Elevated concentrations of γ-enolase in renal cell tumors in rats: similarity to renal cell carcinoma in man

Concentrations of enolase isozymes in normal kidney and renal cell tumors in rats were determined using a highly sensitive enzyme immunoassay, and the isozymes were immunohistochemically localized in tissue sections. Levels of -enolase in renal cell turnors were significantly lower than in normal kidney, whereas those of -enolase were significantly elevated (mean ±SD:211±129 ng/mg protein, n=15, as compared to 27.1±2.9 ng/mg protein, n=7). The proportion of -enolase in the total enolases in the tumor tissues (1.6±0.5%) was significantly higher than in normal kidney (0.15±0.005). Immunohistochemistry revealed epithelial cells of all nephron segments to be positive for the -isozyme, whereas -enolase staining was strongly positive only in the loops of Henle, being faint in the distal tubules and absent in the proximal tubules. Both - and -enolases demonstrated positive immunostaining in all of the seven renal cell tumors studied. These findings indicate that an isozyme switch from - to -enolase occurs during rat kidney carcinogenesis, taking into account the derivation from proximal tubules, consistent with the findings for renal cell carcinomas in man.     

Immunological comparison between prostate-specific antigen and γ-seminoprotein

Summary Prostate-specific antigen (PA) and -seminoprotein (-Sm) were compared by immunocytochemical, immunodiffusion and immunoblotting methods using rabbit anti-PA antibody and rabbit anti--Sm antibody. Enzyme immunoassys (EIAs) were developed for measurements of PA and -Sm to determine a correlation between serum PA and -Sm levels in patients with prostate cancer. The patterns of localization and distribution of PA and -Sm were identical in prostate tissue sections, including benign and cancerous human prostacs. The immunodiffusion study showed that the antigens with which anti-PA antibody and anti--Sm antibody reacted in seminal plasma and prostate tissue homogenates were identical to each other. In the immunoblotting study, anti-PA antibody and anti--Sm antibody recognized a single antigen corresponding to a molecular weight of approximately 33,000 both in seminal plasma and prostate tissue homogenates. The EIAs developed in this study were sensitive, specific, and reproducible, and the correlation between serum PA and -Sm values determined by these EIAs was highly significant (r=0.99, P(0.001). These results indicated that PA and -Sm were immunologically identical and that serum PA and -Sm determined by immunoassays using anti-PA antibody and anti--Sm antibody should be evaluated as identical tumor markers for serodiagnosis of prostate cancer.     

Changes in the productivity of cytokines and active-oxygen in peripheral blood cells following surgery

An investigation was carried out on the productivity of cytokines and active-oxygen by peripheral blood cells during the pre- and post-operative periods. While the preoperative production of tumor necrosis factor (TNF) and interleukin-l (IL-1) was elevated, that of lymphotoxin (LT) and interferon- (IFN-) were slightly suppressed. In the postoperative period the peak TNF and IL-1 and active-oxygen productivity was elevated, while LT and IFN- productivity was suppressed in patients with an intraoperative bleeding volume of more than 1,000 ml compared to those with that of less than 1,000 ml. Thus, stress stimulates the TNF and IL-1 and active-oxygen producing system, that is, the macrophage-neutrophil system, and suppresses the LT and IFN- system, being, the inflammatory helper T cell system, in the early postoperative period.     

Cyclooxygenase-2 Inhibition Improves Macrophage Function in Melanoma and Increases the Antineoplastic Activity of Interferon γ

Background: Melanoma inhibits macrophage tumoricidal activity and increases the expression of cyclooxygenase-2 (COX-2). In this study, we sought to determine whether inhibition of COX-2 could restore macrophage function and hence maximize the antitumor activity of the immune stimulant interferon (IFN).Methods: Peritoneal macrophages were exposed to B16 melanoma-conditioned medium for 24 hours with or without the COX-2 inhibitor NS-398 and then were stimulated with lipopolysaccharide and IFN. Cytotoxic activity, nitrite production, and cytokine production by the stimulated macrophages were measured. In addition, B16 melanoma cells were implanted intradermally into mice treated with IFN (14,000 U on alternate days) alone or with a combination of IFN and a COX-2 inhibitor (NS-398 or nimesulide). Mice were assessed for tumor growth and survival.Results: Macrophage cytotoxicity and nitrite production were significantly suppressed by melanoma-conditioned medium (P < .01). This was prevented by 200 M of NS-398 (P < .05). In vivo, combined treatment with IFN and a COX-2 inhibitor caused a significant inhibition of tumor growth (P < .01) and improved survival (P = .02) compared with controls.Conclusions: COX-2 inhibition reversed melanoma-induced suppression of macrophage function, and combined treatment of IFN plus a COX-2 inhibitor was maximally effective in reducing tumor growth and improving survival.     

Interrelationship between immunocompetent and structural cells in post-burn scars

It has been suggested that immunological factors play a major role in the pathogenesis of hypertrophic scars. Characteristically there is an onset of typical clinical features and, after a variable period of activity, there is a phase of remission. The factors which produce this progressive change in the scars are not clear, and it is not known if their manipulation could provide a therapeutic progress. In order to further investigate the pathophysiology, morphological studies have been performed. In active hypertrophic scars lymphocytic infiltrates are abundant. Among them activated T-cells represent 70% of infiltrates while in normotrophic scar activated T-cells make up 30% of lymphocytes, suggesting a role of these cells in the mechanisms leading to scar hypertrophy. Upon activation, the lesional T-cells release several cytokines which may induce anomalous expression of activation markers (HLA-DR, ICAM-1, CD36, IL-2R) on keratinocytes and fibroblasts of hypertrophic tissue. A wide range of cytokines has been examined: among those analyzed the only one that changes in the remission phase is IFN. In fact, IFN is highly expressed in lymphocytes in active hypertrophic scars while it is less expressed in the remission phase and in control samples.Presented at the European Burns Association State of the Art Symposium, Control of the Burn Scar, Amsterdam, The Netherlands, October 4–5, 1996     

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.     

Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy

Background: The anticancer role of tumor necrosis factor-alpha (TNF-) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-) activity to abrogate TNF- toxicity. Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF- and anti-IFN- antibody (Ab) to evaluate the effect on the acute lethality of TNF- and their efficacy as evaluated by tumor growth rate, tumor histology, and survival. Results: Anti-IFN- Ab decreased TNF- lethality. Anti-IFN- Ab alone increased tumor growth significantly more than did nonimmune IgG (p₂<0.0001). Tumor-bearing mice that received nonimmune IgG and TNF- had slower tumor growth (p₂<0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN- Ab abrogated the antitumor effect of TNF-, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN- Ab and high-dose TNF- were comparable with those in mice that received a lower, equitoxic dose of TNF- alone. Conclusions: Blocking endogenous IFN- accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF- equally. This suggests that blocking endogenous IFN- activity is not a useful strategy for limiting TNF- treatment toxicity.Presented in part at the 45th Annual Cancer Symposium of The Society of Surgical Oncology, New York, New York, March 15–18, 1992.     

Use of a pericardial fat pad flap for preventing bronchopleural fistula: An experimental study focusing on the angiogenesis and cytokine production of the fat pad

An experimental study was conducted to determine whether pericardial fat tissue could induce neovascularization and produce cytokines related to tissue repair. Neovascularization was examined using chick chorioallantoic membranes. Pieces of pericardial fat tissue, omentum, and intercostal muscle were individually placed on a number of chorioallantoic membranes and neovascularization induced by each material was assayed 6 days after the implantation. The intensity of neovascularization was in the order of pericardial fat omentum > muscle. Cytokines, such as interleukin 1 (IL-1) and , tumor necrosis factor- (TNF), interferon- (IFN-), and interleukin 6 (IL-6) were assayed in a culture supernatant of pericardial fat tissue. The latter was obtained 24h after the addition of lipopolysaccharide (LPS) following various incubation times. All cytokines other than IFN are known to play a part in tissue repair, whereas IFN is negatively related to tissue repair because it inhibits fibroblast growth. The pericardial fat tissue incubated with LPS produced a certain amount of IL-1 on day 1, and TNF on days 1 and 8, whereafter these values decreased to an undetectable level. Irrespective of the addition of LPS, a large amount of IL-6 was observed in the supernatant of pericardial fat tissue and it was detectable until day 29. On the contrary, INF was not detected at any assay time. These observations suggest that a pericardial fat pad flap could possibly be beneficial in the prevention of bronchopleural fistula after pulmonary resection.     

Premature craniosynostosis a retrospective analysis of a series of 52 cases

Summary A retrospective analysis of a consecutive series of 52 cases with premature craniosynostosis is presented.Excellent functional, cosmetic, and social results could be achieved by resection of prematurely fused sutures and the creation of artificial growth sutures. Pronounced skull deformities have been corrected using the basket handle, the visor plasty, and the T-bone techniques or a combination of several of these skull form correction techniques. The surgical correction of the skull base by the frontal advancement technique in combination with orbitotomy was only necessary in 2 of our cases and could have been considered in 2 additional cases viewed retrospectively.Our results support the hypothesis that the primary cause of skull deformity is the premature closure of vault sutures and not a primary deformity of the skull base.     

Effect of tumor necrosis factor-α and interferon-γ on the growth of human prostate cancer cell lines

Human recombinant tumor necrosis factor- (rTNF-, 10^-12–10^-8 M) inhibited the proliferation of androgen-dependent LNCaP cells by 32–56%. In contrast, proliferation of androgen-independent PC-3 and JCA-1 cells was only slightly inhibited, or not inhibited at all, respectively. Human recombinant interferon- (rIFN-, 500 U/ml) decreased proliferation of PC-3 and JCA-1 cells by 35% and 53%, respectively, but had no effect on LNCaP cells. Interestingly, the combination of rIFN- and TNF- had greater antiproliferative effects on JCA-1 cells than treatment with either cytokine alone. However, the antiproliferative effects of this combination were similar to those observed for PC-3 or LNCaP cells treated with rIFN- or TNF- alone, respectively. These data suggest that some forms of androgen-independent prostate cancer may benefit from a combination therapy of IFN- and TNF-, while the use of IFN- alone may be more efficacious in others.     

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.     

Inhibition of parathyroid hormone-induced fetal rat bone resorption in vitro by nerve growth factor

Summary The effects of 7S nerve growth factor (NGF) and its isolated , , and subunits on bone resorption were assessed in a tissue culture system in which the degree of resorption was determined by measuring the release of⁴⁵Ca from prelabeled fetal rat radii and ulnae. It was found that 7S-NGF, through the activity of its , subunit, inhibits parathyroid hormone (PTH)-stimulated but not-unstimulated bone resorption.The following observations suggest that -NGF, a trypsin-like molecule, blocks PTH-induced bone resorption by enzymatic degradation of PTH: (a) -NGF does not inhibit bone resorption stimulated by the steroid, 1,25-dihydroxycholecalciferol; (b) trypsin is as effective as -NGF in inhibiting PTH-stimulated bone resorption; (c) the PTH-inhibitory action of both -NGF and trypsin are eliminated by inactivating these enzymes with diisopropyl fluorophosphate; and (d) addition of -NGF to the cultures 2 days after the inclusion of PTH does not result in inhibition of bone resorption. Similarly, when the subunit is added to the culture medium before the hormone, there is no inhibition of resorption. The latter observation suggests that the target of -NGF is the PTH molecule rather than its membrane receptors.Crystalline bovine insulin inhibits the -NGF suppression of PTH-induced bone resorption. This effect, however, is not mimicked by the addition of zinc, which is present in commerical insulin preparations, to the culture medium. Consequently, insulin must inhibit NGF by some mechanism other than the influence of zinc.     

An immunohistochemical study of glucagonoma conducted on the metastatic lymph nodes from a patient with recurrent metastatic glucagonoma: Report of a case

In this report, we briefly present the case of a 67-year-old woman who developed recurrent glucagonoma with lymph node metastasis. An immunohistochemical study of the metastatic tumor revealed immunoreactivity of glucagon and protein kinase C (PKC)-, -, and - in the tumor cells, two types of which were seen by electron microscopy. One type had abundant secretory granules and mitochondria, while the other had few granules and mitochondria. Some granules were similar to typical A cell granules and others were atypical. An immunoelectron microscopic demonstration revealed PKC-, -, and - immunostaining in the cytoplasm of all the tumor cells, while some secretory granules had PKC immunostaining, and others had no immunostaining. Thus, it appears that metastatic glucagonoma and its associated granules are composed of two types of mature and immature cells or granules. As immunoreactivity of PKC- and - was found in the tumor cells, but not in the normal A cells of the islets of Langerhans, the PKC subspecies and , which are not present in normal pancreatic A cells, may exist in human glucagonoma cells.     

Acoustic Neurinoma and Its Treatment Using the Leksell γ-Knife as a Primary or Secondary Treatment

Over 4 years (1992–1996) we have treated 122 patients with unilateral acoustic neurinoma using the Leksell -knife; 121 patients had a follow-up of 2–48 months (median 24 months). Tumor volume was 0.1–17.8 cm³ (median 2.9 cm³); dose to the tumor margin was 10–17.5 Gy (median 12 Gy) delivered on 40–80% isodose (median 50%). A decrease in the tumor volume was observed in 41.3% of patients, the tumor volume was unchanged in 54.6%, and an increase in the tumor despite radio-surgery was observed in 4.1%. Hearing loss was detected in 17.4% of patients, and 3% of patients gained useful hearing after radiosurgery. The overall risk of the method is 4.3% of hearing loss. Weakness of the facial nerve was observed in 1.9% of patients; normalization of the weakness, which was present before radiosurgery, was observed in 6.3% of patients. The overall risk of facial weakness is 1% for -knife radiosurgery. Impairment of trigeminal neuropathy was observed in 5% of patients and improvement in 31%. Impairment of vertigo was observed in 5.8% of patients and improvement in 46%. Leksell -knife radiosurgery was the primary treatment in 97 patients (80.7%); microsurgical resection preceded radiosurgery in 24 patients (19.8%). Hearing loss and neuropathy of facial and trigeminal nerves before -knife radiosurgery were significantly more frequent in the group of patients with previous microsurgical resection than in the group with -knife radiosurgery as the primary treatment. After radiosurgery there was no significant difference in impairment or improvement of hearing, facial and trigeminal nerve neuropathy, and vertigo and imbalance for the groups of patients with previous microsurgery or primary -knife treatment. After -knife radio-surgery neuropathy of facial and trigeminal nerves in the group of patients with previous microsurgery was significantly worse.     

Die Bedeutung des Antikörpermangelsyndroms für die Chirurgie

Zusammenfassung Bedeutung und Form des Antikörpermangelsyndroms (Synonyma in der Literatur: A- und Hypogammaglobulinämie, Immunkörperparese, Immunkörpermangel) werden beschrieben. Für die Diagnose und erforderliche Therapie sind die anamnestischen und klinischen Daten (Kette von Infektionen; schwerer Verlauf blander Infektionen; klinischer Verlauf durch Antibiotica allein unbeeinflußbar, durch Kombination mit -Globulinlösung gut beeinflußbar; Summation von Infekten mehrerer Organe in der postoperativen Phase) wichtiger als die Laboratoriumsdaten (A- und Hypogammaglobulinämie durch Papier- oder Immunoelektrophorese oder Fehlen des -Globulinanstieges im akuten Stadium der Infektion; Ausbleiben der Antikörperbildung nach Immunisierung).Für die Therapie akuter, insbesonder septischer Infektionen werden empfohlen:Alle 6 Std 0,2 g/kg Körpergewicht=10 ml der 16% igen -Globulinlösung intramuskulär oder 10 ml der 5% igen Lösung intravenös (max. 50–60 ml).Wenn aus anderen Gründen (Flüssigkeits- und Elektrolytersatz) eine Infusionstherapie angezeigt ist, kann man 20–40 ml der 5% igen -Globulinlösung der Infusionslösung zufügen.Als Erhaltungsdosis bei besonderer Infektionsgefährdung sind 0,2 g/kg Körpergewichtmonatlich ausreichend, d.h. pro Woche 10 ml der 16% igen Lösung intramuskulär.Fünf eigene Fälle mit AMS und die Erfahrungen mit der -Globulintherapie bei etwa 30 Patienten werden beschrieben.Mit 1 TextabbildungHerrn Professor Dr.A. Fromme zur Vollendung des 80. Lebensjahres.     

A Rapid Multiparameter Approach to Study Factors that Regulate Osteoclastogenesis: Demonstration of the Combinatorial Dominant Effects of TNF-α and TGF-ß in RANKL-Mediated Osteoclastogenesis

Macrophages differentiate into osteoclasts in response to the critical cytokine RANKL. However, the efficiency of RANKL-mediated osteoclastogenesis can be profoundly influenced by various cytokines. While studies describing the isolated effects of particular cytokines on osteoclastogenesis have been performed, combinatorial effects of cytokines have not been addressed routinely due to the absence of an efficient assay system. To study the effects of cytokine combinations on osteoclast formation, we performed in vitro assays using either the RAW293 cell line or primary murine splenic macrophages as osteoclast precursors. Using a multiparameter cytokine plating method, we analyzed osteoclastogenesis in response to multiple combinations of the following inflammation-related cytokines: RANKL, IFN-, TNF-, IL-1, IL-6, IL-10. We further investigated the role of T-cell-related cytokine combinations on osteoclastogenesis by measuring osteoclast area in response to RANKL with IFN-, IL-2, IL-4, IL-6, TGF-ß, and TNF-. Treatments with RANKL, TNF-, and TGF-ß induced maximal osteoclast formation, suggesting a role for these cytokines in the most aggressive forms of inflammatory bone loss. TNF- alone, however, was unable to induce osteoclast formation in the absence of RANKL despite co-administration of other proinflammatory cytokines. IFN- was a potent inhibitor under all conditions, implicating T cells and NK cells in osteoclast inhibition. These studies demonstrate a rapid screening approach for identifying the potential collective effects of multiple factors on osteoclastic bone resorption.     

Serum protein changes in patients with acute cerebral diseases

Zusammenfassung Es wird über elektrophoretische Untersuchungen der Serumproteinzusammensetzung bei 250 neurochirurgischen Patienten berichtet. Das Serumalbumin war bei 68% der Fälle vermindert, am häufigsten und ausgeprägtesten bei Hirnabszessen, subduralen Hämatomen, meningealen Reizzuständen, Glioblastomen, zentralen und spinalen Metastasen und Hirnstammtumoren. Die quantitativen Veränderungen der Globulinfraktionen zeigten interessante Beziehungen zu dem Ausmaß und dem Grad der Einbeziehung des Hirnstammes in den pathologischen Prozeß und zur Abwehrlage des Organismus. Bei schnellwachsenden Tumoren, metastatischen und entzündlichen Prozessen geht mit dem Albuminabfall ein Anstieg des ₂-Globulins und ein Abfall der -Fraktion parallel. Prozesse, die zu einer chronischen oder intermittierenden Hirndrucksteigerung führen, zeigen eine stärkere Zunahme der -Fraktion bei niedrigem -Globulin. Das Albumin ist dabei je nach dem Grad der Beeinträchtigung des Allgemeinzustandes mehr oder weniger gesenkt. Starke Dysproteinämien mit Senkungen des Albumins, der - und -Fraktionen waren meist prognostisch infaust. Andererseits kann aber auch ein protrahierter Abfall des ₂-Globulins und des Albumins bei stark erhöhtem -Globulin eine schlechte Prognose anzeigen und auf ein akutes Versagen der Leberfunktion und der ergotropen Abwehrreaktionen hinweisen. Wenn man der Beurteilung der Elektrophoresebefunde das hier angewandte Verfahren der Auswertung zugrunde legt, so lassen sich daraus wertvolle Hinweise auf die Störungen des Allgemeinzustandes, auf die Notwendigkeit einer vorbereitenden Behandlung und auf die Operationsfähigkeit der Kranken ableiten.

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Summary Author reports about the electrophoretic examination of serum proteins in 250 neurosurgical patients. Serumalbumin was diminished in 68% of the cases, this being most marked and most frequent in brain abscesses, subdural hematomata, meningeal irritation, glioblastomas, central and spinal metastases and tumors of the brain stem. The quantitative changes of the globuline fractions showed an interesting relationship with the extent and degree of brain stem involvement in the pathological process, and the defensive reaction of the organism. In rapidly growing tumors, metastatic and inflammatory processes there is a decrease in albumin, a rise of ₂-globuline and a decrease of the -fraction. Processes that show a chronic or intermittent rise in intracranial pressure are paralleled by a marked rise in - globuline, the -fraction remaining low. Albumin is diminished according to the degree of interference of the process with the general condition of the patient. Marked dysproteinemias with descent of albumin, - and -fractions, generally had an infaust prognosis. On the other hand a protracted decrease of ₂-globuline and albumine together with a high -globuline dosage may indicate a bad prognosis and be the first signs of an acute failure of the function of the liver and the ergotropic defense mechanisms. Correlating the results of electrophoresis with the data as stated above, allow to draw important conclusions as to the general condition of the patient, the necessity of a preparatory treatment and the operability.

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Resumen Se describen los resultados del estudio electro-forético de la composición de la proteina sérica en 250 enfermos neuroquirúrgicos.La albumina estaba disminuida en el 68% de los casos, con más frecuencia e intensidad en los enfermos que presentaban abscesos cerebrales, hematomas subdurales, irritaciones meníngeas, glioblastomas, metástasis, tanto cerebrales como espinales, y tumores del tronco cerebral. Las alteraciones cuantitativas de las fracciones globulinicas muestran interesante relación con la intensidad del grado de la afectación del tronco cerebral por el proceso patológico y con la capacidad de resistencia del organismo. En los enfermos que presentan tumores de crecimiento rápido, asi como procesos metástásicos y procesos infiamatorios, se observa paralelamente a la disminución de albúmina de la ₂-globulina y una caida en la fracción gamma. Aquellos procesos que ocasionan un aumento crónico o intermitente de la presión intracraneal muestran un acentuado aumento de la globulina con valores bajos de la fracción. En estos casos la albumina esta disminuida en relación directa con el grado de afectación del estado general. Disproteinemias intensas con disminución del albumina y de las - y -globulina fueron, la mayoria de las veces, indice de un pronóstico fatal. Por otra parte una caida subintrante de la ₂-globulina y de la albúmina con un aumento intenso de la fracción y también puede indicar un pronóstico malo demostrando la existencia de un fracaso agudo de las funciones hepáticas y de las reacciones de defense ergotropas. Si nos basamos en el sistema aquí empleado para la valoración de los resultados del estudio electro-forético se pueden obtener del mismo valiosas indicaciones sobre las posibles alteraciones del estado general, la necesidad de un tratamiento preparatorio preoperatorio y en fín, sobre la operabilidad del paciente.

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Résumé Etude chez 250 malades neurochirurgicaux des protéines sériques par électrophorèse. La sérum-albumine était diminuée dans 68% des cas, avec une fréquence et une intensité maxima dans les abcès du cerveau, Ies hématomes sous-duraux, les états irritatifs méningés, les glioblastomes, les métastases cérébrales et médullaires et les tumeurs du tronc cérébral. Les modifications quantitatives des fractions de globulines révélaient des relations intéressantes avec le volume et le degré de l'envahissement du tronc cérébral dans le processus pathologique et le degré de résistance de l'organisme. Dans les tumeurs à développement rapide, les processus métastatiques et inflammatoires, une augmentation des globulines 2 et une diminution de la fraction marchent parallèlement à la diminution des albumines. Les processus qui causent une hypertension crânienne continue ou intermittente montrent une augmentation importante de la fraction avec des globulines basses. L'albumine est plus ou moins abaissée selon le degré de l'atteinte de l'état général. Les dysprotéinémides importantes avec baisse des albumines, des franctions et ont le plus souvent une signification pronostique défavorable.D'autre part, une chute lente de l'₂ globuline et de l'albumine avec une globuline élevée peut aussi indiquer un mauvais pronostic et traduit une déficience aigue de la fonction hépatique et des réactions de défense ergotropes.Si on prend pour base de l'interprétation de l'électrophorèse la méthode d'appréciation que nous indiquons ici, on peut en tirer des indications intéressantes sur les altérations de l'état général, sur la nécessité d'un traitement préparatoire et sur l'opérabilité du malade.

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Riassunto L'A. riferisce su ricerche elettroforetiche concernenti la composizione delle proteine sieriche di 250 pazienti con affezuoni neurochirurgiche.L'albumina sierica era abbassata nel 68% dei casi, più frequentemente, ed in maniera più accentuata, negli accessi cerebrali, negli ematomi sottodurali, negli stati di irritazione meningea, nei glioblastomi, nelle metastasi cerebrali e spinali, e nei tumori del tronco cerebrale. Le alterazioni quantitative delle frazioni globuliniche mostravano interessanti rapporti col grado della compartecipazione del tronco cerebrale al processo patologico e con i poteri di difesa deH'organismo. Nei tumori a rapido sviluppo, nei processi metastatici ed infiammatori si accompagna alla caduta delle albumine un aumento della ₂-globulina ed una caduta della frazione . Processi, che conducono ad un aumento cronico od intermittente della pressione endocranica, dimostrano un maggiore aumento della frazione con diminuzione della -globulina. L'albumina è più o meno diminuita a seconda del maggiore o minore interessamento delle condizioni generali. Forti disproteinemie con diminuzione dell'albumina e delle frazioni - hanno un significato prognostico grave. D'altra parte una caduta graduale della ₂-globulina e della albumina con forte aumento della -globulina può costituire un segno prognostico grave e dimostrare una insufficenza epatica acuta ed una esaurita reazione di difesa ergotropa. Quando si tien conto del processo adoperato nella determinazione della elettroforesi, si possono ottenere indizi di notevole importanza sulle alterazioni dello stato generale, sulla necessita di trattamenti profilattici e sulle possibilitè di resistenza dell'operando.

     

IgG and complement receptor expression in children treated by peritoneal dialysis

Children treated by peritoneal dialysis (PD) are at increased risk of infections. IgG receptors (FcRs) and complement receptors (CRs) on white blood cells (WBCs) are important for the phagocytic process. We have investigated FcR and CR expression on monocytes, macrophages and neutrophils in blood and in peritoneal dialysis effluent (PDE) of 39 PD children. WBCs were isolated from blood and PDE, labelled with FITC-conjugated CD16 (FcRIII), CD32 (FcRII), CD64 (FcRI), CD11b (CR3) and CD35 (CR1) monoclonal antibodies, and analysed by flow cytometry. Peritoneal cells had lower percentages of FcR-positive or CR-positive cells than blood. On the other hand, the receptor number per cell [mean fluorescence intensity (MFI)] was higher on peritoneal macrophages and neutrophils than blood, except for CD16. The FcR and CR expression in blood and dialysate did not change significantly during the first year of PD treatment. During a peritonitis episode the MFI of all receptors in blood increased only on monocytes, with the exception of CD32. The percentages of FcR-positive and CR-positive macrophages and neutrophils in the PDE increased, whereas the MFI did not increase consistently. Peritoneal cells of PD children showed a lower percentage of FcR-positive and CR-positive neutrophils and macrophages, combined with an increased MFI, indicating a state of activation. Blood and peritoneal cells are capable of up-regulating the receptor expression during peritonitis but probably not to a maximum level.     

Photodynamic therapy and γ-irradiation of tumours: Effect of tumour-cell reoxygenation

The presence of adequate oxygen appears to be essential for photodynamic therapy (PDT) of tumours (1, 2). We used the mouse sarcoma 180 tumour model to investigate how the reoxygenation of the tumour cell population after a single exposure to -irradiation influenced the effect of photodynamic therapy. The combination of -irradiation with PDT leads to a significant enhancement of the therapeutic effect. The best effect is observed when the -irradiation precedes the PDT by 24 h, at which time reoxygenation of the tumour is greatest. Also, there is some enhancement of the effect when PDT is given before -irradiation, although the mechanism of this is not yet clear.