Search PubMed⌕ Search

Biomedical subjects

D J White

Publications and source records attributed to D J White.

At least 109 records · Page 6Linked to original sources
PubMed1997

New distribution records of Amblyomma americanum (L.) (Acari: Ixodidae) in New York State.

Amblyomma americanum, commonly called the lone star tick, has been widely-distributed in the southeastern United States for many years. Distribution of this species apparently did not extend to New York State until the 1970s, after which the northern distribution in New York was limited to Long Island (Suffolk and Nassau counties), where it has become locally abundant. Since then, there has been just one published record from New York State, in Westchester County, just north of New York City. From 1988 to 1996, through the Tick Identification Service of the New York State Department of Health, 244 specimens of A. americanum were documented from mammalian hosts in 46 of the 62 New York State counties. These records extend the distribution of A. americanum to several more northern and western New York State counties. With a demonstrated expansion of geographic distribution, continued surveillance of A. americanum is of great public health importance. Besides being a severe pest where abundant, this species is a probable vector of human monocytic ehrlichiosis (HME), and a suspected vector of Borrelia lonestari, the etiologic agent of a Lyme disease-like illness.

Animals↗
PubMed1996

Prevention of hyperacute rejection by human decay accelerating factor in xenogeneic perfused working hearts.

As a potential source of organs for xenotransplantation, pigs that are transgenic for human decay accelerating factor (DAF) have been bred in order to overcome hyperacute rejection. We investigated the protective effect of human DAF in a porcine working heart model perfused by human blood. Hearts of normal landrace pits served as controls. The following parameters were measured: stroke work index, coronary flow and arteriovenous oxygen consumption, 6-keto prostaglandin F1alpha and prostaglandin E2 as markers of endothelial cell activation; creatine phosphokinase and lactate dehydrogenase for evaluation of the extent of myocardial damage; TNFalpha and IL-6 as markers of mononuclear cell activation. Histological and ultrastructural investigations from myocardial tissue sections were done at the end of perfusion. Human (h) DAF appeared to inhibit complement-mediated endothelial cell activation of transgenic pig hearts successfully. This was in contrast to landrace pig hearts, which had a sixfold increase of prostaglandin levels during perfusion with human blood. The cardiac weight increase during perfusion time due to interstitial edema tended to be less in the hDAF group. Myocardial damage was minimal in transgenic hearts, whereas normal pig hearts produced a threefold increase of creatine phosphokinase and lactate dehydrogenase levels. In these hearts, electron microscopy revealed single cell necrosis of myocytes and vacuolization of mitochondria with cristae rupture. According to the results obtained in the working heart model, the breeding of pigs that are transgenic for hDAF represents a promising step to making heart xenotransplantation a clinical reality in the future.

Acute Disease↗
PubMed1996

Cobra venom factor stimulates anti-alpha-galactose antibody production in baboons. Implications for pig-to-human xenotransplantation.

Cobra venom factor (CVF) depletes complement and may therefore be of use in preventing the hyperacute rejection that follows discordant organ xenotransplantation. In two baboons studied, the intramuscular injection of CVF (0.25 mg/kg) was followed by a marked reduction in serum C3 and CH50, and serum cytotoxicity to pig kidney (PK15) cells. There was, however, a very rapid rise in the level of anti-alpha-galactose (alpha Gal) antibody, and a slower rise in anti-CVF antibody. A second intramuscular injection of CVF on day 14 was ineffective in reducing C3, CH50, and serum cytotoxicity. The major oligosaccharide of CVF is known to contain alpha Gal residues, which we suggest stimulate the major increase in anti-alpha Gal antibody level seen in the present study. In the clinical situation, this might lead to an increased immune response to a concomitantly transplanted pig organ.

Animals↗
PubMed1996

Monoclonal antibody to intercellular adhesion molecule-1 reduces cardiac contractile dysfunction after burn injury in rabbits.

Cardiac dysfunction occurs after thermal injury but the pathogenesis is nuclear; leukocytes have been implicated in the pathogenesis of multiorgan dysfunction after burn injury. White blood cell activation and entry into tissue involve the use of a number of adhesion molecules, including intercellular adhesion molecule (ICAM)-1, CD54. We asked the question: will administration of the monoclonal antibody (R6.5) directed against ICAM-1 alter the cardiac dysfunction which we have previously shown to occur after thermal injury? Previously instrumented New Zealand White rabbits were anesthetized and given a full-thickness burn over 30% of the total body surface area by applying brass probes heated to 100 degrees C to the animals' backs for 15 sec. Animals were monitored for 24 hr and given lactated Ringer's (LR) solution (4 cc/kg/% burn, Parkland formula) with additional LR given to maintain cardiac output and urine output. Three experimental groups were studied: sham burn controls had catheters placed and were monitored for 24 hr (N = 8); burn rabbits were divided into vehicle treated (saline, 1 ml/kg, N = 6) or R6.5 treated (2 mg/kg, N = 6). Vehicle or antibody was administered 30 min postburn and every 8 hr until 24 hr postburn; at this time, rabbits were sacrificed and hearts were harvested for in vitro assessment of contractile performance (Langendorff). Compared to values measured in sham burn controls, burn injury caused cardiac contractile depression as indicated by a fall in left ventricular pressure (LVP) (77 +/- 2 vs 56 +/- 3 mm Hg, P = 0.01), +dP/dt (1223 +/- 64 vs 842 +/- 64 mm Hg/sec, P = 0.001), and -dP/dt (973 +/- 63 vs 666 +/- 42 mm Hg/sec, P = 0.01). Administration of R6.5 significantly improved cardiac contractile function compared to the vehicle-treated burns as indicated by higher LVP (67 +/- 2 mm Hg, P > 0.05), +dP/dt (1017 +/- 33 mm Hg/sec, P > 0.05), and -dP/dt (858 +/- 40 mm Hg/ sec, P > 0.05) than values measured in vehicle-treated burns. These results suggest that ICAM-1-mediated WBC activation and/or tissue entry are involved in the pathogenesis of cardiac dysfunction following thermal injury.

Animals↗
PubMed1996

Human and rodent hantavirus infection in New York State: public health significance of an emerging infectious disease.

BACKGROUND: A case of hantavirus pulmonary syndrome with possible exposure in New York and/or Rhode Island was confirmed in February 1994. OBJECTIVE: To conduct four studies to determine the historical and geographic distribution of human and small-mammal infection with hantaviruses in New York State. METHODS: Enzyme-linked immunosorbent assays were performed on serum samples obtained from 130 humans during a 1978 babesiosis survey, 907 small mammals collected in New York State since 1984, 12 rodents collected in 1994 near the residences of the patients with hantavirus pulmonary syndrome, and 76 New York patients with acute respiratory distress syndrome-like illness (as suspected cases of hantavirus pulmonary syndrome). RESULTS: None of the human serum samples from the 1978 serosurvey showed evidence of hantavirus exposure by enzyme-linked immunosorbent assay. Statewide historical serum samples from white-footed mice showed evidence of Sin Nombre virus infection in 12.0% (97/809) and Seoul-like virus infection in 9.6% (78/809). Site-specific seropositivity rates were as high as 48.5% with Sin Nombre virus during 1 year (1984). Two of 12 mice captured near the residences of a human patient were positive for Sin Nombre virus by enzyme-linked immunosorbent assay, yet were negative for viral RNA by polymerase chain reaction. None of the patients with suspected hantavirus pulmonary syndrome was serologically reactive for Sin Nombre virus. CONCLUSIONS: We provide serologic evidence of small-mammal infection with hantaviruses in New York State as long ago as 1984. Human cases of hantavirus pulmonary syndrome are rare in New York, and data indicate that transmission to humans is probably infrequent. A unique set of host, agent, and environmental factors may be necessary to cause hantavirus pulmonary syndrome in humans.

Adolescent↗
PubMed1996

Thrombin inhibition in an ex vivo model of porcine heart xenograft hyperacute rejection.

Prominent components of vascularized xenograft rejection such as platelet activation and microvascular thrombosis may be dependent upon thrombin generation in vivo. To study potential therapeutic benefits of a synthetic low-molecular-weight thrombin inhibitor, SDZ MTH 958, in hyperacute porcine heart rejection by human blood ex vivo, a working model of hyperacute rejection of porcine by fresh, heparinized (6 microM/ml) human blood with or without 1 microM SDZ MTH 958 was used. Thrombin-antithrombin complexes (TAT) and prothrombin fragment F1.2 levels as markers of thrombin activation were determined, and biopsies from rejected hearts were analyzed by immunohistopathology. Control porcine hearts (n=8) underwent a rapid and consistent decline in cardiac output, ceasing function by 60 min. Experimental cardiac output values of 14 ml/g (SEM 1.2) were significantly higher than seen in controls (5 ml/g SEM 0.6) after 5 min of cardiac work, and prolonged survival times up to 120 min were noted (P<0.05). Activity of SDZ MTH 958 was confirmed by functional assays throughout perfusion. Levels of TAT and F1.2 increased consistently in control samples when compared with plasma samples containing SDZ MTH 958. Immunohistopathological examination confirmed diminished fibrin deposition, reduced leukocyte adherence to endothelium, impaired diapedesis and less tissue necrosis in the hearts perfused with SDZ MTH 958. SDZ MTH 958, in this xenoperfusion model, prolonged survival, enhanced function of the explanted organ, and improved histological features at the time of rejection. Effective and specific antagonism of thrombin may be useful as an adjunct therapy to complement inhibition for xenograft rejection

Acute Disease↗
PubMed1996

Cardiac contractile and sarcoplasmic reticulum function after acute ethanol consumption.

Since the contractile status of the myocardium depends on tight regulation of calcium concentrations by the sarcoplasmic reticulum (SR), we investigated the possibility that acute ethanol-induced alterations in the calcium pump function of the SR could contribute to the myocardial depression seen after acute ethanol exposure. In this study, LV function (Langendorff preparation) was significantly reduced after ethanol (ETOH, 2.0 ml/kg, iv) in adult guinea pigs. Compared to control hearts (N = 10), hearts from ethanol-treated animals (N = 10) had significantly lower peak systolic LVP (84 +/- 2 vs 67 +/- 4 mmHg, P < 0.005), +dP/dt max (1175 +/- 54 vs 967 +/- 54 mmHg/sec, P < 0.02), and -dP/dt max (1087 +/- 42 vs 892 +/-52 mmHg/sec, P < 0.02) and at a maximal isoproterenol dose of 30 ng/ml, had lower LVP (150 +/- 5 vs 90 +/- 6 mmHg, P < 0.02), +dP/dt max (3400 +/- 120 vs 180 +/- 40 mmHg/sec, P = 0.001), and - dP/dtmax (2500 +/- 50 vs 1520 +/- 40 mmHg/sec, P < 0.002) than control hearts. SR calcium ATPase activity was not altered by ethanol (control: 70.6 +/- 2.6 micromol/mg protein/hr, N = 10; ETOH: 81.3 +/- 6.9, N = 8). Maximal calcium uptake, however, was decreased by 25% in SR vesicles isolated from ethanol-treated (3.8 +/- 0.27 micromol/mg, N = 10) compared to control hearts (5.1 +/- 0.20, N = 10, P < 0.01). Our data confirm that moderate doses of ethanol depress cardiac contractile function, and our finding that acute ethanol exposure decreased calcium uptake by the SR in the face of no change in calcium ATPase activity suggests that ethanol uncoupled ATP hydrolysis and calcium transport.

Acid-Base Equilibrium↗
PubMed1996

Expression of human decay accelerating factor (hDAF) in transgenic pigs regulates complement activation during ex vivo liver perfusion--immunopathological findings.

Ex vivo perfusions of human decay accelerating factor-expressing transgenic (n = 3), and nontransgenic (n = 6) porcine livers with human blood revealed a higher degree of organ damage in non-transgenic pig livers. Transgenic livers were protected from immunohistologically detectable complement deposition, despite corresponding IgM and IgG deposits in both groups. Complement activation and consumption of C3 and C4 turned out to be lower in transgenic pig livers. In contrast to livers of normal landrace pigs, livers from genetically manipulated pigs showed no morphological alterations after perfusion.

Animals↗
PubMed1996

The function of transgenic human DAF-expressing porcine livers during hemoperfusion with human blood.

Extracorporal pig liver perfusion could bridge the deadly problem of acute human liver failure. However, preformed natural antibodies and complement activation (CA) are the predominant mechanisms of hyperacute xenogeneic rejection. The blockade of both pathways of CA in the xenograft, using transgenic livers expressing human decay accelerating factor on the endothelial surface results in prolonged graft survival and lower release of mediators.

Animals↗
PubMed1996

Evidence for multiple foci of eastern equine encephalitis virus (Togaviridae:Alphavirus) in central New York State.

A regional surveillance system for eastern equine encephalitis (EEE) virus was established in central New York in 1984 after the 2nd human EEE fatality occurred in 1983. Extensive mosquito surveillance activities were coordinated with the rapid laboratory processing of mosquito specimens for EEE virus. Active surveillance for EEE infections in humans and equines also was initiated. Results of long-term surveillance detected the presence of multiple Culiseta breeding swamps. A 6-yr interepizootic period (1984-1989) was followed by 2 yr of equine EEE. In 1990, there were 7 equine cases and a record number of EEE virus isolations from mosquitoes (n = 86), wild birds (n = 27), and sentinel pheasants (n = 7). In 1991, 7 equine cases also occurred, although there were fewer isolations from mosquitoes (n = 40). The sequence to the appearance of EEE virus at swamps and upland sites and at individual swam complexes, and the spatial and temporal distribution of equine cases provide evidence for multiple foci of EEE virus in central New York. The role of infected Culiseta melanura (Coquillett) in the transfer of EEE virus between swamp and upland areas and among swamp complexes is advanced.

Animals↗
PubMed1996

Xenotransplantation.

Xenotransplantation of pig organs into humans represents an attractive solution to the worldwide organ shortage. The survival of pig organs in primates has so far primarily been hampered by hyperacute rejection of the xenograft. The immunological mechanisms which underlie hyperacute rejection have recently been clarified. These important elucidations, together with the introduction of genetic engineering in the field of transplantation, have led to the production of genetically manipulated animals with organs that are now not susceptible to the immunological factors responsible for hyperacute rejection. In this article the recent advances in the understanding of hyperacute rejection are reviewed and the latest biomolecular approaches to overcome hyperacute rejection are described.

Acute Disease↗