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Biomedical subjects

M Strauss

Publications and source records attributed to M Strauss.

At least 73 records · Page 4Linked to original sources
PubMed1998

Tumor cell-specific transgene expression prevents liver toxicity of the adeno-HSVtk/GCV approach.

Treatment of colorectal liver metastases with the HSVtk/GCV approach and adenoviral vectors is highly toxic. We present a nontoxic alternative using the cell type-specific CEA promoter instead of the widely used hCMV immediate-early promoter to drive tk gene expression in the context of a recombinant adenovirus. Analysis of CEA promoter-dependent tk gene expression showed significant activity of this promoter in several human and rat tumor-derived cell lines but not in rat primary hepatocytes and in mouse liver, whereas the CMV promoter was highly active in all cell types and tissues investigated. CEA promoter-dependent tk gene expression was sufficient to kill 100% of cancer cells in vitro, even if less than 10% were infected by the adenoviral vector, indicating a significant bystander effect. Moreover, treatment of subcutaneous tumors in SCID mice with Ad.CEA-tk led to a several-fold reduction of tumor growth, and tail vein injection of a high dose of Ad.CEA-tk caused no side-effects in the liver. The CMV promoter was more potent than the CEA promoter in mediating GCV sensitivity to cancer cells in vitro and in vivo, but even a 20-fold reduction of the dose of Ad.CMV-tk did not prevent its liver cell toxicity after systemic application to mice and still resulted in the death of all animals within 4 days after the start of GCV treatment. These results indicate that restriction of tk gene expression to tumor cells in the liver prevents systemic toxicity. Moreover, the CEA promoter is a safe and efficient tool for tumor cell-specific expression of suicide genes in the liver.

Adenoviridae↗
PubMed1998

Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.

The action of antipsychotic drugs on dopamine receptors suggests that dopaminergic signal transmission may play a role in the development of schizophrenia. We tested eight candidate genes (coding for dopamine receptors, the dopamine transporter, and G-proteins) in 59 families from Germany and Israel, for association. A P value of .00055 (.0044 when corrected for the no. of markers tested) was obtained for the intronic CA-repeat marker G-olfalpha on chromosome 18p. The value decreased to .000088 (.0007) when nine sibs with recurrent unipolar depressive disorder were included. Linkage analysis using SSLP markers densely spaced around G-olfalpha yielded a maximum two-point LOD score of 3.1 for a marker 0.5 cM distal to G-olfalpha. Multipoint analysis under the assumption of heterogeneity supported this linkage-whether the affected pheotype was defined narrowly or broadly-as did nonparametric linkage (NPL). In 12 families with exclusively maternal transmission of the disease, the NPL value also supported linkage to this marker. In order to test for association/linkage disequilibrium in the presence of linkage, the sample was restricted to independent offspring. When this sample was combined with 65 additional simplex families (each of them comprising one schizophrenic offspring and his or her parents), the 124-bp allele of G-olfalpha was transmitted 47 times and was not transmitted 21 times (P=.009). These results suggest the existence, on chromosome 18p, of a potential susceptibility locus for functional psychoses.

Chromosomes, Human, Pair 18↗
PubMed1998

Reactivation of the previously silenced cytomegalovirus major immediate-early promoter in the mouse liver: involvement of NFkappaB.

The cytomegalovirus (CMV) major immediate-early promoter/enhancer is active in many cell culture systems and is considered to be one of the strongest promoters in vitro. However, when this promoter was used in in vivo approaches to gene therapy, it was silenced within a few weeks in several organs including the liver. In this study, we demonstrated transcriptional inactivation of the CMV promoter in mouse liver. In contrast to the CMV promoter, a hybrid promoter consisting of a minimal CMV promoter and the enhancer II of hepatitis B virus was active for at least 11 weeks in mouse liver. While investigating the reason for the shutdown of the CMV promoter, we did not find evidence for methylation of adenovirus DNA in the region of transgene insertion, but we could show that the silenced CMV promoter was reactivated after lipopolysaccharide treatment of mice or partial hepatectomy. Both stimuli are known to activate the transcription factor NFkappaB, which binds to four sites in the CMV promoter/enhancer. We show that expression from the CMV promoter in hepatocyte-derived cell lines in vitro depends on NFkappaB. In vivo experiments demonstrate that NFkappaB, which is not present in mouse hepatocytes in vivo, is activated after infection with recombinant adenoviruses and that the time course of NFkappaB activation parallels that of CMV promoter-dependent expression. Moreover, adenovirus infection of transgenic mice carrying a CMV promoter-driven lacZ gene leads to strong activation of the expression of this gene in the liver. Thus, NFkappaB is involved in the activation of the CMV promoter in the liver.

Adenoviruses, Human↗
PubMed1998

Hyperbaric oxygen and thrombolysis in myocardial infarction: the 'HOT MI' randomized multicenter study.

In a previous pilot study, we demonstrated that adjunctive treatment with hyperbaric oxygen (HBO) appears to be feasible and safe in patients with acute myocardial infarction (AMI) and may result in an attenuated rise in creatine phosphokinase (CPK), more rapid resolution of pain and ST changes. This randomized multicenter trial was organized to further assess the safety and feasibility of this treatment in human subjects. Patients with an AMI treated with recombinant tissue plasminogen activator (rTPA) or streptokinase (STK), were randomized to treatment with HBO combined with either rTPA or STK, or rTPA or STK alone. An analysis included 112 patients, 66 of whom had inferior AMIs (p = NS). The remainder of the patients had anterior AMIs. The mean CPK at 12 and 24 h was reduced in the HBO patients by approximately 7.5% (p = NS). Time to pain relief was shorter in the HBO group. There were 2 deaths in the control and 1 in those treated with HBO. The left ventricle ejection fraction (LVEF) on discharge was 51.7% in the HBO group as compared to 48.4% in the controls (p = NS). The LVEF of the controls was 43.4 as compared to 47.6 for those treated, approximately 10% better (no significant difference). Treatment with HBO in combination with thrombolysis appears to be feasible and safe for patients with AMI and may result in an attenuated CPK rise, more rapid resolution of pain and improved ejection fractions. More studies are needed to assess the benefits of this treatment.

Adolescent↗
PubMed1998

Oropharyngeal fatty infiltration in obstructive sleep apnea patients: a histologic study.

It has been suggested that due to fatty infiltration, obstructive sleep apnea (OSA) patients have a narrower pharyngeal airway than normal persons. To identify potential fatty infiltration of pharyngeal tissues that may contribute to OSA, a histologic study of the distal soft palate was performed. Histologic sections of 46 oropharyngeal specimens were evaluated. This included 25 overweight OSA patients (25/31), 6 normal-weight OSA patients (6/31), and a control group of 15 healthy (non-OSA) individuals. A semiquantitative analysis of the fatty tissue was performed. In all 31 OSA patients an excess of fatty infiltration was found in the histologic oropharyngeal specimens in comparison to the control group. No correlation was found between the pharyngeal fatty infiltration degree, the body mass index, and the apnea index. Irrespective of their body weight, in none of the patients without OSA was excessive fatty infiltration seen. It is suggested that excessive pharyngeal fatty infiltration plays a role in upper airway obstruction in OSA and that it can be associated with the development of apnea.

Adipose Tissue↗
PubMed1998

Myocardial interatrial septum loses its epithelial organization by mesenchymal influence. Structural and ultrastructural study.

During atrial septation, the septum primum fuses with the atrioventricular endocardial cushions and myocardial-mesenchymal interactions occur. In order to evaluate the cellular events that take place during this particular interaction a structural, ultrastructural and histochemical study was performed. Our findings indicate that from the fourth day of development, the distal myocardium of the interatrial septum, which interacts with mesenchymal tissue, loses its appearance of an epithelial sheet and becomes a loosely organized tissue. The distal myocytes of the interatrial septum which get progressively separated show features of migratory cells, the final localization of which is the mesenchymal tissue of the adjacent endocardial cushions. These tissue changes involve basal membrane disruption, reduction in the number of desmosomes and intercalated discs with the subsequent appearance of large intercellular spaces between myocytes, myofibrillar disarrangement and acquisition by myocytes of a secretory phenotype characterized by numerous cytoplasmic vesicles. These events occur in a similar way in the atrioventricular canal, where a myocardial-mesenchymal interaction also occurs. In both regions the mesenchymal endocardial cushions and its associated extracellular matrix seem to direct the dissociation of the myocardial tissue and the subsequent migratory cellular behaviour of the interacting myocytes. This is an interesting, and little known, example of a cellular phenotypic transformation during cardiac development.

Animals↗
PubMed1997

Wig-1, a new p53-induced gene encoding a zinc finger protein.

Wild type p53 expressed from a temperature-sensitive (ts p53) construct induces both G1 cell cycle arrest and apoptosis in the p53-negative J3D mouse T lymphoma line (Wang et al., 1995). Using differential display analysis, we have identified one new p53-induced gene, wig-1 (for wild type p53-induced gene 1), whose 7.6 kb and 2.2 kb transcripts are upregulated in ts p53-transfected J3D cells following induction of wild type p53 expression by temperature shift to 32 degrees C. The wig-1 transcripts were also induced in irradiated NIH3T3 and p21-/- fibroblasts but not in irradiated p53-/- fibroblasts. Whole body gamma irradiation caused induction of both wig-1 transcripts in mouse brain, testis, kidney, spleen and lung. A basal wig-1 expression was detected in brain, testis and kidney. The WIG-1 protein contains three zinc finger motifs and a putative nuclear localization signal.

Amino Acid Sequence↗
PubMed1997

[p16 and p53 genes transferred with the help of adenovirus to induce apoptic tumor cell death].

Based on studies of the cell cycle in tissue cultures of cancer cell lines and cells from normal tissue interference in the regulatory network of pRB/cdk4/cyclin D1/p16 in combination with the tumour suppressor gene p53 was investigated. It was shown that overexpression of p53 and p16, but not p53 on its own, induced apoptotic cell death only in tumour cells. Gene transfer of the same two genes to tumours transplanted subcutaneously in mice also caused fast regression of some of the tumours.

Adenoviruses, Human↗
PubMed1997

The retinoblastoma protein: a master regulator of cell cycle, differentiation and apoptosis.

The retinoblastoma susceptibility gene is a tumour suppressor and its product retinoblastoma protein (pRb) has been known for 10 years as a repressor of progression towards S phase. Its major activity was supposed to be sequestration or inactivation of the transcription factor E2F which is required for activation of S phase genes. However, within recent years growing evidence has been accumulating for a more general function of pRb at both the transcriptional level and the cellular level. pRb not only regulates the activity of certain protein-encoding genes but also the activity of RNA polymerase pol I and pol III transcription. This protein appears to be the major player in a regulatory circuit in the late G1 phase, the so-called restriction point. Moreover, it is involved in regulating an elusive switch point between cell cycle, differentiation and apoptosis. Here, it seems to cooperate with another major tumour suppressor, p53. Thus, pRb sits at the interface of the most important cell-regulatory processes and therefore deserves close attention by specialists from different fields of research. This review provides an introduction to the complex functions of pRb.

Animals↗
PubMed1997

Cre-mediated somatic site-specific recombination in mice.

Conditional mutant mice equipped with heterologous recombination systems (Cre/lox or Flp/frt) are promising for studying tissue-specific gene function and for designing better models of human diseases. The utility of these mice depends on the cell target specificity, on the efficiency and on the control over timing of gene (in)activation. We have explored the utility of adenoviral vectors and transgenic mice expressing Cre under the control of tissue-specific promoters to achieve Cre/lox-mediated somatic recombination of the LacZ reporter gene, using a newly generated flox LacZ mouse strain. When adeno Cre viruses were administered via different routes, recombination and expression of LacZ was detected in a wide range of tissues. Whereas in liverbeta-galactosidase activity was quickly lost by turnover of expressing cells, even though the recombined allele was retained,beta-galactosidase in other tissues persisted for many months. Our data indicate that the flox LacZ transgenic line can be utilized effectively to monitor the level and functionality of Cre protein produced upon infection with adeno Cre virus or upon crossbreeding with different Cre transgenic lines.

Actins↗
PubMed1997

A 29 residue region of the sarcomeric myosin rod is necessary for filament formation.

Myosin is a motor protein whose functional unit in the sarcomere is the thick filament. The myosin molecule is capable of self-assembly into thick filaments through its alpha-helical coiled-coil rod domain. To define more precisely the sequence requirements for this assembly, segments of the human fast IId skeletal myosin rod were expressed in Escherichia coli and examined differential solubility and the formation of ordered paracrystals. We show that both properties appear to require a 29 residue sequence (residues 1874 to 1902) near the C terminus of the rod region. To test further the role of this region in assembly, a protein was constructed which consisted of this assembly competence domain (ACD) fused to the carboxy terminus of an assembly-incompetent myosin rod fragment. This chimeric fragment exhibited myosin's characteristic solubility properties and formed ordered paracrystals. To complement these in vitro experiments, both a full-length myosin heavy chain (MYH) and one from which the 29 residues were deleted were transfected into cultured mammalian cells. While the full-length construct formed the spindle-shaped structures characteristic of arrays of thick filaments, the deleted MYH showed only diffuse staining throughout the cytoplasm by light microscopy. Thus, there appears to be a specific sequence in the C-terminal region of the myosin heavy chain rod which is necessary for ordered paracrystal formation and is sufficient to confer assembly properties to an assembly-incompetent rod fragment.

Amino Acid Sequence↗
PubMed1997

Hyperbaric oxygen and thrombolysis in myocardial infarction: the "HOT MI" pilot study.

Hyperbaric oxygen treatment (HBO) in combination with thrombolysis has been demonstrated to salvage myocardium in acute myocardial infarction in the animal model. Therefore a randomized pilot trial was undertaken to assess the safety and feasibility of this treatment in human beings. Patients with an acute myocardial infarction (AMI) who received recombinant tissue plasminogen activator (rTPA) were randomized to treatment with HBO combined with rTPA or rTPA alone. Sixty-six patients were included for analysis. Forty-three patients had inferior AMIs (difference not significant) and the remainder had anterior AMIs. The mean creatine phosphokinase level at 12 and 24 hours was reduced in the patients given HBO by approximately 35% (p = 0.03). Time to pain relief and ST segment resolution was shorter in the group given HBO. There were two deaths in the control group and none in those treated with HBO. The ejection fraction on discharge was 52.4% in the group given HBO compared with 47.3% in the control group (difference not significant). Adjunctive treatment with HBO appears to be a feasible and safe treatment for AMI and may result in an attenuated rise in creatine phosphokinase levels and more rapid resolution of pain and ST segment changes.

Adolescent↗
PubMed1997

Looming vulnerability to spreading contamination in subclinical OCD.

The present study examined the hypothesis, stimulated by the looming vulnerability model of anxiety (Riskind, in press, Behaviour Research and Therapy), that subclinical OCD is associated with a subjective sense of looming vulnerability. One-hundred and four undergraduates rated vignettes of common, everyday situations involving exposure to possible dirt, germs, or contamination. Participants in a subclinical obsessional group had a far higher sense of looming vulnerability to spreading contamination than did those in a control group. Results verified that the subjective sense of looming vulnerability still had separate, distinct and significant contributions to fear-of-contamination symptoms, with the effects of cognitive appraisals of other aspects of threat (such as probability of harm, or lack of control) removed. In contrast, these other cognitive appraisals had no significant associations with symptoms that proved to be independent of the subjective sense of looming vulnerability. A path analysis further explored the dependency of these other cognitive appraisals on looming vulnerability. This analysis found that part of the effects of the subjective sense of looming vulnerability on fears may be indirect and mediated via correlated effects of other cognitive appraisals.

Adult↗
PubMed1997

Lipoinjection in the paralyzed feline vocal fold: study of graft survival.

Six adult domestic strain cats were used to study the long-term histologic outcome of injected autologous fat for augmentation of the paralyzed vocal fold. Each animal had surgically induced left vocal cord paralysis via sectioning of the recurrent laryngeal nerve, followed by injection of 0.1 to 0.2 ml of autologous fat into the paralyzed vocal fold. The animals were killed at 6 weeks, and at 4, 6, 8, and 12 months after the injection. Photographic and videolaryngoscopic data were obtained. Histologic studies of the larynges were performed. The results documented histologic viability and persistence of a portion of the injected adipose tissue graft at 8 months after the injection, but only minimal graft survival at 12 months. The outcome suggests that autologous lipoinjection has potential use for short-term (several months) augmentation of the paralyzed vocal cord. Further investigation is warranted before recommending this technique for such use or as an alternative to currently available long-term injectable laryngeal biomaterials.

Adipose Tissue↗
PubMed1997

Cephazolin and metronidazole prophylaxis in head and neck surgery.

A seven-day course of cephazolin and metronidazole chemoprophylaxis for clean-contaminated head and neck oncological procedures is compared to results with previously published antibiotic regimens. Aetiological factors associated with increased rates of wound complications are analyzed. Retrospective analysis of procedures over a six-year period was performed. The overall wound complication rate was 28.1 per cent, comparing favourably with previously published results. A major fistula was the most common complication with a rate of 9.2 per cent. Factors statistically associated with increased rates of wound complications included: radical neck dissection, extended surgical procedures requiring flap reconstruction, previous tracheotomy, and race. This is the largest single institutional study to show that a seven-day course of cephazolin and metronidazole is an effective chemoprophylactic regimen in head and neck surgery.

Black or African American↗
PubMed1997

Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death.

Repression of cell cycle progression by tumor suppressors might provide a means for tumor therapy. Here we demonstrate that ectopic overexpression of the p16INK4/CDKN2 tumor suppressor from an adenovirus vector in various cell lines results in block of cell division and, subsequently, in a gradual reduction of the levels of the product of retinoblastoma susceptibility gene, pRb. Overexpression of p53 and p16INK4/CDKN2, but not p53 on its own, induces apoptotic death only in tumor cells. Simultaneous adenoviral transfer of p16 and p53 genes leads to inhibition of tumor growth in nude mice. These results suggest that combined delivery of two cooperating genes like p16 and p53 could be the basis for the development of a new strategy for cancer gene therapy.

Adenoviridae↗