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Biomedical subjects

S Lang

Publications and source records attributed to S Lang.

At least 163 records · Page 9Linked to original sources

Mucosal prelaminated flaps for physiological reconstruction of intraoral defects after tumour resection.

In order to provide vascularised mucosa for reconstruction of intraoral defects after radical tumour resection, 5 distal radial forearm flaps and 1 fibula flap were prelaminated. Prelamination was performed by fixing small, full thickness mucosa pieces onto the fascia and covering the mucosa with an alloplastic sheet as large as the future flap. The alloplastic material was a silicone sheet (n = 2), a Gore-tex sheet (n = 3) or a titanium sheet (n = 1). The mucosa and the alloplastic material were covered by the skin and subcutaneous tissue which had been elevated to expose the fascia. With the silicone and titanium sheets, the mucosa spread on the fascia and the final flaps were thin, pliable, mucus-producing and larger than the original mucosa pieces. With the Gore-tex sheets, extension of the mucosa was prevented by adhesions and the area of mucosa on the final flap was the same size as the original graft. The six prelaminated flaps were harvested after 8-10 weeks. During this time the patients had radiotherapy and chemotherapy. Preserving the skin and subcutaneous tissue reduced donor site morbidity. Six patients had intraoral defects successfully reconstructed with mucus-producing prelaminated flaps.

Adult↗

Observer variability in the histopathological reporting of needle biopsy specimens of the prostate.

The Scottish Pathology Consistency Group has in previous studies examined the consistency of histopathological reporting of biopsies from the cervix, bladder, bronchus, and rectum. In the current study, consisting of 100 needle biopsy specimens of the prostate, a single hematoxylin-eosin (H&E) slide from each case was circulated in batches of 10 to the 12 pathologists, who filled in a simple proforma. This had two sections: a diagnostic category (benign; suspicious or malignant) along with a standard Gleason score for those regarded as malignant. The majority diagnosis of the 100 cases was benign, 53; suspicious, 1; and malignant, 46. The Kappa value for benign cases versus others was 0.86 and for malignant cases versus others was 0.91. Analysis of the data on Gleason scores showed a value of 0.54 when cases were divided into two categories (2 to 6 v 7 to 10) and 0.41 when three categories were used (2 to 4; 5 to 6; 7 to 10). Although not initially part of the design of the study, the majority diagnosis was compared with the original reported diagnosis. In a small subset, examination of further levels, basal cell antibody staining, along with further clinical information, was obtained. With this added information, it appears that there were probably 52 benign and 48 malignant cases. Of the 48 malignant cases, the group majority diagnosis was malignant, 46; suspicious, 1; and benign, 1. The original reported diagnosis was 56 benign, 1 suspicious, and 43 malignant. The group therefore appeared to perform better than the original reporting pathologists. When compared with the results of our previous studies, this study has shown that the diagnosis of carcinoma of the prostate on a needle biopsy is robust.

Biopsy, Needle↗

Captopril (an inhibitor of angiotensin converting enzyme) inhibits obstructive changes in the neonatal rabbit bladder.

OBJECTIVES: To investigate whether angiotensin II has a role in the regulation of bladder smooth muscle growth and function, we developed a model of bladder neck obstruction (BNO) in the neonatal rabbit and investigated the effect of captopril (angiotensin converting enzyme inhibitor) on the obstructive changes in the developing bladder. METHODS: Partial BNO was induced in a group of 2-day-old rabbits (n = 8) by placing a loose 2-0 silk ligature around the vesicourethral junction. A second group of rabbits subjected to the identical partial BNO procedure (n = 8) was given captopril (1 mg/kg/day). Twelve days postobstruction, bladders from these animals, along with paired controls (n = 8), were harvested and assayed for total protein, DNA, and collagen content. RESULTS: Partial BNO resulted in a 170% increase in wet weight (P < 0.05), 132% increase in protein/deoxyribonucleic acid (DNA) ratio (P < 0.05), 75% increase in total DNA (P < 0.05), and 115% increase in total collagen (P < 0.05). When compared with obstructed animals, captopril administration significantly inhibited the increase in total DNA (P < 0.05) and reduced the amount of total collagen (P = 0.054). Examination of histology specimens demonstrated that captopril inhibited the serosal hyperplasia and collagen deposition associated with obstruction. CONCLUSIONS: These data demonstrate that captopril partially inhibits the changes in the neonatal rabbit bladder associated with obstruction, supporting the hypothesis that angiotensin II is involved in the regulation of bladder smooth muscle growth and collagen production.

Angiotensin-Converting Enzyme Inhibitors↗

Plasticity of neuropeptide Y in the rat superior cervical ganglion in response to nerve lesion.

Axotomy of the rat superior cervical ganglion results in a two-fold increase of neuropeptide tyrosine as determined by radioimmunoassay. On the other hand, treatment of sympathetic neuron cultures with leukemia inhibitory factor, a cytokine that is known to be involved in the up-regulation of galanin after axotomy in vivo, decreases neuropeptide tyrosine messenger RNA. These, apparently contradictory findings, prompted us to investigate the regulation of neuropeptide tyrosine in the axotomized superior cervical ganglion in vivo. For comparison, the regulation of galanin was examined under the same conditions. Compared to control ganglia, the number of neuropeptide tyrosine-positive cell bodies decreased while the density of immunoreactive neuronal processes increased one week after transection of the major postganglionic nerves. The nerve fibres were identified as axons by the absence of MAP2, a somatodendritic marker protein. They extended into both carotid nerves and ramified at the lesion site. In situ hybridization revealed that, although the number of neuropeptide tyrosine messenger RNA-positive neurons was not different from controls, the average grain density/neuron decreased by 40%. When axotomized ganglia were decentralized simultaneously, a three-fold elevation of neuropeptide tyrosine immunoreactivity was detectable by radioimmunoassay and an additional increase in numerical density of neuropeptide tyrosine-immunoreactive nerve fibres was observed. Levels of neuropeptide tyrosine messenger RNA were significantly reduced within postganglionic neurons. This synergistic effect of combined axotomy and decentralization on peptide content was also detected for the neuropeptide galanin that, in contrast to neuropeptide tyrosine, is induced by axotomy or decentralization on protein and messenger RNA level. Therefore, while neuropeptide tyrosine messenger RNA is reduced in axotomized ganglia (most likely in response to leukemia inhibitory factor), the peptide accumulates in axonal processes resulting in increased peptide levels as determined by radioimmunoassay.

Animals↗

Expression of VS38 in osteoblasts and stroma cells of bone tumors.

VS38 is a mouse monoclonal antibody which recognizes an intracytoplasmic antigen of 64 kilodaltons present in normal and neoplastic cells. It was reported to be of potential value in identifying myeloma or plasmacytoma in bone marrow or other tissues. During diagnostic analysis of bone marrow biopsies we noticed a consistent staining of osteoblasts with VS38. This led us to investigate the immunoreactivity in a range of bone lesions. 58 lesions were examined in the current study, including benign and malignant tumors as well as tumor like lesions and processes with reactive bone formation. The Streptavidin-peroxidase complex technique was applied on paraffin embedded sections, with 3-amino-9-ethylcarbazole serving as chromogen. All osteoblasts of reactive origin and part of the osteoblasts of benign neoplasms showed positive immunostaining. The antibody stained stroma cells in 81.25% (13/16) of the cases of benign osteogenic tumors and in 82.35% (14/17) of the osteosarcomas. Additionally, VS38 labelling was observed in bone tumors of fibrohistiogenic origin such as nonossifying fibroma and giant cell tumor, the histogenesis of which is still being debated. On the whole, it can be concluded that antibody VS38 lacks specificity as a plasma cell marker. It shows, however, a striking affinity to osteoblasts and in part also to stroma cells of osteogenic and fibrohistiogenic bone tumors.

Antibodies, Monoclonal↗

Clinical manifestations and diagnostic approach to metastatic cancer of the mandible.

In a 12-month period, metastatic cancer was diagnosed in eight patients. Six of them presented with pain mimicking toothache, temporomandibular joint disorders or trigeminal neuralgia, while two showed osteopenic bone lesions in the panoramic radiography, and perimandibular swelling. Anesthesia of the lower lip was the only common clinical feature. In seven of the eight patients, a whole body bone scintigraphy and single photon emission computed tomography (SPECT) of the skull in combination with a whole body and SPECT anti-granulocyte (Tc-99m MAK 250/183) bone marrow scintigraphy was performed. One patient did not have combined scintigraphy performed secondary to severe systemic illness. In six of the seven, the results were conclusive for a metastatic bone lesion. Biopsies confirmed three patients to have a previously unrecognized primary cancer, one patient to have previously unrecognized recurrent cancer, and three patients to exhibit new metastatic spread of an already diagnosed cancer. Histology revealed breast, lung, renal cancer and a malignancy of inconclusive origin. In the remaining patient, combined scintigraphy suggested osteomyelitis, yet biopsy revealed a prostate cancer metastasis with acute inflammatory cell infiltration. Thus, the scintigraphy pattern of a hot spot in the bone scan and a cold lesion in the bone marrow scintigraphy is highly suggestive of a mandibular metastasis, if accompanied by anesthesia of the lower lip.

Aged↗

Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers.

Due to the low effective permeabilities of peptides at many absorption sites, their structure-permeation relations are of high interest. In this work structure-permeation relations of Met-enkephalin analogues are presented using confluent Caco-2 cells as an in vitro permeation model. Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size. Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to 9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No correlation of permeability and the log(apparent octanol/buffer partition coefficient) was observed. A 40-fold increase of the permeability of metkephamid in the presence of 10 mM EDTA suggested a significant contribution of paracellular transport. Independent support for this conclusion was obtained by visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was observed in the intercallular space only. Metkephamid permeabilities were found to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The addition of verapamil equalized the permeabilities in the a-to-b and b-to-a directions, suggesting the involvement of a P-glycoprotein-mediated secretion mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide, but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met-enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met-enkephalin). The data is in agreement with the literature showing that most compounds secreted by the P-glycoprotein transporter carry a positive charge.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Mucosal prelamination of a radial forearm flap for intraoral reconstruction.

For reconstruction of intraoral soft-tissue defects after radical resection of squamous-cell carcinomas, the microvascular jejunal patch has been a reconstructive graft option of first choice. in addition to other advantages, these jejunal grafts are able to produce mucus. In cases in which the use of jejunal grafts is contraindicated, the fasciocutaneous radial forearm flap has enlarged the spectrum of reconstructive options. A disadvantage is that mucus production will be absent, because mucosal and lining reconstruction is performed with tissue lacking mucus-providing qualities. The authors successfully prelaminated a distal radial forearm flap with buccal mucosa in five patients. Mucosal prelamination of the distal radial forearm flap enables a physiologic reconstruction with resultant mucus production, in combination with the provision of thin, pliable, and resistant flaps. The technique lowers donor-site morbidity because of the preservation of skin and subcutaneous tissue. Reconstruction with fasciomucosal, osteomyomucosal, and myomucosal flaps by this method seems feasible.

Adult↗

[Receptor mediated gene transfer in squamous epithelial carcinoma of the head-neck area].

BACKGROUND: The "Adeno-Virus-Enhanced-Receptor-Mediated" (AVET)-System uses the receptor-mediated endocytosis route to introduce DNA into mammalian cells. By the help of a replication defective adenovirus with endosomolytic activity the coentry of receptor-bound DNA particles is faciliated. The transport to the nucleus followed by gene expression is multifold enhanced. METHODS: Two different permanent cell lines from head and neck squamous cell cancer were transfected with the reportergene for luciferase with either AVET or different liposoms in vitro. RESULTS: In comparison it becomes obvious, that AVET shows a multifold higher transfection rate in vitro than the liposomal formulations applied. CONCLUSIONS: AVET could be used for efficient transfection of epithelial cells, that are fairly reluctant to DNA transfer. Further trials in the mouse model must prove a possible application in vivo.

Adenoviruses, Human↗

The effect of angiotensin converting enzyme inhibition and angiotensin II receptor antagonism on obstructed rat bladder.

PURPOSE: Others have demonstrated that inhibition of angiotensin II production partially ameliorates obstructive changes in the neonatal rabbit bladder. We examined the effect of angiotensin II converting enzyme inhibition and receptor antagonism on the obstructed rat bladder. MATERIALS AND METHODS: Three groups of animals were investigated. Partial bladder neck obstruction was created in 23 rats by placing a 2-zero silk ligature around the vesicourethral junction. Eight rats were given untreated tap water, 9 were given water supplemented with 50 mg./kg. of the angiotensin-converting enzyme inhibitor captopril and 6 were given water with 30 mg./kg. of the angiotensin II subtype AT1 receptor antagonist losartan potassium. Eight unobstructed rats served as controls. After 2 weeks of partial outlet obstruction the animals were sacrificed and bladders were harvested. Routine histological evaluation and assays for total protein, deoxyribonucleic acid and collagen content were performed. RESULTS: Histological evaluation revealed that administration of captopril or losartan potassium resulted in a mild decrease in the degree of obstructive bladder changes. Biochemically neither captopril nor losartan potassium caused a significant decrease in the amount of total deoxyribonucleic acid, protein or collagen content per bladder compared to untreated obstructed bladders. CONCLUSIONS: In contrast to previous studies in neonatal rabbits, neither captopril nor losartan potassium significantly ameliorated the histological or biochemical features of partial bladder outlet obstruction in the rat. Further investigation is necessary into species specific differences to understand better the role that angiotensin II may have in mediating the bladder changes of experimentally induced obstruction.

Angiotensin Receptor Antagonists↗

Localization of transforming growth factor-beta-expressing cells and comparison with major extracellular components in aural cholesteatoma.

Transforming growth factor-beta (TGF-beta) plays an important role in the regulation of extracellular matrix (ECM) deposition by stimulating the synthesis of individual matrix proteins like tenascin and fibronectin. Cholesteatoma shows significant changes in the ECM, supporting the view of a disturbed cell-matrix interaction. The purpose of our present study was to evaluate the distribution of TGF-beta in comparison to the deposition of tenascin, fibronectin, and collagen as major components of the ECM in cholesteatoma (n = 12) by means of histochemistry and immunohistochemistry. We found TGF-beta in lymphocytes and fibrohistiocytes in the stroma of 7 cholesteatomas. In corresponding sections, a marked expression of tenascin and fibronectin was seen manifesting as a continuous band along the epidermal-stromal junction, extending to the deeper stroma. In addition, in those cases of TGF-beta expression, beginning collagen fibril formation was seen in adjacent deeper stroma layers, indicating beginning stromal fibrosis. These results suggest that TGF-beta may be involved in the stimulation of the synthesis of tenascin, fibronectin, and collagen. Furthermore, the enhanced expression of tenascin and fibronectin provides evidence for a deregulated cell-matrix interaction in cholesteatoma associated with the enhanced proliferative process of cholesteatoma formation.

Cholesteatoma, Middle Ear↗

[What are you doing when you are doing nothing? ERP components without a cognitive task].

Two experiments, an "active" and a "passive" oddball-paradigm (1. phase) with visual and auditive stimuli were performed. In both, two stimuli with a probability of 0.7/0.3 were presented. The oddball-sequence was replaced in the 2. phase without knowledge of the subjects by a sequence, in which only targets were presented. One group of the subjects has got an active task (counting the rare stimulus), the other group was told to view the stimuli passively. The rare stimulus in the oddball-sequence evoked a larger parietal P3, the auditive stimulation additionally a larger fronto-central N1 and the visual stimulation a larger central P2. The non-expected change into the 2. phase resulted in a reverse of the ERP-lateralization between 150-300 ms: Before the change of the probability the amplitudes were more negative left than right, thereafter more negative right than left. All components and effects in the active task maintained without task, but they decreased. The differences were larger with the visual stimuli. These results suggest, that the passive paradigm could be applied to patients with motoric deficits. From a theoretical point of view these results lead to certain difficulties in the interpretation of the functional importance of the P3. It can be explained better by the context-closure theory (Desmedt, 1980; Verleger, 1988) than by the context-updating theory (Donchin, 1981).

Adult↗

Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer.

Our previous observations in LNCaP cells in vitro demonstrated an association between apoptotic cell death resistance and SGP-2 (Clusterin) overexpression. Accordingly, we hypothesized that high levels of cellular SGP-2 would aid in identifying biologically aggressive prostate cancer cells with unique survival advantages. To test this hypothesis, 40 archival radical prostatectomy and/or biopsy specimens of varying grades of prostate cancer were subjected to immunohistochemical SGP-2 staining. The resulting epithelial stains were quantified subjectively on a scale of 1-3 by four independent observers. Benign prostatic epithelial cells from young donors served as controls and showed a consistently weak staining intensity. In contrast, prostate cancer specimens showed varying degrees of staining intensity that correlated with a Gleason pattern (P = 0.006). This correlation supports the hypothesis that protection from apoptotic death may account, in part, for biologically aggressive tumor behavior.

Adenocarcinoma↗