Characterization of MBT-2 tumour cell “variant” resistant to tumour necrosis factor

Summary Previously we reported sensitivity of MBT-2 murine bladder tumour to tumour necrosis factor (TNF) in vivo and in vitro [8]. We showed that with prolonged exposure of cultured MBT-2 tumour cells to TNF, a resistant MBT-2 variant tumour cell population emerged in vitro. This concurred with the finding of trasient in vivo cytotoxic effect of TNF against MBT-2 tumour. Herein, we delineate phenotypic changes in MBT-2 cells associated with TNF resistance. Parent MBT-2 (MBT-2P) and the TNF-resistant variant MBT-2R cells were compared in terms of in vitro sensitivity to TNF, DNA profile, karyotype and in vitro growth kinetics. We conclude that acquisition of resistance to TNF may be due to cell cycle derangement and differences in in vitro growth characteristics. DNA indices and karyotype of variant MBT-2R cells were not altered, indicating the anti-tumour action of TNF is not-mutagenic.     

Demonstration of the 5-flap technique

Summary Demonstration of the 5-flap technique which is double opposed Z-plasty and Y – V advancement is presented. A 4×4 gauze serves to demonstrate this technique.The authors dedicate this paper to the dear memory of their teacher, the late Prof. Zvi Neuman, who passed away untimely on March 22, 1977     

Osteosarcoma of the Hand and Forearm: Experience of the Cooperative Osteosarcoma Study Group

Background Osteosarcoma is extremely rare in the hand and forearm. Therefore, only limited data are available for planning treatment or predicting the outcome and prognosis of osteosarcoma in the peripheral upper extremity.Methods Epidemiological, clinical, and histopathologic data were analyzed in 39 patients with osteosarcoma of the forearm or hand who were enrolled in studies of the Cooperative German-Austrian-Swiss Osteosarcoma Study Group from 1977 to December 2000. In patients with high-grade osteosarcoma, the treatment entailed surgical resection in combination with chemotherapy, whereas patients with low-grade osteosarcoma underwent only surgery.Results The 5-year overall survival rate among the 33 patients with high-grade central osteosarcoma of the distal upper extremity was 86.2%±6.4%. The 5-year event-free survival rate was 65.4%±9.6%. Five of the eight patients with secondary metastases were in remission at the time of analysis. Four patients died of their disease, and two patients died of chemotherapy-related complications. The mean overall survival rate was 88.0%±6.5% in patients treated by wide or radical tumor resection and was 75.0%±21.7% in patients with nonwide margins of resection. Whether amputation or local resection was performed had no significant influence on the prognosis. All six patients whose osteosarcoma was not classified as high-grade central osteosarcoma were in remission at the time of analysis.Conclusions The results demonstrate a remarkably high survival rate for patients with high-grade osteosarcoma of the hand and forearm and confirm that multiagent chemotherapy in combination with wide excision is a highly effective treatment for this malignant tumor.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Complex role of tumor cell transforming growth factor (TGF)-βs on breast carcinoma progression

Growth inhibition by the TGF-s has been extensively studied in both normal and transformed mammary epithelial cells. It has been proposed that loss of autocrine TGF- mediated growth regulation is a critical event in breast tumorigenesis and several lines ofin vitro andin vivo data support this hypothesis. However, a positive association between the expression of TGF-s by tumor cells and the progression or maintenance of breast cancinoma cells has been observed in many studies inin vivo tumor models. Possible mechanisms for these growth enhancing effects of TGF- include immunosuppression mediated by tumor TGF-s, enhanced angiogenesis, increased peritumoral stroma formation, and cell adhesion. The net effect of tumor cell TGF- on the biology of breast carcinogenesis would depend on the balance between autocrine growth inhibition of mammary epithelial cells and these growth enhancing effects.     

Vertical lengthening of the unilateral cleft lip after a triangular flap repair

Summary A triangular flap repair for unilateral cleft lip is stated to have the potential problem of creating a lip that is too long. Although preoperative measurements were performed with calipers, the gap created in the medial segment was directly measured during the procedure, in order to determine the size of the flap more precisely. Ninety patients with complete unilateral cleft lips underwent a triangular flap repair using this method. The symmetry of the Cupid's bow was evaluated at a follow-up period averaging between six years and three months. Sixty-two lips obtained symmetry and the remaining 28 cases showed a lip which was too long; none of the lips were too short. The comparison between 27 primary palate clefts (UCLA) and 63 primary and secondary palate clefts (UCLP) showed no significant difference in the surgical result. The preoperative shortness of the lip on the cleft side was significantly greater in the too long group (5.01 ± 0.95 mm) than in the symmetry group (4.40 ± 0.87 mm). The width of the flap used was significantly larger in the too long group (3.76 ± 0.79 mm) than in the symmetry group (3.42 ± 0.69 mm). The triangular flap repair with intraoperative measurements is considered to be beneficial, although preoperative measurements provide an optimal design in most cases. It is suggested that the use of a wider triangular flap results in a lip which tends to be too long in spite of the preoperative shortness on the cleft side.     

Differentiation of pancreatic ductal carcinoma cells associated with selective expression of protein kinase C isoforms

Background: The signal transduction pathways important in regulating the growth and differentiation of malignant cells are poorly understood. Recent evidence has implicated activation of the protein kinase C (PKC) family of signaling proteins in pancreatic carcinoma during cytokine-induced cytostasis and differentiation. Methods: A human pancreatic adenocarcinoma (HPAC) cell line was exposed to tumor necrosis factor- (TNF-; 40 ng/ml) for 6 days. Cytostasis and viability were confirmed by daily MTT [(3(4,5)-dimethyl-thiazol-2-yl) 2,5-diphenyl-tetrazolium bromide] and trypan exclusion assay. Protein fractions were isolated daily and subjected to immunoblot analysis for the normal (terminally differentiated) pancreatic ductal cell marker carbonic anhydrase II (CA II) as well as specific PKC isoforms (, , , , and). Results: Growth arrest occurred in HPAC cells after exposure to TNF- for 48 h, with viability maintained above 90% throughout the 6-day time course. CA II immunoreactivity was not detected in untreated controls but appeared after 2 days of TNF- exposure, peaking on day 6. Concurrently, TNF- induced the selective downregulation of PKC-, whereas PKC- levels increased. PKC- and PKC- immunoreactivity did not change. The atypical PKC- isoform developed a doublet banding pattern in response to TNF-, although overall PKC- levels did not change. Conclusions: TNF--induced growth arrest and differentiation in HPAC cells is associated with the selective downregulation of PKC- and upregulation of PKC-.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

Antibodies directed at mouse IL-2-R α and β chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo

The anti-mouse IL-2-R chain mAb TM-1 which, by itself, does not affect IL-2-dependent proliferation throught the high affinity mouse IL-2 receptor, was shown to cooperate in a synergistic way with a set of anti-IL-2-R chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-1/anti- mAb association was four to ten times more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a similar concentration of anti- mAb alone. In addition, a bispecific antibody in which a Fab' fragment of TM-1 was covalently linked to a Fab' fragment of one of the anti- mAb (5A2) was shown to be as efficient as the TM-1/5A2 association. The association of TM-1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-1 which, by itself, had no effect on DTH, induced a two- to threefold decrease in the doses of 5A2 required to suppress this cell-mediated immune reaction.     

The ultrastructure of the epiphyseal plate

A method of fixation has been developed for the cartilage cells of the epiphyseal plate. Improved preservation of the flattened chondrocytes reveals small vesicles that seem to originate in the rough endoplasmic reticulum and are found in large amounts in the Golgi area. Different types of vacuoles can be distinguished in the Golgi complex, e.g. intermediate vacuoles and large vacuoles, the latter usually containing inclusions. It seems likely that the vesicles and vacuoles each play a specific role in the transport and production of sulfated protein polysaccharides.

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Zusammenfassung Es wurde eine Methode zur Fixation der Knorpelzellen aus der Epiphysenplatte entwickelt. die besser erhaltenen abgeflachten Chondrocyten zeigen kleine Bläschen, welche aus dem groben endoplasmatischen Reticulum zu stammen scheinen und in großen Mengen im Golgi-Bereich vorliegen. Verschiedene Arten von Vacuolen können im Golgi-Apparat unterschieden werden, z.B. intermediate vacuoles und large vacuoles, wobei die letztgenannten gewöhnlich Einschlüsse enthalten. Es ist wahrscheinlich, daß die Bläschen sowie die Vacuolen eine spezifische Rolle beim Transport und der Bildung von sulfatierten Proteinpolysacchariden spielen.

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Résumé Une méthode de fixation des cellules cartilagineuses de la métaphyse est mise au point. Une meilleure préservation des chondrocytes applatis montre de petites vésicules qui semblent naître dans l'ergastoplasme et se trouvent en grande quantité au niveau de l'appareil de Golgi. Différents types de vacuoles sont visibles dans cet appareil, à savoir des vacuoles intermédiaires et de larges vacuoles contenant des inclusions. Il parait probable que les vésicules et vacuoles jouent un rôle spécifique dans le transport et la production de polysaccharides de protéines sulfatées.

     

What makes red cells dysmorphic in glomerular haematuria?

Although red cell morphology has been used to localise the site of haematuria in the urinary tract, the cause of red cell deformity is still speculative. We have conducted experiments in vitro using venous red cells which indicate that hypochromia depends mainly upon sodium concentration and occurs when this falls below 75 mmol/l. We simulated the passage of red cells through the renal tubule by sequentially treating them with fluids of composition similar to those in different tubular segments, and produced anisocytosis and hypochromia but not the typical bizarre deformity — the hallmark of glomerular haematuria. We conclude that dual injury is required to produce the typical dysmorphic red cells in glomerular haematuria. First, mechanical damage caused by passage of red blood cells through the glomerular basement membrane followed by a second, osmotic, injury sustained by red cells during passage through the hypotonic tubular segment.     

242. Korrelation klinischer und biochemischer Befunde mit dem Schweregrad einer bakteriellen Peritonitis

Zusammenfassung Anhand von Verlaufsdaten 66 chirurgischer Patienten mit einer bakteriologisch gesicherten Peritonitis sollten harte und weiche Kriterien zur Beurteilung des Schweregrades differenziert werden. Untersuchungskriterien: 1) regionale Ausbreitung, 2) Entwicklung eines Organod. Systemversagens, 3) Leukocytose/Thrombopenie, Körpertemperatur, 4) die Plasmamediatoren Endotoxin/Prostaglandin F₂ (PGF₂), 5) Anamnesedauer (Erstsymptom bis OP), 6) Anzahl erforderlicher Reoperationen und 7) Lebensalter. Zuzuordnende Schweregrade: Grad 1: überlebt, Grad 2: mit Komplikationen überlebt, Grad 3: nicht überlebt. Danach erweisen sich als harte Kriterien: 1) Lokalisation, 2) Anamnesedauer, 3) Leukocytose, 4) Endotoxin > 100 Eu/ml, PGF₂ > 500 pg/ml, 5) Körpertemperatur 38,5°C.     

Diagnostic approach in instability and irritative state of a “lumbar motion segment” following disc surgery—Failed back surgery syndrome

Summary A diagnostic protocol for patients with suspected instability and irritative state of a lumbar motion segment following lumbar disc surgery is presented and the results of internal fixation are analyzed.In this group of patients the clinical picture and physical signs may be quite distinct and suggestive of instability and irritation of a lumbar motion segment, however, in isolation, they do not allow to decide upon surgery. Radiological studies favour a decision for surgery only in cases with an obvious instability of a motion segment. Anaesthethizing the articular nerves permits localization of the irritable segment and non-surgical therapeutic decisions (thermocoagulation) can only be taken in cases of an isolated facet-syndrome when instability has been ruled out. The trial plaster jacket holds the most important position with respect to the indication for internal fixation as demonstrated by the conformity of the results of the plaster jacket and the results of surgery.After internal stabilization excellent, good, satisfactory and moderate results were obtained in 20, 3, 1 and 1 patients, respectively.The German term Bewegungssegment comprises all parts which are involved in the movements of one vertebral segment, i.g. disc, facet joints, ligaments and related muscles.     

Osteosarcoma with multiple skeletal metastases

Summary Osteosarcoma of the thoracic spine developed in a 15-year-old Japanese boy, After his first admission with paralysis, multiple skeletal metastases were demonstrated in the absence of pulmonary metastasis. This rare condition may possibly be considered as a unicentric osteosarcoma with bone metastases, since there were no precursor lesions or history of exposure to radio-active materials or chemical agents. These multiple lesions may be an example of so-called organ-specific metastasis, although this nonstochastic process is rare.     

173. Tierexperimentelle Ergebnisse mit einem voll implantierbaren Distraktionsgerät zur operativen Beinverlängerung

Zusammenfassung Zur operativen Beinverlängerung wurde ein neues Femur-Distraktionsgerät entwickelt. Das Gerät besteht aus einem elektronisch programmierbaren Distraktionsaggregat einschließlich Kraftquelle und einer zweiteiligen Führungsschiene. Das Gesamtsystem ist voll versenkbar und schafft Übungsstabilität während der Distraktionsphase. Die Funktionen Vorlauf — Stop —Rücklauf können transcutan induktiv gesteuert werden. Ein für das Tierexperiment speziell entwickelter Prototyp des Gerätes wurde an Schafen erfolgreich erprobt.     

Expression of cytokines and growth factors in human glomerulonephritides

Numerous experimental studies point to the potential role of cytokines and growth factors in the pathogenesis of renal disease. However, from the various autocrine and paracrine mediators identified in vitro and in animal models, so far only a few have been demonstrated in selected human glomerulopathies. We examined two types of glomerulonephritis (GN): extracapillary GN with anti-neutrophil cytoplasmic autoantibodies (ANCA), an example of an acute form of GN, and mesangial IgA GN, usually a chronic form of GN, with immunocytochemistry, in situ hybridization and the polymerase chain reaction. Normal renal tissue from tumour nephrectomies served as a control. In ANCA-positive GN with active renal lesions (crescents, glomerular and vascular necrosis), infiltrating mononuclear cells in glomeruli and in the interstitium expressed interleukin (IL)-1, tumour necrosis factor (TNF)-, IL-2, interferon (IFN)-, platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-. Cytokine expression was also observed in activated resident cells, including endothelial cells, capsular epithelial cells, smooth muscle cells of vessel walls, fibroblasts and some tubular epithelial cells. In addition, we noted an increase in the cytokine and growth factor receptors TNF-R, IL-1R type II, IL-2R, IFN-R and PDGF-R. In contrast, in mesangial IgA-GN, IL-1, TNF-, IFN- and IL-2 were usually absent in glomeruli. Mesangial expansion in this disorder was accompanied by an increased expression of PDGF, PDGF-R, TGF- and IL-6 in mesangial areas. In both conditions a good correlation was observed between cytokine expression at the mRNA (in situ hybridization) and protein level (immunocytochemistry). These results demonstrate that different cytokine and growth factor patterns are expressed in the various forms of GN, and suggest that the local production of these peptides plays an important role in the pathogenesis and progression of human glomerulonephritides.     

Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate,benign prostatic hyperplasia and prostatic cancer

Summary The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors 1 (TGF-1), TGF-2 and TGF-3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-1 increased, whereas that of TGF-3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-1, TGF-3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.     

Nasal anatomy: The muscles and tip sensation

The author stresses the importance of columellar sensation, nasal tip sensation, and the role of the nasalis muscles in determining the postoperative results of corrective rhinoplasty, especially as these have an influence on the drooping tip and the columellar base. Specific anatomic details of this area are emphasized in order to help the plastic surgeon understand better the normal anatomy of this region and the effects that operative procedures have on successful results if the surgeon understands especially the role of the nasalis muscles.     

Low peripheral perfusion: The cause of pressure sores in patients after open-heart surgery

Summary Pressure sores occurring in patients undergoing open-heart surgery have been accepted as accidental diathermy burns. This etiologic factor is an incorrect explanation. The mechanism must be similar to the one causing urethral strictures in these patients, namely, low peripheral perfusion during pump time. Statistical workup is not available to determine the exact magnitude of the problem, but there seems to be a difference in incidence in various cardiac surgery units. Most of the sores heal spontaneously. Prevention is strongly advocated.     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Über den immunoelektrophoretischen und immunohistologischen Nachweis von Serumeiweißkörpern im Ganglion

Zusammenfassung Im Inhalt von Ganglien konnten in der immunoelektrophoretischen Analyse zahlreiche Serumeiweißkörper — Albumin, Transferrin, ₂-Globulin, weniger ₁-Glykoprotein, ₂-Lipoprotein und Haptoglobin — nachgewiesen werden, während ₂- und _1M-Makroglobuline stets fehlten. Immunohistologisch fand sich bei Verwendung von Antiseren gegen Humanvollserum, Humanalbumin und Human--Globulin eine markierende Fluorescenz auch auf den Fasern der Ganglionkapsel. Bei der immunohistologischen Untersuchung mit einem Antihuman-_1M-Globulinserum ergab sich keine solche markierende Fluorescenz. Der Ganglioninhalt ähnelt offenbar nicht nur durch seinen bekannten Gehalt an Hyaluronsäure, sondern auch in bezug auf die in ihm nachzuweisenden Serumeiweißkörper der Gelenkflüssigkeit.Mit 3 TextabbildungenArbeit auf Anregung und unter Leitung von Priv.-Doz. O. Haferkamp.     

Comparative study of intravenous administration of Ringer’s lactate,Ringer’s acetate and 5% glucose containing these Ringer’s solutions in human being

The effects of the administration of Ringers lactate (L) and Ringers acetate (A) solution on blood biochemistry in human subjects operated for tympanoplasty under general anesthesia were investigated. And the feasibilities of the clinical use of Ringers lactate (LD) and Ringers acetate (AD) solution containing 5% glucose were also assessed. In all cases the rate of infusion was 500ml for initial 20min, and then 5ml·hr^–1·kg^–1 B.W. for 3hr and 10min.There were significant increases in blood L- and D-lactate, pyruvate, and L-lactate/pyruvate ratio in L group. A significant increase in blood acetate but not lactate was found in A group. These metabolic changes were minimal and considered as clinically not significant. The urinary excretion of lactate, pyruvate, acetate and glucose were also negligible. In both LD and AD group, the higher blood concentrations of lactate, pyruvate, acetate and glucose were found than in L and A group. Urinary excretions of these metabolites were much higher in LD and AD group than in L and A group. So glucose containing Ringers lactate or acetate solutions should be administered in appropriate amounts and rate not to induce clinically significant metabolic alterations.(Kuze S, Naruse T, Ito Y et al.: Comparative study of intravenous administration of Ringers lactate, Ringers acetate and 5% glucose containing these Ringers solutions in human being. J Anesth 4: 155–161, 1990)