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H Schreiber

Publications and source records attributed to H Schreiber.

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

Immunodominance deters the response to other tumor antigens thereby favoring escape: prevention by vaccination with tumor variants selected with cloned cytolytic T cells in vitro.

Variant cancer cells which arise from the parent tumor during tumor progression can escape immunity but retain antigens. We have mixed highly immunogenic (A+B+) murine parental cancer cells with less immunogenic (A-B+) variant cancer cells to construct a model of a cancer containing escape variants. When such mixtures of cancer cells were injected into normal mice, the variant cells grew out because immune responsiveness to the B antigen on the variant was hindered by dominance of the A antigen on the surrounding parental tumor cells. However, A-B+ variant cells inoculated alone at a separate site induced B specific cytolytic T cells and were rejected. Moreover, mice immunized with A-B+ cells rejected a challenge which contained a mixture of variant and parental cancer cells, while immunization with A+B+ cells was ineffective. Thus, variant tumor cells selected from parental tumor cells by cytolytic T cells in vitro can be used to induce protective immunity against variants expected to escape tumor immunity in vivo. The immunodominance of the A antigen may be related to its ability to induce a much more rapid CTL response than the B antigen, since we show in another model that the pre-existence of a CTL response to one antigen prevented the subsequent induction of CTL to another antigen injected at the same site, even if both antigens were equally efficient at inducing CTL. These results indicate that immunodominance can affect strong as well as weak antigens. Vaccination with individual antigens at separate sites rather than with multiple antigens at one site may, therefore, be needed to prevent tumor escape and tumor recurrence or to counteract infectious diseases.

Animals↗
PubMed1996

Conservative management strategy for pancreatitis-associated mesenteric venous thrombosis.

Mesenteric venous thrombosis is a rare, but potentially lethal, complication of pancreatitis. Although management is usually directed toward the underlying pancreatitis, there is no standard defined for treatment of the associated mesenteric venous thrombosis. Anticoagulant therapy was chosen as treatment for the case presented in this report, but other management methods for this entity have been described in the literature. Based on our experience and review of the literature, a management strategy for patients with pancreatitis-associated mesenteric venous thrombosis has been developed.

Acute Disease↗
PubMed1996

Radiation can inhibit tumor growth indirectly while depleting circulating leukocytes.

The growth of certain UV-radiation-induced tumors is suppressed by T lymphocytes, but it has been proposed that non-T lymphocytes stimulate the growth of several of these tumors. In this study, the indirect effects of X irradiation on the growth of one such tumor in T-cell-deficient nude mice was tested. Even when the site of tumor cell injection was shielded, whole-body irradiation with 6 Gy before tumor challenge inhibited subsequent tumor growth significantly. The interval during which this indirect inhibition was observed correlated with the depletion of circulating leukocytes, which did not return to normal levels until 12-21 days after irradiation. These data are consistent with earlier results using an antibody to deplete Gr-1+ leukocytes and indicate that radiation can inhibit the growth of certain tumors indirectly without direct effects on the tumor cells or the tumor bed.

Animals↗
PubMed1996

[Electrophysiologic correlates of selective attention in children and adolescents at increased risk of schizophrenia].

Electrophysiological correlates of selective attention in children and adolescents at high risk for schizophrenia. As part of a research project on electrophysiological correlates of attention in young subjects at high genetic risk for schizophrenia, auditory event-related potentials (ERPs) associated with selective attention and automatic information processing were recorded in 21 adolescent (offspring of at least one parent with schizophrenia) and 21 control subjects matched for age, sex and socioeconomic status. The experimental task was a dichotic listening task, and accuracy of counting target pips served as a psychometric control variable. The results showed group-related differences in the ERPs, with a significant reduction being present in the high-risk group concerning the amplitude of the fronto-precentrally located negative difference (Nd) wave and the F3 component elicited by selectively attended stimuli. Comparison of individual matched pairs showed that reduced Nds, characterized 14/21 high-risk individuals and reduced P3s 16/21. Moreover, there were significant correlations between ERP reductions and psychometric deficit (counting accuracy). Finally, 13 latencies tended to be prolonged in the high-risk group. Mismatch negativity (MMN), an ERP correlate of automatic information processing, did not differ significantly in the two groups, although there was a marked reduction in amplitude in the high-risk group. The ERP alterations point to impaired selective attention in a considerable proportion of subjects at high genetic risk for schizophrenia.

Adolescent↗
PubMed1995

Antigenic cancer cells that escape immune destruction are stimulated by host cells.

Cancers induced by UV light in murine skin often regress completely when transplanted into normal syngeneic recipients and grow progressively only in T-cell-deficient hosts. Heritable cancer variants that grow progressively and kill normal mice occasionally evolve in vivo. It is surprising that most of these variants appear to retain their antigenicity and immunogenicity. We have compared three such variants (4102-PRO, 6132A-PRO, and 6134-PRO) with the parental tumors to determine why the variants acquired progressive phenotypes without antigen loss. We found that all three variants grew substantially faster than the parental tumors in T-cell-deficient hosts; one variant, 6132-PRO, also grew faster in vitro. Furthermore, the growth of all of the variants was stimulated by soluble factors released by tumor-induced peritoneal exudate cells, and all attracted more leukocytes than the parental cells. Finally, pretreatment of mice with antigranulocyte antibody reduced the growth of variant but not parental 4102 and 6134A tumor cells. The treatment reduced the growth of both the parental and the variant 6132A lineage cells. We found no evidence for acquired resistance of variant tumors to immune destruction by a host defense mechanism. The parental cells did not grow faster in beige nude mice deficient in natural killer and alpha beta T cells or in SCID mice deficient in B and T cells. The variant parental cells had a similar sensitivity to lysis by polyinosinic-polycytidic acid-induced natural killer cells or thioglycolate- and LPS-induced macrophages. Together, our results are consistent with the notion that these variants escape from immune destruction in vivo by attracting leukocytes that stimulate tumor cell growth.

Animals↗
PubMed1995

Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection.

During tumor progression, variants may arise that grow more vigorously. The fate of such variants depends upon the balance between aggressiveness of the variant and the strength of the host immunity. Although enhancing host immunity to cancer is a logical objective, eliminating host factors necessary for aggressive growth of the variant should also be considered. The present study illustrates this concept in the model of a spontaneously occurring, progressively growing variant of an ultraviolet light-induced tumor. The variant produces chemotactic factors that attract host leukocytes and is stimulated in vitro by defined growth factors that can be produced or induced by leukocytes. This study also shows that CD8+ T-cell immunity reduces the rate of tumor growth; however, the variant continues to grow and kills the host. Treatment with a monoclonal anti-granulocyte antibody that counteracts the infiltration of the tumor cell inoculum by non-T-cell leukocytes did not interfere with the CD8+ T-cell-mediated immune response but resulted in rejection of the tumor challenge, indicating a synergy between CD8+ T-cell-mediated immunity and the inhibition of paracrine stimulation.

Animals↗
PubMed1995

NMR cross-relaxation investigated by molecular dynamics simulation: a case study of ubiquitin in solution.

A one nanosecond molecular dynamics simulation of ubiquitin in solution has been used for the calculation of the total dipolar, the radial and the reorientational correlation functions of 174 interproton NOEs and the 76 peptide chain NH vectors. The NOEs have been classified according to the structural elements they are associated with. Using multiexponential fits of the raw data spectral densities and cross-relaxation rate constants have been determined. Statistical distributions of correlation function parameters are given. On the basis of these data the assumptions underlying the standard method for distance measurement using NOE enhancements have been scrutinized. The separability of elongation and reorientation is verified for the vast majority of NOEs, but the rigid-body assumption is not supported by the simulation results. Relying on a spectral density expression that neither makes use of the product approximation nor neglects spatially restricted motion, a "bias-free" (with regard to molecular motion) distance measurement method is suggested and compared with the standard method. Errors in distances up to 24% and 50% occur due to the neglect of the dispersion of order parameters and correlation times, respectively. The preconditions for a class-specific calibration method have been investigated. Within the framework of the product approximation a method for decomposing the total cross-relaxation rate constant into contributions from radial and angular motion has been developed and applied. In several cases distance fluctuation contributes significantly to cross-relaxation with both amplitude and time behaviour.

Animals↗
PubMed1995

Improved event-related potential signs of selective attention after the administration of the cholecystokinin analog ceruletide in healthy persons.

Cholecystokinin (CCK) is co-localized with dopamine (DA) in neurons of the mesolimbic-frontocortical dopamine (DA) system, considered essential for the pathology of psychotic behavior and associated attention deficits. The present experiments in 13 healthy men aimed at examining the effects of the CCK analog ceruletide on attention as reflected by event-related brain potentials (ERPs). Subjects were tested according to a double-blind cross-over design on three occasions, following intravenous infusion of placebo, 0.5 microgram ceruletide, and 2.5 micrograms ceruletide. ERPs were recorded during the subject's performance on an auditory selective attention task including the concurrent presentation of frequent standard tones and infrequent deviant tones which the subject had to listen to, or to ignore. The processing negativity (PN) over frontocentral cortical areas, reflecting selective attention, was higher after ceruletide than placebo, this increase being most pronounced after the 2.5 micrograms dose (placebo -1.29 +/- 0.38 microV versus ceruletide -3.02 +/- 0.65 microV, p < .05). ERP signs of a general increase in cortical arousal after ceruletide did not reach significance. Likewise, mismatch negativity, an indicator of preattentive processing of stimulus deviance, was not significantly affected by the peptide. The results indicate that ceruletide affects human brain function primarily by improving selective attention.

Adult↗
PubMed1995

Changes in ascorbate peroxidase activities during fruit ripening in Capsicum annum.

The ascorbate peroxidase (APX) system was studied in Capsicum annum during fruit ripening. A large increase in organelle APX activity was found during chloroplast-chromoplast transition whereas only a slight difference was detected in total fruit extracts. On native gels, four different isoforms were found in total fruit extracts but the patterns for red and green fruit were quite different. In isolated organelles, six isozymes were found and a comparison of the patterns showed significant differences. A cDNA encoding a cytosolic APX was cloned and sequenced. The corresponding transcript was shown to increase 3-4-fold during fruit ripening.

Amino Acid Sequence↗
PubMed1995

Inhibition of tumor growth by elimination of granulocytes.

As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth.

Animals↗
PubMed1995

A unique tumor antigen produced by a single amino acid substitution.

Mice immunized against a cancer recognize antigens unique to that cancer, but the molecular structures of such antigens are unknown. We isolated CD4+ T cell clones recognizing an antigen uniquely expressed on the UV-induced tumor 6132A; some clones inhibited the growth of tumors bearing the specific antigen. A T cell hybridoma was used to purify this antigen from nuclear extracts by RP-HPLC and SDS-PAGE using T cell immunoblot assays. A partial amino acid sequence was nearly identical to a sequence in ribosomal protein L9. The cDNA sequence of L9 from 6132A PRO cells differed from the normal sequence at one nucleotide; this mutation encoded histidine instead of leucine at position 47. A synthetic peptide containing this mutation was over 1000-fold more stimulatory of T cells than was the wild-type peptide. These results indicate that this unique tumor antigen is derived from a single amino acid substitution in a cellular protein.

Amino Acid Sequence↗
PubMed1995

Comparative assessment of saccadic eye movements, psychomotor and cognitive performance in schizophrenics, their first-degree relatives and control subjects.

This study is aimed at detecting biological markers for schizophrenia. For this purpose, a total of 70 subjects (21 schizophrenic patients, 27 first-degree relatives and 22 controls) performed a series of tests assessing various attentional, psychomotor and cognitive functions and saccadic eye movements. The schizophrenics performed significantly poorer than both high-risk and control subjects in most of the tests demanding attention, concentration and psychomotor speed (d2 concentration test, reaction times and Stroop test of perceptual interference) as well as cognition (Wechsler intelligence scales). On the other hand, these tests did not differentiate between the high-risk and control subjects. This distinction, however, could be made by two other parameters: hypometria score of saccadic eye movements and ratio of verbal to performance intelligence scores. Both parameters were significantly increased in both the schizophrenic and the high-risk group, distinguishing both from the control group. The relevance of these findings in indicating a schizophrenic disposition is discussed.

Adult↗
PubMed1995

[Effectiveness of home ventilation of young children and infants].

BACKGROUND: The home care ventilation of patients with chronic respiratory insufficiency is a well-established method. In treating infants and newborns a lot of problems arise that deal with indication, prognosis and management. PATIENTS AND METHODS: We investigated 7 newborns and infants with chronic respiratory insufficiency after cervical spine trauma causing "pentaplegia" or due to inherited neuromuscular disorders (spinal muscular atrophy, myopathy) during homecare ventilation. RESULTS AND DISCUSSION: In contrast to experience with adults the management of the children with "pentaplegia" was relatively harmless. All were tracheostomized primarily, but 1 tracheostomy could be closed, because the patient finally achieved to be ventilated only during night-time in the iron lung. The 3 children with neuromuscular diseases were ventilated noninvasively by specially fitted nasal masks. Despite coming to the frontiers of feasibility, and taking into account the psychological stress for patients, relatives, doctors and nurses, satisfactory results were obtained.

Child, Preschool↗
PubMed1994

Scalp recorded direct current potential shifts associated with the transition to sleep in man.

Cortical direct current (DC) potentials are considered to reflect the state of cortical excitability which may change characteristically from wakefulness to sleep. The present experiments examined changes in the scalp recorded DC potential in 10 healthy humans at the transition from wakefulness to nocturnal sleep. For each subject, DC recordings obtained from Cz were evaluated for a 15 min pre-sleep onset interval and for a 20 min post-sleep onset interval, on 2 separate nights. Sleep stages were determined from standard sleep recordings. The transition from wakefulness to sleep coincided with a significant (P < 0.05) shift in the DC potential of negative polarity. Maximum negative potentials of (mean +/- S.E.M.) 500 +/- 130 microV (first night) and of 760 +/- 200 microV (second night) were reached at the end of the 20 min post-sleep onset interval. A number of possible technical and biological artifacts were controlled. It is reasonable to assume that the slow negative shift of the DC potential at the transition from wakefulness to sleep reflects increased cortical excitability. Whether the negative potential shift pertains during sleep, or is of transient nature and closely linked to the process of falling asleep, remains to be clarified.

Adolescent↗
PubMed1994

Chemical, bacteriological and biological examination and evaluation of sediments from drinking water reservoirs--results from the first sampling phase.

Between September 1992 and April 1993, samples of sediment were taken from a total of 16 drinking water reservoirs from seven water suppliers. Five different types of raw water were examined, samples being taken with varying frequency. The comparison of surface reservoir water and ground water constituted a central aim in this first series of investigations. The composition of the sediment was determined in terms of its chemical, bacteriological and biological characteristics. It was established that the deposits that normally accumulate in the course of an operating period contain, in addition to the familiar mass-determinant inorganic constituents such as iron, manganese and calcium compounds, in some cases considerable quantities of organic substances. Total organic carbon (TOC) contents of up to 11 weight-% were found. Besides an increased concentration of heavy metals, in particular cadmium, nickel and zinc, were measured in some sediments. The bacteriological examination of the sediments, in accordance with the German drinking water regulation (TrinkwV) showed, in part, very high colony counts. However, there was apparently no influence on the effluent water as the reservoir was emptied. The microscopical examination showed independent of the raw water source the sediments being colonized by invertebrates. Up to 9000 organisms per litre of fresh sediment were recorded. The predominant group of animals, in terms of numbers, was the rotifers followed by threadworms. The comparison of water from impounding reservoirs and ground water made evident that the presence of organisms in reservoir sediments is not restricted to the use of surface water.

Animals↗
PubMed1993

A tumor escape variant that has lost one major histocompatibility complex class I restriction element induces specific CD8+ T cells to an antigen that no longer serves as a target.

After loss of expression of a major histocompatibility complex class I Kk allele, the escape variant of an immunogenic tumor grows progressively in normal mice. This progressor variant is resistant to killing by cytotoxic T lymphocytes (CTLs) directed against the A and B antigens presented by Kk. Although the variant retains the expression of the Dk allele and is sensitive to CTLs directed against the C antigen presented by Dk, the variant failed to induce CTLs to this antigen in vivo. Instead, the variant induced CD8+ T cells directed to the A antigen. This was shown at the molecular level by T cell receptor beta chain sequence analysis of the responding cells. Further evidence for the presence of A antigen in the variant came from the finding that spleen cells of mice injected intraperitoneally with the variant tumor cells were primed for an anti-A CD8+ CTL response in vivo. Thus, in contrast to other variants that lost a target antigen and induced a CTL response to remaining target antigens, the Kk loss variant continued to induce an immune response to a tumor antigen that is no longer presented on the tumor cell surface. Even though the variant escapes in a single step because an effective CTL response to secondary antigens is prevented, these secondary antigens remain as potential targets of immunotherapy on the variant's cell surface.

Animals↗