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Biomedical subjects

H Schreiber

Publications and source records attributed to H Schreiber.

At least 109 records · Page 6Linked to original sources

Computerized microscopic image analysis method in tissue-biomaterials interaction.

The use of computer-based image analysis belongs to the new methods of biocompatibility testing. When materials were implanted subcutaneously in animals the cells of the connective tissue capsule can give a good standard for the evaluation of biocompatibility. The application of image processing systems allows the automation of a great number of measurings and test - techniques. It is also possible to get quantitative information on cell - and haemocompatibility testing. With the help of the automatic microscopic image analysis the accuracy of morphometric methods increased and scientists time was saved.

Animals↗

A prospective, multi-center clinical trial of the Taylor intragastric balloon for the treatment of morbid obesity.

This report describes the result of a prospective, multicenter clinical trial of the Taylor intragastric balloon for the treatment of morbid obesity. Sixty patients, who had failed sustained weight loss on prior dietary restriction and behavior modification programs, were enrolled in four clinical centers. The Taylor intragastric balloon, a 550-ml, pear-shaped, liquid-filled, silicone device, was inserted in all patients for a period of 16 wk, and patients were maintained on a dietary restriction and behavior modification program. During the study period, patients experienced a 11.6% decrease in mean weight and an 11.4% decrease in body mass index. Seven balloons deflated spontaneously. Examination of these balloons revealed a manufacturing defect that was subsequently corrected. No further deflations occurred. Effects of the balloons on gastric mucosa were minimal with no gastric erosions or ulcerations noted.

Adult↗

[The question of the transmissibility of the results of subcutaneous tests of biomaterials from animals to humans].

The histologic estimation of the subcutaneous connective-tissue reaction at implants forms an important part of the biocompatibility test. The connective-tissue capsulae around titanium implants in man, guinea-pig, and Wistar-rat were analysed by a special test system because of the question concerning the transmission of results of animal experiments on the man. The subsidence process of the thickness of the connective-tissue capsule and of the cell count per measuring fields were represented in dependence on the time. The findings showed the fundamental similar course of wound healing in man, guinea-pig, and Wistar-rat by the influence of an implant.

Animals↗

[Computer-assisted identification and comparative studies of the human skull].

The comparison of reconstructed skull profiles with photographic or other patterns for identification up to the reply to questions for sex, age, and race by the help of image analysis represents a relatively new development in forensic medicine. Using a Robotron image analyzing system 20 human skulls of different races were analysed morphometrically. Standardized profile functions, which were put through a morphometric analysis, showed characteristic individual features. By the help of the computerbased identification method mathematic differences between skulls of varions races became veritable.

Cephalometry↗

Tumor antigens defined by cloned immunological probes are highly polymorphic and are not detected on autologous normal cells.

We have isolated UV light-induced and spontaneous tumors along with nonmalignant cells and tissues from each host. CD8+ CTL clones generated to a number of highly immunogenic UV-induced tumors did not react with autologous normal fibroblasts nor with autologous second tumors. Using up to 25 independently induced tumors as targets, these CTL clones were found to be uniquely specific for the particular tumor used for immunization even when multiple tumors isolated from the same animals were used as targets. In addition to this extensive antigenic diversity of independently induced tumors, we found that a single cancer cell can express multiple independent antigens that were uniquely expressed on the tumor but were not detectable on autologous nonmalignant fibroblasts. A poorly immunogenic spontaneous tumor was also found to express an antigen that was uniquely specific for the immunizing tumor in that it was absent from any of 25 other tumors tested. This antigen was recognized by a mAb and not detected on autologous nonmalignant fibroblasts or on an autologous second spontaneous tumor. These findings demonstrate that syngeneic CTL clones or mAbs can define unique antigens on UV-induced or spontaneous tumors. The use of autologous nonmalignant fibroblast targets made it unlikely that these antigens were widely expressed on normal cells. The availability of cloned immunological probes to antigens on tumors isolated with autologous normal cells will allow a reliable identification of the genetic origins of unique antigens on experimentally induced and spontaneous tumors and permit a decisive answer to whether these unique antigens are encoded by normal genes or by genes that have undergone somatic mutations; i.e., whether these antigens are truly tumor specific.

Animals↗

Generation of antigenic variants from a nonantigenic murine tumor cell line by transfection with a gene encoding a novel tumor-specific transplantation antigen.

Tumors induced in mice by UV radiation often express highly immunogenic tumor-specific transplantation antigens (TSTA). The 216 gene, which encodes a TSTA of the C3H tumor UV-1591, has been cloned and characterized as a novel major histocompatibility complex Class I antigen. The purpose of this study was to determine whether the 216 gene-encoded TSTA can function as a tumor rejection antigen when expressed on unrelated, nonantigenic murine tumor cells or whether its function is restricted to UV-induced tumors. A cell line (10T-1) derived from a spontaneous transformant of C3H 10T1/2 cells was cotransfected with DNA from p216 and pSV2-neo plasmids. About 2 wk after transfection, G418-resistant colonies were isolated randomly and tested for cell surface expression of the 216 gene product using a monoclonal antibody specific for 216 gene-encoded TSTA. Of 20 clones tested, four expressed high levels of 216 gene-encoded TSTA. These four clones were highly antigenic in that they were completely rejected in normal mice but grew progressively in nude mice. Furthermore, the 216-positive clones were immunologically cross-reactive with UV-1591, as determined by in vitro cytotoxic T-lymphocyte and in vivo immunization and challenge assays. Surprisingly, 216-positive 10T-1 transfectants also cross-reacted with 10T-1 cells, both in vitro and in vivo. These results demonstrate that the product of a cloned TSTA gene from a UV-induced murine tumor is capable of functioning as a tumor rejection antigen when expressed on unrelated, nonantigenic tumor cells. In addition, these results indicate that this approach could be used to augment the immune response against poorly antigenic tumors.

Animals↗

Prolonged latencies of the N2 and P3 of the auditory event-related potential in children at risk for schizophrenia. A preliminary report.

In previous studies investigating long latency components of the event-related potential (ERP), schizophrenic patients generally showed reduced P3 amplitudes and in some studies prolonged N2 or P3 latencies. As there is a higher risk of offspring of schizophrenics than of mentally healthy parents developing this disease, the present study was intended to clarify whether ERP components (in particular the N2 and P3) differ between these two groups of children. Twelve high-risk and 12 age-matched control children (aged 9-16 years) performed an auditory oddball task in order to assess late ERP components. This task required the subject to covertly count rare target tone pips (P = 0.2) irregularly interspersed among frequent standard tone pips (P = 0.8) in two series of 400 pips. ERPs were recorded from midline electrodes (Fz, Cz, Pz). The results indicated distinctly prolonged N2 and P3 latencies in ERPs to target stimuli in children of schizophrenic patients. These findings suggest a slowed target classification in these children.

Adolescent↗

Highly immunogenic regressor tumor cells can prevent development of postsurgical tumor immunity.

Highly immunogenic malignant cells form small tumors that spontaneously regress after initial growth because the tumor induces specific immunity. However, variants may arise during the initial tumor growth that lose antigens, grow progressively, often become the predominant tumor population, and eventually kill the host. These progressively growing variants usually have not lost all tumor antigens and remain susceptible to rejection by T cells specific for antigens present on the parental tumor and retained by the progressively growing variants. Thus, it would seem logical for therapy to actively immunize with the parental highly immunogenic tumor (or sublines made similarly immunogenic by tumor heterogenization) after maximal surgical removal of the growing tumor. However, the present findings suggest that such a strategy may be ineffective and have adverse effects: the parental highly immunogenic tumor cells, either remaining or reintroduced, may perpetuate unresponsiveness to both the parental and the variant tumor. These findings suggest that unless tumor-induced suppression is first abrogated, immunization with highly immunogenic tumor cells may be counterproductive because this maneuver may maintain preexisting immune suppression and prevent development of postsurgical tumor immunity.

Animals↗

Cardiac surgery in septuagenarians: is there a difference in mortality and morbidity?

Open heart surgery is being performed with increased frequency in elderly patients. Results vary considerably probably as the profile of the surgical population changes. A comparison was established by means of univariate analysis between two consecutive series of 100 patients undergoing bypass grafting or valvular replacement. Group A patients were 70 years of age or older; group B patients were less than 65 years of age. Various clinical, operative, and postoperative parameters were monitored. A significant difference was found between the two groups. Elderly patients tended to be white, female, with poor left ventricular and renal function, had carotid or peripheral vascular disease, and new onset of symptoms. Fewer patients had single-vessel disease and received internal mammary artery grafts. Operative mortality rate was higher in group A subjects and postoperative neurologic complications were also more frequent in this group. Factors influencing operative mortality were the association between vascular disease, presence of left main coronary artery disease, and urgency of the procedure. The mortality rate was 17.2% in 29 patients with associated vascular disease and 4.8% (3/63) in those without vascular disease (p = 0.048). Operative mortality was 4.1% without left main coronary artery disease, 15% with left main coronary artery disease (p = 0.083), and 4% in 84 patients having elective operations versus 31.2% in patients having 16 emergency procedures (p = 0.001). Short-term follow-up revealed a higher late mortality rate in elderly subjects and suggested an increased incidence of early pulmonary embolus. Nevertheless, elective cardiac surgery may be safely performed in septuagenarians with an expected operative mortality rate under 5%.

Age Factors↗

Coronary artery bypass grafting with saphenous vein.

Occlusion rate of the saphenous vein is around 12-20% during the 1st year and 2-4% annually for the next 4 or 5 years. Subsequently, this rate doubles, so that at 10 years, approximately 50% of grafts become occluded due to the occurrence of graft atherosclerosis. A similar percentage of patent grafts show atherosclerotic changes at the end of the 1st decade. Sequential vein grafts probably suffer the same fate although late follow-up is lacking. Reoperation is estimated to be 30% at 10 years, as judged by angiographic criteria. The operative risk of reoperation is at least double that of primary operation; symptomatic relief appears to be of shorter duration. Recent technical changes to better preserve medial and endothelial function and to pharmacologically inhibit platelet function may lead to longer duration of the venous conduit.

Coronary Artery Bypass↗

Tumor necrosis factor/cachectin. Induction of hemorrhagic necrosis in normal tissue requires the fifth component of complement (C5).

TNF induces hemorrhagic necrosis (HN) when injected into skin exposed to bacterial agents but not when injected into normal skin. In this paper, we present several lines of evidence suggesting that TNF requires the fifth component of complement (C5) to induce HN in skin exposed to bacteria. First, mouse strains that do not have C5 did not develop HN after injection of TNF and bacteria into skin. Second, plasma from C5-sufficient mice could correct the defect in these C5-deficient mice. Third, heating at 56 degrees C for 30 min inactivated the capacity of plasma to reconstitute C5-deficient mice. Fourth, CVF, which is known to inactivate complement, abrogated the capability of C5-sufficient mice to respond. Fifth, depleting plasma of hemolytic activity while generating C5a did not affect the capacity of the activated plasma to reconstitute C5-deficient mice. Finally, only the plasma fraction containing molecules of the size range of C5a reconstituted C5-deficient mice. These findings indicate that C5a and not the membrane attack complex is required for HN. Although we do not know through which mechanism C5a participates in the development of HN, we propose that the described HN response is related to a local defense mechanism in which TNF and C5a lead to the disruption of capillaries in the direct vicinity of bacteria. By this mechanism the rapid spread of bacteria or their products into the circulation is prevented. Such a tissue response is consistent with the known higher susceptibility of C5-deficient mice to bacterial infections and provides a model with which to search for the multiple steps involved in this important local defense mechanism.

Animals↗

In vivo administration of anti-CD3 prevents malignant progressor tumor growth.

Malignant progressor tumors are only weakly immunogenic and can evade host recognition and rejection. One approach to therapy involves activation of the host antitumor cellular effector mechanisms. Since monoclonal antibodies to CD3 (anti-CD3) can activate T cells in vitro, an attempt was made to determine if tumor immunity could be achieved by the administration of anti-CD3 in vivo. T lymphocytes from mice injected with anti-CD3 showed increased interleukin-2 receptor (IL-2R) expression, increased proliferation to recombinant IL-2 (rIL-2), and enhanced reactivity in both an allogeneic mixed lymphocyte reaction and a mixed lymphocyte tumor culture. Malignant tumor growth in treated mice was also examined. The anti-CD3 treatment prevented tumor outgrowth that would have killed untreated animals and also stimulated an in vivo response against a malignant progressor tumor providing lasting tumor immunity.

Animals↗

Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice.

We find a strong synergism between tumor necrosis factor (TNF) and bacteria or their products. Endotoxin-"free" recombinant TNF, even at very high doses (160 micrograms), did not alone cause hemorrhagic necrosis (HN) in the skin of normal mice. Similarly, TNF alone had a low systemic toxicity in tumor- and pathogen-free mice. However, TNF given intravenously with nanogram quantities of the endotoxin lipopolysaccharide caused lethal shock. Furthermore, subcutaneous injection of lipopolysaccharide made skin susceptible to subsequent induction of HN by TNF injected in the same site 24 hr later. Mycoplasma-infected cells or corynebacteria also synergized with TNF to cause HN or lethal shock. In addition, we find that lymphotoxin, a cytokine functionally and genetically related to TNF, also synergized with the bacteria to cause HN, whereas interleukin 1 alpha or interferon gamma did not. Together, the results indicate that a synergy between TNF and bacteria or their products causes HN and lethal shock in normal mice.

Animals↗

Elevated levels of 6-keto-prostaglandin-F1a from a lower extremity during external pneumatic compression.

The synthesis of either fibrinolytic serine proteases or platelet inhibitory ecosonoids by the intact endothelial cell may limit thrombus development. In a preliminary study from this laboratory, an elevation in the level of 6-Keto-prostaglandin-F1å, the stable metabolite of prostacyclin (PGI2) was demonstrated in femoral vein plasma obtained during surgical treatment from an extremity undergoing external pneumatic compression. Simultaneously, no elevations in thromboxane B2, the stable metabolite of thromboxane A2, were observed. The present study is an inclusive prospective series of 26 patients. A single pneumatic compression stocking was applied to the left limb in patients who underwent an operation under general anesthesia. Base line venous samples (3 milliliters) were obtained from the femoral vein on the experimental side and the control contralateral side, as well as from the upper limb. Additional samples were drawn at 30 and 60 minutes after the onset of compression. Nine samples per patient (234 total) were analyzed for 6-Keto-prostaglandin-F1å by competitive binding radioimmunoassay in duplicate in a single blind manner. Base line values for the upper limb, right leg and left leg were 0.08 + 0.01 nanogram per milliliter; 0.14 + 0.03 nanogram per milliliter, and 0.13 + 0.02 nanogram per milliliter, respectively (no statistical difference). By 60 minutes of compression, control samples increased to 0.40 + 0.07 nanogram per milliliter (right leg) and 0.42 + 0.08 nanogram per milliliter (upper limb) while the experimental leg increased to 0.71 + 0.13 nanogram per milliliter (p less than 0.05 versus right leg, p less than 0.005 versus upper limb). There was no statistical difference at 60 minutes between the men and women.

6-Ketoprostaglandin F1 alpha↗