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Biomedical subjects

C Roth

Publications and source records attributed to C Roth.

At least 109 records · Page 6Linked to original sources
PubMed1995

Interleukin-2 and interleukin-4 display potent antitumour activity on rat medullary thyroid carcinoma cells.

Currently, surgical resection is the only treatment used for human medullary thyroid carcinoma (MTC). However, as metastases are commonly observed, we investigated the potential of adjuvant therapy with interleukin-2 (IL-2) and interleukin-4 (IL-4) in a rat model. The interleukins were delivered by means of xenogeneic tumour cells engineered to secrete IL-2 and IL-4. We found that when a mixture of MTC cells and IL-2 or IL-4 secreting cells were implanted in rats, the growth of the resulting tumours was inhibited as a function of the number of interleukin-secreting cells in the inoculum. Moreover, association of the two interleukins exerted a synergistic antitumour effect. These experimental results, showing thyroid C cell tumour rejection, are of major interest, as they show the potential therapeutic application for these two interleukins, which could be used, in particular, as postsurgical adjuvants.

Animals↗
PubMed1995

Physical properties of aerosolized immunoglobulin for inhalation therapy.

Animal studies suggest that passive immunization by intratracheal application of gammaglobulins may succeed in treating small children and infants with severe lower respiratory tract infection caused by respiratory syncytial virus (RSV). Since proteins foam easily when stirred up or used with compressed air, the feasibility of nebulization of the immunoglobulin solution (IVIG, Sandoglobulin) had to be tested. The therapeutic effect of a drug delivered via inhalation is proportional to the mass of aerosol deposited in the lungs. For a fixed breathing pattern, the amount deposited per unit of time in the thoracic region depends on mass flow rate and distribution of aerosol mass by droplet size. Both these variables were determined in relation to the weight concentration (osmolality), viscosity, and surface tension of the IVIG solution for four compressed air nebulizers. The mass flow rate of the spray decreases as the weight concentration of the solution increases, but droplet size distribution does not change. If the IVIG solution does not exceed 5% and the airflow rate is 6 L/min, a mass flow of about 150 mg to 250 mg (7.5 to 12.5 mg IVIG) per minute is obtained, depending on the physical characteristics of the nebulizer used. Low mass median diameter of about 2 microns and a mass distribution with a high percentage of the droplets below 6 microns will allow optimum intrapulmonary deposition in infants.

Aerosols↗
PubMed1995

Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2.

Electrochemotherapy is an antitumor treatment that combines a cytotoxic drug with the local administration of electric pulses delivered at the tumor site. We previously found that in mice the cure rate of subcutaneous transplanted tumors treated by electrochemotherapy is increased by repeated systemic interleukin-2 (IL-2) injections. Moreover, histoincompatible cells engineered to secrete IL-2 allow the rejection of syngeneic tumor cells when both cells are inoculated together. In this study of preestablished tumors in mice we show that after electrochemotherapy, delayed peritumoral injections of histoincompatible IL-2-producing cells result in the cure of almost all the tumors. Moreover, this combined local treatment leads to cures of untreated, contralaterally transplanted tumors. This systemic antitumor immunity also resulted in complete protection of the cured mice against further inocula of the tumor cells. These results, which were obtained using allogeneic as well as xenogeneic IL-2-secreting cells, suggest that electrochemotherapy combined with such cellular immunotherapy might be a useful approach for the treatment of metastasizing cancers.

Animals↗
PubMed1995

Posttraumatic stress disorder in peers of adolescent suicide victims: predisposing factors and phenomenology.

OBJECTIVE: To examine the factors predisposing to posttraumatic stress disorder (PTSD) in peers of adolescent suicide victims. METHOD: One hundred forty-six adolescents who were the friends of 26 suicide victims were studied. Five percent (n = 8) developed PTSD after exposure to suicide. These 8 subjects with PTSD were compared to the remainder of the exposed subjects (n = 138). RESULTS: Subjects with PTSD were more likely than those without PTSD to have had a history of substance abuse, agoraphobia, and suicide attempts. Subjects who developed PTSD were more likely to have developed a new-onset depression, to have more severe grief, and to have been closer to the suicide victim. Subjects with PTSD tended to have more severe exposure to suicide and came from discordant households with a history of disruptions in key relationships. The 8 subjects who developed PTSD were compared to 38 subjects who developed new-onset depression but not PTSD. Those with PTSD were more likely to have had past substance abuse, prior suicide attempts, family history of panic disorder, a history of parent-child disruption, and a history of loss. Symptoms of intrusive visual images, hypervigilance, and avoidance of reminders discriminated subjects who had PTSD from new-onset depressives without PTSD. CONCLUSIONS: PTSD is an expectable outcome in youth exposed to suicide. Further work is required to differentiate symptoms of depression from PTSD.

Adolescent↗
PubMed1994

Ly-49-independent inhibition of natural killer cell-mediated cytotoxicity by a soluble major histocompatibility complex class I molecule.

Natural killer (NK) cells lyse their targets in a non-major histocompatibility complex (MHC)-restricted manner, and the cytotoxicity can be inhibited by a number of MHC class I allele products, suggesting that NK cells may have a "positive receptor" that recognizes the target and a "negative receptor" that receives an inhibitory signal from class I. Since negative receptors could also exert their effect by masking a positive ligand, we have determined whether there may be a direct interaction between class I and an NK surface receptor by measuring cytotoxicity in the presence of a soluble class I molecule, Kd. Soluble Kd at micromolar concentrations could efficiently block NK cell cytotoxicity, suggesting that class I has a direct effect on cytotoxicity, rather than masking another target cell ligand. Inhibition required that Kd be at least divalent, probably because of its higher affinity or its ability to cross-link the NK surface receptor. In addition, the effect was independent of the peptide used to load Kd, and there was inhibition of cytotoxicity of NK cells derived from either H-2d or H-2b mice. Finally, depletion of NK cells expressing Ly-49 had no effect on the specific inhibition by Kd, raising the possibility that NK cells are endowed with additional negative receptors besides Ly-49. Taken together, these results suggest that there may be a family of NK receptors recognizing different class I alleles, which can receive negative signals by directly binding to class I on the target cell surface.

Animals↗
PubMed1994

Suicide in affectively ill adolescents: a case-control study.

Sixty-three adolescent suicide victims with a history of affective illness were compared to 23 adolescent community controls with a lifetime history of affective illness, using a case-control design. Suicide victims were more likely to have had major depression, comorbid substance abuse, a past suicide attempt, family history of major depression, treatment with a tricyclic antidepressant, history of legal problems, and a handgun available in the home. There was a non-significant trend for bipolar depression to convey a higher risk for completed suicide than unipolar depression. Recommendations for the prevention of suicide among those with early onset affective illness are discussed in light of these findings.

Adolescent↗
PubMed1994

Human parvovirus B19 serology with recombinant VP1 and VP2 antigens: diagnosis of acute infections by detecting B19-specific IgM and IgA antibodies.

BACKGROUND: The availability of immunoassays for the laboratory diagnosis of human parvovirus B19 (B19) infection, which is commonly associated with erythema infectiosum in children and arthropathy and arthralgia in adults has been hampered by the lack of native B19 antigen. The production of abundant supplies of recombinant (r) B19 proteins, through the cloning of the B19 genome into expression vectors, has led to a proliferation of assays for detecting B19-specific antibodies. OBJECTIVES: This study was undertaken to evaluate serological assays for detecting B19-specific IgM and IgA antibodies using rVP1 and rVP2 B19 viral coat proteins. Their suitability in the diagnosis of acute B19 infections and the incidence of non-specific reactivity were determined. STUDY DESIGN: A panel of sera consisting of B19-specific IgM-positive and -negative samples was tested for B19-specific IgM and IgA antibodies in an indirect IFA using rVP1 antigen. These samples and a further panel collected from patients with other virus infections and samples containing rheumatoid factor were tested for B19-specific IgM in an antibody-capture ELISA and an indirect ELISA, both of which utilized rVP2 antigen. RESULTS: Data from the two ELISAs using rVP2 antigen and the IFA with rVP1 antigen all showed significant correlation (P >/= 0.001) with a reference RIA using native B19 antigen. Non-specific reactions were observed with Paul-Bunnell-positive and rubella virus-specific IgM antibody-positive sera in the ELISAs but not in the IFA. B19-specific IgA antibodies were detected in all sera containing B19-specific IgM antibodies but were also found in a small number of sera collected from healthy blood donors with no history of recent B19 infection. CONCLUSION: This study demonstrates the usefulness of assays employing rVP1 and rVP2 B19 antigens for detecting B19-specific antibodies. The use of IgM-specific ELISAs allows the processing of large numbers of samples and the absence of non-specific reactivity in the IFA may indicate a role for this assay as a confirmatory test.

Journal Article↗
PubMed1994

Familial risk factors for adolescent suicide: a case-control study.

Sixty-seven adolescent suicide victims and 67 demographically matched living controls were compared as to family constellation, familial stressors and familial loading for psychopathology. Suicide victims were less likely to have lived with both biological parents, were more likely to be exposed to stressors such as parent-child discord, physical abuse and residential instability and showed greater familial loading for depression and substance abuse. Multivariate analyses showed that family history of both depression and substance abuse and lifetime history of parent-child discord were most closely associated with adolescent suicide. Children who are the offspring of parents with depression or substance abuse should be psychiatrically screened. Family interventions to decrease discord may also be helpful in decreasing the risk of adolescent suicide.

Adolescent↗
PubMed1994

Effect of tyrosine kinase inhibitors on islets of Langerhans: evidence for tyrosine kinases in the regulation of insulin secretion.

In order to determine if tyrosine kinase activation is involved in the changes in islet function, the effect of tyrosine kinase inhibitors on insulin secretion and islet cell proliferation was examined in cultured islets of Langerhans. When islets were exposed to 100 microM genistein or 2 microM herbimycin A, large 5- to 10-fold increases in insulin secretion were observed. The effect on insulin secretion was detected within 1 hr and was maintained for at least 4 days. The glucose sensitivity of islets exposed to genistein was dramatically increased as demonstrated by a shift of the glucose-dose response curve to lower glucose concentrations. In contrast, islet cell proliferation was dramatically reduced in the presence of these tyrosine kinase inhibitors in the absence or presence of PRL. These very large changes observed in islets suggest that tyrosine kinases may have important roles in the regulation of beta-cell function.

Animals↗
PubMed1994

Improvements in volumetric quantification of circumscribed hepatic lesions by three dimensional sonography.

The size of hepatic tumors is commonly estimated by ultrasound as well as by computed tomography by measuring the three diameters followed by computing of the volume by applicating the ellipsoid formula. Using the new technique of three-dimensional-sonography it is possible to perform volume measurement by computer-linked planimetry. Initial tests with water filled balloons of defined volume revealed the accuracy (mean error of 3.0%) and high reproducibility (low intra- and inter-observer variance) of the method applied by one investigator (intraindividual SD +/- 1.3%) as well as by four different investigators (interindividual SD +/- 2.1%). Circumscribed hepatic lesions of 63 patients were investigated by using conventional sonography (ellipsoid formula), computed tomography (ellipsoid formula) and three-dimensional-sonography (ellipsoid formula, ortrip, planimetry). As a volume of reference a mathematical approximation for infinite sonographical slices (planimetry) of a very well circumscribed hemangioma of the liver was defined. Based on these results a mean error of -6% (SD +/- 39%) was determined for conventional sonography. For computed tomography a mean error of 2+ (SD +/- 35%) was found, for three-dimensional-sonography that figure was -6% (SD +/- 5%). Follow up investigations can only demonstrate significant alterations of volume when the SD-interval is exceeded. Therefore, three-dimensional-sonography provides a more sensitive and reliable recognition of volumetric changes of liver tumors than conventional sonography or computed tomography does.

Carcinoma, Hepatocellular↗
PubMed1993

Identification of T cell peptides from C gamma 2ab involved in IgG2ab T cell-induced allotypic suppression. Relationship with the MHC haplotype of the suppressor T cell-donor Igha mice.

Using the algorithm of the peptidic self-model we selected, from the constant part of the IgG2ab polypeptidic heavy chain, four peptides susceptible to being recognized by the T cells of Igha mice that prevent IgG2ab expression. Among these four peptides, two were capable of enhancing in vivo this T cell activity of Igha mice almost as well as the whole IgG2ab allotype. One of these peptides, C gamma 2ab-248-263, located in the CH3 domain of IgG2ab, was effective in H-2d mice, while the other one, C gamma 2ab-103-118, located in the hinge region of IgG2ab, was efficient in H-2b mice. This demonstrates for the first time that this suppression involves the TCR of the effector cells and peptides derived from the allotype presented in the context of MHC molecules of the target cells, the presentation specificity being dependent on the MHC haplotype. The availability of these peptides will allow us to further understand the role of class I and/or class II MHC molecules in this suppression.

Amino Acid Sequence↗