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Biomedical subjects

S Meyer

Publications and source records attributed to S Meyer.

At least 19 recordsLinked to original sources

[Increasing frequency of soft tissue sarcomas in The Netherlands].

Recent data from literature show an increase in incidence and mortality due to soft tissue sarcoma (STS). In the Netherlands age-standardised mortality rates of soft tissue sarcoma (STS) over the period 1950-1988 show a more than fivefold increase. Males predominate over females by a factor of 1.17. Age-adjusted hospital admission rates in 1980-1988 show an increase by a factor of 1.36. The mean estimated incidence is 4.74 per 100,000 person years over a three-year period (1988-1990). The most prevalent histological types in that period were leiomyosarcoma (20.1%), malignant fibrous histiocytoma (16.2%), Kaposi's sarcoma (13.9%) and liposarcoma (13.8%). The distribution of the different histological types changes in time. The increasing incidence of Kaposi's sarcoma is due to the increasing prevalence of AIDS. Hospital admission rates for STS increased from 0.67% of admission rates for all malignant neoplasms in 1970, to 0.96% in 1988. Further epidemiological studies are needed to elucidate the increase of STS throughout the world.

Adolescent

ATPase state and activity in thylakoids from normal and water-stressed lupin.

To compare with the case of phosphorylation, ATP hydrolysis was investigated in thylakoids from plants submitted to drought. For medium stresses the relationship between hydrolysis rate and deactivation constant of the de-energized enzyme when delta pH varies is unchanged, hence the basic mechanisms are preserved; (PS1-driven) energization than is neither affected, at any light intensity. As drought intensifies, hydrolysis and monogalactolipids fall somewhat in parallel, whereas the deactivation constant changes with digalactolipids and phosphatidic acid content. This alteration of the F0 lipid environment must be transduced to F1, the subunits of which, however, are preserved, as shown by LDS-PAGE. ATP synthesis (thiol-oxidized enzyme) and hydrolysis (thiol-reduced enzyme) show an identical decrease with stress. Thus the latter impairs a common early step, probably the activation of the oxidized enzyme.

Adenosine Triphosphatases

Determination of the DNA sequence recognized by the bHLH-zip domain of the N-Myc protein.

The DNA-binding domain of the murine N-Myc protein, comprising the basic helix-loop-helix-zipper (bHLH-zip) region was expressed as a fusion protein in E. coli. The affinity purified glutathione-S-transferase-N-Myc fusion protein (GST-N-MYC) was used to select the N-Myc specific DNA-recognition motif from a pool of random-sequence oligonucleotides. After seven rounds of binding-site selection, specifically enriched oligonucleotides were cloned and sequenced. Of 31 individual oligonucleotides whose sequences were determined, 30 contained a common DNA-motif, defining the hexameric consensus sequence CACGTG. We confirm by mutational analysis that binding of the N-Myc derived bHLH-zip domain to this motif is sequence-specific.

Base Sequence

Thoracic spine trauma.

Thoracic spine fractures are most commonly flexion injuries resulting from vehicular accidents or falls. The initial evaluation of any multiple trauma victim should include AP and cross-table lateral radiographs of the thoracic spine. Conventional and computed axial tomography can add additional information regarding posterior element integrity and spinal canal encroachment. MRI can also be useful in that it directly images the effects of fractures on the spinal cord.

Humans

Evidence that a cytoplasmically located version of a v-erbB-encoded protein can transform both fibroblasts and erythroblasts.

We previously isolated an avian erythroblastosis virus, AEV-GEE35, in which the complete extracellular and transmembrane domains of the v-erbB oncoprotein were replaced with sequences from the gag and env proteins. The GEE35 virus was capable of transforming both fibroblasts and erythroblasts as efficiently as wild-type v-erbB. Analysis of the v-erbB proteins encoded by GEE35 revealed two proteins of similar molecular weights of approximately 130,000 Da. One of these proteins was an N-linked glycosylated membrane protein, whereas the other was a cytoplasmic protein. Biochemical characterization of these two proteins revealed that the transmembrane protein has the v-erbB domain outside the cell, such that it no longer had access to its tyrosine kinase substrates. This implies that it is the cytoplasmically located v-erbB-encoded protein that is responsible for the efficient transforming ability of this virus.

Alpharetrovirus

Effect of dominancy on severity in rheumatoid arthritis.

Joint use has been felt to increase the severity of rheumatoid synovitis. Ninety-three patients with definite or classical rheumatoid arthritis (RA) were studied blind for clinical and radiological findings to see the effect of dominancy on the severity of the arthritis. The dominant side showed significantly greater total swelling scores (P less than 0.0001) and total tenderness scores (P less than 0.01). This was explained predominantly by greater severity of arthritis in dominant arms and hands. X-rays of the dominant hands and wrists showed more joint space narrowing (P less than 0.04) and erosion (P less than 0.01), but no differences in malalignment scores. There were no differences between dominant and non-dominant sides on frequency of intra-articular injections or use of splinting, but the dominant side received more surgical operations (P less than 0.02).

Adolescent

Subjective and objective effects of intravaginal electrical myostimulation and biofeedback in patients with genuine stress urinary incontinence.

A group of 36 patients (18 premenopausal and 18 postmenopausal), all suffering from genuine stress urinary incontinence, underwent conservative treatment with 6 sessions of intravaginal electromyostimulation followed by 6 sessions of biofeedback; 89% of patients reported an improvement, 5.5% considered themselves cured and 5.5% reported no change. Intravaginal pressure measured before and after therapy increased by an average of 11 cm H2O in premenopausal patients and 17 cm H2O in the postmenopausal group. Intravaginal pressure increased in all patients and, according to maximal urethral closure pressure, this increasing intravaginal pressure was observed even in patients with low pressure urethras. The urodynamic factors studied were functional length, maximum urethral closing pressure and pressure transmission, together with urethral surface at rest and during stress, and residual surface. No significant changes were noted before and after treatment. The excellent subjective results contrast with the absence of improvement in these values.

Adult

Rabies virus neuritic paralysis: immunopathogenesis of nonfatal paralytic rabies.

Two pathogenetically distinct disease manifestations are distinguished in a murine model of primary rabies virus infection with the Evelyn-Rokitnicky-Abelseth strain, rabies virus neuritic paralysis (RVNP) and fatal encephalopathogenic rabies. RVNP develops with high incidence in immunocompetent mice after intraplantar infection as a flaccid paralysis restricted to the infected limb. The histopathologic correlate of this monoplegia is a degeneration of the myelinated motor neurons of the peripheral nerve involved. While, in this model, fatal encephalopathogenic rabies develops only after depletion of the CD4 subset of T lymphocytes and without contribution of the CD8 subset, RVNP is identified as an immunopathological process in which both the CD4 and CD8 subsets of T lymphocytes are critically implicated.

Animals

The impact of intraoperative ultrasonography of the liver on the surgical strategy of patients with gastrointestinal malignancies and hepatic metastases.

Intraoperative ultrasonography (IOUS) of the liver is a very useful tool during surgery for gastrointestinal tumors or hepatic tumors. In a prospective study of 82 elective operations for 57 gastrointestinal tumors and 25 hepatic tumors or metastases, we compared IOUS with preoperative ultrasonography, CT-scanning and MRI. IOUS supplied additional information in 38% of the operations. In 22% of the cases, this had a major impact on the intraoperative strategy with an alteration of the procedure. IOUS has a higher detection rate of intrahepatic lesions, discriminates better between solid or cystic nature of the tumor and offers the possibility of performing a safe and radical hepatic resection by its ability to localize lesions in relation to vascular structures. IOUS is a safe and simple technique which will be more cost-effective than extensive preoperative evaluation of the liver. It provides a more complete clinical staging of patients for whom adjuvant therapy is considered after resection of a colorectal carcinoma.

Adult

Amniotic fluid components and changes due to storage conditions.

The composition of amniotic fluid was found to vary in dependence on storage conditions. Catalytic concentrations of creatine kinase and lactate dehydrogenase were considerably decreased after storage at -20 degrees C, and the decreases were less marked after storage at -70 degrees C. Other analytes were more stable. Consequently, the optimal storage conditions for amniotic fluid samples may differ for various analytes. The low inter-individual variability of some analytes (Na, K, Ca, Cl) suggests that their concentrations are homeostatically controlled during the gestational period studied. In contrast, the high variability of enzyme activities may be due to more rapid quantitative changes during normal gestation; in addition, enzyme activities may be affected by certain pathological and non-pathological conditions of the fetus.

Amniotic Fluid

Transcriptional and post-transcriptional effects of glucose on liver phosphoenolpyruvate-carboxykinase gene expression.

The present study investigates the effect of glucose on the gene expression of the hepatic glucoregulatory enzyme, phosphoenolpyruvate carboxykinase (PPrvck). By use of hepatocytes in culture and FAO hepatoma cells it could be demonstrated that glucose suppressed the effect of dibutyryl cyclic AMP (Bt2cAMP), glucocorticoids or both, to increase PPrvck mRNA and consequently PPrvck enzyme activity. Glucose had a dual effect; it reduced PPrvck gene transcription and it accelerated the rate of PPrvck mRNA degradation. The effect was specific for glucose, as glucose-related carbohydrates such as mannose, galactose and sorbitol were without effect on PPrvck mRNA. The repressive effect of glucose was limited to certain proteins; glucose had no effect on Bt2cAMP and glucocorticoid provoked induction of tyrosine aminotransferase (TAT). Also the pattern of mRNA in vitro translation products was virtually unaffected when FAO hepatoma cells were incubated either in the presence or absence of glucose, demonstrating the specificity of the effect of glucose on gene expression of selected proteins. In FAO hepatoma cells and in hepatocytes in culture, insulin, like glucose, also decreased PPrvck mRNA. While the effect of glucose and insulin was additive in FAO hepatoma cells, in primary hepatocytes in culture an effect of glucose by itself on PPrvck mRNA could only be demonstrated in the absence of insulin. Correspondingly also in vivo, the effect of glucose was demonstrated in the absence of insulin (provoked by streptozotocin diabetes); glucose application reduced the amount of hepatic PPrvck mRNA. To summarize, glucose is capable of suppressing the effect of glucocorticoids and Bt2cAMP on increasing the PPrvck mRNA level. The carbohydrate reduces the rate of PPrvck gene transcription and accelerates the rate of PPrvck mRNA degradation. While in FAO hepatoma cells the effect is evident in the presence of insulin, in hepatocytes in culture the effect of glucose cannot be demonstrated in the presence of insulin, questioning its role under physiological conditions.

Animals

Characterization and preliminary attempts for derivatization of crystals of large ribosomal subunits from Haloarcula marismortui diffracting to 3 A resolution.

An improved form of crystals of large (50 S) ribosomal subunits from Haloarcula marismortui, formally named Halobacterium marismortui, diffracting to 3 A resolution, has been obtained by the addition of 1 mM-Cd2+ to the crystallization medium, which contained more than 1.9 M of other salts. The improved crystals, grown from functionally active particles to an average size of 0.3 mm x 0.3 mm x 0.08 mm, are isomorphous with the previously reported ones, which diffracted to 4.5 A. They are of space group C222(1), cell dimensions a = 210 A, b = 300 A, c = 581 A, and contain one particle in the asymmetric unit. Their superior internal order is reflected not only in their high resolution, but also in their reasonable mosaicity (less than 0.3 degrees). In contrast to the previously grown crystals, the new ones are of adequate mechanical strength and survive well the shock-cooling treatment. Due to their weak diffracting power, all crystallographic studies have been performed with synchrotron radiation. At cryotemperature, these crystals showed no measurable decay for a few days of irradiation and a complete diffraction data set could be collected from a single crystal. Efforts for initial phasing by specific and quantitative derivatization with super-dense heavy-atom clusters are in progress.

Crystallization

Viral transcription in human keratinocyte cell lines immortalized by human papillomavirus type-16.

Human papillomavirus type-16 (HPV-16) transcription in two human keratinocyte cell lines (HPK) immortalized by transfection of viral DNA in vitro was analyzed by nucleotide sequencing of cDNA clones, and in addition by primer extension analysis and S1 nuclease and exonuclease VII digestion of poly(A)+ RNA. A novel mRNA species which probably initiates in the E7 ORF and in which the 5'-part of the E1 ORF (splice donor at position (pos.) 880) is joined to an exon comprising the entire E2 ORF (splice acceptor at pos. 2708) was found in both cell lines. This mRNA has the potential to encode a full-length E2 protein, which is known to function as a repressor of transcription initiated at P97. cDNAs derived from the late region of the viral genome and the use of a late polyadenylation signal at pos. 7320-7325 are described. In agreement with RNA data published by others the major promoter for HPV-16 transcription is located at pos. 97. mRNA species encoding full-length or truncated forms of the E6 protein, and species characterized by an E1i [symbol see text] E4 splice junction (which provided the E4 open reading frame (ORF) with an ATG triplet) were identified.

Base Sequence

Long-term follow-up of non-seminomatous testicular cancer patients with mature teratoma or carcinoma at postchemotherapy surgery. EORTC Genitourinary Tract Cancer Cooperative Group (EORTC GU Group)

From 1979 to 1983 the EORTC GU Group treated 239 patients with disseminated non-seminomatous testicular cancer with combination chemotherapy comprising cisplatin, vinblastine and bleomycin in a prospectively controlled trial. The protocol required complete resection of residual masses after induction chemotherapy, provided that serum tumour markers were normal. 102 patients were operated on. 27 patients had mature teratoma (teratoma differentiated) in the resected specimens and 23 had viable cancer. Follow-up data were available for 26 and 22 of these patients, respectively. 23 of 26 patients (88%) with mature teratoma are alive and disease free after a follow-up of 53-110 months (median 92 months). 3 patients developed progressive disease; 1 died. A peculiar case of growing mature teratoma on the forearm is described. 13 of 22 patients (59%) with residual carcinoma are alive and disease free after a follow-up of 74-112 months (median 95 months). The prognosis of patients with carcinoma is shown to be correlated with the completeness of surgery, which in turn is correlated with the initial tumour mass before chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Effect of occluding the urethra while recording urethral stress profile.

The correlation between clinical and tonometric incontinence is frequently poor, with urethral profile results that do not correspond to clinical reality. Among potential causal factors, we have attempted to determine the importance of the absorption of kinetic energy from the mass of urine driven against the urethral captor (the hydraulic ram effect). Twenty patients (average age 50 +/- 10 years, para 2) suffering from genuine stress urinary incontinence, underwent urodynamic investigation with a constant air-flow pneumatic catheter equipped with two captors separated by an inflatable cuff located just above the urethral captor to block the inrush of urine into the urethra. After cystometric examination had excluded an unstable bladder, two urethral profiles were registered successively, first with cuff deflated, and then with cuff inflated. The values for urethral functional length (FL) and transmission factor (TF) show no significant changes. The values for the maximal urethral closing pressure (MUCP) were significantly lower in the second profile (cuff inflated) in 18 of 20 cases (average decrease 7 cm H2O), which corresponds to 14 percent of the average MUCP measured during the first profile (cuff deflated). The depression quotient increased from an average 0.80 to 1.05 from first to second profile. This study allows quantification of the urethral "hydraulic ram effect" which modifies determination of the MUCP during registration of urinary stress profile.

Female