PubMed Health⌕ Search

Biomedical subjects

N A Parfrey

Publications and source records attributed to N A Parfrey.

33 records · Page 2Linked to original sources
PubMed1989

Immunologic and genetic studies of diabetes in the BB rat.

The spontaneous development of diabetes in the Bio-Breeding (BB) rat is an excellent model of human insulin-dependent diabetes mellitus (IDDM). Disease expression is dependent on several genetically determined abnormalities, including specific major histocompatibility complex (MHC) genes. At least one MHC class II locus of the U haplotype is a necessary, but not sufficient, condition for disease expression. The immune system of BB rats is markedly abnormal. There is a striking reduction in the number and function of mature cytotoxic/suppressor T cells, a poor proliferative response to mitogens and in mixed lymphocyte culture, poor interleukin-2 production, and a reduced ability to reject skin allografts. While these immune system abnormalities are closely related to the development of diabetes, the immune recognition and effector mechanisms resulting in islet cell destruction are still poorly understood. The hypothesis that MHC class II induction on pancreatic beta cells serves to target these lymphokines, natural killer (NK) cells, macrophages, etc.) have been implicated in islet cell killing. The incidence of IDDM is reduced by immunosuppressive therapy in both rats and humans, further supporting the role of immune mechanisms in this disease.

Animals↗
PubMed1989

Evidence that nonlymphoid tissue injury in acute graft-versus-host disease is limited to epithelial cells aberrantly expressing MHC antigens.

To explore the relationship between aberrant MHC antigen expression and tissue injury in acute graft-versus-host disease, we performed a sequential histological and immunohistochemical analysis of multiple tissues in acute GVHD generated across complete MHC and multiple minor H incompatibilities in the rat. Two patterns of MHC antigenic modulation were recognized. Aberrant MHC class I and class II antigen expression occurred simultaneously on the epithelial cells of nonlymphoid target tissues early in acute GVHD. This coincided with a lymphoproliferative phase that preceded nonlymphoid tissue injury. The extent of epithelial class II antigen induction predicted the extent of subsequent histological injury. Changes in MHC class II antigen expression were also seen on nonepithelial cells. Interstitial dendritic cells (IDCs) expressing recipient MHC class II antigens increased in both target and nontarget tissues during early GVHD. Recipient class II antigens were also induced on large numbers of microglialike cells in the brain and Kupffer cells in the liver. However, tissue injury did not follow MHC class II antigen induction on nonepithelial cells. These findings are consistent with a role for aberrant epithelial MHC antigen expression in nonlymphoid tissue injury in acute GVHD.

Animals↗
PubMed1988

Autoimmunity-prone BB rats lack functional cytotoxic T cells.

BB rats are prone to develop an autoimmune form of insulin-dependent diabetes mellitus (IDDM) and thyroiditis. Development of autoimmunity is thymus dependent. Previous studies have shown that BB rats lack a population of T cells bearing the RT6 antigen and have very low numbers of suppressor/cytotoxic T cells. In this study, we confirm that BB rats have decreased numbers of phenotypic T suppressor/cytotoxic (Ts/c) cells (OX19+, OX8+ cells) in their lymphoid organs. Moreover, we find that the phenotypic Ts/c cells of BB rats lack apparent cytotoxic activity. These T cells fail to kill allogeneic target cells in a cell-mediated lympholysis assay and fail to generate lectin-dependent cytotoxicity. The addition of interleukin 2, gamma-interferon, and other lymphokines to cultures of BB T cells does not induce functional cytotoxic T lymphocytes. We find that the activated T cells of newly diabetic rats are incapable of killing major-histocompatibility-complex-matched islet cells, despite the ability of these cells to cause IDDM in passive transfer experiments. We conclude that autoimmune disease occurs in BB rats in the absence of functional cytotoxic T cells.

Animals↗
PubMed1986

Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection.

To determine the pattern of cellular expression of donor MHC class I and class II antigens during the course of rat cardiac allograft rejection, ACI cardiac allografts transplanted to BN recipients were examined from day 2 to day 6 using immunohistologic and immunoelectron microscopic methods. We used both monomorphic and donor-specific mouse anti-rat MHC class I and class II mAbs in this study. In normal ACI hearts, MHC class I reactivity was confined to the vascular endothelium and to interstitial cells. Ongoing rejection was characterized by an increased donor MHC class I staining intensity of microvascular endothelium and induction of donor class I surface reactivity on cardiac myofibers. Donor MHC class II reactivity was exclusively confined to interstitial dendritic cells (IDC) in both normal ACI hearts and in rejecting allografts, although rejection was associated with marked fluctuations in class II IDC frequency. An early numerical depression in class II IDC present in both allografts and syngeneic heart grafts was attributed to a direct effect of the transplantation procedure. By days 3-4, allografts showed an absolute overall increase in donor class II IDC frequency, which was associated with the presence of multiple localized high-density IDC-lymphocyte aggregates. The lymphocytes present in the focal areas were predominantly of the class II-reactive Th cell subpopulation. These aggregates may thus represent the in vivo homologue of dendritic cell-lymphocyte clustering, which has been shown to be required for primary class II allosensitization in the rat and mouse in vitro. During the late phase of rejection, there was a marked numerical fall in donor class II IDC, which correlated with extensive overall graft destruction. This study has shown that acute rat cardiac allograft rejection can occur in the absence of donor MHC class II expression by allograft vascular endothelium and cardiac myofibers. The IDC, which are believed to represent the principal class II alloantigen presenting cells in the rat heart, remain the sole class II-expressing cellular constituents of the graft throughout the course of rejection.

Animals↗
PubMed1986

Hepatic fibrosis in the mucopolysaccharidoses.

The mucopolysaccharidoses are a group of clinically progressive, heritable, lysosomal storage disorders. Many organ systems are affected due to widespread accumulation of incompletely degraded mucopolysaccharide. The novel finding of hepatic fibrosis in each of six cases of mucopolysaccharidosis examined at autopsy (including examples of Hurler syndrome, Hunter syndrome, and Sanfilippo syndrome) is described. In each instance, the liver was diffusely involved by fibrosis that outlined the lobules, and there was extensive hepatocyte and Kupffer cell vacuolization. The pattern of hepatic fibrosis is not explained by either cardiac failure or drug toxicity. It is hypothesized that the hepatic fibrosis is due to the abnormal accumulation of a hepatotoxic metabolite. The frequency and severity of liver disease in the mucopolysaccharidoses deserve further study. In particular, with the advent of bone marrow transplantation as therapy for some of the mucopolysaccharidoses, the question of whether cirrhosis develops in these patients and, if so, what its rate of progression is, should be addressed.

Adolescent↗
PubMed1986

Improved diagnosis and prognosis of mucormycosis. A clinicopathologic study of 33 cases.

Mucormycosis is an uncommon, frequently fatal, fungal infection which rarely arises in otherwise healthy people (15, 18, 92). An underlying disease, frequently diabetes mellitus, is almost always present. It appears stereotypically in different anatomic sites: paranasal, rhinoorbital, rhinocerebral, cerebral, pulmonary, and gastrointestinal areas; and in the soft tissue of the extremities. It can also appear as disseminated disease. Tissue invasion by the hyphae of mucormycosis must be seen microscopically to establish the diagnosis, but culture is required to identify the fungal species involved. A study of 33 cases seen in one hospital over five decades suggests that the incidence of this infection is increasing. There has been a dramatic improvement in outcome, which has been paralleled by a major shift from postmortem to premortem diagnosis. Premortem diagnosis gives the opportunity for metabolic stabilization, surgical excision, and amphotericin-B therapy appropriate to this disease.

Adolescent↗
PubMed1986

The decreased incidence of aseptic necrosis in renal transplant recipients--a case control study.

Before 1971 the incidence of aseptic necrosis in renal transplant recipients was 29%, and after 1971 it was 5%. To investigate the reasons for this decreased incidence and to elucidate the causes of aseptic necrosis we studied all 26 transplant patients with aseptic necrosis and 42 controls matched for year of transplantation, age, and sex. Development of aseptic necrosis was not related to duration of dialysis before transplant, severity of uremia at the time the patient started dialysis, adequacy of dialysis before transplantation, transplant dysfunction at the time aseptic necrosis was diagnosed, hyperparathyroidism before or after transplantation, lack of Vitamin D supplementation after transplantation, or fatty infiltration of liver. Total steroid dose 1 month after transplantation was actually lower in aseptic necrosis compared with the control group (2.47 +/- 0.3 g vs. 3.6 +/- 0.3 g SEM g) and was similar after 4 months (6.72 +/- 0.55 g vs. 7.14 +/- 0.6 g), as were total numbers of i.v. doses of methylprednisolone or hydrocortisone. However, blood urea nitrogen (BUN) during the dialysis period was significantly higher in the aseptic necrosis group. Of the aseptic necrosis group, 27% had a previous transplant compared with 5% of controls. Half the aseptic necrosis group (5/10) had parenchymal iron on liver biopsy one year after transplant compared with 15% (2/13) of those without aseptic necrosis. Patients transplanted before 1971 (with and without aseptic necrosis) received significantly more i.v. hydrocortisone and less i.v. methylprednisolone, had higher BUN levels at the time of starting dialysis, and had lower serum calcium and higher serum phosphate at transplantation compared with patients transplanted in or after 1971. The incidence of aseptic necrosis following transplantation has decreased during the past 13 years for reasons that are unclear. Risk factors for aseptic necrosis may include previous transplantation, severe iron overload that may lead to marrow fibrosis and osteopenia, and increased protein catabolism/turnover during dialysis.

Adult↗
PubMed1985

Malignant large cell lymphoma of B-cell type with multilobated nuclei. Report of a case and review of the literature.

Malignant lymphomas with multilobated nuclei are rare, recently recognized neoplasms of the immune system initially thought to be of T-cell type. Reported is a case of large cell lymphoma with multilobated nuclei in which immunologic marker studies demonstrated that the neoplastic cells had characteristics of B-lymphocytes. The neoplastic cells possessed surface and cytoplasmic immunoglobulin of the IgG, lambda type, and stained diffusely with monoclonal antibodies to B1, Leu-10 and OKIaI antigens and focally with anti-B2. The lymphoma cells did not react with monoclonal antibodies directed against T-cells and monocytes/granulocytes. As documented here with multiple monoclonal antibody lymphocyte markers, the multilobated lymphoma can have a B-cell phenotype as well as the cell phenotype described previously. Thus, even the unique finding of multilobated nuclear morphologic features is unreliable in predicting the lymphocyte lineage.

Adult↗
PubMed1985

Elastosis in benign and malignant breast disease.

Elastosis, the presence of clumps of elastic fibers, is known to occur frequently in association with breast carcinoma. To test the hypothesis that the degree of elastosis increases progressively in fibrocystic disease with the severity of epitheliosis (epithelial hyperplasia, papillomatosis; widely believed to be the only premalignant component of fibrocystic disease) and increases further with intraductal and infiltrating duct carcinoma, breast tissue stained for elastic fibers from 84 women in the fifth decade of life was studied. Fourteen cases were evaluated in each of six disease categories: fibrocystic disease without epitheliosis; fibrocystic disease with epitheliosis, graded subjectively as mild, moderate, or severe (based on the degree of epithelial hyperplasia); intraductal carcinoma; and infiltrating duct carcinoma of the breast. Periductal elastosis and stromal elastosis were graded on a scale of 0 to 4 (absent to massive). The grades of both periductal elastosis and stromal elastosis were compared with those for the six disease categories ranked by increasingly advanced disease. The results indicate that the grades of periductal elastosis (Spearman rank correlation coefficient [R] = 0.54; P less than 0.001) and stromal elastosis (R = 0.75; P less than 0.001) increase progressively with the severity of breast disease.

Breast Diseases↗
PubMed1985

Is pain crisis a cause of death in sickle cell disease?

It has been a matter of controversy as to whether patients with sickle cell disease die of crisis or merely in crisis. The authors reviewed the 74 patients with sickle cell disease autopsied at The Johns Hopkins Hospital. From clinical review, there were 20 (27%) who died with pain crisis, 51 (69%) who died without pain crisis, and 3 (4%) for whom documentation was insufficient. On pathology review, death was attributable to infection in 19 (26%), uremia in 9 (12%), sequestration crisis in 9 (12%), necrotic bone marrow emboli in 7 (9%), and miscellaneous causes in 14 (19%); in 16 (22%) patients no cause of death could be identified. Death was explained in 47/51 (92%) patients without pain crisis; but only in 11/20 (55%, P less than 0.01) patients dying in pain crisis. The disproportionately large number of patients dying in pain crisis with an unexplained cause of death suggests that pain crisis may account for the death of some patients with sickle cell disease.

Adolescent↗
PubMed1984

Ehlers-Danlos syndrome IV due to a novel defect in type III procollagen.

Ehlers-Danlos syndrome type IV (EDS IV) is characterized by variable changes in the skin, arterial fragility, bowel perforation, minimal joint involvement, and either autosomal recessive or autosomal dominant inheritance. The unifying biochemical abnormality is a deficiency of type III collagen; all patients studied thus far have shown a defect in either synthesis or in secretion of type III procollagen. We report on an adolescent boy who inherited EDS IV from his father and who developed a spontaneous subclavian artery aneurysm. In vitro studies of collagen production in dermal fibroblasts showed normal amounts of pro alpha 1 (III) messenger RNA and synthesis and secretion of nearly equal amounts of normal and of structurally abnormal pro alpha 1 (III) monomers. This patient is biochemically distinct from previous cases of EDS IV and is likely heterozygous for a mutation that results in an aberrant type III procollagen that is particularly susceptible to protease degradation.

Adolescent↗
PubMedDate not supplied

Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and phenotype analysis indicates variable expression and low or delayed penetrance.

We report linkage of a family affected with autosomal dominant hereditary spastic paraparesis (HSP) and/or cognitive impairment to the HSP locus on chromosome 2p. To date all families linked to this locus have been affected with 'pure' HSP. The specific pattern of cognitive impairment in this family is characterised primarily by deficits in visuo-spatial functions. We also present genetic studies that indicate variable expression and low or delayed penetrance. We have constructed a haplotype flanked by polymorphic markers D2S400 and D2S2331 that was present in 12 individuals affected with spastic paraparesis. The severity of spasticity varied markedly among these individuals. In addition four of these individuals (aged 62-70) also had a specific form of cognitive impairment. The disease haplotype was also present in an individual (age 57) who had an identical pattern of cognitive impairment as the only sign of the disease supporting the hypothesis that spastic paraparesis and cognitive impairment are the result of variable expression of a single gene (rather than a co-incidental occurrence). Haplotype reconstruction for all participating family members revealed the presence of this disease haplotype in six individuals who had normal neurological and neuropsychological examinations. All six are below the maximal age of onset in the family--60 years. This is evidence for low or late penetrance of the AD HSP gene in this family. The identification of normal individuals carrying the disease haplotype demonstrates the importance of genetic studies in combination with clinical examination when counselling at risk family members.

Aged↗