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Biomedical subjects

S Griffiths

Publications and source records attributed to S Griffiths.

At least 73 records · Page 4Linked to original sources
PubMed1989

Ultrastructural changes accompany inhibition of proteoglycan synthesis in chondrocytes by Cyclofenil diphenol.

Cyclofenil diphenol, a weak non-steroidal oestrogen, profoundly inhibits [35S]proteoglycan synthesis in cultures of Swarm chondrosarcoma chondrocytes under conditions in which protein synthesis is only marginally reduced. In the present experiments it was shown that after a 40-min treatment with Cyclofenil diphenol (90 micrograms ml-1) most of the normally abundant Golgi stacks in these cells disappeared and after 60 min they were absent. After 2-3 h treatment the cisternae of the endoplasmic reticulum (ER) were grossly distended and transformed into large ribosome-studded vesicles containing flocculent and filamentous material. These changes were dependent on the concentration of Cyclofenil and were fully reversible within 21 h of withdrawing the drug. The ultrastructural changes differed in some aspects if protein synthesis was blocked with cycloheximide for 15 min or 180 min before and during treatment with Cyclofenil. The Golgi disappeared but the ER cisternae, though distended, formed a continuous network and swollen ribosome-studded vesicles did not develop. However, non-membrane-bounded structures containing lipid droplets and material of low electron density developed in the cytoplasm under these conditions. The ultrastructural changes induced by Cyclofenil differ from those induced by monensin and diethylcarbamazine, suggesting that the drug acts at a different point in the secretory pathway for macromolecules.

Animals↗
PubMed1989

Red cell membrane protein distribution during malarial invasion.

Immuno-gold labelling electron microscopy of thin sections was used to determine the distribution of red cell membrane and membrane skeleton proteins in the vicinity of internalized malaria parasites. When examined immediately after invasion (young ring-stage parasites), the parasitophorous vacuole membranes of both Plasmodium falciparum and P. knowlesi were found to be characterized by the essentially complete absence of spectrin, ankyrin and the most abundant transmembrane protein, band 3. P. knowlesi merozoites were trapped in the attached but not internalized state by pretreatment with cytochalasin B. In this merozoite-red cell complex antibody labelling showed that band 3 had been eliminated from the region of the host cell membrane in contact with the parasite. Internal vesicles, originating apparently from the site of attachment, were often observed in the red cell. Opposite the attached parasite a cavity was also sometimes seen in the host cell, presumably representing an incipient internal vesicle. The membrane was intact, as judged by the absence of protein (haemoglobin) in the cavity, and, like the membranes surrounding the internal vesicles, was devoid of membrane proteins. A large multilamellar body was sometimes seen in the merozoite close to its point of attachment. The lamellar spacing was about 50 nm. The electron microscope images suggest a diffusion of electron-dense material from the lamellar body into the cavity in the host cell.

Animals↗
PubMed1989

Class II antigens on dendritic cells from the synovial fluids of patients with inflammatory arthritis.

Dendritic cells were enriched from synovial fluids (SF) of patients with inflammatory arthritis and studied by immunogold labelling and electron microscopy for expression of histocompatability antigens of the HLA-D locus. Dendritic cells from SF were larger than most of these from peripheral blood with a more extensive Golgi region and more lysosomes and microfilaments. Class II histocompatability antigens HLA-DR, -DP, -DQ and that labelled by the antibody RFDI were abundant on the dendritic cells. The macrophages in the enriched cells showed labelling for DR but little labelling with the other antibodies. DR, DP and RFDI were often concentrated at areas of contact between dendritic and other cells (other dendritic cells, macrophages or lymphocytes). On incubating labelled cells at 37 degrees C for 30 min many macrophages lost their DR label but dendritic cells always retained some surface label. Some gold labelling DR and DP was found in characteristic channels between the veils and became internalized in membrane-bound structures. A small proportion of the RFDI label internalized in areas resembling coated pits. Less DQ label internalized and appeared on vesicles inside vacuoles. Material bound to different class II molecules may thus be internalized or processed differently by dendritic cells. The presence in inflammatory lesions of large activated dendritic cells with high expression of class II antigens suggests that these cells could be presenting antigen to lymphocytes within the joints.

Arthritis↗
PubMed1988

Prevalence of maternal Ro (SS-A) and La (SS-B) autoantibodies in relation to congenital heart block.

The prevalence of autoantibodies to ribonucleoprotein antigens in cases of congenital heart block was established using immunofluorescence, counterimmunoelectrophoresis, double immunodiffusion and Western blots. All of 35 mothers of babies with congenital heart block, none of five mothers of babies with other types of heart block, 10 of 29 women with connective tissue disease but no babies with heart block, four of 445 normal pregnant women and two of 109 healthy nonpregnant women had either Ro (SS-A) or La (SS-B) antibodies. Of 15 babies with congenital heart block, 10 of 10 who were less than 3 months old possessed antibody. Antibody titres in affected but not in normal infants were lower compared with their mothers' titres, suggesting deposition of antibodies in the baby's tissues. The findings indicate that placental transfer of anti-Ro (SS-A) or anti-La (SS-B) is essential for development of congenital complete heart block.

Antibodies, Antinuclear↗
PubMed1987

Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies.

We have examined the cells involved in the development of contact sensitivity to FITC in CBA mice. After skin painting with antigen, the number of dendritic cells (DC) in the draining lymph nodes increased by 30 min, was maximal at 48 h, and returned to normal by 6 d. Derivation of some DC from Langerhans' cells of the skin was indicated from the presence of Birbeck granules observed in some DC isolated 24 h after skin painting. The DC acquired FITC and by 8 h there were two populations, one highly fluorescent and the other less fluorescent. The highly fluorescent cells were present between 8 h and 3 d after sensitization, and during this period the DC were potent at initiating primary proliferative responses of normal syngeneic T lymphocytes in vitro. Between days 3 and 5 the numbers of lymphocytes in the draining lymph node increased. During this period purified T lymphocytes did not express detectable levels of antigen, but enriched B cell populations expressed antigen transiently on day 1, 2, or 3 after exposure to antigen. The results showed that, during a 3-d period after exposure to antigen, DC expressed antigen and stimulated T cell proliferation. We speculate that low amounts of FITC binding selectively to veiled cells or lymph node DC in the first hours after exposure to antigen are not immunogenic but that Langerhans' cells acquire high levels of antigen, enter the nodes, and initiate immune responses.

Actin Cytoskeleton↗
PubMed1987

Demonstration of human papillomavirus types in paraffin processed tissue from human ano-genital lesions by in-situ DNA hybridisation.

A sensitive in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin-streptavidin polyalkaline phosphatase complex has been successfully applied to formalin-fixed, paraffin processed tissue obtained from a selected series of patients with ano-genital lesions. Benign condylomata from males and females showed the presence of HPV 6 and 11. Two cases of vulval intraepithelial neoplasia showed HPV 16. Four cases of squamous carcinoma of the anal canal also showed HPV 16 in the tumour or in the adjacent pre-invasive neoplastic epithelium. A case of malignant transformation in a cervical condyloma was associated with HPV 6 and 11. This technique permits the retrospective evaluation of routinely processed material thus widening the investigative spectrum for HPV.

Adolescent↗
PubMed1987

Demonstration of human papillomavirus types 6 and 11 in juvenile laryngeal papillomatosis by in-situ DNA hybridization.

A study is reported in which an in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin--streptavidin polyalkaline phosphatase complex has been successfully applied to formalin-fixed paraffin-processed tissue obtained from ten patients with juvenile laryngeal papillomatosis. In all cases, positive results were obtained for either HPV type 6 or 11. Normal vocal cord epithelium was negative.

DNA, Viral↗
PubMed1987

Sensitive in situ hybridisation technique using biotin-streptavidin-polyalkaline phosphatase complex.

A sensitive in situ hybridisation technique, using a biotin-streptavidin-polyalkaline phosphatase complex detection system, was successfully applied to smears of fresh cultured cells, frozen sections, and formalin fixed paraffin processed tissue: the procedure was successful for DNA-DNA hybridizations using a variety of DNA probes. The detection method is rapid, reliable, and economical producing a purplish-blue precipitate at the site of hybridisation and clearly visible by low power light microscopy.

Alkaline Phosphatase↗
PubMed1987

Low-output left ventricular failure in end-stage renal disease.

To determine the factors associated with low-output left ventricular failure (LVF) in endstage renal disease (ESRD), we performed echocardiography and gated cardiac scan on 217 nondiabetic dialysis and transplant patients. The prevalence of low-output LVF (ejection fraction less than 55% and left ventricular end diastolic diameter greater than or equal to 5.5 cm) in dialysis patients was 18% and in transplant patients 2%. The 26 patients with LVF were compared to 52 controls without LVF, matched by age, sex and year of starting treatment for ESRD, but not for current ESRD therapy. Mean age was 55 +/- (SEM) 14 years; 73% of the patients in both groups were males. Duration of treatment for ESRD was 5.6 +/- 4.3 years in patients, compared to 5.1 +/- 4.1 years in controls. Significant differences between LVF patients and controls included current treatment (73% of cases were on hemodialysis and 8% were transplanted, compared to 48 and 42%; chi 2 = 9.9, p less than 0.01), high serum creatinine, smoking and high serum alkaline phosphatase. There were no differences for current blood pressure, proportion on treatment for hypertension, left ventricular wall thickness, symptomatic ischemic heart disease, proportion with functioning vascular access, degree of weight gain between dialyses, hemoglobin level or high transfusion requirement. Multiple logistic regression demonstrated the most significant and independent variables associated with LVF were high alkaline phosphatase (suggestive of hyperparathyroidism), smoking and high serum creatinine levels (reflecting degree of uremia). Dialysis patients with LVF (n = 23) were compared to dialysis patients who had normal echocardiograms (n = 29).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗
PubMed1987

Class II histocompatibility antigens on human dendritic cells.

Histocompatibility antigens of the HLA D locus on the surface of human dendritic cells (DC) were visualized in the electron microscope using immunogold labelling. DC from peripheral blood expressed DR that was frequently concentrated at junctions between aggregating DC and lymphocytes or DC and macrophages. Labelling with an antibody to DQ was more diffuse and was not concentrated at points of cell-cell contact. The D locus antibody RFD1 labelled DC in distinct patches that were sometimes located at points of cell contact. Upon labelling DC with antibody to DR and incubating the cells at 37 degrees, some label remained on the cell surface but some was found in deep channels which appeared to be formed between veils at the surface of the cell and became internalized in membrane-bound structures. Under the same conditions, gold bound to DQ molecules remained on the surface of DC. Gold labelling RFD1 also remained mainly on the cell surface but there was occasionally internalization of patches into the cells through depressions in the cell membrane. The changes in distribution of the label on warming the cells suggests that materials bound to different D locus products may be 'processed' differently.

Cell Adhesion↗
PubMed1986

Bier's block--an improved technique.

A simple modification to the method of regional anaesthesia known as Bier's block is presented. This was applied to patients with Colles' fractures. In a controlled trial the technique produced anaesthesia more quickly than the other method.

Anesthesia, Conduction↗