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Biomedical subjects

W Lehmann

Publications and source records attributed to W Lehmann.

At least 73 records · Page 4Linked to original sources

Decreased activity of erythrocyte membrane ATPases in depression and schizophrenia.

Erythrocyte ATP-ase activities were determined in 32 drug-free patients with depression in the course of affective illness, during acute episode, in 24 drug-free patients with schizophrenia, during exacerbation of the illness, and in 25 healthy control subjects. In both depression and schizophrenia, the activities of all three ATP-ases studied (Na-K ATPase, Mg ATPase, Ca-Mg ATPase) were significantly lower than in control subjects. No difference was found between patients with depression in the course of bipolar and unipolar affective illness. In patients with schizophrenia, the activity of Na-K ATPase was lower in the paranoid type of the illness. The results are discussed in the light of contemporary biochemical concepts of major psychoses.

Adenosine Triphosphatases↗

[Positron emission tomography (PET) in the preoperative evaluation of cervical lymph node metastasis of ORL cancer].

The distribution of specific radiolabeled biological compounds in tumor tissues can be imaged by positron emission tomography (PET). The substance used is fluorodeoxyglucose, labeled with the positron emitter fluorine-18. This substance is partly trapped in tumor cells with increased glucose metabolism. This noninvasive imaging technique allows to assess quantitatively and in three dimensions the extent of metastatic disease in ENT cancer. The case presented illustrates the important value we foresee for this new imaging modality in the presurgical staging of cervical metastatic disease of ENT tumors. Sensitivity and specificity of the PET-FDG imaging technique for the loco-regional staging of ENT cancer are, according to preliminary results of an ongoing, prospective clinical study, very high.

Aged↗

Tissue culture of bovine subcommissural organ.

Tissue of the secretory, glial subcommissural organ (SCO) of adult, male cattle was cultured in serum-free medium for 70 days in vitro. Only minor alterations in the histoarchitecture and the cytology of the explanted SCOs could be observed by light and electron microscopy. Light- and electron-microscopic immunocytochemical investigations with an antiserum raised against bovine SCO secretory proteins revealed intra- and extra-cellularly localized immunoreactive material in tissue sections of SCO explants cultured up to 69 days in vitro. An indirect competition enzyme-linked immunosorbent assay (ELISA) was developed to detect minor quantities of SCO secretory products. By means of this assay, approximately 35 ng RF protein per ml was detected in culture medium supernatants conditioned for 3 days in SCO tissue cultures at 3, 38, and 69 days in vitro. These studies demonstrate that the bovine SCO can maintain its secretory activity throughout long periods in vitro.

Animals↗

Immunological cross-reactivities between proteins secreted by the subcommissural organ, and plant lectins.

The glial subcommissural organ (SCO) discharges a glycoprotein-rich secretory product into the third ventricle to form Reissner's fibre (RF). The SCO proteins bear N-linked oligosaccharides, such as mediate many cell-cell and cell-matrix interactions. In such interactions the corresponding partner molecule recognising the sugar chain is often a sugar-specific protein (lectin). We present here evidence that the constituents of the SCO secretory product include proteins immunologically cross-reactive with certain plant lectins. Polyclonal antisera directed against Phaseolus vulgaris agglutinin-L (PHA-L) labelled the apically released RF-material of the rat SCO. Indirect ELISA studies shows in addition that anti-RF antisera bound to certain plant lectins (PHA-L, Con A). Dot spot assays demonstrated binding of anti-PHA-L to RF proteins. In Western blots of RF proteins anti-PHA-L, anti-RCA and anti-Con A bound to distinctive subsets of the RF protein fractions.

Animals↗

Fine-needle aspiration in the diagnosis of head and neck growths: the pitfalls of false-positive diagnosis.

The results of fine-needle aspiration cytology (FNA) performed on 235 patients with head and neck growths were analyzed. The accuracy rate was 83%. The FNA was nondiagnostic in 9%, false negative in 7% and false positive in 1% of the cases. These results are similar to those in other centers. Due to false-negative diagnoses, FNA rarely allows the making of a major clinical decision. False-positive diagnoses oblige the clinician to perform several investigations to assess the diagnosis of nonmalignancy and to reassure the patient. Thus, in our opinion, FNA is helpful for the diagnosis of head and neck growths in some rare situations only.

Biopsy, Needle↗

Bombesin, vasopressin, and endothelin rapidly stimulate tyrosine phosphorylation in intact Swiss 3T3 cells.

The mitogenic neuropeptides bombesin and vasopressin markedly increased tyrosine and serine phosphorylation of multiple substrates in quiescent Swiss 3T3 fibroblasts, including two major bands of Mr 90,000 and 115,000. Tyrosine phosphorylation of these proteins was increased as judged by immunoprecipitation of 32Pi-labeled cells and immunoblotting of unlabeled cells with monoclonal antiphosphotyrosine antibodies, elution with phenyl phosphate, and phospho amino acid analysis. Phosphotyrosyl proteins generated by bombesin and vasopressin did not correspond either by apparent molecular weight or by immunological and biochemical criteria to several known tyrosine kinase substrates, including phospholipase C gamma, the microtubule-associated protein 2 kinase, GTPase-activating protein, or phosphatidylinositol kinase. The effect was rapid (within seconds), concentration dependent, and inhibited by specific receptor antagonists for both bombesin and vasopressin. The endothelin-related peptide, vasoactive intestinal contractor, also elicited a rapid and concentration-dependent tyrosine/serine phosphorylation of a similar set of substrates. These results demonstrate that neuropeptides, acting through receptors linked to GTP-binding proteins, stimulate tyrosine phosphorylation of a common set of substrates in quiescent Swiss 3T3 cells and suggest the existence of an additional signal transduction pathway in neuropeptide-induced mitogenesis.

1-Phosphatidylinositol 4-Kinase↗

Abnormalities of lithium transport across the erythrocyte membrane in depression and schizophrenia.

Three mechanisms of lithium transport across erythrocyte membrane [lithium-sodium countertransport (LSC), lithium-potassium cotransport (LPC), and passive lithium diffusion (PLD)] were estimated in 27 acutely schizophrenic patients, 27 acutely depressed affective patients and in 18 control subjects. The activities of all mechanisms studied were significantly lower in both schizophrenic and depressed patients compared with controls. Analysis by gender showed that in control subjects, mean values of erythrocyte LSC and LPC were significantly higher in males compared with females. The decrease of LSC and LPC in depression and LSC in schizophrenia compared with control subjects was observed only in male patients but not in female ones. The results obtained suggest that lithium transport abnormalities during acute psychotic episodes are not specific to affective patients where lithium exerts its therapeutic action, but are also observed in schizophrenia. These abnormalities are more evident in male patients.

Acute Disease↗

Interdisciplinary rehabilitation of the laryngectomee.

It is to be hoped that human aspects have not been forgotten in spite of all these statistics. Behind all these numbers lie the personal fates of approximately 700 laryngectomees in Switzerland. The interview findings reflect their situation in life. In summary, we can say that: --Half of the laryngectomees lose their job and feel restricted in their daily lives; every third one mentions financial problems. --A third of the laryngectomees are totally or partly unsatisfied with the speech rehabilitation program. --There appear to be remarkable differences within the various language regions in Switzerland with regard to preparation for the operation, speech rehabilitation, and the current life situation of laryngectomees. From our study, we conclude that extensive medical, psychological, and social counseling and assistance for those affected is of great importance. Here we must especially mention the preparation of the patients and their relatives for the operation and its consequences. This should be the task not of one person but of an interdisciplinary team, including a logopedist, a social worker, and also another laryngectomee, with whom contact is often very valuable for the patient. Early speech therapy, reintegration into working life, and improvement of financial status are further factors of great importance.

Female↗

Acinic cell carcinoma of minor salivary gland origin.

The occurrence of acinic cell carcinoma in the minor salivary glands appears to be exceptional. A review of the English language literature revealed about 80 previously reported cases. In this paper, the clinical behaviour and pathological findings in three cases are reported. The tumours took their origin from the hard palate, soft palate and lower lip. The three cases presented with malignant clinical behaviour; all three recurred. In one case the local recurrence was multinodular with capsular infiltration. Two cases developed regional lymph node metastasis, and one metastasized to the lung and liver. In one the tumour infiltrated bony structures, and nerve in another. These cases tend to support the belief of some authors that acinic cell 'tumours' are clinically malignant and should be included in the carcinoma group.

Aged↗

Methylene blue attenuates vasodilation and enhances vasoconstriction in response to endothelin-1 in the pig nasal mucosa.

In thiopentone anaesthetized pigs (n = 10), simultaneous recordings of the vasomotor response to local intra-arterial infusion of endothelin-1 and -3 were performed in three different vascular compartments of the nasal mucosa. Sphenopalatine artery blood flow (reflecting nasal blood flow), nasal cavity volume (representing blood content in capacitance vessels) and laser Doppler flowmeter signal (reflecting superficial mucosal blood flow) increased in response to low doses (4 x 10(-9) to 4 x 10(-8) moles) of endothelin-1. In contrast, marked vasoconstriction (up to 50% of arterial blood flow reduction) occurred upon higher doses (4 x 10(-7) to 4 x 10(-6) moles). Endothelin-3 (4 x 10(-9) to 4 x 10(-6) moles) evoked at the highest dose a long-lasting increase of systemic arterial blood pressure resulting in a 22 +/- 4% increase in nasal vascular resistance. After local intra-arterial pretreatment with methylene blue (4 x 10(-4) mol), the vasodilatory responses to low doses of endothelin-1 were abolished for the three vascular parameters studied, whereas the vasoconstrictor responses in resistance and capacitance vessels evoked by higher doses of endothelin-1 were increased. In contrast, the laser Doppler flowmeter signal reduction in response to endothelin-1 was markedly attenuated. The vasodilatatory effect of substance P was abolished after methylene blue probably due to interference with effects of endothelium dependent relaxing factor (EDRF). These observations suggest that in the pig nasal mucosa in vivo, exogenous endothelin-1 induces a dose-dependent reduction of blood flow in resistance and capacitance vessels and in superficial mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Topographic classification, clinical characteristics, and diagnostic delay of cancer of the larynx/hypopharynx in Torino, Italy.

The case series of a population-based case-control study of laryngeal and hypopharyngeal cancers in Torino, Italy, included 281 men with clinical and anamnestic data. Two hundred fifteen, 28, and 38 cancers originated from the endolarynx, epilarynx, and hypopharynx, respectively. Regions invaded by the tumor were divided into 26 subsites. A classification based on the number of invaded subsites was proposed, which agreed well with the T classification of the TNM system. Cancers originating from the hypopharynx invaded more subsites than cancers from the endolarynx, and among the latter, supraglottic were more invasive than glottic lesions. The number of invaded subsites was strongly associated with nodal involvement. Among symptoms at onset of disease and at diagnosis, patients with endolaryngeal lesions reported dysphonia and dyspnea more frequently, and patients with lesions from other regions had a higher prevalence of dysphagia, odynophagia, otalgia, and adenopathia. Clinical and epidemiologic results of this study suggest considering the endolarynx, epilarynx, and hypopharynx as separate anatomic entities. Diagnostic delay was not associated with tumor size and showed a negative trend with involvement of cervical lymph nodes, suggesting that stage at diagnosis is due to intrinsic differences in tumor aggressiveness.

Carcinoma, Squamous Cell↗

[The role of human papillomavirus in the pathogenesis of papillomas of the upper aero-digestive tract].

The term 'papilloma' is used to describe a highly diverse group of exophytic pathologic lesions in the upper aero-digestive tract. These lesions differ according to anatomic site, constituent epithelium and endoscopic appearance. The varying pathogenesis of papillomas is incompletely understood, but appears to be related both to host factors, e.g. regional differences in the susceptibility of epithelial cells, and to a number of cofactors. Among the cofactors already identified, the human papilloma virus is increasingly recognized as playing an important role in the pathogenesis of laryngeal papillomata and some specific oral proliferative lesions. The systematic identification and characterization of human papilloma viruses in tissues from papillomas will provide the basis for a better understanding of the potential pathogenetic role of these viruses in the development of benign and malignant proliferation in the upper aero-digestive tract.

Head and Neck Neoplasms↗

Bombesin receptor in membranes from Swiss 3T3 cells. Binding characteristics, affinity labelling and modulation by guanine nucleotides.

Bombesin-like neuropeptides, including mammalian gastrin-releasing peptide (GRP), are potent mitogens for Swiss 3T3 cells. In this study, we have characterized the bombesin receptor in membrane preparations from these cells. Addition of Mg2+ during cell homogenization was essential to preserve 125I-GRP binding activity in the resulting membrane preparation. The effect of Mg2+ was concentration dependent, with a maximum at 5 mM. Specific binding of 125I-GRP was saturable; Scatchard analysis indicated a single class of high-affinity sites of Kd = (2.1 +/- 0.3) x 10(-10) M at 15 degrees C and Kd = (1.9 +/- 0.4) x 10(-10) M at 37 degrees C, and a maximum binding capacity of 580 +/- 50 fmol/mg of protein (15 degrees C) or 604 +/- 40 fmol/mg of protein (37 degrees C). The kinetically derived dissociation constant was 1.5 x 10(-10) M. 125I-GRP binding was inhibited in a concentration-dependent manner by various peptides containing the highly conserved C-terminal heptapeptide of the bombesin family, including bombesin, GRP, neuromedin B and the 8-14 fragment of bombesin. In contrast, a variety of structurally unrelated mitogens and neuropeptides had no effect. The cross-linking agent ethyleneglycolbis(succinimidylsuccinate) covalently linked 125I-GRP to a single Mr 75 000-85 000 protein in membrane preparations of 3T3 cells. Affinity labelling of this molecule was specific and dependent on the presence of Mg2+ during membrane preparation. Finally, the non-hydrolysable GTP analogue guanosine-5'-[gamma-thio]triphosphate (GTP[S]) caused a concentration-dependent inhibition of 125I-GRP binding and cross-linking to 3T3 cell membranes [concentration giving half-maximal inhibition (IC50) approximately 0.2 microM]. The inhibitory effect was specific (GMP, ATP or ATP[S] had no effect at 10 microM) and was due to an increase in Kd from (1.7 +/- 0.2) x 10(-10) M to (4.3 +/- 0.6) x 10(-10) M in the presence of 10 microM-GTP[S]. This modulation of ligand affinity and cross-linking implies that the bombesin receptors that mediate mitogenesis in Swiss 3T3 cells are coupled to a guanine-nucleotide-binding-protein signal-transduction pathway.

Animals↗

Bombesin stimulation of c-fos expression and mitogenesis in Swiss 3T3 cells: the role of prostaglandin E2-mediated cyclic AMP accumulation.

Bombesin is a potent mitogen for Swiss 3T3 cells and can stimulate DNA synthesis in the absence of any other growth factor. This effect is mediated by multiple synergistic signaling pathways, including an accumulation of intracellular cyclic AMP (cAMP) and an increase in c-fos mRNA expression. The cyclooxygenase inhibitor indomethacin abolished prostaglandin E2 release and substantially depressed cAMP levels induced by bombesin (EC50 congruent to 10 nM). In contrast, indomethacin at 1 microM did not affect 80K phosphorylation or Ca2+ mobilization by bombesin, indicating that cAMP synthesis can occur through a phospholipase C-independent pathway. Indomethacin caused a 30 to 35% decrease in c-fos induction and DNA synthesis in cells treated with bombesin (EC50 congruent to 40 nM). Significantly, the inhibitory effect of indomethacin was reversed in the presence of forskolin, a direct activator of adenylate cyclase. We conclude that cAMP plays a regulatory role in c-fos induction and mitogenesis in Swiss 3T3 cells treated with bombesin.

Animals↗

Fine-needle aspiration in the diagnosis of head and neck growths: is it necessary?

The results of fine-needle aspiration cytology performed on 150 patients at the Geneva Clinic of Otolaryngology were analyzed. The accuracy rate was 80%. The study was nondiagnostic in 10% of the cases and falsely negative in another 10%. These results are similar to those in other centers. Nevertheless, several recent reports attest to the accuracy of fine-needle aspirations cytology, and in some clinics it is now part of the initial workup of every patient with a growth in the head and neck. On the basis of our own retrospective analysis, we believe fine-needle aspiration is a useful study only in patients with a previously treated malignancy and who have a new lump in the neck suspected to be a recurrence.

Biopsy, Needle↗

Early signals in the mitogenic response of Swiss 3T3 cells: a comparative study of purified PDGF homodimers.

Platelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB. Two distinct receptor subunits, alpha and beta, have been identified which bind either all three isoforms of PDGF (alpha) or PDGF-BB only (beta). Here, we have compared the effect of purified PDGF homodimers on the early intracellular signaling events and mitogenesis in Swiss 3T3 cells, which possess equivalent numbers of the alpha and beta subunits. Both PDGF-AA and PDGF-BB stimulated receptor phosphorylation, inositol phosphate formation, activation of protein kinase C, calcium mobilization, EGF receptor transmodulation, sodium uptake, arachidonic acid release, cyclic AMP accumulation, and c-fos induction in a comparable, dose-dependent manner (half-maximal values for all these response were in the 2-10 ng/ml range for both homodimers). At high concentrations of PDGF (greater than 10 ng/ml), the BB homodimer effect on early membrane and cytosolic signals was 20-30% greater than PDGF-AA, reflecting the greater number of available binding sites for PDGF-BB. DNA synthesis studies indicated that PDGF-AA and PDGF-BB were potent mitogens for Swiss 3T3 cells, displaying identical dose-response effects. Moreover, the mitogenic activities of both homodimers were equally potentiated in the presence of insulin. These results indicate that both PDGF-AA and PDGF-BB stimulate the full complement of molecular responses required for the synergistic interactions mediating long-term mitogenesis. We conclude that alpha and beta receptor subunits do not differ in their ability to transduce PDGF-mediated signals leading to DNA synthesis in Swiss 3T3 cells.

Animals↗