Biomedical subjects

S Nakeeb

Publications and source records attributed to S Nakeeb.

16 recordsLinked to original sources

PubMed2004

Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heatstroke.

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory and hemostatic responses to heat stress, suggesting that immunomodulation may improve outcome. We postulated that an experimental baboon model of heatstroke will reproduce human responses and clinical outcome to allow testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio hamadryas) were subjected to heat stress in an incubator maintained at 44-47 degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0 and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic inflammation and activated coagulation, indicated by increased plasma IL-6, prothrombin time, activated partial thromboplastin time, and D-dimer levels, and decreased platelet count. Biochemical markers and/or histology evidenced cellular injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase, lactic dehydrogenase, and alanine aminotransferase were increased, and varying degrees of tissue damage were present in liver, brain, and gut. No baboon with severe heatstroke survived. Neurological morbidity but no mortality was observed in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater coagulopathy, inflammatory activity, and tissue injury than survivors. Sham-heated animals had an uneventful course. Heat stress elicited distinct patterns of inflammatory and hemostatic responses associated with outcome. The baboon model of heatstroke appears suitable for testing whether immunomodulation of the host's responses can improve outcome.

Animals↗

PubMed2000

Intraoral distraction osteogenesis in the baboon mandible using a tooth and bone-anchored appliance.

PURPOSE: The purpose of this study was to determine the feasibility of using an intraoral, bone and tooth-anchored appliance to distract baboon mandibles using the principles of distraction osteogenesis (DO). MATERIALS AND METHODS: Seven juvenile baboons were used in this study. Mandibular corticotomies were made in the ramus of the mandible unilaterally (n = 5) or bilaterally (n = 2), and a "pin-in-tube" (PIT) distraction appliance was applied. The device was secured to the mandibular ramus posterior to the cortical cut with a bicortical screw and anteriorly to an occlusal splint. The appliance was activated an average of 0.86 mm/d (0.5 to 1.3 mm/d) for an average of 12.4 days (10 to 14 days). Predistraction and postdistraction measurements were made between metallic markers placed in the distraction area, in the dental midline, and of the overjet and overbite. RESULTS: Bone healing was complete in all mandibles. The average mandibular lengthening measured between the metallic markers was 7.9 mm. The mandibular midlines showed an average of 4.25 mm of lateral movement in the unilaterally distracted mandibles. There were no infections. CONCLUSIONS: The results of this study indicate that an intraoral bone and tooth-anchored distraction appliance is an effective method to produce lengthening in the mandible by distraction osteogenesis.

Animals↗

PubMed2000

Evaluation of a new device for quick sutureless coronary artery anastomosis in surviving sheep.

OBJECTIVE: A new device for performing quick sutureless vascular anastomosis by means of stent technology has recently been developed by Jomed International, Helsingborg, Sweden. The efficacy of this GraftConnector was studied in a sheep model. METHODS: In adult sheep, a left anterior thoracotomy under the fourth rib extended across the sternum gave good access to the left anterior descending branch (LAD) and the right internal mammary artery (RIMA). On beating hearts, the GraftConnector group had the RIMA connected to the LAD by means of the new device, while the control animals had the same anastomoses sutured with continuous 7-0 polypropylene sutures. The time for completing the anastomosis (ischemic time) was recorded and the blood flow in the RIMA was recorded with the proximal LAD open and closed, respectively. An intra-operative fluoroscopy with contrast injection directly into the graft was done. Finally the proximal LAD was ligated. The surviving animals are to be followed up. RESULTS: Seven (46%) of the 15 animals operated on with the traditional suturing technique and seven (63%) of the 11 GraftConnector sheep survived the procedures and are to be followed up. The 11 anastomoses done with the GraftConnector were completed in 2.41+/-0.2 min, and the 14 anastomoses sutured with continuous suture were completed in 6.93+/-0.419 min (P<0.0001). The RIMA blood-flows in the two groups were comparable and are presented. All the surviving animals had open anastomoses at fluoroscopy. CONCLUSIONS: Quick coronary artery anastomoses without suturing on beating hearts can be completed with the new GraftConnector. The GraftConnector creates reproducible anastomoses in much less time than suturing, the per-operative mortality in the GraftConnector Group was accordingly lower. Long-time follow-up of the patency in surviving animals is pending. The presented device may ultimately permit quick anastomoses endoscopically.

Anastomosis, Surgical↗

PubMed1995

Retrovirus-induced lymphoproliferative disease in mice: role of humoral immunity in perinatally exposed mice.

The mice born to female mice infected with LP-BM5 MuLV, the etiologic agent for lymphoproliferative disease and nursed for 4-6 weeks by them were less susceptible upon reinfection by i.v. transfusion of blood or plasma from infected donors with fully developed disease. Sera of 7 week or older perinatally exposed mice were capable of a complete in vitro neutralization of virus in plasma or blood from mice with fully developed disease. In contrast, sera from 3-week old perinatally exposed mice were ineffective. The neutralizing ability of the sera was drastically reduced or abrogated after their absorption with anti-mouse IgM. These observations are consistent with the notion that perinatally exposure results ina moderate form of the disease of the offspring. This perinatal infection is followed by a production of neutralizing antibodies of predominantly the IgM class that significantly alters the course of the lymphoproliferative disease and, in some instances, even prevents its development.

Animals↗

PubMed1995

Retrovirus-induced lymphoproliferative disease in mice undergoing graft-versus-host reaction.

The effect of graft-versus-host reaction on the course of concommitant retrovirus-induced lymphoproliferative disease was investigated. The graft-versus-host reaction was elicited by a single i.v. injection of 1.2 x 10(8) parental spleen cells into adult F1 mice. Lymphoproliferative disease was induced by a single transfusion of 0.2 ml of whole blood from donors with fully developed disease, induced by infection with retrovirus LP-BM5 MuLV. Graft-versus-host reaction and the lymphoproliferative disease each separately produced similar syndrome consisting of splenomegaly, lymphadenopathy, leukopenia, neutrophilia, reduced in vitro proliferation of spleen cells and suppression of in vivo immune responsiveness. The above symptoms were usually less pronounced during graft-versus-host reaction. Ongoing graft-versus-host reaction neither aggravated nor accelerated the course of the virus-induced lymphoproliferative disease in genetically susceptible F1 hybrids. Likewise, an ongoing graft-versus-host reaction in genetically resistant F1 hybrids did not alter their susceptibility to the retrovirus infection. The apparent lack of the effect of graft-versus-host reaction -dependent immunosuppression on the severity and the course of the concommitant retrovirus-induced lymphoproliferative disease suggests pathogenic differences between the murine syndrome and human AIDS for which the murine disease is considered by some to be an animal model.

Animals↗

PubMed1995

Quantative aspects of transfusion-transmitted retrovirus-induced lymphoproliferative disease in mice.

Healthy, adult C57BL/6Kh mice of both sexes were transfused with blood or blood products from syngeneic donors with retrovirus (LP-BM5)-induced lymphoproliferative disease. The disease produced in the recipients 8 weeks after transfusion was characterized by splenomegaly, disseminated lymphadenopathy, leukopenia with neutrophilia, abrogation of the primary immune response to SRBC, decreased in vitro proliferation of spleen cells co-stimulated with phorbol ester and IL-2 or ionomycin and abrogation of synergistic effect of the co stimulators. Quantitative analysis of the blood or blood products used for transfusion show that a single transfusion of 0.2 ml of PBS containing 0.2 mu 1 of whole blood or 2 microliters of plasma or 400 Ficoll-isolated peripheral blood mononuclear cells was sufficient for the inducing the disease. The results suggest that the retroviruses were present in preparations of peripheral blood mononuclear cells and plasma of mice with the disease. However, the latter was 10-fold less efficient in inducing the disease. Transfusion of 1.8 x 10(6) isolated erythrocytes failed to induce the disease suggesting a marginal role, if any, in transmission of the disease via transfusion of these cells. Thus, a simple, reliable and reproducible method for propagation of the murine lymphoproliferative disease in the laboratory has been elaborated. These results also point to some important differences with regard to blood transfusion between human and murine AIDS.

Animals↗

PubMed1994

Murine AIDS: a model for the human disease or a distinct entity?

The LP-BM5 mixture of murine retroviruses elicits a disease in mice referred to as murine immunodeficiency syndrome (MAIDS) that is considered by some to be an animal homologue of human AIDS. In this article, we present and discuss some recent findings on the pathogenesis of the murine disease and their implications for the proposed homology between murine and human syndromes. The murine disease seems to display as many similarities to as it does differences from human AIDS. Among the latter are: definitive and exclusive viral etiology, a strong genetic effect on susceptibility to infection, expansion of the CD4+ cell population in spleen and peripheral blood, consistent transmissibility by a single transfusion of the minute amounts of blood or plasma from infected donors, and striking similarity between virus-induced alteration of the in vitro spleen cell proliferation and those caused by treatment with a protein kinase inhibitor K252a. With this in mind, the use of the noncommittal term retrovirus-induced murine lymphoproliferative disease instead of MAIDS appears to be more appropriate at this time.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Acquired immunodeficiency in murine lymphoproliferative disease: considerations on pathogenesis.

C57BL/6Kh mice were infected with a single i.p. injection of 1 x 10(5) FFU of LP-BM5 MuLV. The development and progress of the virus-induced lymphoproliferative disease was followed for 12 weeks after infection. As anticipated, progressive splenomegaly and lymphadenopathy, as well as almost total abrogation of immune responsiveness ensued. In contrast to previous reports, there was a dramatic increase in the frequency of CD4+ cells in spleens among which over 20% expressed V beta 5 TCR, as compared with fewer than 3% in spleens of normal mice. Spleen cells from infected mice retained their in vitro ability to proliferate upon stimulation with IL-2 and anti-CD3, but were unable to respond when stimulated with phorbol ester and either a low dose of IL-2 or calcium ionophore (ionomycin). A similar pattern of in vitro proliferative responses was obtained when normal spleen cells were treated with K252a compound, a known inhibitor of protein kinase C activity. Together with the observations that viral infection impaired down-regulation of the phorbol-induced kinase activity and that the kinase inhibitor only marginally enhanced suppression of virus-infected cells proliferation, this finding suggests that disturbances of protein kinase C activity may underly the pathological effects seen after viral infection. However, since no apparent quantitative and qualitative changes in protein kinase C itself and its translocation were observed, it is more likely that the virus may interfere with either the substrate or product of kinase activity.

Animals↗

PubMed1994

Blood transfusion as a means for transmission of retrovirus-induced lymphoproliferative disease in mice.

Lymphoproliferative disease was elicited in C57BL/6KH and (BALB/c x C57BL/6)F1 hybrids by a single intraperitoneal injection of 10(5) FFU of LP-BM5 virus preparation. The disease could reproducibly be transferred by a single intravenous transfusion of 0.2 ml of whole blood as well as 0.1 ml of blood cells, plasma or serum from the infected animals. F1 hybrids displayed a delayed development of the disease when an acellular virus preparation was administered, but they were fully susceptible to the disease when syngeneic blood from infected F1 donors was transfused. Blood from donors in the prodromal stage was as effective in transmission of the disease as blood from donors with fully developed disease. This indicated that in murine lymphoproliferative disease viremia develops very early in the course of the disease. It seems that using the blood transfusion one could develop a reliable semiquantitative assay for the infectiveness of the animals suffering from LP-MB5-induced lymphoproliferative disease.

Animals↗

PubMed1994

Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS.

C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Experimental congenital syphilis: guinea pig model.

Neonates born to female guinea pigs of either a highly susceptible (C4D) or a resistant (Albany) strain, infected prior to or during pregnancy with a single dose of Treponema pallidum, showed in their sera from the first day of life immunoglobulin M (IgM) antibodies to T. pallidum, circulating immune complexes consisting of IgM antibodies and treponemal antigens, and IgM rheumatoid factor. Although the animals were asymptomatic for a 6-month observation period, several lines of evidence indicated that they were infected in utero. Molecular analysis of whole sera, purified serum IgM fraction, or dissociated immune complexes demonstrated IgM reactivity against one (47 kDa) or more of several T. pallidum peptides (15, 17, 37, 42, 45, and 87 kDa) recognized as integral membrane components. Sequential analysis of the neonates' sera by immunoblot and enzyme-linked immunosorbent assay, using alcohol-treated T. pallidum, T. phagedenis biotype Reiter, and T. vincentii, demonstrated early IgM antibodies followed 3 to 4 months later by IgG2- and IgG1-specific antibodies to T. pallidum. Moreover, an infectivity test done in five rabbits with pooled tissue extracts prepared from liveborn or stillborn animals evoked a seroconversion in two rabbits (reactive Venereal Disease Research Laboratory and fluorescent treponemal antibody tests), suggesting the presence of T. pallidum in the organs. Sera from neonates born to either T. phagedenis biotype Reiter-injected mothers or three normal pregnant females were all serologically negative. The model offers new possibilities for exploration of factors responsible for asymptomatic infection often observed in human congenital syphilis.

Animals↗

PubMed1990

Experimental neonatal syphilis in a susceptible (C4D) and a resistant (Albany) strain of guinea pig.

Despite similar levels of natural antibodies and treponemicidal activity, 83% of fourth complement component-deficient (C4D) mother guinea pigs developed ulcerative lesions to a challenge of 5 x 10(7) Treponema pallidum, whereas 75% of offspring 1 to 5 days old were temporarily (2-3 months) resistant to development of dermal lesions. In contrast, only 17% of Albany-strain mothers developed small papular lesions, while 68% of 1- to 5-day-old newborns developed large papular or ulcerative lesions within 9-15 days postinfection. These findings, together with the late development of both dermal lesions and antibodies in C4D neonates, preclude the concept of an antibody-associated natural resistance. T. pallidum infection in either C4D or Albany neonates was not associated with depletion of any particular cell population in lymphoid tissue. However, marked age- and strain-dependent histologic differences were noted. Histologic examination of lymph nodes and spleens from 17-day-old and 3- to 4-month-old animals showed that maturation of lymphoid tissues in C4D animals lagged behind the Albany strain at either age. Moreover, 75% of C4D newborns contained significantly higher levels of immunomodulatory alpha 1 fetoprotein than Albany neonates. The possibility that differences in susceptibility to T. pallidum infection between C4D and Albany guinea pigs as neonates and again as adults is the result of genetically associated changes in immunologic recognition is discussed.

Animals↗

PubMed1988

Effect of irradiation and depletion of C3-complement component on the course of Treponema pallidum infection in a resistant guinea pig strain.

The role of complement and ionizing radiation in the natural resistance to Treponema pallidum infection of Albany guinea pigs was explored. Depletion of C3 by cobra venom factor for a period of 14 days affected neither the host's susceptibility to infection nor the humoral response. Total body irradiation with 420 or 800 R was fatal within 20-30 days and there was no multiplication of treponemes in the infected host. Animals showing lethal signs were euthanized and tissues removed for examination. Exposure to a nonlethal dose of 300 R increased the susceptibility to infection (46% symptomatic lesions) and facilitated multiplication of treponemes at the site of inoculation and in the lymphoid organs, but the humoral response was not different from that of non-irradiated controls. The results seem to suggest a defect in antigen recognition by the immunocompetent cells in the resistant Albany guinea pigs.

Animals↗

PubMed1988

The toxicity and mutagenicity of S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (IBZM), a new CNS D-2 dopamine receptor imaging agent.

IBZM is one of several benzamide derivatives showing a high affinity for the CNS D-2 dopamine receptor. Carrier-free [123I]IBZM is potentially useful as a nuclear medicine imaging agent for investigating CNS D-2 dopamine receptor in humans. This study describes the acute toxicity of IBZM in the rat and rabbit, its subchronic toxicity in the rabbit and its mutagenicity measured by the Ames test. IBZM had a 24 hour LD50 of 400 mg/kg in the rat and 50 mg/kg in the rabbit when administered i.v. Deaths occurred within minutes of dosing. Some necrosis was evident at the injection site in IBZM treated animals which was not found in the controls. No gross or histological differences between experimental animals and controls were evident in surviving animals when necropsied 14 days after dosing. Repeated exposure of rabbits to IBZM at a total cumulative dose of 100,000 times the expected clinical dose revealed no consistent changes in hematology, blood chemistry, blood enzymes or tissue pathology. IBZM was not mutagenic in the modified Ames assay with or without metabolic activation in the TA98 and TA100 tester strains. It is therefore unlikely that acute adverse effects will be associated with the diagnostic use of this drug in man.

Animals↗

PubMed1983

Experimental syphilis: guinea pig model.

Outbred Hartley male guinea pigs (300-400 g) were infected intradermally with various concentrations of Treponema pallidum Nichols strain in the pubic region. The median lethal dose (ID50) was approximately 10(5). The animals produced lesions visible by darkfield microscopy, treponemal antibodies (IgG only), and histopathological changes in the lymphoid organs. Though less susceptible to T pallidum infection than the rabbit when infected with a sufficient number of organisms, the guinea pig may be a useful model in experimental syphilis.

Animals↗

PubMed1977

Chronic cutaneous candidiasis in bottle-nosed dolphins.

In a 20-month period, generalized chronic cutaneous candidiasis developed in 3 performing bottle-nosed dolphins kept in an indoor pool. Extensive esophagogastric ulcerations were observed in 2 of the dolphins, each of which died, presumably because of these lesions. The 3rd dolphin died during a surgical procedure and did not have any esophagogastric ulcerations. Candida albicans was the only organism isolated from skin lesions but was not isolated from adjacent normal skin of dolphins. Treatment with antifungal drugs was unsuccessful. Subsequently, immunopotentiating treatment with levamisole phosphate resulted in formation of granulation tissue and healing of the skin lesions.

Animals↗