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A T Tiebosch

Publications and source records attributed to A T Tiebosch.

At least 19 recordsLinked to original sources
PubMed2001

Renal expression of endothelial and inducible nitric oxide synthase, and formation of peroxynitrite-modified proteins and reactive oxygen species in Wegener's granulomatosis.

To investigate the role of nitric oxide (NO) in glomerular inflammation, the expression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was studied in conjunction with inflammatory cell influx, H2O2 production, and the formation of nitrotyrosines in renal biopsies from patients with Wegener's granulomatosis (WG). Renal cryostat sections from patients with WG (n=15) were stained by immunohistochemistry for eNOS, iNOS, endothelial cells (CD31), nitrotyrosines, polymorphonuclear cells (PMNs, CD15), and monocytes/macrophages (CD14, CD68). Production of H2O2 was identified by enzyme cytochemistry using diaminobenzidine. In control tissues, strong staining for eNOS was found in glomerular and interstitial tubular capillaries and cortical vessels. A significant reduction in eNOS expression was found in WG biopsies, which was associated with a reduction in CD31 expression. Expression of iNOS was found in infiltrating inflammatory cells, mainly located in the interstitium. H2O2-producing cells were detected in glomeruli and were abundantly present in the interstitium. Nitrotyrosine-positive cells, however, were almost exclusively found in the interstitium. It is concluded that renal inflammation in WG is associated with the induction of iNOS in inflammatory cells and the formation of nitrotyrosines. Expression of eNOS in glomerular capillaries is lost, most likely due to endothelial cell damage. These results suggest that decreased NO production by endothelial cells, in conjunction with increased NO production by iNOS-positive inflammatory cells, is involved in renal tissue injury in WG.

3,3'-Diaminobenzidine↗
PubMed2001

Chronic blockade of angiotensin II action prevents glomerulosclerosis, but induces graft vasculopathy in experimental kidney transplantation.

Long-term renin-angiotensin system blockade is beneficial in a variety of renal diseases. This study examines the long-term (34 weeks) effects of the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor type I blocker L158,809 in the Fisher to Lewis rat model of chronic renal transplant failure. Treatment in allografted rats with lisinopril or L158,809 was initiated 10 days after transplantation, or at the time when proteinuria exceeded 50 mg/24 h. Untreated allografts and syngrafts served as controls. In contrast to syngrafts, untreated allografts developed proteinuria, hypercholesterolaemia, interstitial damage, and glomerulosclerosis. Lisinopril or L158,809 treatment in allografts starting at day 10 after transplantation completely prevented this, with the exception of interstitial damage, but this treatment also caused a reduction in blood pressure and renal function. Moreover, the intimal surface area of the renal arteries was dramatically increased in allografts treated with either lisinopril or L158,809 compared with untreated allografted rats. Treatment once proteinuria had developed was less effective in preventing glomerulosclerosis, but also caused less intimal expansion. Thus, chronic renin-angiotensin system blockade preserves glomerular morphology in the absence of proteinuria, but enhances intimal hyperplasia and reduces renal function in experimental transplantation. In view of these results, it should be questioned whether such treatment benefits renal transplant patients in the long term.

Angiotensin II↗
PubMed2001

Frozen section investigation of the sentinel node in malignant melanoma and breast cancer.

BACKGROUND: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients. METHODS: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis. RESULTS: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively. CONCLUSION: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.

Breast Neoplasms↗
PubMed2001

The content and distribution of troponin I, troponin T, myoglobin, and alpha-hydroxybutyric acid dehydrogenase in the human heart.

We studied the content and distribution of heart-specific markers troponin I and troponin T in relation to conventional non-heart specific myoglobin and alpha-hydroxybutyric acid dehydrogenase (HBD) in the hearts of 34 patients who died of various causes. Tissue was obtained from the right and left ventricles, the interventricular septum, and the right and left atria. We found significant differences in the contents expressed per gram wet weight tissue in the right and left ventricles for troponin I (by 1 of the 2 methods used), troponin T, myoglobin, and HBD and no differences per gram of protein. The biochemical contents per gram wet weight tissue and per gram protein were significantly lower in the right and left atria for all studied markers compared with the right and left ventricles. No significant differences were found in biochemical contents between the right and left atria. These findings imply that estimation of myocardial damage through cardiac markers levels in serum depends on the site of injury (atrium or ventricle). Comparison of myocardial injury among individuals using marker levels in serum is not reliable because of the varied ranges of markers in tissue contents.

Adult↗
PubMed2000

Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection.

BACKGROUND: Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers of kidney allograft rejection. METHODS: Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice weekly after an overnight fast in 18 consecutive patients following renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy specimens with or without acute rejection (AR). RESULTS: Serum NOx levels increased days before AR and were significantly higher at the moment of AR (27+/-12.4 micromol/L) compared with recipients with an uncomplicated course (13+/-7.6 micromol/L), but not compared with recipients with cyclosporine (CsA) toxicity (20+/-13.0 micromol/L). Urinary NOx levels were significantly lower during AR (20+/-13.6 micromol/mmol creatinine) compared with an uncomplicated course (64+/-25.2 micromol/mmol creatinine) or CsA toxicity (53.8+/-28.3 micromol/mmol creatinine). Interstitial and glomerular iNOS expression was significantly increased in biopsy specimens showing AR. Unexpectedly, glomerular eNOS expression was significantly decreased in patients with AR. CONCLUSIONS: This study reports differences in NOx levels in serum and urine, which may help discriminate AR episodes from an uncomplicated course or CsA toxicity. As expected, renal iNOS expression is increased in acute allograft rejection. The decrease in glomerular eNOS expression suggests an intriguing link between acute and chronic rejection.

Adult↗
PubMed2000

Frozen section analysis of sentinel lymph nodes in melanoma patients.

BACKGROUND: The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS: Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22-81) years, and who were 55% male and 45% female. Serial sections (500 micrometer interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS: Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24-54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION: The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM.

Adult↗
PubMed2000

Lymphatic mapping with intralesional tracer administration in breast carcinoma patients.

BACKGROUND: The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis. METHODS: A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining. RESULTS: A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1-4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%). CONCLUSIONS: Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients.

Adult↗
PubMed2000

Limitations of the nested reverse transcriptase polymerase chain reaction on tyrosinase for the detection of malignant melanoma micrometastases in lymph nodes.

The specificity and sensitivity of the nested reverse transcriptase polymerase chain reaction (RT-PCR) on tyrosinase was studied, for the detection of micrometastases of malignant melanoma. The specificity was assessed in the blood of six healthy donors, four patients with non-melanoma cancers of which one patient was treated with granulocyte-colony stimulating factor. Lymph nodes of nine patients without malignant melanoma were tested and four cell lines of various other tumours. Six of the nine non-melanoma lymph nodes were positive in this assay. The sensitivity was tested in a spike experiment in vitro, using a melanoma cell line. The detection limit was ten melanoma cells per 10(7) peripheral blood lymphocytes.

Biomarkers, Tumor↗
PubMed1999

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.

Biopsy↗
PubMed1999

Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats.

This study aims to dissociate the respective roles of systemic nephrosis and of the intrarenal effects of proteinuria in the pathogenesis of focal segmental glomerulosclerosis (FGS) in adriamycin nephrosis. To this purpose, this study examined proteinuria and FGS in bilateral (BAP) and unilateral proteinuria (UAP) in two different rat strains. UAP was obtained by protecting one kidney from exposure to adriamycin by temporary clipping of one renal artery during adriamycin injection. At sacrifice (week 12), FGS was present in BAP and in exposed kidneys in UAP, but not in unexposed kidneys. FGS correlated significantly with proteinuria per kidney in BAP and UAP. Remarkably, for a given proteinuria per kidney, the sclerosis score was higher in BAP than in UAP, reflected by a higher ratio of FGS score per mg proteinuria per kidney (Wistar: 0.09 +/- 0.01 in BAP versus 0.05 +/- 0.01%/mg protein per d in UAP, P < 0.05; Lewis: 0.12 +/- 0.01 in BAP versus 0.07 +/- 0.01%/mg protein per d in UAP, P < 0.05), indicating that the local damaging effects of proteinuria are modified by other factors. Cholesterol correlated with total proteinuria in BAP and UAP. FGS score was positively correlated with cholesterol. The latter correlation was similar in BAP and UAP, indicating that cholesterol was a more uniform predictor for FGS than proteinuria per kidney. This was independent of strain-specific factors. On multilinear regression analysis, cholesterol turned out to be the most consistent predictor of FGS in proteinuric kidneys, with a stronger predictive value than proteinuria per kidney. It is concluded that although systemic sequelae of nephrosis do not induce renal damage in nonproteinuric kidneys, they modify the severity of proteinuria-induced FGS in proteinuric kidneys.

Animals↗
PubMed1998

Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease.

Nitric oxide (NO) and reactive oxygen species (ROS) are important mediators in the pathogenesis of inflammatory bowel disease (IBD). NO in IBD can be either harmful or protective. NO can react with superoxide anions (O2.-), yielding the toxic oxidizing agent peroxynitrite (ONOO-). Peroxynitrite induces nitration of tyrosine residues (nitrotyrosine), leading to changes of protein structure and function. The aim of this study was to identify the cellular source of inducible nitric oxide synthase (iNOS) and to localize superoxide anion-producing cells in mucosal biopsies from patients with active IBD. Additional studies were performed to look at nitrotyrosine formation as a measure of peroxynitrite-mediated tissue damage. For this, antibodies against iNOS, endothelial NOS (eNOS), and nitrotyrosine were used. ROS-producing cells were detected cytochemically. Inflamed mucosa of patients with active IBD showed intense iNOS staining in the epithelial cells. iNOS could not be detected in non-inflamed mucosa of IBD patients and control subjects. eNOS was present in blood vessels, without any difference in the staining intensity between IBD patients and control subjects. ROS-producing cells were increased in the lamina propria of IBD patients; a fraction of these cells were CD15-positive. Nitrotyrosine formation was found on ROS-positive cells. These results show that iNOS is induced in epithelial cells from patients with active ulcerative colitis or Crohn's disease. Nitration of proteins was detected only on the ROS-producing cells at some distance from the iNOS-producing epithelial cells. These findings indicate that tissue damage during active inflammation in IBD patients is probably more related to ROS-producing cells than to NO. One may speculate that NO has a protective role when during active inflammation other mucosal defence systems are impaired.

Adult↗
PubMed1998

Early-onset phenytoin toxicity mimicking a renopulmonary syndrome.

Phenytoin is a commonly used anti-epileptic drug. Adverse reactions including fever, skin reactions and lymphadenopathy are well known but atypical reactions can also occur. A patient is described with a lag time of only 4 days between onset of phenytoin and the development of a syndrome with acute lung injury and renal failure. The symptoms mimicked a renopulmonary syndrome, and resolved completely after cessation of phenytoin and addition of steroids.

Acute Kidney Injury↗
PubMed1997

Which cytological criteria are the most discriminative to distinguish carcinoma, lymphoma, and soft-tissue sarcoma? A probabilistic approach.

The reliability of fine-needle aspiration cytology (FNA) for distinguishing between carcinoma, lymphoma, and sarcoma was established in a previous study (Thunnissen et al., Cytopathology 1993; 4:107-114). The purpose of this study was to investigate which criteria were useful for a probabilistic diagnosis. A total of 78 randomly chosen FNA smears (31 carcinomas, 24 lymphomas, and 23 sarcomas) was sent around and read "blindly" by six cytopathologists. Each pathologist completed a list of 16 criteria for every case. Histology was used as a reference standard. A statistical analysis led to the selection of three criteria: "lymphoglandular bodies," "well-defined clusters," and "spindle-cell nuclei," associated with lymphoma, carcinoma, and soft-tissue sarcoma, respectively. Given the scores on these criteria, the probabilities to be assigned to the three diagnostic categories can be read from a table. It turns out, as one might expect, that the classification of the most probable disease is pretty reliable if one cytologic criterion scores much higher than the other two criteria. On other cases, fuzziness appears and misclassifications are far from improbable. This study offers a general cytologic approach. The cytologic criteria "lymphoglandular bodies," "well-defined clusters," and "spindle-cell nuclei" can be used both in daily practice and in education to assign posterior probabilities to carcinoma, lymphoma, and soft-tissue sarcoma.

Biopsy, Needle↗
PubMed1996

Abnormal glomerular basement membrane in idiopathic multicentric osteolysis.

The primary cause of nephropathy in idiopathic multicentric osteolysis is as yet unknown. We report a young girl with idiopathic multicentric osteolysis and nephropathy. An abnormal glomerular basement membrane was the only abnormality found in a renal biopsy taken 2 years before the development of end-stage renal failure. We believe that this biopsy finding represents or is related to the unknown primary lesion causing nephropathy in idiopathic multicentric osteolysis.

Basement Membrane↗
PubMed1996

Tumor angiogenesis: an independent prognostic parameter in cervical cancer.

OBJECTIVE: The purpose of this study was to investigate whether the intensity of tumor angiogenesis, expressed as microvessel density, is a parameter predicting the probability of lymph node metastasis and survival in patients with cervical cancer stages IB and IIA. STUDY DESIGN: In a retrospective study of 114 patients with cervical cancer stages IB and IIA, microvessel density, lymph node status, and several other prognostic parameters were correlated with disease-free survival by a multivariate analysis according to Cox proportional-hazards model. RESULTS: There was a significant difference in mean microvessel density between tumors with and without pelvic lymph node metastasis (p = 0.002). Both microvessel density (vessels per square millimeter of stroma). (p = 0.05) and pelvic lymph node metastasis (p = 0.007) correlated significantly and independently with disease-free survival. CONCLUSION: This study demonstrates that microvessel density is an independent prognostic parameter for disease-free survival in patients with cervical cancer stages Ib and IIa.

Female↗
PubMed1995

Basement membranes in cervical cancer: relationship to pelvic lymph node metastasis and prognosis.

In this retrospective study, the pattern of basement membrane expressed by type IV collagen immunostaining was evaluated in 156 patients with cervical cancer FIGO stage IB-IV. Staining patterns were assessed semiquantitatively and divided into three patterns, according to intensity and continuity of staining: thick basement membranes with minimal discontinuity (pattern I), thin basement membranes with moderate discontinuity (pattern II), and fragmentary or absent basement membranes (pattern III). Correlations between basement membrane pattern, FIGO stage, and pelvic lymph node status were tested using chi 2 statistics. Kaplan-Meier estimates of disease-free survival were calculated for groups of patients with basement membrane pattern I, II, or III and compared using the log-rank test. A fragmented or absent basement membrane, pattern III, was more frequently observed in advanced cervical cancer stage IIB/IV (P = 0.02). In patients with early cervical cancer stage Ib/IIA this pattern was associated with the presence of pelvic lymph node metastasis (P < 0.0001) and significantly associated with a decreased survival rate (P = 0.05). In advanced-stage disease no prognostic value was observed. These data indicate that in patients with early-stage cervical cancer the basement membrane pattern, expressed as the type IV collagen staining pattern, may be a useful marker in predicting lymph node metastasis and survival.

Adenocarcinoma↗
PubMed1993

The role of the spleen in pancreas transplantation.

Early graft thrombosis and rejection of the graft are the two major causes of graft failure in pancreas transplantation. Inclusion of the spleen in the pancreatic graft has been purported as a possible solution to both complications, but severe graft-versus-host disease led to abolishment of this procedure. By irradiating the donor spleen ex vivo during cold storage, we successfully prevented graft-versus-host disease, allowing us to evaluate the advantages of clinical pancreaticosplenic transplantation. This study reports our experience with 12 pancreaticosplenic transplantations. Using Doppler flow measurements, we have been able to examine the hemodynamic advantages. Our results confirm the purported benefit. Vascular resistance indices in the pancreatic graft are significantly lower when the donor spleen is included. This, however, did not lower the incidence of thrombosis (2 out of 12 cases) in our study. Serial radionuclide studies with 99mTc-hexamethyl propylene amine oxime were performed for further evaluation of graft perfusion. With time the spleen uptake diminishes, compatible with atrophy of the organ. This was confirmed histologically. No indication of an immunologic advantage of transplanting the pancreas together with the spleen was found. All patients went through severe rejection crises. A transient reduction in platelet count (55-88%, mean 71%) of preoperative values was observed. This platelet drop is not seen in patients with a pancreas without spleen transplantation. We conclude that in pancreas transplantation, inclusion of the irradiated spleen has no obvious advantages for early graft thrombosis and rejection of the graft.

Adult↗