyte triggering.

Animals↗
PubMed1985

Vascular anomalies and pyrimethamine-induced malformations in the rat.

Pyrimethamine injected into the rat on days 12, 13, and 14 of gestation induces several types of malformations, including limb and facial deformities. These malformations appear in the same location as the hemorrhages and hematomas induced by this substance. In order to visualize the extent of the vascular disorders in the affected areas, a polymerizable substance was injected intravenously into the fetus. After pyrimethamine treatment, the fetal vascular network was simplified and reorganized in a different way according to the severity of the malformations. The appearance of vascular pathology, followed by malformations in the same regions, raises the hypothesis of a vascular cause of fetal defects.

Abnormalities, Drug-Induced↗
PubMed1985

Circadian rhythm in tolerance of mice for etoposide.

Etoposide (40 mg/kg/day X 3 days and 60 mg/kg/day X 3 days) was best tolerated by male B6D2F1 mice when given in the second half of the rest span of their sleep-wake circadian cycle. Such a time-qualified treatment resulted in increased long-term survival rate, highest peripheral leukocyte count at nadir, and lowest body weight loss, as compared to results from drug dosing in the activity span. Assuming that such results may be extrapolated to human beings, the treatment time of etoposide associated with an optimal tolerance would be located in the second half of the sleeping span (usually near 5.00 hrs).

Animals↗
PubMed1984

Functional activity in vivo of effector T cell populations. II. Anti-tumor activity exhibited by syngeneic anti-MoMULV-specific cytolytic T cell clones.

The functional activity in vivo of murine tumor-specific cytolytic T lymphocyte populations and clones was studied. Tumor cell destruction induced after the i.v. injection of cytolytic effector cells was quantitated by monitoring the elimination of 131IUdR-labeled tumor cells in the peritoneal cavity by using whole-body counting techniques. Mixed leukocyte-tumor cell cultures were established by using spleen cells from C57BL/6 regressor mice that had rejected an intramuscular tumor induced by the injection of MSV-MoMuLV virus. This effector cell population was observed to eliminate syngeneic MoMuLV-induced tumor cells in a dose-dependent manner. Treatment of the effector cell population with monoclonal anti-Lyt-2 antibodies plus complement totally abrogated their ability to induce tumor cell destruction in the peritoneal cavity. MSV-MoMuLV-specific Lyt-2+ cytolytic T cell clones derived by micro-manipulation of T lymphocyte-tumor cell conjugates were also tested for functional activity in vivo. Several clones induced a rapid, specific elimination of 131I-labeled MBL-2 tumor cells from the peritoneal cavity after i.v. injection, whereas others were inactive. Both active and inactive clones were highly cytolytic and secreted MAF/IFN-gamma lymphokines. In contrast to previous results obtained in a tumor allograft model, the MSV-MoMuLV-specific cytolytic T cell clones that were active in vivo did not proliferate in vitro in response to stimulation with irradiated tumor cells plus filler spleen cells in the absence of an added source of interleukin 2.

Animals↗
PubMed1984

Determination of aromatic amino acids by ion-pair reversed-phase liquid chromatography in human sera from healthy and phenylketonuric individuals.

A simple chromatographic procedure is described for simultaneous analysis of aromatic amino acids in serum samples obtained from normal individuals and from phenylketonuric patients. Quantitative measurement of phenylalanine, tyrosine, histidine and tryptophan is made in samples as small as 10 microliter after deproteinization with trichloroacetic acid. With phenoxyacetic acid as the internal standard, samples are analyzed by reversed-phase chromatography isocratically by an ion-pairing agent in the eluent, and the amino acids are detected with the UV detector at 210nm. Total analysis time was about 30 minutes. Using this method in serum samples from phenylketonuric patients phenylalanine was increased (as expected), and histidine was decreased, at a statistically significant level.

Amino Acids↗
PubMed1983

Anisotropic membranes with carboxypeptidase G1.

Anisotropic polysulfone membranes were prepared with carboxypeptidase G1 embedded in the polymer structure. The enzymatically active flat and hollow-fiber membranes were obtained by precipitating the polymer from solution in an organic mixture in which an aqueous solution of the enzyme had been dispersed. The process has been found to be particularly suitable for the immobilization of enzymes in anisotropic hollow fibers that exhibited no detectable enzyme leakage upon perfusion. The pH profiles measured with the enzyme in free solution and in the embedded form were similar. Kinetic parameters of multitubular enzyme reactors were investigated by measuring the rate of hydrolysis of glutamate from folic acid or methotrexate at different flow rates and substrate concentrations. The relatively slow mass transfer in such reactors was found to affect strongly the observed kinetics. The results of in vitro experiments with 5000 fiber reactors suggest that hollow fiber cartridges prepared with such membranes have clinical potential for the extracorporeal removal of methotrexate from blood.

Carboxypeptidases↗
PubMed1982

Functional activity in vivo of effector T cell populations. I. Antitumor activity exhibited by allogeneic mixed leukocyte culture cells.

The in vivo activity of murine cytolytic T lymphocyte-containing effector cell populations generated in vitro was studied in a tumor allograft model system by monitoring the elimination of 131I-IUdR-labeled tumor cells with whole-body counting techniques. Mice were irradiated sublethally and 16 hr later 131I-labeled tumor cells were injected either subcutaneously or i.p. Simultaneously, graded doses of various effector cell populations were injected i.v. and the mice were counted daily to assess the potential elimination of the radiolabeled tumor cells. Thus, allogeneic 2 degrees mixed leukocyte culture cells were observed to eliminate allogeneic but not syngeneic tumor cells in a dose-dependent manner, with as few as 0.2 x 10(6) effector cells causing significant destruction of 2 x 10(6) allogeneic tumor cells. The protective effect of the mixed leukocyte culture cells was considerably reduced when Lyt-2+-bearing lymphocytes were eliminated by treatment with monoclonal antibody plus complement. In additional experiments, Lyt-2+ lymphocytes positively selected by enrichment on antibody-coated petri dishes gave efficient protection, in the absence of Lyt-2- cells. Surprisingly, when several different cloned, specific, long-term allogeneic cytolytic T cells lines were injected either i.p. of i.v., tumor cell destruction was observed only after i.p. injection.

Animals↗