Biomedical subjects

K W Schmid

Publications and source records attributed to K W Schmid.

At least 19 recordsLinked to original sources

PubMed2000

Potential embolization by atherosclerotic debris dislodged from aortic wall during cardiac catheterization:: histological and clinical findings in 7,621 patients.

Embolic events during cardiac catheterization have been attributed to atherosclerotic aortic debris dislodged by catheter manipulation. We evaluated the frequency and the histologic morphology of atherothrombotic material retrieved during placement of coronary catheters in patients undergoing diagnostic or interventional cardiac procedures. Over a 4-year period, macroscopically visible aortic debris from coronary catheters, if present after advancement to the ascending aorta, was obtained for histologic examination. In 41 of 7,621 patients (0.54%), visible atherothrombotic material was present in the backflow of catheters. Debris occurred most frequently with 8 Fr guiding catheters (98%). Histologic examination showed foam cells, cholesterol crystals, and amorphic lipoid substance as markers of atheromatous material from atherosclerotic plaques in 38/41 patients (93%) with former plaque hemorrhage in 55% of them. In three patients, fresh thrombus material was observed (7%). None of these patients showed in-hospital ischemic complications. Although visible atheromatous material is a rare phenomenon in cardiac catheterization, an increased risk of scraping debris is associated with large-lumen guiding catheters. In order to avoid vascular embolization, the use of smaller guiding catheters and sufficient free backflow of catheters after advancement are recommended.

Adult↗

PubMed1999

Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts.

BACKGROUND: Apoptosis is a cellular phenomenon generally found within rejecting transplants. It may play a role in physiological or therapy-associated deletion of infiltrating lymphocytes or in graft cell destruction. Our study focuses on apoptosis of infiltrating lymphocytes during acute kidney rejection after the initial steroid pulse therapy and on possible prognostic implications. METHODS: Renal biopsy specimens of 23 transplant recipients with acute tubulo-interstitial rejection were examined for appearance of apoptosis and compared with 11 transplant biopsies with unspecific organ injury accompanied by lymphocyte infiltration. In all patients, biopsies were performed after steroid pulse therapy, and, after confirmation of rejection, antilymphocytic antibody treatment was carried out. Apoptosis was determined via terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling analysis and confirmed by electron microscopy. RESULTS: Apoptosis of lymphocytes or of tubular epithelium was detected in 11 cases of acute rejection (48%), respectively. Four biopsies showed lymphocytic as well as tubular apoptosis, whereas five sections showed no signs of programmed cell death. In biopsies revealing unspecific injury, tubular cell apoptosis was more frequently found (73%) compared with lymphocyte apoptosis (27%, P<0.05). Most interestingly, patients with a beneficial recovery from acute rejection had a higher proportion of lymphocyte apoptosis compared with patients with poor rejection outcome. The Bcl-2 oncoprotein was widely found within infiltrating lymphocytes without counter-regulating apoptosis. CONCLUSIONS: Lymphocyte apoptosis is found as frequently as tubular cell apoptosis in rejecting renal grafts after steroid pulse therapy and might have prognostic value for rejection outcome.

Acute Disease↗

PubMed1999

[Kikuchi-Fusimoto disease: the differential diagnosis of cervical lymphadenitis with recurrent attacks of fever].

HISTORY AND CLINICAL FINDINGS: A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years. Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin. At admission there were several enlarged cervical lymph nodes and subfebrile temperatures. INVESTIGATIONS: Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease. TREATMENT AND COURSE: After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis. CONCLUSION: Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy. Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.

Biopsy↗

PubMed1999

Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes, and their precursors.

Leukocytes with ring-shaped nuclei (ring cells) are present in bone marrow (BM; approximately 50% of BM cells), in peripheral blood (PB), and in inflammatory infiltrates of mice, but also in humans during myeloproliferative disorders. They are usually referred to as polymorphonuclear cells (PMN), but we demonstrate that they additionally encompass different types of mononuclear (MNC)-like ring cells. PMN ring cells had constricted ring-shaped nuclei with a wide cytoplasmic center and were sorted among the GR-1high fraction. The MNC-like ring cells belonged to the GR-1low fraction. Their nuclei were not segmented and the cytoplasmic center of their nuclei was small. They were heterogeneous with one subgroup containing monocytes/macrophages according to ultrastructure, immunophenotype (BM8, F4/80, CD13, ER-HR3), activity of unspecific esterase, and phagocytosis of Leishmania major. A second subgroup contained myeloic precursor cells as they proliferated (Ki67), expressed ER-MP12, and showed on ultrastructure distribution patterns of peroxidase activity compatible with myelocytes, promyelocytes, or promonocytes. A third subgroup of cells had large, sometimes lobulated nuclei, was lineage marker(negative/low) (GR-1, Mac-1, B220 etc.), CD38-, but c-kit+ and sca-1+, and thus belonged to a close progeny of murine hematopoietic stem cells. In PB, ring cells encompassed mainly PMN, but also monocytes and cells with characteristics of both the granulocytic and monocytic lineage. Thus, ring cells comprise mature and precursor forms of myeloic cells. Their analysis revealed that in mice a clear distinction between the granulocytic and monocytic lineage beyond the GM-CFU stage is not always feasible.

Animals↗

PubMed1999

Differential effects of angiotensin II receptor blockade on pressure-induced left ventricular hypertrophy and fibrosis in rats.

The effects of the angiotensin II receptor type 1 (AT1) antagonist losartan on pressure overload-induced left ventricular (LV) hypertrophy were studied in female Sprague-Dawley rats. Starting on the day of surgery, losartan (L, 12 mg/kg/day) was administered as continuous intraperitoneal infusion for 2 weeks by using alzet mini-osmotic-pumps (model 2002). This dose of losartan shifted the in vivo dose-response curve of the angiotensin II-induced elevation of left ventricular systolic pressure (LVSP) to the right. Pressure overload was achieved by placing a band around the aortic arch. This caused an aortic stenosis (AS) with an outer diameter of 1.0 mm. The hemodynamic effects were measured in the intact, anesthetized rats (n = 15). The hearts were excised, and the weights of the left (LV) and right ventricle (RV) were determined. Some of these hearts (n = 7) were perfused with collagenase to obtain isolated cardiac myocytes for the measurement of cell volume. Other hearts (n = 8) were examined for morphological changes. In the animals with AS, LVSP was markedly elevated. Furthermore, LV weight and LV myocyte cell volume were increased in this group, while RV weight and RV myocyte cell volume remained stable in all the groups. L had no significant effect on the AS-induced increase in LVSP and cell size parameters, nor on the weight gain of the LV. Histological analysis revealed that the AS-induced enlargement of the mean myocyte diameter was not affected by L. The interstitial collagen fraction was increased in the AS rats and became normalized by L. These data suggest that the renin-angiotensin system might not be involved in the development of pressure-induced cardiac hypertrophy within the time-frame of these experiments, but that it does play a major role in the genesis of the interstitial fibrosis which is a typical feature of this pathophysiological condition.

Angiotensin Receptor Antagonists↗

PubMed1999

Transepithelial transport processes at the intestinal mucosa in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown etiology. Oral absorption studies have shown an increased intestinal permeability for various sugar molecules in patients with IBD and their healthy relatives as a possible pathogenetic factor. However, the various transport pathways through the mucosal barrier have not yet been examined. This study therefore investigated whether antigens pass the epithelial barrier by a transcellular or a paracellular pathway. Mucosa of freshly resected specimens from CD (n = 10) or UC (n = 10) patients was investigated by immunoelectron microscopy and compared with healthy mucosa. Epithelial transport was studied with the antigens ovalbumin and horseradish peroxidase after defined incubation. Labeling density of subunit c of ATP synthetase was determined in mitochondria of enterocytes of all specimens. In all specimens epithelial transport of OVA and HRP was principally transcellular through enterocytes with normal ultrastructure, although some tight junctions in CD and UC were dilated. Antigens were transported within vesicles to the basolateral membrane 2.5 min after incubation. The level of enterocytes with electron-lucent cytoplasm containing a high amount of antigens was higher in CD and UC than in healthy mucosa, depending on the grade of inflammation. ATP synthetase was significantly decreased in electron-lucent cytoplasm of CD and UC to normal ultrastructure of healthy mucosa. Our study shows that ovalbumin and horseradish peroxidase taken up by the apical membrane reach the paracellular space by vesicular transport in healthy and IBD enterocytes within a few minutes. Transcellular pathway is affected in both CD and UC, which is indicated by a high level of antigens within the cytosol. We speculate that increased intestinal permeability in IBD results substantially from enhanced transcellular transport.

Adult↗

PubMed1999

Standardized in situ AgNOR analysis in breast pathology: diagnostic and cell kinetic implications.

The aim of the present study was to assess the diagnostic value of the recently standardized morphometric analysis of silver-stained nucleolar organizer region-associated proteins (AgNORs) [30] in a variety of 155 routinely processed benign and malignant breast lesions. 5 normal breast samples, 21 adenoses, 20 ductal hyperplasias, 10 atypical ductal hyperplasias, 20 in situ and 43 invasive ductal carcinomas, 10 in situ and 26 invasive lobular carcinomas were investigated. A statistically highly significant difference was found between normal/ordinary hyperplastic and neoplastic breast lesions with all 4 consensus AgNOR parameters (mean area, mean number, CV of area, CV of number) evaluated. AgNOR quantity was significantly related to histological grade of both in situ and invasive carcinomas. However, variable overlap was found between AgNOR values in different diagnostic groups. We conclude that standardized AgNOR analysis is a prerequisite for objective and reproductible AgNOR assessment in archival tissues. Despite its limited diagnostic utility for individual breast lesions, standardized AgNOR analysis bears a significant potential for characterizing cell kinetic and metabolical activity of breast lesions. This may give insight into the biological background of breast carcinogenesis, differentiation and tumor progression and may also underlie the independent prognostic value of AgNORs in breast cancer.

Breast↗

PubMed1999

Metallothionein: localization in human transplant endomyocardium, relation to cytokines and allograft function.

BACKGROUND: The aim of this study was to investigate the role of metallothionein in cardiac transplants in relation to cytokines and allograft function. Recent studies have revealed an association of allograft dysfunction with elevated proinflammatory cytokines independent of cellular rejection. In animal experiments, cytokines induced overexpression of metallothionein, a low-molecular-weight protein implicated in cellular stress response. METHODS: In 105 consecutive biopsies from 15 patients during the first 3 months after heart transplantation, metallothionein expression was investigated immunohistochemically. Its relation to serum interleukin-6, tumor necrosis factor-alpha, interleukin-2 (IL-2), soluble interleukin-2 receptor rejection, and echocardiographic parameters was determined. Forty-three biopsies of 12 patients with idiopathic ventricular tachycardia served as controls. RESULTS: Metallothionein expression was demonstrated in small vessels, cardiomyocytes, fibrocytes, and interstitial round cells. A positive relation between interleukin-6 levels and the number of metallothionein-positive small vessels (p < 0.028) was observed. Patients with lower serum IL-2 levels showed significantly higher numbers of metallothionein-positive small vessels (p < 0.043). Grafts with prolonged ischemic time (>150 minutes) showed a significantly higher myocardial metallothionein score (p < 0.021). Metallothionein expression was associated with lower fractional shortening, larger left ventricular end-systolic diameter, and lower mean arterial pressure but not with acute cellular rejection. CONCLUSIONS: Metallothionein expression is associated with elevated interleukin-6 and decreased interleukin-2 serum levels and left ventricular allograft dysfunction in the absence of rejection.

Acute Disease↗

PubMed1999

Immunophenotypic analysis of normal mucosa and squamous cell carcinoma of the oral cavity.

Detection of tumor-associated alterations in peritumoral normal mucosa may give insight into the molecular pathogenesis of oral cancer. In the present study, 100 archival oral squamous cell carcinomaswith adjacent nontumorous mucosa were immunohistochemically investigated with antibodies against p53, Mdm2, Bcl-2, WAF1, MIB1, epidermal growth factor receptor (EGF-R), and various CD44 isoforms. Additionally a standardized argyrophilic nucleolar organizer region (AgNOR)-associated proteins analysis was performed. No correlation was found between p53, Mdm2, Bcl-2, and WAF1 immunophenotypes of the respective tumors and adjacent mucosa. The proliferation-associated markers MIB1 and AgNORs showed a statistically significant sequential increase from normal to dysplastic mucosa to invasive carcinoma. Investigation of various CD44 adhesion molecules revealed a highly variable expression pattern in overt carcinomas with a significantly decreased expression of CD44 v4 and v9 variants and unaltered strong expression of v5 and v6 isoforms compared with normal oral epithelium. We conclude that proliferation markers (MIB1 and AgNORs), as well as selected CD44 isoforms, represent useful markers for the assessment of precancerous lesions. They may be utilized for screening patients at high risk for the development of oral cancer.

Biomarkers, Tumor↗

PubMed1999

Mean weighted nuclear volumes in colonic adenocarcinomas. Evaluation of prognostic significance.

OBJECTIVE: To investigate the correlation of stereologically estimated mean weighted nuclear volumes of tumor cell nuclei (MWNV) with other prognostic factors and survival in colonic adenocarcinomas. STUDY DESIGN: The study group consisted of 42 patients with colonic adenocarcinomas who were treated by a standardized protocol and had a mean follow-up of 89 months. The point sample intercepts method was used to estimate MWNV. In addition, immunohistochemical expression of p53 and Ki-67 was evaluated semiquantitatively. RESULTS: The calculated nuclear volumes correlated significantly with histologic grading and with the extent of tumor progression (organ confined/nonorgan confined). There was no correlation with p53 expression or proliferative activity determined by MIB-1 positivity. No correlation could be demonstrated with sex, age or clinical outcome of the patients. CONCLUSION: Assessment of MWNV in colonic adenocarcinomas does not provide additional information concerning the clinical course.

Adenocarcinoma↗

PubMed1998

Decreased HER-2 tyrosine kinase expression in rectal mucosa of FAP patients following low-dose sulindac chemoprevention.

As a part of the mechanisms of action in reversing FAP adenomas by the low-dose sulindac maintenance therapy (2 x 25 mg/patient per day), the extent of HER-2 proto-oncogene expression in the rectal mucosa seems to be of interest. Immunocytochemical analyses were performed in plasma and in rectal tissue of sulindac-treated FAP patients during an 18 months follow-up and compared with rectal tissue of patients with FAP, Crohn's disease, or rectal cancer or with healthy volunteers. HER-2 was significantly reduced and maintained in tissue under sulindac chemoprevention below base line levels of healthy individuals, but not in plasma. Therefore, a direct or indirect effect of sulindac as a tyrosine kinase inhibitor may be implicated. During NSAID treatment HER-2 protein expression as a prognostic tool seems to be of little clinical relevance.

Adenomatous Polyposis Coli↗

PubMed1998

Possible relationship between heat shock protein 70, cardiac hemodynamics, and survival in the early period after heart transplantation.

BACKGROUND: Heat shock proteins (HSPs) are produced by cells in response to a wide variety of stresses. To determine a possible relationship between hemodynamic parameters and HSP 70 in the early postoperative period after heart transplantation, we examined immunohistochemically the inducible HSP 70 (anti-HSP 72) response in human heart biopsies, as well as the effect of myocardial rejection on HSP. METHODS: A total of 105 routinely processed endomyocardial biopsies from 15 consecutive patients who underwent heart transplantation were examined. Analysis of hemodynamic and echocardiographic parameters were performed within 30 min and 12 hr after the biopsies. RESULTS: Immunohistochemically detected inducible HSP 70 was mainly located in the cytoplasm and nucleus/nucleolus of cardiomyocytes. Two specimens additionally showed HSP 70-positive interstitial cells and smooth muscle cells of arteries, whereas lymphocytes were consistently negative. There was a significant relation between the echocardiographically determined increased relaxation time and positive HSP 70 staining (P < 0.011). Patients with elevated right atrial pressure (P < 0.098), as well as those with increased left ventricular end systolic diameter (P < 0.06), showed a trend to higher HSP expression. Three patients who died of sepsis or multiorgan failure showed significantly higher cytoplasmic HSP 70 expression compared with 12 patients with stable clinical course. In case of rejection, significantly more patients showed no HSP expression. CONCLUSION: Although only five patients showed organ rejection, our results suggest an inverse relationship between HSP expression and rejection with the possibility of a role for HSP 70 as a graft marker to assess graft function.

Biopsy↗

PubMed1998

[Thyroid gland carcinoma].

Carcinoma of the thyroid is a rare tumour, comprising approximately 1% of human malignancies. Thyroid carcinoma is classified according to its origin (thyroid follicular cell or calcitonin-producing C cell) and grade of differentiation (differentiated, poorly differentiated or anaplastic). Due to their different biology, genetical background and clinical course, which result in fundamentally different therapeutic strategies, the various types of thyroid carcinoma have attracted a lot of interest by both clinicians and pathologists. This review article deals with the most important aspects (definition, epidemiology, clinical course, prognosis, differential diagnosis and genetic background) of the various thyroid carcinomas.

Adenocarcinoma, Follicular↗

PubMed1998

Clonal overexpression of metallothionein is induced by somatic mutation in morphologically normal colonic mucosa.

Metallothionein (MT) overexpression occurs frequently in human tumours but the underlying mechanism is unknown. Morphologically normal-appearing mucosa from human colorectal carcinoma resection specimens and of the colons of ageing laboratory mice contains scattered single crypts whose cells show uniformly increased MT immunostaining, suggesting that MT overexpression arises directly from random crypt stem cell somatic mutation, followed by colonization of the clonal unit by the mutated progeny. This hypothesis has now been tested by quantifying the frequency of immunocytochemically detectable monocryptal colorectal MT overexpression, 5 and 30 days after injection of 8-week-old mice with a single dose of the mutagen dimethylhydrazine (DMH, 30 mg/kg subcutaneous). Otherwise normal-appearing MT-positive crypts were recorded as either wholly or partially involved by the overexpressing phenotype. Five days after DMH injection, the median frequency of partially involved MT-positive crypts was 11.7 x 10(-4), declining significantly to 1.8 x 10(-4) at 30 days (Mann-Whitney U, P < 0.01). In contrast, the median frequency of wholly involved crypts was 0.2 x 10(-4) at 5 days, increasing significantly (P < 0.005) to 12.9 x 10(-4) at 30 days. The frequency of MT-positive crypts and the time course of evolution of partially involved to wholly involved forms were similar to those described for mutation-induced crypt-restricted loss of glucose-6-phosphate dehydrogenase activity in mice treated with an identical DMH regimen. The findings indicate that cellular MT overexpression can occur as a direct consequence of somatic mutation, either cis-activating mutation(s) of the MT gene itself, or trans-activating mutation(s) of other genes involved in controlling MT expression. This is likely to be an important mechanism underlying MT overexpression in neoplasia. Such mutation-induced aberrant MT expression may be involved in the acquisition of selective cellular growth of survival advantage during tumour progression.

1,2-Dimethylhydrazine↗

PubMed1998

Molecular assessment of p53 abnormalities at the invasive front of oral squamous cell carcinomas.

BACKGROUND: The prognostic significance of the invasive tumor front in squamous cell carcinomas has recently been recognized. The aim of the present study was to investigate possible molecular mechanisms underlying the significance of this area in oral squamous cell carcinomas. METHODS: We used immunohistochemical and molecular genetic techniques to investigate whether p53 alterations at the invasive tumor front could determine the aggressiveness of oral cancers. RESULTS: p53 Overexpression was detected in 52% to 56% (four different p53 antibodies) of 100 carcinomas studied. The concordance rate between results of immunohistochemistry and genetic analysis was 60%. No correlation was found between p53 status of the tumors and clinicopathologic parameters analyzed statistically. CONCLUSIONS: p53 Alterations have no prognostic impact in oral squamous cell carcinomas and apparently do not represent a molecular basis for the biologic significance of the invasive tumor front. The detection of discordant p53 aberrations between primary and second primary carcinomas in some patients provide evidence for their independent origin, with possible impact on prevention and therapy.

Adult↗

PubMed1998

Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study.

Annexins constitute a family of Ca2+- and phospholipid-binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. To elucidate a possible correlation of those functional proposals with the tissue distribution of annexins, we analysed immunohistochemically the expression of annexins I, II and IV in a broad variety of human tissues. Annexins I and II were chosen for this study since their functionally relevant N-terminal domains are structurally closely related, whilst annexin IV is structurally less related to the former two proteins. The study revealed distinct expression patterns of annexins I, II and IV throughout the body. Annexin I was found in leucocytes of peripheral blood, tissue macrophages and T-lymphocytes and in certain epithelial cells (respiratory and urinary system, superficial cells of non-keratinised squamous epithelium), annexin II in endothelial cells, myoepithelial cells and certain epithelial cells (mainly respiratory and urinary system), whereas annexin IV was almost exclusively found in epithelial cells. Epithelia of the upper respiratory system, Bowman's capsule, urothelial cells, mesothelial cells, peripheral nerves, the choroid plexus, ependymal cells and pia mater and arachnoid of meninges generally strongly expressed all three annexins investigated. The characteristic expression in different tissues and the intracellular distribution indicates that the three annexins investigated are involved in aspects of differentiation and/or physiological functions specific to these tissues.

Annexin A1↗

PubMed1998

"Atypical" medullary thyroid carcinoma with little or no calcitonin expression.

In a retrospective analysis of 142 medullary thyroid carcinomas, four sporadic cases with an unusual histological and immunohistochemical appearance were found. Three cases (two males, one female) had very few calcitonin-positive tumour cells, while the fourth case (male) completely lacked calcitonin immunoreactivity at both mRNA and protein levels, whereas a variety of neuroendocrine markers were positive in at least 50% of tumour cells. The four tumours were completely devoid of carcinoembryonic antigen expression and of amyloid. Differential diagnosis and histogenetic considerations are discussed.

Adolescent↗

PubMed1998

Cell death mechanisms in multiple system atrophy.

The presence and distribution of apoptotic cell death in multiple system atrophy (MSA) and morphologically related diseases were investigated by means of a modified terminal deoxynucleotidyl transferase-mediated nick end labeling method, comparing their distribution with that of glial cytoplasmic inclusions, immunohistochemically demonstrated bcl-2 protein, bax protein, CD95, TNFalpha, and p53-protein expression, as well as activated microglia. Apoptosis occurred almost exclusively in oligodendrocytes in multiple system atrophy and its general distribution was comparable to the already known oligodendroglial pathology in this disorder. Additionally, in about a quarter of glial cytoplasmic inclusions, there was upregulation of bcl-2-protein and coexpression with ubiquitin, suggesting a final attempt of involved cells to counteract apoptotic cell death. Bax protein was also demonstrated in oligodendroglial cells. A significant neuronal apoptosis was not observed in MSA; these cells might be destroyed secondarily to oligodendroglial apoptosis by necrosis or other forms of programmed cell death. These results emphasize the central role of oligodendroglial pathology in multiple system atrophy, making this disease unique among neurodegenerative diseases.

Adult↗