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D M Painter

Publications and source records attributed to D M Painter.

At least 19 recordsLinked to original sources
PubMed2001

In vivo image-guided (1)H-magnetic resonance spectroscopy of the serial development of hepatocarcinogenesis in an experimental animal model.

Histology on a core or open biopsy is considered the gold standard for the diagnosis of tumours. While the non-invasive technique of magnetic resonance imaging can direct some of the decision diagnostic making, it has limitations and disadvantages, that can be partly overcome with the use of in vivo magnetic resonance spectroscopy (MRS). In vivo MRS is able to provide a specific biochemical profile on tumour tissue, compared with normal tissue. The capability of this technique is demonstrated here by the long-term development of hepatocellular carcinoma in an animal model. It allows the observation of the biochemical changes that occur in tumour tissue during its progression from preneoplastic nodules to hepatocellular carcinoma. Specifically the changes in the lipid profiles of tumour tissue at various stages of development are observed with proton ((1)H) MRS. Significant increases occurred in the lipid acyl chain methylene and methyl hydrogens during the early developmental stages of hepatocarcinogenesis, whereas during later stages associated with tumour development there was a significant increase in the levels of olefinic acyl chain hydrogens from unsaturated lipids. It is anticipated that this model will precede the application of the same technology to the non-invasive diagnosis and grading of human hepatocellular carcinoma.

Animals↗
PubMed2001

Posttransplant administration of donor leukocytes induces long-term acceptance of kidney or liver transplants by an activation-associated immune mechanism.

Donor leukocytes play a dual role in rejection and acceptance of transplanted organs. They provide the major stimulus for rejection, and their removal from the transplanted organ prolongs its survival. Paradoxically, administration of donor leukocytes also prolongs allograft survival provided that they are administered 1 wk or more before transplantation. Here we show that administration of donor leukocytes immediately after transplantation induced long-term acceptance of completely MHC-mismatched rat kidney or liver transplants. The majority of long-term recipients of kidney transplants were tolerant of donor-strain skin grafts. Acceptance was associated with early activation of recipient T cells in the spleen, demonstrated by a rapid increase in IL-2 and IFN-gamma at that site followed by an early diffuse infiltrate of activated T cells and apoptosis within the tolerant grafts. In contrast, IL-2 and IFN-gamma mRNA were not increased in the spleens of rejecting animals, and the diffuse infiltrate of activated T cells appeared later but resulted in rapid graft destruction. These results define a mechanism of allograft acceptance induced by donor leukocytes that is associated with activation-induced cell death of recipient T cells. They demonstrate for the first time that posttransplant administration of donor leukocytes leads to organ allograft tolerance across a complete MHC class I plus class II barrier, a finding with direct clinical application.

Animals↗
PubMed2000

Early up-regulation of macrophages and myofibroblasts: a new marker for development of chronic renal allograft rejection.

BACKGROUND: Increased numbers of macrophages and myofibroblasts are observed to occur in chronic renal allograft rejection (CR). The aim of this study was to examine the expression of cellular markers for the macrophage and myofibroblast in early renal transplant biopsy specimens and correlate these findings with allograft outcome. METHODS: The first postengraftment biopsy specimens from 53 patients who underwent renal transplantation between January 1993 and December 1995 were studied using immunohistochemistry with antibodies to alpha-smooth muscle actin, which identifies myofibroblasts and CD68, a marker for monocytes and macrophages. Patients were followed until December 1998 (mean follow-up 4.7+/-1.2 years). RESULTS: Nine patients had progressed to CR by the time of the study, whereas 44 patients continued to have stable renal function. A marked increase in both macrophages (P=0.02) and myofibroblasts (P=0.04) was noted in the first biopsy specimen obtained after engraftment in the patients who developed CR compared with those with stable allograft function. There was a positive correlation between alpha-smooth muscle actin and collagen expression (P=0.0001). CONCLUSION: Significant increases in macrophages and myofibroblasts occur in the first renal biopsy specimen in those patients who later develop CR.

Actins↗
PubMed2000

Post-transplant quasispecies pattern remains stable over time in patients with recurrent cholestatic hepatitis due to hepatitis C virus.

BACKGROUND/AIMS: Several studies have shown that cholestatic recurrent hepatitis is associated with very high HCV RNA loads in liver transplant recipients. The aim of this study was to investigate whether a correlation exists between cholestatic hepatitis post-transplant and the population of viral quasispecies. METHODS: One hundred and nine serial sera samples were tested from 15 recurrent HCV patients. Four of these patients showed severe cholestatic recurrent hepatitis, 11 patients demonstrated non-cholestatic recurrent hepatitis post-transplant. Quasispecies were detected by RT-PCR amplification of the HVR1 followed by single-stranded conformational polymorphism analysis. RESULTS: Forty-one samples from four cholestatic patients were tested. All four patients showed very stable quasispecies patterns post-transplant. One cholestatic patient also showed a stable quasispecies band pattern following retransplantation, again associated with severe cholestatic hepatitis. Sixty-eight samples were tested from the 11 non-cholestatic patients. In contrast, these patients showed significantly more quasispecies bands than the cholestatic patients. The noncholestatic patients also displayed fluctuating band patterns post-transplant. Serial samples were tested after retransplantation in one non-cholestatic patient, with a fluctuating pattern again seen. There was a negative correlation between the HCV RNA load in serum and the number of quasispecies bands. CONCLUSIONS: Stable hepatitis C viral quasispecies associated with persistently high viral load in post-transplant cholestatic hepatitis suggest that viral escape from immune pressures may play a role in the pathogenesis of this condition.

Adult↗
PubMed1999

A deficiency of placental IL-10 in preeclampsia.

Accommodation of the fetoplacental unit in human pregnancy requires maternal immune tolerance to this "semiallograft". Local antiplacental immunity is modified by synthesis of uncommon histocompatibility Ags (e.g., HLA-G), growth factors, and cytokines by the placenta. Placental interleukins have been identified in reproductive tissues, but their roles in adaptive maternal immunity and determining term pregnancy outcomes have not been fully clarified. This study examined the distribution of IL-10 and TNF-alpha staining in term placentas. Women with proteinuric hypertension (PE, n = 10) were compared with an age-matched group with normal pregnancy (NP, n = 14) and gestational hypertension (GH, n = 6). Using immunohistochemistry of parrafin-fixed tissues, trophoblast cells were identified by cytokeratin 7 and cytokeratin 18 staining. The cytokine binding of villous trophoblast cells was scored depending on the extent of circumferential cytoplasm staining (<25%; intermediate or >75%). The cytokine positive decidual cells were scored as a percentage of total extravillous trophoblast cells. There was a reduction in villous IL-10 immunostaining compared with normal term placenta (PE, 10.2 +/- 1.1, mean +/- SEM; NP, 14.07 +/- 1.16 Mann-Whitney U test; p = 0.02). In these patients, there was an increase in TNF-alpha immunostaining. Sparse endovascular extravillous trophoblast cells demonstrated nuclear IL-10 staining in 30% of patients with preeclampsia. Serum IL-10 was diminished in women with preeclampsia compared with normal pregnancy. In conclusion, villous trophoblast demonstrated diminished immunostaining of IL-10 in preeclampsia. This abnormality may be associated with heightened maternal antifetal immunity and therefore inadequate placental development in preeclampsia.

Adult↗
PubMed1999

Vascular endothelial growth factor expression in human chronic renal allograft rejection.

BACKGROUND: Chronic renal allograft rejection is characterized by interstitial fibrosis and vasculopathy. Vascular endothelial growth factor (VEGF) is an endothelial mitogen with increased expression in inflammation and vasculopathy. METHODS: Renal tissue from 17 patients with chronic rejection was examined for VEGF protein and the presence of CD 68-positive macrophages, and compared to biopsies from patients with temporary allograft dysfunction, acute rejection, and native kidneys with thin membrane disease. RESULTS: In the chronic rejection group, there was markedly increased expression of VEGF protein in the interstitium (P<0.0001). In serial sections, VEGF colocalized with the expression of CD 68-positive macrophages. Significantly more macrophages were in the tubulointerstitium in tissue with chronic rejection than in those with temporary allograft dysfunction (P<0.005). Additionally, VEGF protein expression in the glomeruli and the vascular compartment of patients with chronic rejection was increased. CONCLUSION: The up-regulation of VEGF in chronic renal allograft rejection may be important in inflammation and development of fibrosis.

Antigens, CD↗
PubMed1999

A new vascularized skin transplant model in rats.

The aim of this work was to develop a vascularized skin transplantation model in the rat to allow comparison of the immunological events with those of classic free skin grafts and vascularized organ grafts. Seventy-nine syngeneic transplants were performed using inbred Wistar and PVG rats to develop the model. Epigastric skin flaps were taken with a vascular pedicle of common femoral artery and vein and implanted on the back of the neck. The graft vessels were anastomosed end-to-end and end-to-side to the recipient common carotid artery and external jugular vein with interrupted 10-0 nylon sutures under an operating microscope. A high success rate (11 of 11) was achieved in the final method developed, with light microscopy confirming normal skin structure in the flaps following transplantation. The advantages of the model include comparable skin size to that commonly used for nonvascularized skin grafts, while the physiology in terms of blood supply is similar to that of vascularized organ grafts; the grafts are visible with free access for biopsy; and the size of the graft can easily be varied to allow studies concerning antigen load.

Animals↗
PubMed1999

Nonspecificity of monoclonal antibody Tordji-22 for the detection of hepatitis C virus in liver transplant recipients with cholestatic hepatitis.

Detection of hepatitis C virus (HCV) antigens in liver tissue provides important diagnostic and pathological information. Limited studies have been performed on tissue taken after liver transplantation for HCV. In this study, serial post-liver transplantation biopsy tissue from patients with recurrent HCV was tested, with particular interest in patients showing severe cholestatic hepatitis. HCV-related antigens were detected using the commercial monoclonal antibody, Tordji-22. Initial results were promising, showing intense positive staining, especially in areas of hepatocyte ballooning. HCV-negative donor tissue was consistently negative by staining. However, as a final control for the level of tissue damage, HCV negative posttransplantation biopsy tissue showing hepatocyte ballooning was examined. These tissues also showed positive staining. All attempts to eliminate this nonspecific interaction failed. In conclusion, Tordji-22 was associated with nonspecificity in this posttransplantation population, and care is warranted when using this monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1999

Hepatocellular carcinoma metastasizing to the orbit diagnosed by fine needle aspiration cytology.

Hepatocellular carcinoma (HCC) rarely metastasizes to the orbit. We report a case of a 78-year-old man with a past history of HCC, who presented with a periorbital mass, which was diagnosed as metastatic HCC by fine needle aspiration cytology (FNAC) and subsequently confirmed on excision biopsy. The cytological, histopathological and immunohistochemical findings are presented and the differential diagnosis is discussed. To our knowledge there has been no previously reported case of HCC metastatic to the orbit diagnosed by FNAC.

Aged↗
PubMed1998

Case report: an inherited APC mutation in the first reported Australian case of Turcot's syndrome.

The objective of this study was to determine the inherited gene mutation responsible for the first reported Australian case of Turcot's syndrome. DNA was extracted from the archival tissue blocks obtained at the time of the patient's original surgery and from fresh blood samples obtained from selected family members. These were analysed for mutations of the familial adenomatous polyposis gene (APC). Analysis of DNA from the archival blocks and from each of the affected family members revealed an inherited 5 base pair deletion at codon 1061 of APC. In this case, the central nervous system tumour represents an extracolonic manifestation of familial adenomatous polyposis. The underlying inherited mutation of APC has been identified. In some cases of Turcot's syndrome, other genes appear to be involved. Recent literature examining the molecular basis of Turcot's syndrome is reviewed.

Adenomatous Polyposis Coli↗
PubMed1998

Parotid and submandibular sialadenitis treated by salivary gland excision.

BACKGROUND: The purpose of the present study was to compare and contrast the clinicopathological features and treatment outcome of chronic sialadenitis involving the parotid and submandibular glands, among patients who were treated by excision of the affected gland. METHODS: In a series of 88 patients treated over an 8-year period, 47 had parotid sialadenitis and 41 had submandibular sialadenitis. In the parotid group, 63% of patients were symptomatic for longer than 6 months compared with 27% in the submandibular group. Calculi were implicated in the disease process in 24% of patients with parotid sialadenitis, compared with 73% of patients with submandibular disease. RESULTS: Patients with parotid sialadenitis had superficial (n = 14) or near-total parotidectomy (n = 35), while those with submandibular sialadenitis underwent total gland excision. Complications occurred twice as frequently in the parotidectomy group. The rate of temporary facial nerve weakness was 29% after parotidectomy while marginal mandibular nerve dysfunction occurred after 12% of submandibular excisions. Both procedures were highly effective in permanently relieving the symptoms of sialadenitis. CONCLUSIONS: Parotid sialadenitis is infrequently associated with stones and tends to run a longer course before surgical intervention is necessary. Submandibular sialadenitis usually presents earlier, is secondary to calculi and requires early intervention.

Chronic Disease↗
PubMed1996

Intrahepatic hepatitis C RNA levels do not correlate with degree of liver injury in patients with chronic hepatitis C.

The balance between a direct cytopathic effect by hepatitis C virus (HCV) and immune-mediated injury remains unclear. This report aims to test the following hypotheses: (1) that intrahepatic HCV load would correlate with the degree of liver injury; (2) that interferon alfa (IFN-alpha) would decrease intrahepatic HCV-RNA levels. Liver tissues (n = 56) were obtained from 47 patients with chronic HCV (9 before and after IFN-alpha therapy). Total RNA was isolated and quantitated for specific HCV RNA by dot-blot polymerase chain reaction (DB-PCR) using a standard curve created from synthetic HCV RNA of known titer to calculate actual RNA levels. A multivariate analysis was undertaken to determine the relationship of intrahepatic HCV-RNA levels with risk factors, length of HCV exposure, and histological injury scores. The confounding effect of HCV genotype was examined by direct sequencing of the NS5b region. Liver HCV RNA ranged from 10(2) to 3.1 x 10(7) molecules per microgram total liver RNA. The multiple regression analysis showed no effect of length of HCV exposure, risk factors, degree of bile duct damage, steatosis, or total Scheuer or Knodell score on RNA levels. No significant confounding effect of HCV genotype on the degree of liver injury was observed. However, genotype 1b had a significantly higher mean intrahepatic HCV-RNA load compared with the other genotypes detected. In the 9 patients who received IFN-alpha, treatment, 7 had no detectable HCV after treatment. This was associated with a significant decrease in intrahepatic HCV-RNA levels (7.57 +/- 2.53 X 10(5) to 1.82 +/- 1.80 x 10(3) molecules per microgram total liver RNA +/- SEM, n = 9, P = .0005). These results do not directly support our hypothesis that increased intrahepatic HCV load is associated with more severe liver injury. Intrahepatic viral load appears to be significantly increased in patients with genotype lb. IFN-alpha treatment does significantly lower intrahepatic HCV load.

Adult↗
PubMed1996

Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines.

An imbalance between T helper cell (Th)1 and Th2-like cytokines has been described in several chronic infectious diseases. We therefore analyzed the intrahepatic messenger RNA (mRNA) expression of Th1-like (interleukin [IL]-2, interferon [IFN]-gamma) and Th2-like (IL-4, IL-10) cytokines in chronic hepatitis C patients (n = 17) and controls (n = 6) and correlated the results with liver histology and intrahepatic viral load. Intrahepatic cytokine mRNA and hepatitis C virus (HCV) RNA were quantitatively assessed by polymerase chain reaction (PCR) using a dot-blot hybridization technique. Liver biopsy specimens were histologically graded using the Scheuer Score. IFN-gamma and IL-2 mRNA expression were significantly upregulated in chronic HCV vs. controls (P < .002, P < .04, respectively). Both correlated significantly with histological fibrosis and portal tract inflammation. In contrast, the expression of IL-10 mRNA was decreased in cirrhosis and chronic HCV compared with controls (P < .02, P < .0001, respectively). IL-4 mRNA was detected inconsistently at low levels in all groups. Intrahepatic viral load did not correlate with either cytokine expression or tissue injury. In conclusion, the progressive liver injury seen in chronic HCV is associated with the upregulation of intrahepatic Th1-like cytokines and the downregulation of IL-10, a Th2-like cytokine. These results suggest a role for delayed-type hypersensitivity immune reactions in HCV related liver injury.

Adult↗
PubMed1996

Chrysiasis after low-dose gold and UV light exposure.

We describe a case of chrysiasis in a 54-year-old woman. The diagnosis was confirmed by light microscopy, transmission electron microscopy, and radiographic microanalysis. The condition developed after a relatively low dose of gold. We propose that chrysiasis developed because of the patient's exposure to the intense UV light in Australia.

Antirheumatic Agents↗
PubMed1996

Vesiculobullous Hailey-Hailey disease: successful treatment with oral retinoids.

A 56-year-old male presented with a pruritic, generalized vesiculobullous eruption. His past history revealed classical symptoms of limited Hailey-Hailey disease for 34 years. Clinically, vesicles, bullae and occasional pustules were present and multiple biopsies confirmed this to be an unusual presentation of Hailey-Hailey disease. Various therapeutic modalities including topical and oral antibiotics, oral prednisone and dapsone failed to achieve sustained remission. Treatment with low-dose oral etretinate (25 mg daily) produced marked clinical improvement with complete suppression of new vesicle formation after 6 weeks.

Administration, Oral↗
PubMed1995

Fraternal sisters with adult polycystic kidney disease and adenoma of the ampulla of Vater.

The cases of two fraternal sisters with symptomatic biliary obstruction due to adenomas of the ampulla of Vater are reported. Both sisters had autosomal dominant adult polycystic kidney disease. There are no previous reports of a familial occurrence of ampullary adenomas in the absence of familial adenomatous polyposis, nor has an association between autosomal dominant polycystic kidney disease and ampullary adenoma been described. The coexistence of both disorders in these sisters raises the possibility of a genetic link between autosomal dominant polycystic kidney disease and ampullary adenoma.

Adenoma↗
PubMed1994

Histopathological prediction of hepatitis B recurrence in liver allografts.

The aim of this study was to review the clinical, serological and histopathological features of 20 patients who underwent orthotopic liver transplantation for hepatitis B virus (HBV) related liver disease in an attempt to identify factors which predict recurrence of HBV infection, pattern of disease and disease severity. Hepatitis B recurrence occurred in 11 patients (55%). Positive immunoperoxidase staining for HBsAg and HBcAg of the hepatectomy specimen were shown to have a sensitivity (82% and 64% respectively) and specificity (55% and 66%) in predicting recurrence. This was comparable to serological markers such as HBV DNA (36% sensitivity and 89% specificity). The staining for HBcAg in some cases was weak, focal and had a reticular pattern. Therefore, examination of multiple blocks with a high magnification was necessary to detect HBcAg staining. Negative staining of multiple sections for HBsAg and HBcAg were shown to have a good correlation with clearing of HBV infection (5 out of 6 patients). If recurrence occurred, the range of histological and clinical patterns of HBV recurrence was varied, with severe disease occurring in 5 patients. Neither pre-transplant serology nor hepatectomy immunoperoxidase staining characteristics were shown to be of value in predicting the pattern or the severity of disease once HBV recurrence had occurred. This study indicates that lack of staining for HBV antigens on multiple sections of the native liver may predict a subgroup of HBsAg positive transplant patients who will not suffer from recurrent disease. Once disease did occur however, markers for severity of recurrence were not identified.

Base Sequence↗