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Biomedical subjects

T M Sundt

Publications and source records attributed to T M Sundt.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of a polymorphism of CD4 in miniature swine.

A polymorphism of CD4 in miniature swine has been identified by failure of cells from some animals to react with mAb 74-12-4. The phenotypic, molecular genetic, and functional characteristics of these animals have been defined. Cells from heterozygous animals bear approximately 50% the number of 74-12-4-reactive molecules on their surface as do cells from animals homozygous for the wild type. Animals of both phenotypes demonstrate similar flow cytometric profiles for CD8+ T cells. Northern blot analysis confirms the presence of mRNA for CD4 among PBL of animals failing to stain with 74-12-4. CD4 allelism is confirmed by Southern blot analysis, revealing RFLP. Function of the CD4 subset in vivo, as demonstrated by antibody production against a T cell-dependent Ag, is similar between animals of both phenotypes. Proliferative responses to PHA and alloantigen stimulation by a full haplotype mismatch or a class II mismatch alone are equivalent for animals of both phenotypes. These data suggest that the allelic form of CD4, designated CD4.2 in contrast to the wild-type CD4.1, is capable of performing normally as an accessory molecule in the generation of immune responses. Furthermore, antixenogeneic responses to C57B10.BR were equivalent, suggesting that both CD4 molecular types may be capable of interacting with xenogeneic class II molecules. Although the polymorphism includes differences in exons 3 and 4, regions thought to encode portions of the molecule interacting with MHC class II, these results imply that this naturally occurring CD4 polymorphism does not affect the interaction with class II molecules.

Animals↗
PubMed1992

Influence of coronary heart disease on morbidity and mortality after carotid endarterectomy: a population-based study in Olmsted County, Minnesota (1970-1988)

To evaluate the prognostic importance of coronary artery disease among patients undergoing carotid endarterectomy, 177 residents of Olmsted County, Minnesota who underwent carotid endarterectomy during the period 1970 through 1988 were followed up to July 1, 1989. Patients were stratified as to the presence (n = 64) or absence (n = 93) of overt coronary artery disease or prior myocardial revascularization (n = 20) at the time of endarterectomy. At 30 days after carotid endarterectomy, there were no significant differences between patients with or without coronary artery disease in the occurrence of death, myocardial infarction or stroke. Kaplan-Meier estimate of 8-year relative survival after carotid endarterectomy (assessed as a percent of survival in age- carotid endarterectomy (assessed as a percent of survival in age- and gender-matched control subjects) was 89% in those without and 75% in those with overt coronary artery disease. Of the 59 total deaths, 29 (49%) had a cardiac cause and 4 (7%) were due to stroke (p less than 0.0001). The cumulative incidence of a cardiac event at 8 years after carotid endarterectomy was greater in those with than in those without overt coronary artery disease (61% vs. 25%, p less than 0.0001). In multivariable analysis, uncorrected coronary artery disease and diabetes were the only independent predictors of subsequent cardiac events, whereas age was the only independent predictor of death. These population-based data suggest that carotid endarterectomy can be safely undertaken in patients with stable coronary artery disease. In long-term follow-up of these patients, coronary rather than cerebral vascular disease is the most frequent cause of morbidity and mortality. Thus, these data lend strong support to the concept of early identification and management of coronary artery disease in patients undergoing carotid endarterectomy.

Cohort Studies↗
PubMed1992

Induction of specific tolerance to class I-disparate renal allografts in miniature swine with cyclosporine.

Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag----ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration of an immunosuppressive agent capable of inhibiting lymphokine production during this period to lead to the induction of tolerance to class I MHC antigens in two-haplotype class I mismatched renal allografts (i.e., gg----dd), which are otherwise uniformly and acutely rejected. This hypothesis was tested in eight two-haplotype class I disparate, class II matched donor-recipient pairs, in which recipients were treated with cyclosporine 10 mg/kg, i.v. q.d. for 12 days. This protocol led to the induction of long-term (greater than 100 days) specific tolerance in 100% of recipients, as compared with control animals that rejected grafts in 13.7 +/- 0.9 days (P less than 0.0001). The specificity of tolerance was assessed both in vivo with subsequent skin grafts and in vitro by mixed lymphocyte response (MLR) and cell-mediated lymphocytotoxicity (CML). Survival of donor-specific skin grafts was prolonged compared with skin grafts bearing third-party class I antigens (19.5 +/- 2.0 versus 11.5 +/- 2.0 days, n = 4, P less than 0.05). Tolerant recipients had markedly diminished or absent anti-donor MLR and CML responses, but maintained normal reactivity to third party. Four of eight CsA-treated recipients showed detectable levels of anti-donor IgM, while none demonstrated the presence of anti-donor IgG, which was found in all rejecting controls.

Animals↗
PubMed1992

Patterns of T cell-accessory cell interaction in the generation of primary alloresponses in the pig.

Partially inbred, MHC-homozygous miniature swine provide a unique model for the study of organ transplantation and the induction of tolerance in large animals. Models of both vascularized solid organ transplantation and bone marrow transplantation have previously been established. The availability of monoclonal antibodies reactive with porcine leukocyte subset antigens now makes possible studies of the cellular immunology in this species, affording the opportunity to examine mechanisms of transplant tolerance and graft rejection in increasing detail. Using such antibodies and peripheral blood leukocytes from pigs of recombinant MHC haplotypes, we have examined porcine T cell-accessory cell interactions in vitro with attention to T cell subsets and the class of MHC alloantigen stimulation. Primary allospecific MLR and CML cultures were studied after depletion of accessory cells from responder and/or stimulator populations. Although class II MHC antigens were expressed on the majority of porcine T cells before and after depletion, these cells were insufficient for antigen presentation, since there was an absolute requirement for ACs in the generation of primary alloresponses. Proliferative and CTL alloresponses could be generated provided that ACs of either stimulator or responder type were present. Selective depletion of CD4+ T cells from the responder population demonstrated: (a) that the interaction mediated by self ACs was CD4-dependent; (b) that two pathways exist for interaction involving allogeneic ACs; and (c) that the interaction involving allogeneic class II is CD4-dependent, while that with allogeneic class I is not.

Animals↗
PubMed1992

Reduced production of cGMP underlies the loss of endothelium-dependent relaxations in the canine basilar artery after subarachnoid hemorrhage.

Endothelium-dependent relaxations are inhibited during chronic vasospasm after subarachnoid hemorrhage in the canine basilar artery, although the luminal release of endothelium-derived relaxing factor (EDRF) is maintained. The present study investigated the mechanisms underlying the impaired vascular reactivity and in particular whether the loss of responsiveness of the smooth muscle to EDRF is due to an impaired production of cGMP. Bradykinin and nitric oxide evoked concentration-dependent relaxations in isolated canine basilar arteries with and without endothelium, respectively, which were reduced in the subarachnoid hemorrhage group. Relaxations evoked by M&B22,948 (an inhibitor of cGMP phosphodiesterases) were smaller, but those evoked by the lipophilic cGMP analogue 8-bromo-cGMP were potentiated slightly in the subarachnoid hemorrhage group. The resting levels of cGMP in rings with endothelium (reflecting the effect of spontaneous release of EDRF) and those evoked by bradykinin in rings with endothelium and by nitric oxide in rings without endothelium were diminished in the subarachnoid hemorrhage group. These data indicate that the altered endothelium-mediated relaxations of the smooth muscle after subarachnoid hemorrhage is due, at least in part, to an impaired activation of soluble guanylate cyclase leading to a reduced production of cGMP in the smooth muscle.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

High-energy phosphate levels in the cerebral artery during chronic vasospasm after subarachnoid hemorrhage.

High-energy phosphate levels were measured in the canine cerebral artery during chronic vasospasm. Subarachnoid hemorrhage and vasospasm were induced by percutaneous injections of autologous venous blood into the cisterna magna. Narrowing of the artery was confirmed by angiography 7 days later. Levels of adenosine phosphates (adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP)), guanosine phosphates (guanosine triphosphate (GTP) and guanosine diphosphate (GDP)), and creatine phosphate (CrP) in the basilar artery were quantified using high-performance liquid chromatography. The total creatine (Crtotal) content was measured by a spectrophotometric method after acid hydrolysis of CrP. Levels of ATP, GTP, and CrP were markedly reduced in the spastic arteries, and ratios of ATP:ADP, GTP:GDP, and CrP:Crtotal were significantly decreased. The results indicate a serious disturbance in the energy metabolism that takes place in the cerebral artery during chronic vasospasm.

Adenosine Diphosphate↗
PubMed1991

Intracranial cerebrovascular vasa vasorum associated with atherosclerosis and large thick-walled aneurysms.

Atherosclerotic plaques that develop in the extracranial circulation are usually extensively vascularized by vasa vasorum. However, human vasa vasorum associated with intracranial atherosclerosis has not been adequately addressed. Anterior and posterior circulation specimens from fresh autopsy material were studied under the magnification of a dissecting microscope and proliferative vasa vasorum was found to be frequently associated with intrinsic atheromatous plaques. Vasa vasorum associated with an incidental large aneurysm supports the radiological literature demonstrating that many large and giant thick-walled aneurysms exhibit vascularized walls on contrast computed tomography scans. This information may aid in the preoperative assessment and possible repair of these aneurysms.

Adolescent↗
PubMed1991

The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity.

Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine.

Animals↗
PubMed1979

Spontaneous internal carotid dissection, hemicrania, and Horner's syndrome.

We describe five patients with angiographic features of dissecting aneurysm of the cervical portion of the internal carotid artery who were seen initially with unilateral headaches and ipsilateral oculosympathetic paresis. This combination of symptoms is a rather common mode of manifestation of this entity.

Adult↗
PubMed1979

Intracellular redox states under halothane and barbiturate anesthesia in normal, ischemic, and anoxic monkey brain.

Cortical reflectance, mean arterial blood pressuees, electroencephalograms, and cortical blood flow were continuously recorded together with fluorescence of reduced pyridine nucleotides (PN) at various carbon dioxide tensions before, during, and following middle cerebral artery occlusion in 10 squirrel monkeys receiving halothane or babiturate anesthesia. Measurements were continued through a nitrogen breathing cycle and to death produced by anoxia. The anesthetic agent produced no detectable differences in PN fluorescence in cerebral tissue during ischemia and anoxia. The known cerebral protective action of barbiturates is apparently unrelated to the intracellular redox state.

Animals↗
PubMed1979

Surgical approach to giant intracranial aneurysms. Operative experience with 80 cases.

The authors report experience with the surgical management of 80 giant intracranial aneurysms (greater than 2.5 cm in diameter) during a 10-year period in which they performed 594 operations for aneurysms. The overall incidence of giant aneurysms was 13% but varied according to location: 20% of aneurysms of the internal carotid artery (ICA); 13% of middle cerebral artery (MCA) aneurysms; 1% of anterior cerebral artery (ACA) aneurysms; 15% of aneurysms of the basilar artery caput (BAC); and 18% of vertebrobasilar trunk (VB) aneurysms. Twenty-five patients had a subarachnoid hemorrhage (SAH), 49 had mass effect from the aneurysm, and six had ischemic events. There was no apparent difference in results related to the presence or absence of an SAH. Poor results were attributable to the operation except in the two cases of ACA aneurysm in which preexisting dementia persisted. Mortality was 4% and morbidity was 14%, varying from a combined low morbidity-mortality of 8% for ICA lesions to a high to 50% for BAC aneurysms. During the period of the study, different techniques were developed in an attempt to lower the risks of surgery. Ultimately ICA aneurysms were monitored with cerebral blood flow measurements and electroencephalography before and after temporary ICA ligation, then approached following resection of the anterior clinoid or treated with bypass in combination with ICA ligation. Aneurysms of the MCA were either opened during temporary MCA occlusion or resected in combination with a bypass procedure. Bypass grafts and circulatory arrest with extracorporeal circulation may have a role in giant aneurysms of the posterior circulation.

Brain Ischemia↗
PubMed1979

Arteriovenous malformation affecting the transverse dural venous sinus--an acquired lesion.

Dural arteriovenous malformations of the transverse sinus are relatively well localized to the occipitomastoid regions and occur predominantly in women who are more than 40 years of age. The signs and symptoms, except for pulsatile tinnitus, vary and apparently depend on the presence of impaired venous drainage, which may produce increased intracranial pressure, papilledema, and transient or persistent neurologic deficits. Eight of the 14 patients described had occlusion of one or both transverse or sigmoid sinuses. Two patients had angiographic demonstration of sigmoid or transverse sinus occlusion (one 1 year and the other 4 years) before the development of an arteriovenous malformation in the appropriate sinus. Dural sinus occlusion may precede the development of a dural arteriovenous malformation, and the pathogenesis may be partial recanalization of a thrombus.

Adult↗
PubMed1979

The ocular aspects of bypass surgery of the carotid artery.

A new neurosurgical procedure, anastomosis of the superficial temporal artery to the middle cerebral artery, is being performed with increasing frequency. Over a 7-year period (1971 through 1977), 121 patients have undergone this operation in our institution. Ophthalmodynamometry may be of great help in identifying occlusion of an internal carotid artery. Progressing venous stasis retinopathy and ischemic orbital pain are believed to be indications for bypass surgery of the carotid artery.

Arterial Occlusive Diseases↗