The role ofγδ T cells in the normal and disordered immune system

Summary A small population of T cells does not express the conventional T cell receptor characterized by the and polypeptide chains (TCR) but instead, two polypeptides termed and (TCR). This alternative receptor is able to recognize antigen. It appears early in T cell ontogeny, but its role in the thymus prior to the availability of TCR remains unclear. In selected sites such as skin or gut TCR predominates in mice which might suggest a role of T cells in the first line of defense against infection, T cells secrete lymphokines and display cytotoxic activity. However, their activation requirements may differ from what is known for T cells since MHC-nonrestricted and also CD4 and CD8 negative T cells have been described. Preferential activation by mycobacterial antigens possibly indicates a special repertoire of the T cells. In various diseases slightly increased numbers of T cells were found, but these preliminary studies have not yet provided evidence for a major pathogenetic role of T cells.List of abbreviations C constant region (immunoglobulin or TCR gene segment) - CD4 cluster of differentiation 4 (mainly on helper cells) - CD8 cluster of differentiation 8 (mainly on cytotoxic cells) - D diversity region (immunoglobulin or TCR gene segment) - DNA desoxyribonucleic acid - IL2 interleukin 2 - J joining region (immunoglobulin or TCR gene segment) - kD kiloDalton - MHC major histocompatibility complex - NK natural killer (cells) - RA rheumatoid arthritis - TCR T cell receptor - V variable region (immunoglobulin or TCR gene segment)     

Distinct mechanism of human neuroblastoma cell adhesion to fibronectin

We investigated the adhesion of three morphologically distinct human neuroblastoma cell lines (NCG, GOTO and SK-N-DZ) to intact fibronectin, central cell binding domain fragment (CBF) and CS peptide-IgG conjugates in the fibronectin molecule. Each cell line was found to express different integrin fibronectin receptors ( _{3 1}, _{4 1} and ₅₁), although similarly attached on intact fibronectin. To CBF, NCG attached well, while GOTO moderately and SK-N-DZ poorly attached. Only GOTO adhered to CS1-IgG. RGDS inhibited the spreading of NCG and SK-N-DZ on intact fibronectin, but it barely inhibited that of GOTO. The analysis by fluorescence-activated cell sorting (FACS) revealed that NCG expressed abundant ₃₁ and ₅₁, but little ₄₁, while GOTO expressed a large amount of ₄₁ as well as ₅₁. SK-N-DZ was undetectable in any of these molecules, but expressed _v1, which was identified by immunoprecipitation and immunoblotting. Polyclonal antibody to _v3 inhibited the adhesion of SK-N-DZ but not that of NCG or GOTO on intact fibronectin. These results suggest the existence of a distinct mechanism of cell adhesion to fibronectin among human neuroblastoma cell lines. It remains to be determined if such heterogeneous adhesion properties are related to the unique metastatic character of human neuroblastoma.     

Untersuchungen zur kurzzeitigen Induktions- und zyklischen Erhaltungstherapie beim inoperablen kleinzelligen Bronchialkarzinom

Zusammenfassung Seit Juli 1978 wurden 103 Patienten mit inoperablem kleinzelligem Bronchialkarzinom mit der Zytostatikakombination Adriamycin, Cyclophosphamid und Vincristin (ACO) behandelt. Im Stadium limited disease (n=64) erfolgte während des zweiten Chemotherapiekurses eine prophylaktische Schädelbestrahlung, nach dem vierten eine konsolidierende thorakale Bestrahlung. Nach Erreichen einer kompletten Remission erhielten die Patienten prospektiv randomisiert Etoposid oder keine weitere spezifische Therapie. Ein objektives Ansprechen konnte bei 88/100 auswertbaren Patienten erzielt werden. Im Stadium limited disease fanden sich 72%, im Stadium extensive disease nur 33% komplette Remissionen. Im Stadium limited disease betrug die hochgerechnete mediane Überlebenszeit 15,8, im Stadium extensive disease 9,3 Monate (p<0.005). Es leben noch 29 Patienten, 4 rezidivfrei länger als 24 Monate. Patienten mit kompletter Remission hatten eine statistisch signifikant (p<0.001) längere Überlebenszeit als Patienten mit geringerem Ansprechen. Regelmäßig traten gastrointestinale und hämatologische Nebenwirkungen auf, drei Patienten starben während der Induktionsphase an Infektionen. Die kurzzeitige Induktionsbehandlung verbesserte jedoch den Krankheitsverlauf subjektiv und objektiv. Bisher ist kein positiver Effekt der zyklischen Etoposid-Gabe nach ACO festzustellen.Vorliegende Untersuchungen wurden gefördert im Rahmen des Forschungsprogramms Arzneimittelentwicklung und -testung für die Krebstherapie des BMFT     

Immunocytochemical study of human lymphoid tissues with monoclonal antibodies against S-100 protein subunits

Summary The present study concerns the immunocytochemical localization of S-100 protein and subunits in the cells of human lymphoreticular tissue and their related tumours. The subunit is mainly localized in dendritic cells, most likely the dendritic reticulum cells (DRCs) located within the germinal centers, while the subunit is mainly localized in the interdigitating reticulum cells (IRCs) in the paracortical area and in Histiocytosis X cells. No immunoreactivity for either subunit was found in the majority of normal lymphocytes, macrophages, malignant lymphoma cells, or xanthoma cells.The DRCs and IRCs are generally considered to show different distribution in the lymphoid tissues and demonstrate some difference in their immunocytochemical and enzyme-histochemical features. It is suggested that S-100 subunits can be used as useful markers for these two types of dendritic cells and investigation of these subunits may provide more information for the study of human lymphoreticular system.     

Association of Phenotypic Changes in B Cell Lymphocytes and Plasma Viral Load in Human Immunodeficiency Virus-Infected Patients

Many B cell abnormalities have been reported in human immunodeficiency virus (HIV)-infected patients, including changes in the expression of , , and CD22 molecules on the cell surface. Phenotypic changes in these markers on B cells isolated from HIV-seropositive patients with high or low levels of plasma viremia were measured. The phenotypic changes in B cells isolated from such patients were compared with the markers on B cells isolated from HIV-seronegative individuals using three-color flow cytometry. HIV patients showed a reduction in the proportion of mature B cells isolated from peripheral blood mononuclear cells compared with B cells isolated from HIV-seronegative individuals. An increase in the proportion of B cells expressing both and molecules on the cell surface was also seen in association with high-HIV plasma viremia. A low plasma viral load was accompanied by a reduction in the proportion of B cells expressing both and molecules to a level comparable to those seen in HIV-seronegative individuals. HIV-seropositive individuals demonstrated an increase in the proportion of committed B cells, as indicated by an increase in the proportion of B cells expressing molecules. This observation may explain the poor humoral response of HIV seropositive patients to neo-antigens. Our results demonstrate that phenotypic changes indicative of in vivo B cell activation and an increase in immature cells are associated with HIV infection, particularly with a high plasma viral load. Phenotypic changes in B cell markers may correlate with functional deficits of B cells.     

Differential expression of SM22 isoforms in myofibroblasts and smooth muscle cells from rabbit bladder

The E-11 and 1-B8 monoclonal antibodies raised to the smooth muscle (SM)-specific SM22 protein from pig stomach were used to study the in vivo and in vitro phenotypic characteristics of myofibroblasts (MF) and SM cells (SMC) from the bladder detrusor muscle and serosal thickening of male rabbit. The 22-kDa SM22 band found in the SM extract appeared to be composed of distinct isoforms when examined in non-equilibrium two-dimensional gel electrophoresis (2D-EF): (the most basic), , , and (the most acidic) in the ratio of 34():23():36():8(). Western blots of 2D-electrophoresed bladder extracts treated with E-11 and 1-B8 showed that , , and , but not isoforms were labeled with E-11, whereas , , and isoforms were stained with 1-B8. This differential immunoreactivity was not influenced by phosphorylation. The tissue distribution of SM22 immunostaining was heterogeneous in the bladder SM and serosal thickening developed as a consequence of partial outflow obstruction of the urinary bladder. At the cellular level, the 1-B8 and E-11 antibodies stained the SMC in a diffuse (the whole cytoplasm) and honeycomb (the peripheral cytoplasm) manner, whereas MF immunostaining was quite homogeneous. The two antibodies also reacted with cultured primary bladder SMC and MF grown in low serum conditions showing a heterogeneous SM22 cell distribution but an identical subcellular localization, i.e., the actin-containing filamentous network, distinguishable in part from that found in vivo. The immunocytochemical, Western blotting and 2D-EF patterns of MF from thickened serosa indicated that the isoform alone is expressed in this tissue. This SM22 variant appeared before the completion of the cellular transition from MF to fully differentiated SMC. This pattern is reminiscent of bladder ontogenesis where SM22 expression in the developing bladder wall precedes that of SM myosin. Taken together these data suggest that: (i) SM22 isoforms are differently assorted in MF vs. SMC; (ii) SM22 is a SMC-lineage marker inasmuch as its expression occurs in an experimental condition characterized by a time-related cell phenotypic transition from MF to SMC, and (iii) cell conversion ability of serosal cells in the adult might take place via the reactivation of a specific foetal gene programme.     

Zur Frage der organspezifischen cytostatischen Wirkung von Diäthylstilböstroldiphosphat auf das Prostatacarcinom

Zusammenfassung Bei Implantationen von Diäthylstilböstrol in einen ventralen Prostatalappen der Ratte konnte im Gegensatz zum Bayer E 39 keine direkte zellschädigende Wirkung auf das Prostatagewebe beobachtet werden. Ein antigonadotroper und damit antimaskuliner Effekt war dagegen neben einer Nebennierenrindenstimulierung sicher nachweisbar. Es wird daraus geschlossen, daß auch das wasserlösliche Diäthylstilböstroldiphosphat bei der Behandlung des Prostatacarcinoms nicht als Cytostaticum sondern als Östrogen wirkt.Eingeführt als St-52 von Asta, Brackwede; jetzt Honvan (Asta) bzw. Cytonal (VEB Beropharm, Berlin-Johannisthal).     

„Leptospira Mini“ ein neuer Serotyp pathogener Leptospiren

Zusammenfassung Auf Grund ihres immunbiologischen Verhaltens gehören die Leptospirenstämme Sari, Ghidorsi und Szwajizak zu demselben serologischen Leptospirentyp, für den der Name Leptospira Mini vorgeschlagen wird.Der Stamm Sari wurde 1942 vonMino sowieVercelli in Italien isoliert. Der Stamm Ghidorsi wurde von uns im Zuge unserer Leptospirenforschungen bei einer Reisfeldarbeiterin der Po-Ebene nachgewiesen. Der Stamm Szwajizak, der vonSmith, Brown, Tonge u. Mitarb. im Jahre 1954 beschrieben wurde, ist in Nord-Qeensland gefunden worden. Der Stamm Sari und Ghidorsi gehören dem kompletten Biotyp (AB), der Stamm Szwajizak dem inkompletten (A) an.Leptospira Mini gehört zur Serogruppe hebdomadis. Ihre Virulenz ist schwach und ihre Bedeutung als Erreger menschlicher Leptospiren-infektionen scheint gering zu sein.     

Scope for the “eye — hand” psychophysiological test in screening for cerebrovascular insufficiency

Conclusions 1. During performance of the eye hand PPT the reaction time to input signals at the same time contains information on the trend and level of noise and pulsation of the afferent and efferent pathways of the CNS in man.2. The eye — hand PPT is best performed for detecting subjects with possible CVI, and also to determine the precise degree of its severity.3. Introduction of the eye — hand PPT during mass prophylactic examinations is of economic importance because it enables the early discovery of abnormalities of the workers' health and optimal implementation of the tests in industry characterized by two or three shifts.Riga Medical Institute. Translated from Meditsinskaya Tekhnika, No. 2, pp. 5–7, March–April, 1991.     

Diskrepanz der Geschlechtsdiagnose

Zusammenfassung Bei einem Neugeborenen wird aus dem Mundepithelabstrich die Geschlechtsdiagnose männlich und aus den Leukocytenkernen weiblich gestellt. — Beide Methoden sollten stets nebeneinander ausgeführt werden. Fälle mit derartigen Diskrepanzen zeigen eine besondere Problematik in der Intersexualität.     

Activity of trimethoprim/ sulfamethoxazole plus polymyxin B against multiresistantStenotrophomonas maltophilia

The inhibitory activity of eight antibiotics and the inhibitory and bactericidal activities of combinations of trimethoprim/sulfamethoxazole (TMP/SMX) plus three fixed concentrations of polymyxin B (0.01 g/ml, 0.1 g/ml and 0.5 g/ml) against 30 multiresistant strains ofStenotrophomonas maltophilia were tested. Polymyxin B at 0.01 g/ml modified the inhibitory activity of TMP/SMX against only 40% of strains. At 0.1 g/ml and 0.5 g/ml, polymyxin B enhanced the inhibitory activity of TMP/SMX activity against all strains. Polymyxin B enhanced the bactericidal activity of TMP/SMX only at concentrations near the minimum inhibitory concentration of polymyxin B alone.     

Causal dimensions of college students' perceptions of physical symptoms

According to attribution theory, controllability, locus, and stability are important dimensions underlying causal explanations. The extent to which these theoretical dimensions underlie lay explanations for physical symptoms is unclear. Accordingly, in this study, attributes relevant to the lay public were empirically derived using a multidimensional scaling (MDS) procedure. Undergraduates (N=194) provided similarity judgments for 18 potential causes of physical discomfort. The MDS analysis yielded a three-dimensional solution. The first dimension captured the distinction between physical and nonphysical causes. The second dimension distinguished either variable versus stable causes or those that are controllable versus uncontrollable by health care professionals. The third dimension differentiated causes under low versus high personal control. These findings empirically confirm the theoretically proposed dimensions of personal control and stability and suggest the utility of considering the physical/nonphysical and controllability by health care professional distinctions in future work on attributions in the health domain.     

Susceptibility to beta-lactam antibiotics in septicemia isolates from twenty-nine European laboratories

In 1984 the European Study Group on Antibiotic Resistance (ESGAR) consecutively collected gram-negative bacilli and staphylococci blood isolates and performed susceptibility testing with 11 antibiotics using the microdilution method. In all 2,578 isolates were collected: 68% gram-negative bacilli and 32% staphylococci. The MICs of ampicillin and cefazoline for the susceptible gram-negative bacilli were 1–8g/ml; of piperacillin0.5–4; of Sch 34343, cefotaxime, moxalactam, ceftazidime and aztreonam0.5–2g/ml; of cefoxitin, cefuroxime and cefamandole0.5–8g/ml. For susceptible staphylococci the MICs of cefazoline and cefuroxime were0.5–1g/ml, and of cefoxitin, moxalactam, ceftazidime and cefotaxime,0.5–32 g/ml. The resistance levels varied between laboratories and countries, being lower in Northern Europe. In clinical protocols on patients with gram-negative septicemia from whom cefazoline-resistant strains were isolated, cefotaxime was the beta-lactam most commonly used (12%). In protocols on patients with staphylococcal septicemia from whom gentamicin-resistant or cefazoline-resistant strains were isolated, the most commonly used beta-lactam was cloxacillin (6%).     

Oncogenic activity of the BK type of human papova virus in inbred rat strains

Summary The oncogenicity of the human polyomavirus BK (BKV) was tested in newborn inbred rats.It was found that the tumor rate was negatively correlated with the levels of T antibody 3 months after inoculation and the frequency of animals with detectable T antibodies 1.5 months after inoculation.By contrast, no influence of viral HI titers on the tumor rates was found. Thymectomy of animals resulted in most experiments in increased tumor rates. Inoculation with BKV of animals later than 24 hours after birth yielded a decrease of tumor rates.The results obtained suggest that T antibody titers present at a critical time after inoculation are associated with low oncogenicity of BKV.The oncogenicity of BKV was comparatively tested in rat strains possessing the allele l or the allele a, respectively. The oncogenicity was significantly higher in rats with the allele l than in rats with the allele a. Rats with the allele l showed lower T antibody response than rats with the allele a.These differences could be explained by the finding that cells of a origin showedin vitro a higher percentage of T antigen bearing cells than did cells of a strain possessing the allele l. In comparison to previous results obtained with BKV inoculated outbred WISTAR rats, the oncogenicity of comparable BKV doses in inbred rats was generally higher and the latency period of tumor manifestation shortened.     

Distribution of renal integrin receptors and their ligands in congenital nephrotic syndrome of the finnish type

The aim of this study was to examine the distribution of 1 and v integrins (Ints) and some of their ligands in the kidneys of patients with congenital nephrotic syndrome of the Finnish type (CNF) and in controls using indirect immunofluorescence with monoclonal antibodies. The mesangial reactivity of Int 1 and Int 1 subunits was more variable and an increased glomerular reactivity with Int 3 and Int-6 antibodies was found in CNF kidneys than in controls. Int 2 subunit was either completely missing from or found in significantly lesser amounts in CNF kidney glomeruli. The immunoreactivity for Int v was more variable, fainter and also more granular in CNF samples than in control kidneys. The glomerular reactivity for Int 5 was more diffuse and weaker, and in sclerotic Bowman's capsules more intense in CNF kidneys than in controls. Immunoreactivity for Int 6 was restricted and was comparable in extent in CNF and control kidneys. Of the extracellular matrix components studied, the expression of EDAFn, EDBFn, OncFn, Ln 2 chain, Ln 1 chain and tenascin was increased. This is also seen in several glomerular diseases with inflammation and sclerosis. Immunoreactivity for vitronectin was decreased. Several differences were found in the intensity or location of the immunostaining for the 1 and v Ints and their ligands in CNF kidneys compared with controls, which have not been found in any other proteinuric disease. Disturbed Int expression pattern in CNF may specifically reflect the disturbance of glomerular function caused by the primary defect in this disease.     

A cyclin protein modulates mitosis in the budding yeast Saccharomyces cerevisiae

Summary For the budding yeast Saccharomyces cerevisiae the mitotic cell cycle is coordinated with cell mass at the regulatory step start. The threshold amount of cell mass (reflected as a critical size) necessary for start is proportional to nutrient quality. This relationship leads to a transient accumulation of cells at start, termed nutrient modulation, upon enrichment of nutrient conditions. Nutrient enrichment abruptly increases the critical size needed for start, causing the smaller cells, produced in the previous cell cycle, to be delayed at start while growing larger. Here we show that, in S. cerevisiae, a second cell-cycle step, at mitosis, also exhibits nutrient modulation, and is, therefore, another point of cell-cycle regulation. At both mitosis and start, nutrient modulation was found through mutation to be regulated by the activity of the cyclin-related WHI1 (CLN3) gene product.     

Convergent inputs from articular,cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord

Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (s cells), 17 neurones excited by receptors in deep tissues (d cells), 15 units with a convergent input from receptors in skin and deep tissues (sd cells), and 25 neurones with a convergent input from the knee joint and either skin (sj cells), deep tissues (dj cells) or both (sdj cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. S and sj cells were found almost exclusively in the dorsal horn, whereas many d, sd, sdj and dj units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (sj cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (sdj cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 dj cells, the receptive fields included not only the knee joint but also deep fields like those of sdj cells. 6. Cutaneous receptive fields were classified as low threshold (cells excited best by innocuous intensities of mechanical stimulation), wide dynamic range (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.     

Immunglobuline γG, γA und γM im Serum von Schwangeren

Zusammenfassung Der Gehalt an Immunglobulinen G, A und M im Serum schwangerer, gesunder Frauen wurde in Abhängigkeit vom Alter der Gravidität geprüft und verglichen mit den Werten aus Seren eines Kollektivs weiblicher Blutspender gleicher Altersstufe. Es wurde festgestellt, daß der Serumspiegel an G stark absinkt, der Gehalt an A eine sinkende Tendenz zeigt und der M-Spiegel unbeeinflußt bleibt.

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Summary Serum of pregnant healthy women was investigated for its percentage of Ig G, Ig A and Ig M dependent from the stage of pregnancy. These measurements were compared with results from a group of female blood-donors of the same age. It was concluded, that the serumcontent of G decreases very distinctly, the Ig A percentage is somewhat diminished whereas the M content shows no differences between the two groups.

     

Determination of the cation content of the mammalian muscle fiber under normal and pathological conditions

Ohne ZusammenfassungMit 4 Textabbildungen. Albrecht Bethe zum 80. Geburtstag in treuer Verehrung.Ermöglicht wurde diese Untersuchung durch Unterstützung des Baruch Center of Physical Medicine and Rehabilitation und durch Kontrakt zwischen der Office of Naval Research und dem Medical College of Virginia.     

Flow Cytometric Analysis of In Vitro Proinflammatory Cytokine Secretion in Peripheral Blood from Multiple Sclerosis Patients

The cytokines, interferon- (IFN-), tumor necrosis factor- (TNF-rpar;, and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-, IL-2, and TNF- from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-, IL-2, and TNF- secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF- secreting CDS cell percentage is correlated with the IFN- and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF- secreting CD3 cell percentage is correlated with IFN-. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.