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Biomedical subjects

C Hammer

Publications and source records attributed to C Hammer.

At least 145 records · Page 8Linked to original sources

Effects of therapeutic ribose levels on human lymphocyte proliferation in vitro.

Ribose has been used successfully in the treatment of ischemic heart disease and muscular enzyme deficiencies, and its administration also facilitates the diagnosis of coronary artery disease by influencing thallium-201 scintigraphy. Concerns about the safety of ribose therapy have been triggered by reports about inhibitory effects of ribose on cell proliferation in vitro. This study examines possible side effects of ribose on human lymphocytes. Unstimulated and mitogen-stimulated human lymphocytes were incubated with ribose concentrations associated with high-dose oral administration, i.e., 3.5 mM, and with two- (7 mM) and tenfold (35 mM) higher concentrations. Cell cultures with matching glucose concentrations served as controls. Incorporation of [3H]thymidine into cells was used to measure cell proliferation. No significant inhibition of human lymphocyte proliferation in vitro was observed in mitogen-stimulated cells. Unstimulated cultures showed significant inhibition only at 35 mM ribose. It is concluded that ribose plasma levels associated with high-dose oral administration do not inhibit human lymphocyte proliferation in vitro. No evidence was found that short-term ribose therapy is harmful to human lymphocytes.

Administration, Oral↗

[Cartilage transplantation in the area of the head-neck: comparative study of HLA class II antigen induction to chondrocytes in various culture systems].

Autologous and homologous cartilage grafts are often used in reconstructive head and neck surgery. Unfortunately, sometimes the outcome of such operations is endangered by graft rejection or resorption. Among other reasons, immunological reactions with HLA class II antigen expression are thought to be involved at least in failures of vitally grafted cartilage. Up to now, only one case of class II antigen expression in a cartilage graft "in vivo" has been reported. Nevertheless, it has already been demonstrated that stimulated cartilage cells are able to express "in vitro" class II antigens if grown in monolayer cultures. However, it has also repeatedly been shown that chondrocytes reveal strong dedifferentiating features if cultured in monolayers. Therefore, it was the aim of this study to examine whether isolated and stimulated chondrocytes also express class II antigens if cultured under in vitro conditions closer to the relevant in vivo situation. Hence monolayer, suspension, agar, alginate and organ cultures were prepared simultaneously and kept for up to 60 days. Chondrocytes were stimulated by the addition of IFN-gamma and tested for class II antigens. For the detection of the antigens immunocyto- and immunohistochemical APAAP stainings as well as flow cytometric measurements were made. In all examined culture systems a class II antigen induction could be observed. Any significant differences between the various cultures as to the intensity of antigen expression could not be detected. Consequently, the expression of class II antigens on stimulated human chondrocytes seems not to be a specificity of monolayer cultures. Therefore, class II antigen induction may be considered to play a role in the rejection/resorption of vitally grafted cartilage in reconstructive surgery.

Cartilage↗

[In vitro studies of possible transmission of human immunodeficiency virus (HIV) by allogeneic cartilage transplants].

With the increasing prevalence of the human immunodeficiency virus (HIV), the possibility of a transmission of HIV via allogenic transplants has increased. To assess the risk of transferring HIV with allogenic cartilage grafts we investigated the susceptibility of chondrocytes to the virus. Our results indicate the absence of the HIV receptor (CD-4-molecule) on chondrocytes by immunohistochemistry and FACS analyses. Furthermore cultures from chondrocytes and high doses of HIV-1 did not show an active replication. Hence, we conclude that normal cartilage cells cannot be infected by HIV. This means that the risk of HIV transmission by cartilage allografts is very low if no contaminating tissues like blood, perichondrium and calcifications etc. are present.

CD4 Antigens↗

A new device for the measurement of the arterial compliance using implantable sensors. Description and first experimental application.

To determine the compliance of experimental arterial grafts and its chronic adaptation after implantation, a new device for measurements was developed which is combined with implantable sensors. The system is based on the physical induction phenomenon. Each sensor comprises two small coils of copper wire which are sutured opposite to each other to the arterial vessel. Up to 3 sensors are adapted to one electrical connector which can be covered subcutaneously. The device is able to read pulsatile diameter excursions of arterial vessels down to 0.02 mm. It was applied first to evaluate the elastic properties of a 4-mm dialdehyde-starch-preserved bovine internal mammary artery implanted in the canine femoral artery position. For comparison an ePTFE graft was used. At implantation the compliance of the biograft was calculated to be 0.028 +/- 0.009% mm Hg-1, which was half of the compliance of the native femoral artery (0.06 +/- 0.0025% mm Hg-1), but superior if compared to the PTFE (0.008 +/- 0.005% mm Hg-1). Within 6 months the compliance of the femoral artery decreased to 0.039 +/- 0.013% mm Hg-1, which was well matched now to the compliance of the biograft (0.027 +/- 0.005% mm Hg-1).

Animals↗

[Cartilage-specific autoimmunity in otosclerosis].

The otic capsule of patients with otosclerosis contains premature bone with numerous cartilaginous remnants. Some investigators have proposed that the pathogenesis of otosclerosis is related to these cartilaginous rests in the otic capsule. In this study we investigated the presence of a humoral immune reaction against cartilage-specific antigens using ELISA-methods in patients with otosclerosis. Concomitantly, 8 age- and sex-matched healthy blood donors, free of any symptoms of autoimmune disease, served as controls. The following antigen substrates were used: collagen (I, II, III, VI, IX and XI), chondrocytes and chondrocyte membranes. Findings then showed that the levels of antibodies to collagens type II and IX as well as to chondrocytes were higher in the otosclerosis patients than in the control subjects. The high titer of antibodies against chondrocytes was not accompanied by an increase in antibodies against the chondrocyte membranes. To our knowledge these observations represent the first evidence for the existence of autoantibodies against minor collagens and chondrocyte-specific antigens and support a possible role for a cartilage-specific autoimmunity in the etiopathogenesis of otosclerosis.

Adult↗

Xenotransplantation: state of the art.

Today, at the beginning of the xenogeneic era of transplantation, only simple and single observations about comparative physiology and biochemistry, and even anatomy, are known. Very few data exist which in addition inform about mechanisms after successful xenotransplantation. Nothing is known about phenomena following successfully suppressed hyperacute xenogeneic rejection. Neither the elimination of single factors nor the mitigation of whole systems have led to clinically relevant survival times. Pig organs transplanted into nonhuman primates survived a maximum of 22 days. The hope that transgenic manipulation and modification would be useful to prolong survival times of xenogeneic grafts still waits for evidence. But, within a short time, xenotransplantation could enable patients to receive a life-saving animal organ as an alternative to an allograft. Xenotransplantation would, as a new dimension in medicine, shorten if not eliminate waiting lists. Therefore, scientists must vigorously develop xenografting as a viable alternative for transplantation.

Animals↗

Ethical aspects in xenotransplantation.

Ethics aims to achieve optimal human behavior. However, applied ethics depend on the cultural environment. In medicine, ethics could allow an amoral operation in a fetus or in chronically ill patients because it is new and rich in prospects for acquiring knowledge and could improve the quality of life of the patient or at least save the life. The operation itself must not be ill natured or unethical and the patient must not be misled or given false hope over the outcome. Ethics would allow us to offend the dignity of man, such as by xenotransplantation, because the wish for well being is often greater than the desire to retain dignity. Ethics in xenotransplantation must be based on the interests of the poor and unlucky patient and must aim for the good of everyone, but especially meet the patient's demands.

Animal Rights↗

The use of FK506 and RS61443 for reversal of small-bowel rejection.

Successful clinical small-bowel transplantation is still difficult to achieve. Two features render the small intestine unique among vascularised solid organ grafts. First, the bowel contains a large amount of lymphoid tissue within the Peyer's patches, mesenteric lymph nodes, and intraepithelial lymphocytes, which are thought to mediate graft-versus-host disease and provide a major stimulus for the recipient's immune system. Unfortunately, mere surgical reduction of these tissues, by using segmental allografts, does not furnish any immunological advantage. Second, the small bowel lacks specific serum markers such as blood urea nitrogen (BUN) in the kidney or bilirubin in liver transplantation. Clinical signs such as fever, pain, or tenderness of the abdomen may indicate an already advanced destruction of the graft. Therefore, very potent immunosuppressive regimens are necessary to avoid small-bowel allograft rejection or even to reverse an ongoing rejection process. Cyclosporin was shown in small and large animal models to control rejection reactions sufficiently. However, there are two even more promising immunosuppressive agents currently under investigation. FK506, a macrolide lactone isolated from Streptomyces tsukubaensis, leads to long-term survival of small-bowel allografts in a rodent model and has already been used in a few clinical small-bowel transplantations. RS61443, a mycophenolic acid morpholinoethylester, selectively inhibits T- and B-cell proliferation. We have investigated the use of FK506 and RS61443 for the reversal of small-bowel allograft rejection in a small animal model.

Animals↗

Allogeneic heart transplantation following xenogeneic bridging.

Xenografting seems to be a solution to bridge the time intervals when an essential allograft cannot be obtained. A subsequent allograft was never tried. Eight dogs (20-24 kg) of 2 years of age underwent right cervical heart transplantation. Donors were silver foxes (3-4 kg). The animals were treated by triple drug therapy consisting of cyclosporin A, methylprednisolone and azathioprine in clinical dosages. For control, six recipients received allogeneic heart transplantation (AHTP) and the identical immunosuppression. After rejection of the xenograft, a second allogeneic heart was anastomosed to the same right cervical vessels. Routine histology and immunohistology were performed. Thromboxane B2 and 6-keto-prostaglandin Fla were determined daily in peripheral blood. After final rejection sensitization of the recipient was controlled by haemagglutination tests. Survival times of the xenografts were 9.6 +/- 1.2. The subsequent hearts under the same therapy beat for 4.5 +/- 5.0 days. The average survival time of control hearts was 18 +/- 1.9 days. The five hyperacute second allografts showed signs of humoral rejection by absence of inflammation. The release of thromboxane B2 was different in hyperacute, accelerated or cellular rejection. In contrast to the long-functioning grafts, thromboxane B2 persisted during hyperacute rejection at a high level. However 6-keto-prostaglandin Fla showed no significant differences between long-time survivors and hyperacute rejecting hearts. After xenogeneic transplantation all recipients showed haemagglutinating titres between 1:4 and 1:16. Allogeneic grafts have different kinetics of rejection following xenogeneic heart transplantation (XHTP) compared with control hearts. Thromboxane B2 seems to be an important mediator in hyperacute rejection. This type of rejection is not associated with a change in 6-keto-prostaglandin Fla levels. These results indicate, that xenogeneic bridging under a common immunosuppressive regimen could lead to accelerated rejection of the following allograft. Under this condition clinical bridging is not advisable.

6-Ketoprostaglandin F1 alpha↗

Moderate heat treatment of bone allografts. Experimental results of osteointegration.

The use of bone allografts is often essential in orthopedic surgery. Strict donor screening, including HIV testing 3 months postoperatively, is mandatory before a transplant may be used. Yet these measures do not definitely rule out the possibility of HIV transmission, as there is a window period before infection is revealed by blood testing. Accordingly, there is a need for virus inactivation methods that can be used on bone allografts. As radiation treatment and chemical methods have a number of disadvantages, we chose a moderate heat treatment of 65 degrees C for a series of animal experiments. In 12 rabbit femoral condyles, moderate-heat-treated bone allografts were implanted into 6-mm drill holes. Twelve normal allografts and 12 empty drill holes served as controls. Radiologic and histological evaluation up to 12 weeks postoperatively revealed slow spontaneous bone remodeling from the rim to the center of the empty cavities. Normal deep frozen allografts were quickly intergrated after a short period of osteoclast reaction around the transplant, with occasional bone bridges between host and allograft. The examination of heat-treated allografts showed no differences to the controls, including morphologic aspects and the time course of osteointegration. Five zones of bone repair and osteointegration were distinguished. We conclude that thermal treatment of bone allografts has adverse effects on osteointegration in the rabbit femoral condyle. Thus, it may contribute to improving safety in human bone transplantation.

Animals↗

[Immunologic behavior of human tracheal transplants].

In this study we tried to investigate the antigenicity of human tracheal allografts. We found transplantation antigens in the mucosa and the mixed glands using monoclonal antibodies in an indirect immunoperoxidase method. However these antigens were able to be destroyed with a chemical preservation procedure. The diminution of the antigenicity could be also achieved in a tracheal transplant human recipient. These results show that the preserved trachea may be immunologically a suitable material for reconstruction in surgery of the trachea.

Aged↗

Experimental evaluation of the dialdehyde starch preserved bovine internal mammary artery as a small diameter arterial substitute.

A canine femoral artery model was used for evaluation of a dialdehyde starch preserved bovine internal mammary artery (BIMA) (3 and 4 mm internal diameter) in comparison to a polytetrafluoroethylene (PTFE) graft. The study comprised three groups for a 2-hour (n = 7, 3 mm), 3-month (n = 10, 4 mm), and 6-month (n = 10, 4 mm) follow-up. The thrombogenicity of the grafts was measured after 2 hours and 3 months using chromium 51 labeled autologous platelets. In addition, compliance studies were done. To control the wall stability of the xenografts, the collagen content before implantation and after explantation was examined together with the diameter of the grafts. Healing characteristics were studied using appropriate histologic methods. The acute platelet adhesion rate (2 hours) of the BIMA graft was 181 +/- 69 x 10(4) platelets/mm2 as compared to 57 +/- 43 x 10(4) for PTFE (p less than 0.05, t-test). However, after 3 months the thrombogenicity of the biograft had decreased whereas the platelet count at the PTFE graft had increased (BIMA: 79 +/- 48 x 10(4); PTFE: 179 +/- 102 x 10(4), p less than 0.05). At implantation, the compliance of the BIMA graft was 0.028% +/- 0.009% per mmHg as compared to 0.06% +/- 0.0025% of the femoral artery. The PTFE graft was uncompliant (0.008 +/- 0.005). After 6 months, the compliance of the femoral artery had decreased to 0.039% +/- 0.013% per mmHg, which was now well matched to the nearly unchanged compliance of the biograft (0.0027 +/- 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Culture and cryopreservation of chondrocytes from human cartilage: relevance for cartilage allografting in otolaryngology.

One of the reasons for failure of cartilage allografts is the impaired condition of the transplant during storage. In this paper we describe methods for the isolation and culture of viable chondrocytes obtained from nasal septum cartilage. Furthermore, we evaluate the possibility of growing such specific chondrocytes under culture conditions and storing them in a frozen state. Age-dependent differences were observed in the growth rate of the cultured cells. Our results confirm that chondrocytes survive freezing and remain able to proliferate. Knowledge gained from this study may be applied to the culture and freezing of viable intact cartilage for use in reconstructive surgery in otolaryngology.

Adolescent↗

Heterogeneity of alveolar macrophages in experimental silicosis.

The alveolar macrophage (AM) population has been shown to be heterogeneous in composition as well as in function. The aim of our study was to assess morphological and functional features of AM in an experimental model of quartz-induced lung fibrosis by flow cytometric methods. Twelve cynomolgus monkeys were exposed 8 hr/day, 5 days/week for 26 months to either normal atmosphere (n = 5) or 5 mg/m3 DQ12 less than 5 microns quartz dust (n = 7). After 20 months of exposure, we studied AM phagocytosis by incubating bronchoalveolar lavage cells with fluorescent polystyrene microspheres (mean diameter 1.91 microns). Using a fluorescence-activated cell sorter analyzer, AM subpopulations were identified via their volume/side scatter properties. After selective electronic "gating" of the AM populations, both the percentage of phagocytic AM and the mean number of ingested microspheres per AM were determined. In addition, a phagocytic index (microspheres/AM x % phagocytic AM x 10(-2) and a hypothetical total phagocytic capacity of one lung (phagocytic index x total number of AM x 10(-6) were calculated. The total bronchoalveolar lavage cell counts rose (75.6 +/- 11.3 x 10(6) versus 10.1 +/- 0.8 x 10(6)) significantly after quartz exposure. In contrast, the percentage of phagocytic AM was significantly (p less than 0.05) reduced (43.5 +/- 5.0% versus 74.2 +/- 1.4%). Flow cytometric measurements revealed the appearance of an AM subpopulation characterized by size/granularity features identical to blood monocytes. Only minimal numbers of these cells were found under normal conditions, but they constituted 50% of the entire AM population in the quartz group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗