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H Schreiber

Publications and source records attributed to H Schreiber.

At least 19 recordsLinked to original sources
PubMed1992

Taming cut-off induced artifacts in molecular dynamics studies of solvated polypeptides. The reaction field method.

In this paper we present a model system of a solvated polypeptide, which is a suitable reference platform for the systematic exploration of methods for taming artifacts introduced by an incorrect treatment of long-range Coulomb forces. The essential feature of the system composed of an alpha-helical peptide and 1021 water molecules is the strict neutrality of all charge groups. The dynamical properties of the peptide, i.e. unfolding or maintenance of the helix, already give first hints on the influence of boundary effects. A rigorous and deeper insight is gained, however, if analyzing the system by means of the generalized Kirkwood g-factor, which projects the net dipole moment of concentric spheres onto the respective dipole moment of the reference charge group. The g-factor is a global measure for, and a sensitive probe of, the orientational structure, which in its turn reflects even the smallest inconsistencies in the treatment of long-range forces. While the cut-off scheme failed the g-factor test, the "reaction field" method, the simplest cut-off correction scheme, enables a consistent description. In other words, with the aid of the reaction field, the correct orientational structure is restored. As a consequence, the helix stability is regained and we were able to calculate the dielectric constant epsilon approximately 55 to 60 for our system, which is slightly below the corresponding value epsilon SPC = 66 of the pure solvent.

Amino Acid Sequence↗
PubMed1992

Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia.

Auditory event-related potentials (ERPs) associated with selective attention were recorded in 21 children at high-risk for schizophrenia and in 21 matched controls. The subjects performed a selective listening task. For behavioral evaluation, target counts on the selective listening task and on cognitive performance were assessed. Group-specific differences of ERP components could be demonstrated, as reflected by significant amplitude reductions of the frontally located negative difference wave (Nd) and of the P3 component, following selectively attended stimuli, in the high-risk children. P3 latencies tended to be prolonged in the high-risk group. Reduced Nd was found in 14 and reduced P3 in 16 high-risk children among the 21 matched pairs. Significant correlations between the ERP reductions and psychometric deficit (counting accuracy) were observed. Mismatch negativity (MMN), an ERP component associated with automatic processing of physically deviant stimuli, did not differentiate significantly between groups, but was distinctly reduced in the high-risk group. The Nd and P3 reductions suggest deficits of selective attention in a considerable number of the subjects genetically at risk for schizophrenia. The present findings are discussed with respect to their relevance as indicators of a predisposition to schizophrenia.

Adolescent↗
PubMed1992

Cutoff size does strongly influence molecular dynamics results on solvated polypeptides.

The behavior of a 17-residue model peptide is analyzed by means of molecular dynamics simulations including explicitly more than a thousand water molecules. On the basis of the charge-group concept, Coulomb interactions are truncated for three values of the cutoff radius: 0.6, 1.0, and 1.4 nm. It is found that the stability of an alpha-helix, which acts as a common starting configuration, is a function of the cutoff size. While the overall stability of the helix is conserved in a simulation using a cutoff of 1.0 nm, it is lost within a very short period of 100 ps when the cutoff is increased to 1.4 nm. This demonstrates that the commonly used cutoff size of 1.0 nm is inappropriate because it does not ensure the convergence of Coulomb interactions. In order to permit an independent judgment, we have performed a 225-ps simulation using the Ewald summation technique, which is more elaborate but circumvents the problem to find an appropriate cutoff value. In contrast to the 1.4-nm cutoff trajectory, the Ewald technique simulation conserves the helical character of the peptide conformation. This demonstrates that even 1.4 nm is too short a cutoff. Due to the fundamental uncertainty introduced by the use of a simple cutoff, this truncation scheme seems questionable for molecular dynamics simulations of solvated biomolecules.

Amino Acid Sequence↗
PubMed1992

Stroma is critical for preventing or permitting immunological destruction of antigenic cancer cells.

Inoculated immunogenic cancer cells after initial growth are potentially rejected by specific host immunity; however, the outcome of the interaction between host and inoculated cancer cells is a function of multiple factors including the route of inoculation, the number of cells, the density of antigens on the injected cancer cells, and the state of the immune system of the host. In the present study, we have examined a different kind of variable: the stroma that inoculated tumor cells initially reside in. The impetus to examine this factor arises from observations that cancer cells from several lines inoculated as fragments of solid tumors often grow progressively, whereas the same number or more than 10-fold larger numbers of identical type cells injected as a suspension are rejected, even though fragments or suspended cells are both tumorigenic at the same doses in nude mice. In the present studies, we found that: (a) indeed, cancer cells inoculated as fragments were more tumorigenic than cancer cells in suspension; (b) the tumorigenicity of suspended cancer cells was increased by injection of the cells into polyurethane sponge implants; (c) cancer cells were more tumorigenic embedded in syngeneic stroma than in transgenic antigenic stroma expressing the K216 major histocompatibility complex class I antigen; and (d) antigenic, bone marrow-derived, stromal components (presumably passenger leukocytes) were sufficient to cause rejection of immunogenic but antigenically unrelated cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Attention, cognition, and motor perseveration in adolescents at genetic risk for schizophrenia and control subjects.

Twenty-three offspring of schizophrenic parents (mean age = 12.1 years, SD = 3.2) and 61 adolescent control subjects (mean age = 12.3 years, SD = 3.3) were compared in their performance of the following psychometric tests: simple reaction times (RTs), warned RTs in a monomodal and cross-modal design, d2 concentration test, a motor perseveration test, and a cognitive performance measure (Wechsler Intelligence Scale). The results were validated in a second analysis in which a subgroup of the control subjects were matched to the high-risk subjects for the following characteristics: age, gender, education, and environmental background. Significant deficits were found in the high-risk group in tests that required sustained attention and information processing under high perceptual load (RT measures and d2 concentration test). Deficits were particularly prominent for the processing of visual stimuli; sensory incongruence might also have been a contributor to this deficit. The attentional dysfunction of high-risk subjects might explain their tendency to show less structured behavior and distractibility as reflected by their higher entropy scores in a motor perseveration test. Cognitive evaluation showed a significant deficit in the high-risk group, primarily as reflected in the verbal IQ score.

Adolescent↗
PubMed1992

Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice.

Tumor necrosis factor alpha (TNF alpha) orchestrates a wide range of effects that combat severe infections in animals. At lower levels, TNF alpha plays an important protective role in stimulating chemotaxis and antimicrobial activity of neutrophils, macrophages, and eosinophils. During chronic illness, TNF alpha secretion can be elevated markedly, giving rise to cachexia, hemorrhage, necrosis and, ultimately, death. Although TNF alpha may mediate many of its effects through macrophages, 30% of TNF alpha injected into animals concentrates in the skin. In recent years, it has been shown that keratinocytes can be induced to synthesize TNF alpha. To explore the role of TNF alpha synthesis in keratinocytes, we used a keratin-14 (K14) promoter to target human TNF alpha expression in the epidermis and other stratified squamous epithelia of transgenic mice. Most mice expressing the K14-TNF alpha transgene stopped gaining weight within 1 week postbirth, and exhibited retarded hair growth. In the skin, adipose production was profoundly inhibited, whereas signs of fibrosis and immune infiltration were evident in the dermis. Over time, the epidermis exhibited an increased stratum corneum, as signs of necrosis began to appear in the skin. Within 3-5 weeks, the mice displayed features characteristic of cachexia and necrosis. Our results suggest that TNF alpha expression by keratinocytes not only plays a role in inflammatory and graft-versus-host-disease-like responses in the skin, but also in other tissues, apparently by virtue of stratified squamous epithelial-derived TNF alpha entering the bloodstream. Our results have enabled the first evaluation of many of the effects of TNF alpha in transgenic animals.

Animals↗
PubMed1992

Tumor antigens.

This review solidifies a new concept that common and rare types of human cancers harbor a variety of tumor-specific mutant proteins that may be recognized as tumor-specific antigens. These mutant proteins are encoded by oncogenes or suppressor genes that have undergone structural mutations resulting from point mutations, chromosomal translocations, internal deletions and viral insertional mutagenesis; several of these changes result in fusion proteins. While there is no evidence that immunosurveillance against these mutant proteins can prevent the development of primary cancers without prior immunization of the host, such tumor-specific molecules might be important for diagnosis and as targets for specific immunotherapy once the cancer has developed or even as targets for preventive cancer vaccines. Evidence further supports the notion that cytolytic or helper T cells are exquisitely selective in recognizing intracellular mutant proteins, and tumor-specific T cell clones presently available may become useful for identifying previously unrecognized tumor-specific mutations. Many tumor-specific mutant proteins clearly play a causative role in the establishment of malignant behavior, whereas other carcinogen-induced changes have at least immunological relevance. In any case strong evidence in mouse and man indicates that a single malignant cell can express multiple independent antigenic target sites. Such multiplicity may allow a multi-pronged immune attack that substantially decreases the chance of tumor escape. Future work must explore whether immune responses to tumor-specific mutant proteins can lead to immunological tumor rejection and explore the possibility of chemically engineering tumor mutant peptides to be highly immunogenic, even in hosts that have previously failed to respond to the tumor.

Antigens, Neoplasm↗
PubMed1992

Ileocolonic anastomosis: a comparison of the patency of stapled versus hand-sewn techniques.

This study compared strength of hand-sewn sutures to that of staples for end-to-end anastomoses of ileocolostomies in 20 mongrel dogs. In ten dogs, the authors used four applications of staples for the anastomoses. In the other ten, they performed single-layer anastomoses using 4-0 polypropylene sutures. Half the dogs were sacrificed on the third postoperative day; half were sacrificed on the fifth postoperative day. Bursting strengths were obtained by infusing air through a catheter inserted into the colon. Results showed the single-layer hand-sewn anastomosis was significantly stronger than the stapled anastomosis. In addition, a histologic comparison of the two closures showed no difference in inflammatory responses.

Anastomosis, Surgical↗
PubMed1992

Carcinoma of the ampulla of vater after curative treatment for Hodgkin's disease.

A 43-yr-old woman developed carcinoma of the ampulla of Vater 20 yr after being successfully treated for Hodgkin's disease with radiotherapy and chemotherapy. Conditions related to the chronic effect of radiation, such as narrowing and fibrosis of abdominal tissue, hampered her diagnosis and treatment. After a total pancreatectomy to remove the carcinoma, the patient recovered. However, 15 months later, she developed severe digestive disturbances, adrenal insufficiency, pulmonary emboli, and vasculitis. She died the next month of sepsis and adult respiratory distress syndrome. Although her complications probably were related to residual effects from therapy and surgery, she had no clinical evidence of tumor recurrence.

Adenocarcinoma, Papillary↗
PubMed1992

Primary midgut volvulus in the adult: two case reports.

Primary midgut volvulus is associated with a high mortality rate. The presentation and management of two patients with primary midgut volvulus are reviewed. Both presented with severe abdominal pain inconsistent with clinical findings. Diagnosis was made intraoperatively in one case and at autopsy in the other. Surgeons need to suspect primary midgut volvulus when they encounter patients with atypical presentation of small bowel obstructions, i.e., when the severity of symptoms is inconsistent with physical findings. Primary midgut volvulus should be considered in the differential diagnosis in these patients, and, if suspected, emergent abdominal exploration is indicated.

Abdominal Pain↗
PubMed1991

Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia.

Two independent groups of high-risk children for schizophrenia and their matched control children were submitted to the following experiments: an auditory oddball paradigm registrating late event-related potentials (ERPs) and a psychometric test battery including the assessment of Wechsler Intelligence Scales, reaction times (after regular and irregular preparatory intervals), and the d2-attention test. The study was intended to clarify whether long-latency ERPs and the selected psychometric tests would contribute to reliably differentiating between these groups. The results showed significantly prolonged latencies of the P3 component of the ERPs to rare, task-relevant target stimuli in both high-risk groups compared with the controls. Similarly, the N2 latencies were delayed in both groups. By contrast, ERP patterns to frequent, nontask-relevant stimuli were very similar, with no significant differences between high-risks and normals; nor did any ERP amplitudes show significant differences. The data are interpreted as a reflection of a subtle deficit in maintaining attention and a subsequent impairment of stimulus discrimination in high-risk children. This is consistent with the psychometric findings of higher error scores in target counts and d2-test, and significantly prolonged reaction times after regular preparatory intervals (PIs) in the high-risks. The findings may hint at a vulnerability for schizophrenia in high-risk children. Given the high prevalence of the attentional dysfunctions in both high-risk groups, however, it is hypothesized their presence does not necessarily imply an unequivocal manifestation of schizophrenia.

Adolescent↗
PubMed1991

Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity.

The relationship between detrimental (cachectic) and beneficial (antitumor) effects of tumor necrosis factor (TNF) was studied in mice bearing murine tumors transfected to secrete human TNF. In vitro, the TNF-producing transfectants were resistant to the secreted TNF and grew at rates similar to those of untransfected cells or transfected cells that did not secrete TNF. However, tumors formed by the TNF-secreting cells in vivo remained much smaller than the nonsecreting (transfected and untransfected) tumors. This inhibition of tumor growth required only relatively low serum levels of TNF, persisted for many weeks, and was independent of T cells since it occurred in nude mice. Growth of the TNF-secreting tumors increased dramatically after treatment with anti-human TNF antibody, indicating that extracellular TNF secreted by the tumor cells was necessary for the tumor inhibition. Severe weight loss characteristic of cachexia only occurred in animals with very high serum TNF levels (250 pg/ml) and could be prevented or reversed by anti-TNF antibody treatment. These data are consistent with the existence of a therapeutic window in which persistent exposure to human TNF can lead to prolonged inhibition of tumor growth in the absence of T-cell immunity or severe weight loss and without development of resistant tumor variants.

Animals↗
PubMed1991

Cytokines and cancer: experimental systems.

The transfer of certain cytokine genes into cancer cells can provide very powerful suppression of tumor growth in the absence of any toxic side effects. Some of these cytokines, such as interleukin-4, granulocyte colony-stimulating factor and tumor necrosis factor, can mediate powerful immune suppression even in T-cell-deficient animals and appear to be effective for poorly or non-antigenic tumors. However, approaches must be found to induce or deliver cytokines locally at the tumor site.

Animals↗
PubMed1991

[Expression of ABH and Lewis antigens in endometrium--relation to hormonal stimulation].

From 138 gynaecological abrasiones appropriate histological preparations were chosen. Case history and pathological diagnosis were known. ABH and Lewis antigens were marked immunohistologically. According to our findings, in the endometrial glands the ABH antigen expression is highest in the proliferation phase and decreases within the secretion phase. The same hormonal dependency could be demonstrated for the Lea antigens present in the superficial epithelium of the endometrium. Exogen application of estrogens enhances ABH antigen marking, application of gestagens does not.

ABO Blood-Group System↗
PubMed1991

MHC class I restricted T cells and immune surveillance against transplanted ultraviolet light-induced tumors.

Studies involving tumor escape from host immune surveillance have focused heavily on loss of major histocompatibility class I antigens as well as loss of tumour-associated antigens as possible mechanisms by which tumors escape recognition and lysis by cytolytic T cells. Examples of both phenomena are found in murine tumors induced by viruses, chemical mutagens, a spontaneous tumor mutagenized in vitro and some u.v.-induced tumors. However, evidence also exists for the escape of tumors from immune destruction without loss of major histocompatibility class I molecules or tumor antigens and additional mechanisms undoubtedly are involved in the complex phenomena of tumor progression.

Animals↗
PubMed1991

The rationale for incidental cholecystectomy during major abdominal vascular surgery.

The finding of gallstones during major abdominal vascular surgery warrants a critical decision regarding incidental cholecystectomy. The potential risk for vascular graft infection must be weighed against the risks of severe postoperative cholecystitis requiring surgery, a situation associated with significant morbidity and mortality. This report supports the safety of an incidental cholecystectomy, as long as the vascular graft is covered before the gallbladder is removed. The data also emphasize the hazards of not performing an incidental cholecystectomy for gallstones during major abdominal vascular surgery.

Abdomen↗
PubMed1990

[Myositis ossificans circumscripta following unusual brain injury].

The case reported here demonstrates the need to consider myositis ossificans after acute injury to the CNS, irrespective of the nature of the trauma. This latter by no means needs to be direct trauma--as the present case shows. When the condition does occur, the time needed for rehabilitation may be significantly lengthened.

Adult↗