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Biomedical subjects

K Stevens

Publications and source records attributed to K Stevens.

At least 55 records · Page 3Linked to original sources

A matrix metalloproteinase-generated aggrecan neoepitope as a marker of skeletal maturation and aging in cartilage.

OBJECTIVE: To quantify the matrix metalloproteinase-induced neoepitope F(M/V)DIPEN (Phe-[Met/Val]-Asp-Ile-Pro-Glu-Asn341) in guinea pig and rabbit cartilage during aging. METHODS: Cartilage was taken from the stifle joint, nasal septum, and xiphoid process in guinea pigs and rabbits at selected ages. The cartilage was then extracted and evaluated for F(M/V)DIPEN levels by radioimmunoassay. RESULTS: In the 3 tissues studied, there were major increases in F(M/V)DIPEN levels during skeletal maturation and aging in both the guinea pig and rabbit cartilage. Except for spontaneous osteoarthritis that develops in guinea pigs with aging, increases in the neoepitope were not correlated with arthritis pathology. CONCLUSION: Increases in the level of F(M/V)DIPEN in cartilage occur as a result of skeletal maturation and aging. This physiologic accumulation of F(M/V)DIPEN in cartilage should be considered when using the neoepitope as a disease marker in arthritis.

Age Factors↗

Health effects of passive smoking in adolescent children.

OBJECTIVE AND DESIGN: To study the effects of passive smoking on health in adolescent schoolchildren by questionnaire, spirometry and laboratory investigations. SETTING: Two schools in the Vanderbijlpark area. PARTICIPANTS: Seven hundred and twenty-six high-school children of average age 16 years. OUTCOME MEASURES: Lung function, serological abnormality or historical (i.e. questionnaire) evidence of ill health. RESULTS: The prevalence of respiratory illness before and after 2 years, respiratory symptoms, earache over the past year, low birth weight and learning difficulties were found to be significantly increased in the children exposed to parenteral smoke in the home, especially those exposed to maternal smoking. Spirometric and laboratory parameters, however, were not affected by passive smoking.

Adolescent↗

Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase.

Mice deficient in inducible nitric oxide synthase (iNOS) were generated to test the idea that iNOS defends the host against infectious agents and tumor cells at the risk of contributing to tissue damage and shock. iNOS-/-mice failed to restrain the replication of Listeria monocytogenes in vivo or lymphoma cells in vitro. Bacterial endotoxic lipopolysaccharide (LPS) caused shock and death in anesthetized wild-type mice, but in iNOS-/-mice, the fall in central arterial blood pressure was markedly attenuated and early death averted. However, unanesthetized iNOS-/-mice suffered as much LPS-induced liver damage as wild type, and when primed with Propionobacterium acnes and challenged with LPS, they succumbed at the same rate as wild type. Thus, there exist both iNOS-dependent and iNOS-independent routes to LPS-induced hypotension and death.

Amino Acid Oxidoreductases↗

Expression of a highly unstable and insoluble transcription factor in Escherichia coli: purification and characterization of the fork head homolog HNF3 alpha.

The HNF3 alpha transcription factor is highly enriched in adult hepatocytes and activates many liver-specific genes; its expression in hepatic primordia and neurogenic tissue implies a developmental role. HNF3 alpha is a member of a family of proteins, including fork head in Drosophila, which bind DNA at specific sites using a newly defined "winged helix" structural motif. We describe here the expression and purification of full-length HNF3 alpha containing an amino-terminal histidine tag and show that the protein binds DNA with dissociation constant in the sub-nanomolar range. The techniques used to isolate HNF3 alpha should be applicable to other members of the HNF3/fork head family which appear to be generally unstable and insoluble in Escherichia coli.

Amino Acid Sequence↗

Femoral nerve palsy. An unusual complication of anterior lumbar interbody fusion.

SUMMARY OF BACKGROUND DATA: Compression neuropathy of the femoral nerve has been reported as an uncommon complication of bleeding into the iliopsoas muscle. OBJECTIVE: The authors detected anatomic reasons of direct injury to the femoral nerve at the lower lumbar level. METHODS: Keeping the hip in extension during the course of carrying out anterior fusion on a previously failed posterior fusion was considered another causative factor of femoral nerve injury. Anatomical dissection confirmed the likelihood of this injury being produced in this situation. RESULTS: Femoral nerve traction and compression can occur after prolonged compression of the nerve within the psoas muscle stretched between an immobile lower lumbar spine and the lesser trochanter when the hip is kept in extension. In the patients described no other reasons for direct or indirect injury were identified. CONCLUSION: Although uncommon, the complication should be kept in mind. It can be avoided by intraoperative hip flexion.

Cadaver↗

Delayed rupture of the extensor pollicis longus tendon: a retrospective study.

Eight patients with delayed rupture of the extensor pollicis longus tendon are presented. Six had suffered from a fracture of the wrist without dislocation. This is in our opinion a predisposing factor in the etiology of delayed tendon rupture. Our treatment of choice is transfer of the extensor indicis proprius tendon. In all patients satisfactory thumb function was restored.

Adolescent↗

Workshop studies on monoclonal antibodies reactive against porcine myeloid cells.

Investigators from eight laboratories analyzed the reactivity of 22 monoclonal antibodies (mAb) against porcine myeloid cells. Based on binding data, clustering analysis and inhibition studies, workshop mAb 74-22-15 (003) and 6F3 (007) were assigned a swine workshop cluster number 3 (SWC3). These mAb recognized macrophages and neutrophils; neutrophils; a monocyte/macrophage-specific mAb was not identified by this workshop.

Animals↗

Iron uptake by plasma cells in haematological disorders.

Bone marrows of 38 patients have been investigated for iron-containing plasma cells. Two patterns emerged. One consisting of iron-laden plasma cells involving myeloma, iron overload and megaloblastic anaemia patients. The second showing no iron in plasma cells of patients with anaemia of chronic disease (ACD). Electron microscopy was done on 3 patients who had excess iron in their bone marrow particles and plasma cells. Perls' stain and scanning transmission electron microscopy were used to confirm the presence of iron in bone marrow plasma cells. The results show that the uptake of iron by plasma cells is dependent on marrow iron stores and the availability of the iron for uptake.

Adolescent↗

Performance of indirect embolectomy aided by a new developed flush-suction catheter system. Forty-seven experimental embolectomy procedures in test animals.

Embolectomy by means of the Fogarty catheter is the therapy of choice in the event of acute occlusions of limb arteries. However, less invasive catheter procedures have become established means to perform embolectomies lately. In order to improve the results after using the above mentioned methods, we have developed a new embolectomy procedure. The system applied consists of a flush-suction catheter as well as a high pressure pump. There is a jet-suction unit on the head of the tubular two-lumen catheter to gather thromboembolic material from the circumference of the head, to erode the collected material and evacuate it. The flushing pressure is generated by the pump. For the experimental testing of the system, the flush-suction embolectomy has been performed in 19 pigs after 47 artificial produced extremities embolism. Angiographically and angioscopically it could be proved that even older thrombotic material could be removed completely and without significant trauma of the vessel. At the pathologic investigation of the vessel in which embolectomy had been performed in no case an essential vessel-wall damage could be found. In almost each case the embolic material was removed completely. Only in 5 cases (10.6%) we have distal microembolism. Due to the experimental tests, the system turns out to be reliable as far as the technique is concerned. In addition, in the event of clinical application, the system allows the expectation of a reduction of the time interval between diagnosis and therapy, as well as a percutaneous application.

Angiography↗

Immune cell distribution in the small intestine of the pig: immunohistological evidence for an organized compartmentalization in the lamina propria.

Using monoclonal antibodies in immunohistochemistry, the distribution of the cells with the following surface antigens was studied in samples of proximal and distal small intestine of five 6-month-old pigs: CD2, CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T cells), accessory cell marker (monocyte/granulocyte), MHC Class II (DRw), and interleukin 2 (IL-2) receptor. CD2+ cells were found in high numbers in both the epithelium and the lamina propria. More cells were demonstrated in villis than in crypts (proportion approximately 4:1). At least two subpopulations of intraepithelial lymphocytes were identified: apically in the epithelium there were CD2+CD4-CD8- (double negative) cells, whereas cells expressing CD8 marker were concentrated around the basement membrane. CD4+ cells were localized in the lamina propria towards the villus core. Accessory cells were distributed in crypts and the villus base and more cells were found in ileum than in duodenum. In contrast, MHC Class II+ cells were located predominantly in villi, just underneath the basement membrane, forming a sheath of cells between the CD8+ and the CD4+ cells. Cells expressing IL-2 receptor were sparse but widely distributed in both the lamina propria and the epithelium. This organized cell distribution may be related to the physiology of the mucosal immune system in the gut.

Animals↗

Illusion decrement and transfer of illusion decrement in Müller-Lyer figures.

In the work reported in the literature the reduction or decrement in the magnitude of the Müller-Lyer illusion with continued inspection has been typically investigated with the use of the composite illusion form. Three experiments are reported in which the illusion decrement was separately examined in the underestimated (wings-in) and the overestimated (wings-out) forms of the Müller-Lyer illusion, with particular attention paid to the transfer of illusion decrement between the two forms. Decrement occurred in both forms of the Müller-Lyer illusion, although there was considerable intersubject variability in decrement effects, and nonuniform rates of decrement across the inspection period. In none of the experiments did transfer of illusion decrement between the two forms occur. It is argued that the attentional/differentiation hypothesis of illusion decrement provides a plausible account of the present findings as well as of those found with the composite Müller-Lyer figure.

Adult↗

Regulation of albumin gene expression in hepatoma cells of fetal phenotype: dominant inhibition of HNF1 function and role of ubiquitous transcription factors.

Two widely used hepatoma cell lines, mouse BW1J and human HepG2, express gene products characteristic of fetal hepatocytes, including serum albumin, whereas reporter genes driven by the albumin promoter are expressed at very low levels compared with highly differentiated hepatoma cells. We have investigated the low albumin promoter activity in BW1J cells to understand differences in liver gene regulation between fetal and adult cells. Addition of the albumin upstream enhancer, or any other fragment of the albumin gene, failed to modify expression of the transfected promoter in BW1J cells. Analysis of cis elements of the albumin promoter showed that, in contrast to highly differentiated H4II cells, in BW1J cells the activity largely depends on ubiquitous transcription factors. Both BW1J and HepG2 cells produce the liver-enriched transcription factor HNF1; dimerization and DNA binding properties are identical to those of liver HNF1, yet the protein fails to show the anticipated transcriptional stimulatory activity. A transfected HNF1 expression vector strongly trans-activates the albumin promoter in HepG2 but only weakly in BW1J cells, and in hybrids (BW1J x Fao), inefficient HNF1 function is dominant. We conclude that hepatoma cells of the fetal phenotype are deficient in the use of HNF1 to drive transcription of the albumin gene and that they harbor a dominant modulator of HNF1 function.

Animals↗

Modulation of liver-specific transcription by interactions between hepatocyte nuclear factor 3 and nuclear factor 1 binding DNA in close apposition.

The liver-specific enhancer of the serum albumin gene contains an essential segment, designated eH, which binds the hepatocyte nuclear factor 3 alpha (HNF3 alpha) and ubiquitous nuclear factor 1/CCAAT transcription factor (NF1/CTF) proteins in tight apposition. We previously showed that activation of transcription by the eH site was correlated with an increase in intracellular HNF3 alpha levels during the in vitro differentiation of the hepatic cell line H2.35. We now show that transfection of an HNF3 alpha cDNA expression vector into dedifferentiated H2.35 cells is sufficient to induce transcription from the eH site. Mutational analysis of the enhancer demonstrates that NF1/CTF cooperates with HNF3 alpha to induce enhancer activity. However, when the eH site is removed from the context of the enhancer, NF1/CTF can inhibit transcriptional activation by HNF3 alpha. We conclude that the ternary complex of HNF3 alpha, NF1/CTF, and the eH site forms a novel, composite regulatory element that is sensitive to the local DNA sequence environment and suggest that the transcriptional stimulatory activity of NF1/CTF depends on its higher-order interactions with other proteins during hepatocyte differentiation.

Base Sequence↗