[Ketamine as an anesthetic, analgesic and anti-depressant]. / Ketamine als anestheticum, analgeticum en als antidepressivum.

BACKGROUND: Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression.
AIM: A critical review of the current use of ketamine as an antidepressant.
METHOD: Literature study.
RESULTS: Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules.
CONCLUSION: Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.

Measuring empathy in schizophrenia: The Empathic Accuracy Task and its correlation with other empathy measures.

INTRODUCTION: Empathy is an interpersonal process impaired in schizophrenia. Past studies have mainly used questionnaires or performance-based tasks with static cues to measure cognitive and affective empathy. We used the Empathic Accuracy Task (EAT) designed to capture dynamic aspects of empathy by using videoclips in which perceivers continuously judge emotionally charged stories. We compared individuals with schizophrenia with a healthy comparison group and assessed correlations among EAT and three other commonly used empathy measures. METHOD: Patients (n = 92) and a healthy comparison group (n = 42) matched for age, gender and education completed the EAT, the Interpersonal Reactivity Index, Questionnaire of Cognitive and Affective Empathy and Faux Pas. Differences between groups were analyzed and correlations were calculated between empathy measurement instruments. RESULTS: The groups differed in EAT performance, with the comparison group outperforming patients. A moderating effect was found for emotional expressivity of the target: while both patients and the comparison group scored low when judging targets with low expressivity, the comparison group performed better than patients with more expressive targets. Though there were also group differences on the empathy questionnaires, EAT performance did not correlate with questionnaire scores. CONCLUSIONS: Individuals with schizophrenia benefit less from the emotional expressivity of other people than the comparison group, which contributes to their impaired empathic accuracy. The lack of correlation between the EAT and the questionnaires suggests a distinction between self-report empathy and actual empathy performance. To explore empathic difficulties in real life, it is important to use instruments that take the interpersonal perspective into account.

Metacognitive reflection and insight therapy (MERIT) for patients with schizophrenia.

BACKGROUND: Impaired metacognition is associated with difficulties in the daily functioning of people with psychosis. Metacognition can be divided into four domains: Self-Reflection, Understanding the Other's Mind, Decentration, and Mastery. This study investigated whether Metacognitive Reflection and Insight Therapy (MERIT) can be used to improve metacognition. METHODS: This study is a randomized controlled trial. Patients in the active condition (n = 35) received forty MERIT sessions, the control group (n = 35) received treatment as usual. Multilevel intention-to-treat and completers analyses were performed for metacognition and secondary outcomes (psychotic symptomatology, cognitive insight, Theory of Mind, empathy, depression, self-stigma, quality of life, social functioning, and work readiness). RESULTS: Eighteen out of 35 participants finished treatment, half the drop-out stemmed from therapist attrition (N = 5) or before the first session (N = 4). Intention-to-treat analysis demonstrated that in both groups metacognition improved between pre- and post-measurements, with no significant differences between the groups. Patients who received MERIT continued to improve, while the control group returned to baseline, leading to significant differences at follow-up. Completers analysis (18/35) showed improvements on the Metacognition Assessment Scale (MAS-A) scales Self Reflectivity and metacognitive Mastery at follow-up. No effects were found on secondary outcomes. CONCLUSIONS: On average, participants in the MERIT group were, based on MAS-A scores, at follow-up more likely to recognize their thoughts as changeable rather than as facts. MERIT might be useful for patients whose self-reflection is too limited to benefit from other therapies. Given how no changes were found in secondary measures, further research is needed. Limitations and suggestions for future research are discussed.

Empathy in adults with clinical or subclinical depressive symptoms.

BACKGROUND: Depression is associated with problems in social functioning. Impaired empathic abilities might underlie this association. Empathy is a multidimensional construct and involves both affective and cognitive processes. We reviewed the literature to find out to what extent depression may be associated with abnormal levels of affective and cognitive empathy. We also explored potential gender differences in these associations. METHODS: We used PsycInfo and Medline to conduct a systematic review of all studies on empathy and depression conducted in individuals with a primary diagnosis of major depressive disorder (MDD; patient samples) or in individuals with primarily subclinical depressive symptoms (analog samples). RESULTS: Thirty-seven studies met the inclusion criteria. The results indicated that depression was related to one type of affective empathy. Specifically, depression was related to high levels of empathic stress but not to abnormal empathic concern. Further, depression was related to limited cognitive empathy, as indicated by poor perspective taking, theory of mind, and empathic accuracy. LIMITATIONS: Few studies have considered the variable gender in their design and analyses. Between and within study variation in demographic and clinical variables limits the interpretation of results. Self-report measures of empathy are subjective and vulnerable to bias. Poor performance on the more objective laboratory tasks might partially be explained by the broader cognitive deficits commonly observed in depression. Lastly, because all studies used a cross-sectional design, causality is difficult to establish. CONCLUSIONS: Empathic abilities may be impaired in depression. The relation between empathy, depression, and gender is unclear. Future studies could use implicit and more ecologically valid measures of empathy. Insight into impaired empathy in depression may not only help explain poor social functioning in MDD but also benefit clinician-patient interactions.

Novel DNA glycosylases from Mycobacterium tuberculosis.

Oxidized bases are removed from DNA of Escherichia coli by enzymes formamidopyrimidine DNA glycosylase (Eco-Fpg) and endonuclease VIII (Eco-Nei) of the same structural family Fpg/Nei. New homologs of these enzymes not characterized earlier have been found in genomes of Actinobacteria. We have cloned and expressed two paralogs (Mtu-Nei2 and Mtu-Fpg2) from 36KAZ and KHA94 isolates of Mycobacterium tuberculosis and studied their ability to participate in DNA repair. Under heterologous expression in E. coli, Mtu-Nei2 decreased the rate of spontaneous mutagenesis in the rpoB gene, whereas Mtu-Fpg2 moderately increased it, possibly due to absence of residues crucially important for catalysis in this protein. Mtu-Nei2 was highly active toward double-stranded DNA substrates containing dihydrouracil residues and apurine-apyrimidine sites and was less efficient in cleavage of substrates containing 8-oxoguanine and uracil residues. These lesions, as well as 8-oxoadenine residues, were also recognized and removed by the enzyme from single-stranded DNA. Fpg and Nei homologs from M. tuberculosis can play an important role in protection of bacteria against genotoxic stress caused by oxidative burst in macrophages.

Exposure to bright light is associated with positive social interaction and good mood over short time periods: A naturalistic study in mildly seasonal people.

Bright light is used to treat winter depression and might also have positive effects on mood in some healthy individuals. We examined possible links between bright light exposure and social interaction using naturalistic data. For 20 days in winter and/or summer, 48 mildly seasonal healthy individuals wore a light meter at the wrist and recorded in real-time their behaviours, mood, and perceptions of others during social interactions. Possible short-term effects of bright light were examined using the number of minutes, within any given morning, afternoon or evening, that people were exposed to light exceeding 1000 lux (average: 19.6min). Social interactions were labelled as having occurred under conditions of no, low or high bright light exposure. Independent of season, day, time, and location, participants reported less quarrelsome behaviours, more agreeable behaviours and better mood when exposed to high but not low levels of bright light. Given that the effects were seen only when exposure levels were above average, a minimum level of bright light may be necessary for its positive effects to occur. Daily exposure levels were generally low in both winter and summer. Spending more time outdoors and improving indoor lighting may help optimize everyday social behaviour and mood across seasons in people with mild seasonality.

Efficient differentiation of Mycobacterium tuberculosis strains of the W-Beijing family from Russia using highly polymorphic VNTR loci.

The W-Beijing family is a widespread Mycobacterium tuberculosis clonal lineage that frequently causes epidemic outbreaks. This family is genetically homogeneous and conserved, so ETR-VNTR (exact tandem repeat-variable number of tandem repeats) typing is insufficient for strain differentiation, due to a common ETR-A to E profile (42435). This leads to the false clustering in molecular epidemiological studies, especially in the regions of predominance of the W-Beijing family. In this study, we searched for VNTR loci with a high evolutionary rate of polymorphism in the W-Beijing genome. Here we further evaluated VNTR typing on a set of 99 Mycobacterium tuberculosis clinical isolates and reference strains. These isolates were characterized and classified into several genotype families based on three ETR loci (A, C, E) and eight additional loci [previously described as QUB (Queen's University Belfast) or MIRU (Mycobacterial Interspersed Repetitive Units) or Mtubs]. Ninety-nine strains were divided into 74 VNTR-types, 51 isolates of the W-Beijing family identified by IS6110 RFLP-typing (the restriction fragment length polymorphism-typing) and/or spoligotyping were subdivided into 30 VNTR-types. HGDI (the Hunter-Gaston discriminatory index) for all studied loci was close to that of IS6110 RFLP typing, a "gold standard" method for subtyping M. tuberculosis complex strains. The QUB 26 and QUB 18 loci located in the PPE genes were highly polymorphic and more discriminative than other loci (HGDI is 0.8). Statistically significant increase of tandem repeats number in loci ETR-A, -E, QUB 26, QUB 18, QUB 11B, Mtub21 was revealed in the W-Beijing group compared to genetically divergent non-W-Beijing strains. Thirty-six isolates were subjected to IS6110 RFLP typing. The congruence between results of the IS6110 RFLP typing and 11-loci VNTR typing was estimated on 23 isolates of the W-Beijing family. These isolates were subdivided into 9 IS6110-RFLP types and 13 VNTR types. The poor profiles correlation (0.767) reflects the differences in the rate and type of evolution between genome regions targeted by IS6110-RFLP and VNTR typing. VNTR typing in proposed format is powerful tool for discrimination of M. tuberculosis strains with different level of genetic relationship.

Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers.

BACKGROUND: Serotonergic circuits have been proposed to mediate cognitive processes, particularly learning and memory. Cognitive impairment is often seen in bipolar disorders in relation to a possible lowered serotonergic turnover. METHODS: We investigated the effects of acute tryptophan depletion (ATD) on cognitive performance in healthy first-degree relatives of bipolar patients (FH) (N= 30) and matched controls (N= 15) in a placebo-controlled, double-blind cross-over design. Performance on planning, memory and attention tasks were assessed at baseline and 5 h after ATD. RESULTS: Following ATD, speed of information processing on the planning task was impaired in the FH group but not in the control group. FH subjects with a bipolar disorder type I relative (FH I) showed impairments in planning and memory, independent of ATD. In all subjects, ATD impaired long-term memory performance and speed of information processing. ATD did not affect short-term memory and focused and divided attention. CONCLUSIONS: The results suggest serotonergic vulnerability affecting frontal lobe areas in FH subjects, indicated by impaired planning. Biological vulnerability in FH I subjects is reflected in impaired planning and memory performance. In conclusion, the cognitive dysfunctions in FH subjects indicate an endophenotype constituting a possible biological marker in bipolar psychopathology. Serotonin appears to be involved in speed of information processing, verbal and visual memory and learning processes.

Nuclear A-type lamins are differentially expressed in human lung cancer subtypes.

Nuclear A-type and B-type lamin expression was investigated in the major human lung cancer subtypes: small cell lung cancer (SCLC), squamous cell carcinomas, and adenocarcinomas (both non-SCLC). Twenty-two human lung cancer cell lines and 46 fresh frozen human lung cancer specimens were examined. Expression of B-type lamins was found in all the different cell lines. A-type lamins were expressed in all non-SCLC cell lines but were absent or only weakly expressed in 14 out of 16 SCLC cell lines. The immunocytochemical results were confirmed by immunoblotting and Northern blot analyses. In sections of SCLCs and non-SCLCs, B-type lamins were found to be expressed in all tumors. However, in some non-SCLCs, particularly in adenocarcinomas, a considerable proportion of the tumor cells were negative for B-type lamins. A-type lamin expression in SCLCs was weakly positive or negative in 14 out of 15 cases. In contrast, all non-SCLCs displayed A-type lamins, but in several of these samples, both cytoplasmic and nuclear staining was observed.

Immunotargeting of human small cell lung cancer xenografts in athymic mice using a monoclonal antibody (RNL-1) against a neuroendocrine-related antigen.

A mouse monoclonal antibody (RNL-1) was raised against the variant small cell lung cancer (SCLC) cell line NCI-H82. Immunohistochemical studies on frozen sections showed that the antibody was reactive with most SCLC (15 out of 16) and lung carcinoids (six out of seven), while in general adenocarcinomas and squamous cell carcinomas of the lung were negative. Immunocytochemical studies on 29 different cell lines derived from human lung tumours confirmed the neuroendocrine-related expression of the RNL-1 defined antigenic determinant. Immunoelectron microscopy showed that RNL-1 recognises an extracellular membrane domain, concentrated at adhesion sites between adjacent cells. The tissue distribution of the RNL-1 defined antigen was mainly restricted to neural and neuroendocrine tissues. These immunohistochemical data suggest that RNL-1 is directed against a neuroendocrine-related cell adhesion molecule. Being reactive with an epitope expressed on the surface of most neuroendocrine malignant cells, RNL-1 (IgG1 isotype) is a potential vehicle for targeting SCLC in vivo. We evaluated the ability of radiolabelled RNL-1 to localise human SCLC xenografts in nude mice as a first step in determining the in vivo value for radioimmunodetection. RNL-1 was radioiodinated using the Bolton-Hunter labelling technique. Nude mice bearing NCI-H82 xenografts were injected intravenously with the radiolabelled RNL-1 preparations, and animals were dissected 4, 24, 48, 72 and 120 h post injection (p.i.) to determine the biodistribution of the radiolabel. The iodine-125 label accumulated in the tumour up to 48 h p.i. (6.5% injected dose per gram of tissue [ID g-1]), while the label content of the normal tissues decreased with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel antigens characteristic of neuroendocrine malignancies.

The authors describe the immunochemical detection, biochemical characterization, and tissue distribution of neuroendocrine antigens recognized by three newly developed monoclonal antibodies (MoAb) obtained after immunization of mice with the variant small cell lung cancer (SCLC) cell line NCI-H82. RNL-1 was reactive with neuroendocrine tissues similar to the SCLC cluster-1 MoAb, known to recognize N-CAM. Antibodies RNL-2 and RNL-3 are directed against different epitopes on the same proteinaceous complex. Both MoAb recognize an intracellularly located, water-soluble antigen which has a subunit composition with a protein triplet ranging in molecular weight between 44 and 45 kilodaltons (kD) next to a component of approximately 30 kD. The antibodies RNL-2 and RNL-3 reacted with a subset of neuroendocrine tissues and neuroendocrine neoplasms. In lung cancer both antibodies reacted only with some SCLC and carcinoids and not with nonneuroendocrine lung carcinomas. The potential diagnostic applicability of antibodies RNL-1, RNL-2, and RNL-3 is discussed.

Expression of intermediate filament proteins in fetal and adult human lung tissues.

The expression patterns of intermediate filament proteins in fetal and normal or nonpathological adult human lung tissues are described using (chain-specific) monoclonal antibodies. In early stages of development (9-10 weeks and 25 weeks of gestation) only so-called simple cytokeratins such as cytokeratins 7 (minor amounts). 8, 18 and 19 are detected in bronchial epithelial cells. At later stages of development, the cytokeratin expression patterns become more complex. The number of bronchial cells positive for cytokeratin 7 increases, but basal cells in the bronchial epithelium remain negative. These latter cells show, however, expression of cytokeratin 14 in the third trimester of gestation. Developing alveolar epithelial cells express cytokeratins 7, 8, 18 and 19. In adult human bronchial epithelium cytokeratins 4 (varying amounts), 7, 8, 13 (minor amounts), 14, 18 and 19 can be detected, with the main expression of cytokeratins 7, 8, and 18 in columnar cells and the main expression of cytokeratin 14 in basal cells. Vimentin is detected in all mesenchymal tissues. In addition, fetal lung expresses vimentin in bronchial epithelium, however, to a lesser extent with increasing age, resulting in the expression of vimentin in only few scattered bronchial cells at birth. Also in adult bronchial epithelium the expression of vimentin is noticed in part of the basal and columnar epithelial cells. Desmin filaments, present in smooth muscle cells of the lung, appear to alter their protein structure with age. In early stages of development smooth muscle cells surrounding blood vessels are partly reactive with some cytokeratin antibodies and with a polyclonal desmin antibody. At week 9-10 and week 25 of gestation a monoclonal antibody to desmin, however, is not reactive with blood vessel smooth muscle cells but is only reactive with smooth muscle cells surrounding bronchi. With increasing age the reactivity of cytokeratin antibodies with smooth muscle cells in blood vessels decreases, while the reactivity with the monoclonal desmin antibody increases. Our results show that during differentiation profound changes in the intermediate filament expression patterns occur in the different cell types of the developing lung.

Spontaneous changes in intermediate filament protein expression patterns in lung cancer cell lines.

The usefulness of cell lines in the study and prediction of the clinical behaviour of lung cancer is still a matter of debate. However, lung tumour cell cultures have been of value in investigations concerning molecular and cell biological aspects of these neoplasms. Especially in the examination of characteristics specific for the main types of differentiation (squamous cell carcinoma, adenocarcinoma, small cell carcinoma), in vitro studies have been most important. Twenty eight lung cancer cell lines were cultured for up to four years, and were examined at regular intervals for their intermediate filament protein (IFP) expression patterns using a panel of cytokeratin (CK) and neurofilament (NF) antibodies. These studies showed that the classic type of small cell lung cancer (SCLC) cell lines contain CKs 8, 18, and occasionally CK 19, while the variant-type SCLC cell lines generally express no CKs but can contain NFs. Non-SCLC cell lines, such as squamous cell carcinoma and adenocarcinoma cell lines, contain CKs 7 (in most cases), 8, 18 and 19. In one variant SCLC cell line and in one adenocarcinoma cell line CKs 4, 10 and 13, characteristic of squamous cell differentiation, were found. Although most cell lines have remained stable with respect to growth characteristics and IFP expression patterns, five lung cancer cultures exhibited a transition from one cell type to another, paralleled by changes in IFP expression. Progressions from classic to variant SCLC cell lines have been observed, next to conversions from variant SCLC to cell lines re-expressing cytokeratins. In some cases this resulted in a coexpression of CKs and NFs within a cell line and even within individual tumour cells. These results strongly support the earlier finding that CK expression in SCLC cell lines is a reliable marker for the classic type of differentiation, while the absence of CKs and the presence of NFs marks the variant type of differentiation. Our results are discussed in view of previous histological findings.

Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies.

The expression of cytokeratins (CKs) in human lung cancer was studied using chain-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 18, and 19. When applied to adenocarcinomas (ACs) of the lung, high levels of CKs 7, 8, 18, and 19 were detected in all tumors, while CK 4 was found in high concentrations in some ACs. CK 10 and 13 were completely absent, or only present in low numbers of cells. Small cell lung cancers (SCLCs) and lung carcinoids contained CK 18 and sometimes 8 and 19, but no CK 7 in most cases. Three out of four tumors, histologically classified as SCLC, and expressing CK 7 in a variable number of cells were found by electron microscopic studies to contain regions with AC and/or squamous cell carcinoma (SQC) differentiation. The monoclonal antibody specific for CK 7 can therefore possibly help to distinguish AC differentiation within SCLC. CKs 10 and 13 were completely absent in SCLCs and lung carcinoids, while few CK 4-positive cells were found in some SCLCs and in one lung carcinoid. Within SQCs the monoclonal antibodies revealed a pronounced heterogeneity in CK expression. CKs 4, 7, 8, 10, 13, 18, and 19 could be detected, although not evenly distributed among all tumor cells. Highly differentiated SQCs expressed high levels of the CKs specific for squamoid differentiation, i.e., CKs 4, 10, and 13 in variable numbers of cells. With decreasing histologically detectable SQC differentiation these markers were gradually lost, while the number of cells containing CKs 7, 8, 18, and 19 increased. Application of this panel of monoclonal antibodies can therefore distinguish not only the main subtypes of lung cancer, but can also indicate the degree of differentiation and the degree of heterogeneity. These findings can be used as a diagnostic aid in lung tumor pathology, which may have an impact on treatment and prognosis.

Immunocytochemical detection of human lung cancer heterogeneity using antibodies to epithelial, neuronal, and neuroendocrine antigens.

Lung cancers were investigated for their heterogeneity as expressed by their immunoreactivity for cytokeratins and neurofilament proteins, as well as for the neuroendocrine differentiation antigen MOC-1. Using broadly cross-reacting antibodies, cytokeratins were detected in nearly all cases of lung carcinomas. Keratinization could be detected only in cases of moderately to well-differentiated squamous cell carcinoma (SQC) using a monoclonal antibody to cytokeratin 10, while a monoclonal antibody reactive with cytokeratin 18, and specific for glandular epithelia, reacted with adenocarcinomas, small cell lung carcinomas (SCLC), and lung carcinoids. In SQC this antibody could detect non-squamous cell differentiation, showing increasing numbers of positive cells with decrease of histologically detectable SQC differentiation. Cells positive for neurofilaments were demonstrated in some of the poorly differentiated SQCs and in some of the cases of SCLC, possibly representing the variant type of SCLC. Also in some of the lung carcinoids neurofilament proteins were present, colocalizing with cytokeratins. MOC-1 was present in all SCLC and lung carcinoids. This antibody could also detect neuroendocrine differentiation in all combined small cell carcinomas, in one poorly differentiated adenocarcinoma, and in about 30% of the poorly differentiated SQCs. Therefore, lung cancer heterogeneity can be detected using a panel of well-defined antibodies to intermediate filaments in combination with the MOC-1 antibody. The use of these antibodies in diagnosis can have prognostic significance and can lead to a more selective therapeutic approach.

Detection of epithelial- and neural type of intermediate filament proteins in human lung tumors.

Five different types of lung cancers, i.e. squamous cell carcinomas, adenocarcinomas, small cell lung carcinomas, carcinoids and adenoid cystic carcinomas were examined for their intermediate filament constituents, with special emphasis on the different cytokeratin polypeptides and neurofilament proteins. Polyclonal as well as monoclonal antibodies to these proteins were used in immunocytochemical techniques applied to both tumor frozen sections and paraffin sections. Squamous cell carcinomas and adenocarcinomas could be shown to contain cytokeratins, which could be detected in both frozen sections and paraffin sections. Also small cell lung carcinoma (SCLC) and carcinoid lung tumors showed a positive staining reaction with polyclonal and monoclonal (cyto)keratin antibodies, but were negative with neurofilament antibodies, with the exception of one case of lung carcinoid, which co-expressed neurofilaments and cytokeratins. We have used antibodies to cytokeratin polypeptides, to neurofilament proteins and to a neuroendocrine related membrane antigen (MOC-1) to further subclassify heterogeneously composed squamous cell carcinomas. Using a monoclonal antibody to cytokeratin 18, normally present in glandular tissues and adenocarcinomas, we observed that more than 90% of the squamous cell carcinomas examined can be stained with this antibody. The percentage of tumor cells, however, positive for cytokeratin 18 varies between 1 and 100%. In these same tumors a monoclonal antibody to skin keratins, which is known to react specifically with keratinizing cells, also stained variable numbers of tumor cells. This finding confirms the presence of (keratinizing) squamous cell carcinoma elements in these tumors. Our data show that most lung tumors, heretofore considered pure squamous cell carcinomas, should be considered biologically adenosquamous carcinomas. Also areas positive with MOC-1 were found in these tumors, suggesting the presence of squamous cell carcinomas with neuroendocrine differentiation. Furthermore, in some poorly differentiated squamous cell carcinomas areas with neurofilament positive cells were detected, suggesting a neural differentiation within these neoplasms. Adenoid cystic carcinomas are shown to co-express cytokeratins and vimentin in the tumor cells. This phenomenon can be used to identify such tumors and to distinguish them from other lung tumors.

Monoclonal antibodies in lung cancer pathology.

Monoclonal antibody based immunohistochemistry is a very powerful tool for the establishment of a pathological diagnosis of lung cancer. Applying a panel of intermediate filament antisera and an antibody recognizing neuroendocrine differentiation we have tested about 240 human lung tumors and 15 human lung tumor cell lines. Our results can be summarized as follows: a differential diagnosis between neuroendocrine and non-neuroendocrine lung tumors can be obtained by the application of the monoclonal antibody MOC-1 directed against neuroendocrine antigens. Immunohistochemistry can lead to a better recognition of lung tumor heterogeneity within the established histologies. Examples of this phenomenon are: the presence of neuroendocrine and/or neural components within non-neuroendocrine tumors. The presence of squamous cell or adenocarcinomatous differentiation in non-SCLC can be detected by chain specific anti-cytokeratin antibodies. The degree of differentiation towards the variant type within SCLC can be detected by the monoclonal antibody directed against neurofilaments. lung cancer cell lines can serve as an in vitro model for immunohistochemical studies on different lung cancer subtypes.

Identification of cytoskeletal structures in hormone producing lung cancer cell cultures.

In order to investigate the intermediate filament protein content of hormone producing lung tumor cell cultures a panel of 16 different cytokeratin antisera were tested using immunocytochemical and biochemical techniques on lung carcinoma cell cultures from different origin. These included three cell cultures derived from small cell lung carcinoma, two large cell carcinoma cell cultures, and two cell cultures derived from squamous cell carcinomas. Flow cytometric analysis of the cell cultures demonstrated that all cell lines examined were aneuploid with DNA-indices ranging from 1.7 to 3.1 rimes the DNA-content of normal human lymphocytes. In both immunofluorescence and immunoperoxidase techniques six out of seven cell cultures reacted with most of the cytokeratin antisera used in a filamentous manner, while a large cell carcinoma cell culture did not react with any of the cytokeratin antisera used. None of the cell cultures examined reacted with the antibodies to neurofilament proteins, suggesting that none of these (neuro)hormone producing cell cultures were of neural origin. All cell cultures which were growing as adherent cell cultures did express vimentin. The cell culture that grew with cells floating in aggregates did not express this intermediate filament protein while a subline which did attach, expressed vimentin. This findings strongly indicates the relation between growth pattern in vitro (floating vs. adherent) and the expression of vimentin. No reaction was found with antisera to desmin and GFAP. The presence of cytokeratins and vimentin in most cell cultures could be confirmed using one- and two-dimensional gel electrophoresis. Cytokeratins 7, 8, 18 and 19 were most commonly present.

Intermediate filament proteins in classic and variant types of small cell lung carcinoma cell lines: a biochemical and immunochemical analysis using a panel of monoclonal and polyclonal antibodies.

The intermediate filament protein (IFP) characteristics of a panel of lung cancer cell lines including adenocarcinoma (two cell lines) and small cell lung cancer (SCLC, three classic and three variant cell lines) were examined using one- and two-dimensional gel electrophoretic techniques, immunocytochemical techniques and immunoblotting assays. A panel of 28 monoclonal and polyclonal antibodies to the five different types of IFP were used. The results of our studies indicate that these human lung adenocarcinoma, classic SCLC and variant SCLC cell lines can be differentiated on the basis of their pattern of IFP. The main conclusions from this study can be summarized as follows. The two adenocarcinoma cell lines contain cytokeratins 7, 8, 18, and sometimes 19, next to vimentin intermediate filament (IF). The three classic-type SCLC cell lines contain only cytokeratin IFs but not vimentin IF or neurofilaments (NFs). Cytokeratin polypeptides 7, 8, 18 and 19 could be detected. All three variant-type SCLC cell lines do not contain detectable amounts of cytokeratins. In contrast, two out of three variant SCLC cell lines contain neurofilament proteins. All three variant-type SCLC cell lines contain vimentin IF. Using immunoblotting assays with monoclonal and polyclonal antibodies to defined NF proteins the presence of the 68 X 10(3) Mr and the 160 X 10(3) Mr NF polypeptide could be demonstrated in two variant SCLC cell lines. As patients with SCLC-variant phenotype have a poorer prognosis after cytotoxic therapy than patients with 'pure' SCLC, the use of antibodies to IFP in staining fresh lung tumours, especially anaplastic ones, may differentiate the two subtypes of SCLC. Such a distinction would have a major impact on therapy selections and may be of prognostic importance.

[Lysogeny of the Streptomyces hygroscopicus culture reducing the antibiotic turimycin and some characteristics of its temperate phage]. / Lizogeniia kul'tury Streptomyces hygroscopieus--produtsenta antibiotika turimitsina i nekotorye osobennosti ee umerennogo faga

The culture of Streptomyces hygroscopicus JA 6599 producing antibiotic turimycin was found to be lysogenic. Four variants produced from this culture by the inducing with acridine orange did not synthesize the antibiotic but were also lysogenic. Temperate phages isolated from the parent culture and from its four variants were identical by their main biological properties. Therefore, production of turimycin is not controlled by the isolated temperate phage.