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Biomedical subjects

S Handt

Publications and source records attributed to S Handt.

At least 73 records · Page 4Linked to original sources

Specificity and affinity of monoclonal antibodies against carcinoembryonic antigen.

The binding specificities of 52 well-characterized monoclonal antibodies (Mabs) against carcinoembryonic antigen (CEA) from 12 different research groups were studied by immunohistochemistry and immuno flow cytometry. In addition, the binding constant for the interaction between Mab and CEA was determined by a solution-phase assay. Cryostat sections of colon carcinoma and normal colon, stomach, liver, pancreas, and spleen were studied by immunohistochemistry. Peripheral blood granulocytes, monocytes, and lymphocytes were assayed by immuno flow cytometry. The Mabs used here have previously been classified into five essentially nonoverlapping epitope groups (GOLD 1-5) (Cancer Res., 49: 4852-4858, 1989). Most Mabs cross-reacted with different normal tissues, ranging from highly cross-reactive Mabs (positive reaction with 8 of 9 discriminating tissues) to relatively specific Mabs (positive reaction with 1 of 9 discriminating tissues). Five Mabs (10%) were specific, reacting only with colon carcinoma, normal colon mucosa, and normal gastric foveola. There was a correlation between epitope group and binding specificity. Mabs with a high degree of CEA specificity almost exclusively belonged to epitope groups 1, 2, and 3, while highly cross-reactive Mabs belonged to epitope groups 4 and 5. There was no correlation between antibody specificity and affinity for CEA. Specific Mabs with high as well as low affinity were found.

Adult↗

Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha.

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.

Acanthosis Nigricans↗

Effect of fluoride on aluminum-induced bone disease in rats with renal failure.

Aluminum (Al) accumulation in renal failure is an etiological factor in the pathogenesis of low turnover bone disease. Aluminum-induced impairment of mineralization has been related to a reduced extent of active bone-forming surface. The present study investigated the effect of fluoride, a potent stimulator of osteoblast number, on the toxicity of aluminum in rats with renal failure (Nx). Following a large parenteral aluminum load (3.2 mg/kg x day) over a period of nine weeks, bone histomorphometry of vertebral cancellous bone revealed a severe low-turnover osteodystrophy as evidenced by a fall in osteoblastic osteoid surfaces and mineral apposition rates. Concurrent administration of fluoride [20 mg/liter (F20) or 40 mg/liter (F40) supplied with the drinking water] resulted in a significant increase in the number of osteoblasts (Nx+Al+F40 vs. Nx+Al, 33.75 +/- 2.83 vs. 1.81 +/- 0.43 mm-1, P less than 0.001) together with an overall reduced deposition of aluminum in bone (469.3 +/- 24.6 vs. 592.2 +/- 28.3 micrograms/g, P less than 0.01). However, there was an increase in the fraction of osteoid surface exhibiting stainable aluminum at the bone-osteoid interface (70.7 +/- 7.1 vs. 44.3 +/- 6.0%, P less than 0.005). Fluoride-exposed rats accumulated a significantly larger osteoid volume, suggesting an exacerbation of the osteomalacic lesion, and furthermore, dynamic histomorphometric parameters remained depressed. These results indicate that fluoride has a distinct effect on the pattern of aluminum deposition in bone. In addition, fluoride antagonizes the aluminum-induced reduction in osteoblast number but provides no amelioration of the impaired mineralization in aluminum-intoxicated rats. Thus, in this model a decrease in the extent of osteoblast surface does not account for the development of aluminum-related bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

[EBV in malignant lymphomas].

PCR and in-situ-Hybridization were used to detect EBV-DNA within Hodgkin- and Non-Hodgkin-Lymphomas. By the use of primers for the Bam H1 W fragment we could show EBV-DNA to be associated with 45% Hodgkin- and 25% T-Lymphomas, whereas we could not find EBV-DNA within B-Lymphomas. In about one third of the PCR-positive cases we could localize EBV-DNA mostly in the tumor cell nuclei by in-situ-hybridization.

Base Sequence↗

Induction of intestinal mucosal atrophy by difluoromethylornithine: a nonuremic model of enhanced aluminum absorption.

The intestinal absorption of aluminum (Al) appears to be enhanced in the uremic rat. Since atrophic changes of the intestinal mucosa have been observed in uremia the present study investigated whether intestinal atrophy induced by difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, could affect the absorption of Al. DFMO supplied with the drinking water (5%) to rats with normal renal function for 9 days resulted in a reduced number of microvilli with definite morphological alterations in small intestinal mucosa. Following an oral load of Al urinary excretion rates and 1-hour postload serum concentrations of Al were increased in DFMO-treated rats as compared to controls suggesting enhanced absorption of Al. Pattern and degree of urinary Al excretion as well as ultrastructural alterations of the intestinal mucosa were similar in DFMO-treated rats and uremic rats. The model of DFMO-induced intestinal alterations suggests that structural lesions of the intestine may be involved in the enhanced absorption of Al in uremia.

Aluminum↗

[Vascular architecture of the skin in the postmortem microangiogram].

To demonstrate the detailed vascular architecture of the skin, barium sulphate suspension was injected into the arteries of nine amputated lower limbs. Sections of skin from the foot were fixed in formalin and embedded in paraffin and then examined by high resolution radiography. Subsequently histological sections were prepared and correlated with the micro-angiographic appearances. This technique provided demonstration of the detailed vascular structure of the skin with very little super imposition. The capillary loops in the papillae, the sub-papillary plexus, the glandular components (with the capillaries surrounding the sweat glands), the fine arteries and smallest veins in the cutis could be demonstrated over a prolonged course. Microangiographic and histologic sections were carried out in parallel. These eliminated artifacts and clarified the micro-angiographic appearances. The value of microangiography for demonstrating the vascularity of the skin under normal, pathological and experimental conditions is the subject of further studies.

Aged↗

[The effect of various factors on the progression of kidney insufficiency cause by analgesic nephropathy].

In a retrospective study of 33 patients the influence of different anamnestic, clinical and laboratory parameters on the progression of renal failure was investigated. The analysis of progression of renal failure was evaluated in terms of a reasonable criterium intuitively suggesting itself which is based on a non-linear fitting of the serum creatinine profile. Follow-up serum creatinine levels showed that renal function became worse in 28 cases, with terminal renal failure developing in 6 cases. In 5 patients significant improvement in kidney function was observed. The variables systolic and diastolic blood pressure, total amount of ingested analgesics, continued abuse and cessation of analgesics, frequency of urinary tract infections and amount of proteinuria had no significant influence on progression of renal failure. However, a strong relationship between the initial serum creatinine level and the progression of renal failure could be established. In conclusion our results indicate that long-term prognosis of analgesic nephropathy mainly depends on early diagnosis.

Adult↗

[Percutaneous vascular endoprotheses for occlusions or stenoses of hemodialysis shunts].

In ten patients (four men and six women, mean age 51.7 [26-79] years), with six occlusions and five stenoses of a haemodialysis shunt or shunt-draining subclavian vein, a self-expanding intravascular stent was implanted percutaneously after balloon-dilatation. The implantation was successful in 9 of 11 instances, but the shunt thrombosed in two within 24 hours (in one of the patients, with antithrombin III deficiency, the shunt had to be abandoned). After an average observation period of 7.8 (1-14) months, ten shunts have remained open and suitable for dialysis. A further stent had to be implanted in one of the patients because of stenosis distal to the first stent. In three patients intima hyperplasia within the stent necessitated percutaneous balloon dilatation and/or atherectomy.

Adult↗

[DNA extraction and Southern blot analysis in paraffin embedded material].

DNA was extracted from formaldehyde fixed and paraffin embedded tissue by the use of a modified extraction protocol. In all cases the recovered DNA was more degraded than DNA from fresh or frozen tissue. Fixation times of more than 4 days made it impossible to use the extracted DNA for Southern Blotting; DNA from paraffinized tissues not older than 1 or 2 years could be used for Southern Blotting after digestion with restriction enzymes, but we did not succeed in showing bands with restriction fragments more than 10 kb in length. We conclude that SBA analysis for malignant lymphomas with DNA extracted from routinely paraffin-embedded tissues isn't possible, because the restriction fragments looked for are in many cases longer than 10 kb.

Blotting, Southern↗

What's new in the application of Southern blot analysis of malignant lymphomas?

With the introduction of gene probes for the immunoglobulin and T cell receptor gene segments and the use of the Southern Blot Analysis a new method for the diagnostic characterization of malignant lymphomas was established. Although the method is not absolutely specific for the determination of lineage and clonality of a given lymphoid neoplasm, it provides a lot of additional information for the pathologist. It is the first method that gives proof to the clonality of T cell lymphomas; reactive lymph node processes can be distinguished from true neoplasms; within lymph nodes of mixed lymphoid populations the clonally proliferated can be detected and the lineage can be determined. Therefore the Southern Blot Analysis is a method that should be applied for the diagnosis of malignant lymphomas together with histology and immunohistochemistry. Using the combination of all these methods an extensive characterization of lymphoid neoplasms can be made.

Animals↗

[Transfusion malaria in promyelocytic leukemia].

Five weeks after re-induction treatment and nine days after discharge from hospital, remittent fever occurred in a 34-year-old woman with promyelocytic leukaemia in full remission. She also had haemolytic anaemia and thrombocytopenia, as well as a reduced creatinine clearance. Findings on physical examination were unremarkable, but Falciparum malaria was found in the blood smear. Infusion of erythrocyte or platelet concentrates, administered in treating the leukaemia, was the probable source of the infection. Ten days after starting the administration of chloroquine and sulfadoxine-pyrimethamine she was discharged from hospital, cured of the malaria.

Adult↗

New retrievable percutaneous vena cava filter: experimental in vitro and in vivo evaluation.

A new retrievable percutaneous vena cava filter was tested in vitro and in vivo in 15 foxhounds. In vitro, the new vena cava filter was compared with the standard Kimray-Greenfield filter and the Günther basket filter. The new filter is a stainless steel half-basket filter and is suitable for percutaneous antegrade or retrograde insertion through a 8.5 Fr introducer sheath. In vitro testing showed the filter causing no significant flow alterations and being highly effective in capturing medium- and large-sized thrombi; furthermore, fatigue testing revealed no breakage of the new filter, whereas the Günther basket filter showed breakage of the struts. In vivo studies showed no occlusion, major perforation, or filter migration during follow-up of 2 weeks to 6 months. Tilting of the filter postimplantation occurred in two out of 28 filters. Ten of 11 filters were successfully retrieved by the transjugular approach 2 weeks after implantation. The device seems to be suitable for temporary or permanent protection against pulmonary embolism.

Animals↗

Long-term patency of Wallstent endoprostheses in benign biliary obstructions: experimental results.

PURPOSE: Coated and noncoated Wallstents were implanted in dogs with experimental benign common bile duct stenoses to monitor the long-term patency of self-expanding stents in the biliary system. MATERIALS AND METHODS: Experimental common bile duct stenoses were induced with a thermal laser in 12 dogs. Three silicone-coated and 14 noncoated stents were implanted. The animals were followed up from 3 to 25 months by means of cholangiography, cholangioscopy, measurements of liver enzyme levels, autopsy, and histology. RESULTS: Silicone coated stents failed in all cases, resulting in two total occlusions and one stent dislodgment to the bowel. Noncoated stents led to marked mucosal hyperplasia and stent narrowing in most cases, but with follow-up of more than 12 months, hyperplasia underwent regression and--except in one case--neither an increase in liver enzyme levels nor stent occlusion occurred. Histologically, the extent of hyperplasia was related to the stent position within the duct wall. With stents in the mucosal layer, hyperplasia was excessive. Once the stent entered the submucosal layer, hyperplasia was decreased. CONCLUSION: In an experimental setting, mucosal hyperplasia did not compromise patency of noncoated stents in benign bile duct stenosis and regressed with late follow-up after 12 months.

Animals↗

A large keratan sulfate proteoglycan present in human cervical mucous appears to be involved in the reorganization of the cervical extracellular matrix at term.

OBJECTIVE: To elucidate the function of keratan sulfate proteoglycan (KS-PG) in the human uterine cervix, we analyzed its distribution with respect to physiologic conditions. METHODS: Immunohistochemistry was used to localize KS bearing proteoglycans (mAb 5D4) and decorin (mAb 6B6) in the lower uterine segment. Proteins present in cervical mucous were labeled with biotin, glycosaminoglycan chains were digested enzymatically, and the samples were analyzed by Western blot. RESULTS: Decorin was detected throughout the extracellular matrix, in tissues from menstruating nonpregnant women, in early pregnancy, from women who had cesarean at term, at postpartum hysterectomy, and from postmenopausal women. In menstruating nonpregnant women, in early pregnancy (first trimester), and in postmenopausal women, KS-PG was detectable only in epithelial, mucous-producing cells. Interestingly, in samples obtained either at the time of cesarean at term (lower uterine segment) or after postpartal hysterectomy, KS-PG was detectable throughout the extracellular matrix, indicating that the expression of KS-PG is associated with reorganization of the tissue. Biochemical analysis of the KS present in mucous revealed a core protein in the range of 220 kDa, suggesting an identity with the large KS-PG described previously. CONCLUSION: At parturition, a large KS-PG, which is virtually exclusively present in the cervical mucous of either early or nonpregnant women, was detected in the extracellular matrix. This finding indicates that cervical ripening is accompanied not only by quantitative but also by qualitative changes in the composition of the extracellular matrix.

Adult↗

Imaging of hemodialysis fistulas: limitations of MR angiography.

The clinical feasibility and utility of a three-dimensional (3D) MR angiography (MRA) were evaluated in 20 patients with hemodialysis fistulas. All patients had well functioning shunts and were imaged with a fast imaging in steady precision (FISP) flow rephased and flow dephased sequence. For comparison digital subtraction angiography and color-coded image directed Doppler sonography were used. Of 20 patients studied, 4 interrupted the MR examination due to pain in the shoulder of the extremity imaged. Of the 16 remaining fistulas only 2 were completely displayed on MR including feeding artery, anastomosis, and draining vein(s) on the MRA. Although 15 of 16 feeding arteries were shown by MRA, 10 of 16 draining veins and 14 of 16 anastomoses of the fistulas showed signal voids due to a lack of rephasing. Superimposing the MRA on the dephased images helped to demonstrate the shunt in another four patients having normal shunts. Thus, the utility of 3D MRA in imaging of hemodialysis fistulas is limited by technical problems and by patient's cooperation.

Adult↗

Maxillary sinus augmentation with the xenograft Bio-Oss and autogenous intraoral bone for qualitative improvement of the implant site: a histologic and histomorphometric clinical study in humans.

The aim of the present clinical study was to determine, through histologic and histomorphometric investigations of human bone specimens, whether the addition of autogenous bone to the bone substitute material Bio-Oss can produce a high-quality implant site. To improve vertical bone height, 13 sinus floor elevations were carried out in a total of 12 patients. Augmentation of the maxillary sinus floor was completed using a mixture of Bio-Oss and bone harvested intraorally from the mandibular symphysis, the retromolar space, or the tuberosity region. Following an average of 7.1 months of healing, 36 Brånemark System implants were placed. During this surgical intervention, 23 cylinder-shaped bone biopsies were taken from the augmented maxillary region using trephine burs. Histologic analysis of the bone biopsies revealed that the Bio-Oss granulate was well-integrated into the newly formed bone; 33.1% (+/- 12.4%) of the substitute material surface was in direct contact with bone. Histomorphometric analysis of the samples revealed an average percentage proportion of bone of 18.9% (+/- 6.4%). The bovine substitute material and soft tissue occupied, respectively, 29.6% (+/- 8.9%) and 51.5% (+/- 9.4%) of the measured surface. When the implants were uncovered after an average healing phase of 6 months, all 36 implants had become osseointegrated. The combination of osteoconductive Bio-Oss and osteoinductive autogenous bone thus proved to be a material suitable for application in sinus floor augmentation.

Adult↗

Expression of glucose transporter 1 (Glut-1) in cell lines and clinical specimens from human prostate adenocarcinoma.

BACKGROUND: Increased uptake and metabolism of glucose is a characteristic of malignant transformation. Overexpression of glucose transporters, especially Glut-1, is a common event in human malignancies. To date, little is known about the role of Glut-1 in human prostate cancer (PC). The aim of this study was to investigate the expression of Glut-1 both in PC cell lines and clinical specimens of primary PC. MATERIALS AND METHODS: The PC cell lines DU145, PC3 and LNCaP were assessed for Glut-1 mRNA expression by Northern blot analysis. In a total of 45 primary PC specimens, radioactive (35S) in situ hybridizations (RISH) for Glut-1 mRNA expression were performed on frozen sections. Quantification of Glut-1 expression was obtained by use of an image analysis system. RESULTS: Glut-1 expression was detected in all 3 cell lines. Expression in the more poorly-differentiated cell lines DU145 and PC3 was even higher than in the hormone-responsive LNCaP cell line. In situ hybridizations in primary PC revealed Glut-1 expression just above the detection limit in well-differentiated tumors. Significantly increased Glut-1 expression was detected in moderately- to poorly-differentiated PC. CONCLUSION: Glut-1 is expressed in PC cell lines and primary PC. The level of expression increases with advancing grade of malignancy. These findings support a role for Glut-1 in PC proliferation.

Adenocarcinoma↗

A tricuspid polyurethane heart valve as an alternative to mechanical prostheses or bioprostheses.

The main disadvantages of today's heart valve prostheses are the need for lifelong anticoagulation for mechanical valves and problems with biodegradation for tissue valves. Therefore, a new valve type devoid of these problems would be a major step forward. In order to evaluate a new valve design made by dipmolding with different PU materials, an animal test series was carried out in which two valves from each material were implanted into the mitral position of growing Jersey calves. The surgical procedure and postoperative catheterization data are presented. The survival times ranged between 127 and 291 days. Organs and explanted valves were examined post mortem according to general pathology standards. Specifically, the valves were histologically examined for calcium deposits and investigated by light microscopy, REM and EDAX. All explanted valves showed calcification and immobilization, but the results suggest that at least two PU materials attain survival times which are far beyond the lifetime of bioprostheses under the same implant conditions, justifying further in vivo studies in adult animals.

Animals↗