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Biomedical subjects

J Knight

Publications and source records attributed to J Knight.

At least 163 records · Page 9Linked to original sources
PubMed1986

Tracheo-oesophageal 'puncture speech'. An assessment technique for failed oesophageal speakers.

We describe the assessment procedures used at Charing-Cross Hospital to investigate laryngectomees who failed to develop oesophageal voice and give the results of assessment in 50 patients. Anatomical or physiological abnormalities in the reconstructed pharynx were found in all patients, and we feel these significantly contributed to the failure of achieving an oesophageal voice. The four cases of failure were due to hypotonicity of the pharyngo-oesophageal muscles, hypertonicity, frank spasm and stricture. This distinction can be used as a functional classification of failure as treatment for each group has to be different if successful surgical voice restoration is to be achieved. Patients with hypotonicity need to use external pressure; those with mild hypertonicity are able to use a low pressure tracheo-oesophageal voice prosthesis; those with spasm need a pharyngo-oesophageal myotomy prior to "puncture", while those with stricture need surgical correction.

Esophagus↗
PubMed1985

Biosynthesis and processing of legumin-like storage proteins in Lupinus angustifolius (lupin).

Synthesis, secretion and post-translational proteolysis of the storage proteins in cotyledons of Lupinus angustifolius L. (lupin) have been examined in vivo and in vitro by using a combination of pulse-chase experiments with [3H]- or [35S]-labelled amino acids, subcellular fractionation and cell-free translation from poly(A)+ (polyadenylylated) RNA or membrane-bound polyribosomes. Related polypeptides were identified by immunoprecipitation, separation on sodium dodecyl sulphate/polyacrylamide gels and fluorography. The synthesis and processing of two proteins were compared. Conglutin alpha, the 11 S protein, was found as a family of precursor polypeptides of Mr 68000-88000 when translated from poly(A)+ RNA under conditions where signal segments were not cleaved, and Mr 64000-85000 both when sequestered into the endoplasmic reticulum and when accumulated in the protein bodies. Pulse-chase labelling showed that cotyledons from early stages of development were completely incapable of further proteolysis of these precursors. Nevertheless, in the same juvenile cotyledons, the precursors of the minor storage protein conglutin gamma, two polypeptides with Mr 50000-51000, were proteolytically cleaved to mature subunits of Mr 32000 and 17000 within 2 h. Further cleavage of the precursors of conglutin alpha into families of mature subunits of Mr 21000-24000 and 42000-62000 was detected in more mature cotyledons. A model is proposed which suggests that the mature subunits are produced by a single proteolytic cleavage of each of the three major precursors of conglutin alpha and also suggests that a close similarity exists between these subunits and those of other legumin-like proteins. The enzyme responsible for this cleavage, which appears at a specific stage in the middle of cotyledonary development, seems to be an integral part of the programmed developmental sequence in these pods.

Biological Transport↗
PubMed1985

Monoclonal antibodies specific for subsets of epidermal keratins: biochemical and immunocytochemical characterization--applications in pathology and cell culture.

Keratin composition has been widely used as a biochemical marker of differentiation in normal epithelia, cell culture systems and tumours of epithelial tissues. We have been developing a model system for the study of human squamous epithelial cell differentiation, and among a panel of monoclonal antibodies we have generated for analysing this system are two antibodies recognizing subsets of epidermal keratins. The two antibodies, designated LICR-LON-16a and LICR-LON-29b, were raised to the human squamous carcinoma cell line LICR-LON-HN-5, and we describe here their biochemical and immunocytochemical characterization. Antibody 16a reacts with only epidermal basal cells in normal human skin and shows specificity for the 45 and 46 kdalton keratins. Antibody 29b stains all living layers of the epidermis, and reacts with a broad range of ketain polypeptides, (45-56 kdaltons) in immunoblotting analyses. We have investigated the alterations of cellular staining that occur in chronic hyperproliferative skin diseases and carcinomas and compared this with the staining of multilayered cultures of normal keratinocytes and the HN-5 cell line. We show that in squamous cell carcinomas and in HN-5 cell xenografts 16a and 29b stain only the well-differentiated cell types. Furthermore we found that the basal cell specificity of 16a was lost in all of the hyperproliferative skin lesions examined including psoriasis and eczema. This transition to suprabasal staining pattern was also seen in the cultures of normal keratinocytes and HN-5 cells. We conclude that aberrant keratin synthesis or abnormal post-translational processing of keratins associated with an increased rate of cell turnover could account for the altered expression of the epitope recognized by antibody 16a.

Antibodies, Monoclonal↗
PubMed1985

Immunocytochemical identification of cell types in pleomorphic adenoma, with particular reference to myoepithelial cells.

An immunocytochemical study was carried out on normal salivary gland tissue and ten salivary gland pleomorphic adenomas. Antibodies to myosin were used to stain myoepithelial cells. Duct cells were stained using an antibody to total keratin and a subpopulation of basal duct cells with an antibody to 45/46K keratins. Basement membranes were stained with anti-type IV collagen. The results demonstrated that myoepithelial cells are relatively rare in the majority of pleomorphic adenomas and that many of the cells which have been classically described as myoepithelial in routine histological preparations do not clearly show this type of differentiation. However, the tumors presented a spectrum of differentiation patterns from those that were mainly ductal to the rare tumour which was largely myoepithelial. It is further suggested that the 45/46K keratin antibody is capable of identifying a subpopulation of cells which could possibly be important in the histogenesis of this tumour.

Adenoma, Pleomorphic↗
PubMed1985

The biochemical and immunocytochemical characterisation of an antigen on the membrane of basal cells of the epidermis.

A murine monoclonal antibody, LICR-LON-23.10, which had been raised against a well-differentiated squamous cell carcinoma cell line (LICR-LON-HN5), recognises an antigen which is present on the membrane of basal cells of the epidermis. The tissue distribution of the antigen, as defined using immunohistochemical techniques, suggests that it is expressed preferentially on cells which are adjacent to a basement membrane. In squamous cell carcinomas, the antigen is expressed uniformly on undifferentiated cells, but in areas of keratinisation, the antigen is absent. The antigen recognised by the antibody was characterised as being a pair of glycoproteins with molecular masses of 120 and 135 daltons. The antibody was used for flow-cytometric analyses of epidermal keratinocyte preparations. Together with other basal cell markers, this antibody may be useful in the characterisation of the epidermal basal cell population as well as in broadening our understanding of the interaction between epithelial cell populations and their relationship with basement-membrane components.

Animals↗
PubMed1984

The differential effects of hydrocortisone on activation and tolerance induction in human T lymphocyte clones.

The in vitro effects of hydrocortisone on T cell activation and tolerance induction were investigated using human influenza virus immune T cell lines and clones. Hydrocortisone at 10(-9) to 10(-6) molar concentrations was able to inhibit the antigen induced but not the T cell growth factor (TCGF) mediated proliferative response of both the lines and clones. However, hydrocortisone was able to inhibit TCGF production by cloned T cells. The proliferative response of cloned T cells to intact influenza virus A/Texas/1/77 was more markedly inhibited by equivalent concentrations of hydrocortisone than was the response of that clone to a 24 amino acid sequence (p20) of the haemagglutinin molecule implying that hydrocortisone may also act at the level of antigen processing. Furthermore hydrocortisone was able neither to induce T cell tolerance alone nor to inhibit antigen specific tolerance induction. However, hydrocortisone did lower the antigen threshold for tolerance induction. The possible mechanisms of hydrocortisone activity in the modulation of T cell regulation in autoimmune disease are discussed.

Antigens, Viral↗
PubMed1984

Differentiation of normal and malignant human squamous epithelium in vivo and in vitro: a morphologic study.

We report a light microscopic and ultrastructural analysis of the comparative degrees of differentiation seen in keratinocytes derived from the tongue and epidermis with those of a well-differentiated human squamous carcinoma cell line (LICR-LON-HN5). When growing on plastic substrates, all cultures had a similar morphology, with multilayering and the production of cornified envelopes. When cultured on collagen gels the structure was more organized, with keratohyalin granules and keratin whorl formation in both the normal and the malignant cultures. Normal keratinocytes injected into athymic mice produced epidermal cysts, while cells from the cell line produced well-differentiated squamous cell carcinomas, which were partially solid and partially cystic. the tumor was well organized, with identifiable basal cells, spinous cells, keratohyalin granules, and a prominent basal lamina at the stromal/epithelial interface. This model is to be developed for comparative studies between normal and malignant cells, with particular reference to basement membrane production and to investigations of the relative importance of extrinsic and intrinsic factors in the control of squamous differentiation.

Animals↗
PubMed1984

Microbial hydroxyapatite formation as a model of proteolipid-dependent membrane-mediated calcification.

The study of calcium hydroxyapatite (HA) formation in bacteria can be used as a model for membrane-associated normal and pathologic calcification in vertebrates. While the ability to deposit HA is common to a wide variety of microorganisms, the characteristic is not universal, even within closely related species (e.g., oral streptococci). Clues as to why some microorganisms can support HA formation while others cannot have been derived from analysis of calcification of Bacterionema matruchotii. These bacteria form intracellular HA which is crystallographically indistinguishable from bone mineral. Calcification is proteolipid (Pr)-dependent and involves Ca-phospholipid-Pi (CPLX) formation. Crystal deposition follows a defined series of events including changes in Ca:Mg:Pi ratios, membrane lipids, Pr concentration, protein and phospholipid composition, and mineral phase. Comparison with non-calcifiable Actinomyces naeslundii indicates that under appropriate conditions, most Pr-containing membranes can function as nucleating sites. Enrichment of Pr and CPLX in pathologic calcifications and matrix vesicle membranes suggests that similar mechanisms may operate in vertebrate HA formation.

Bacteria↗
PubMed1984

Coexisting thyroid and gastric autoimmune diseases are not due to cross-reactive autoantibodies.

Some autoimmune diseases tend to cluster within families, patients with one such disease showing an increased tendency to develop certain other autoimmune diseases within the same group. We have investigated the possibility that this clustering arises because some patients produce autoantibodies which cross-react with antigenic determinants which are shared by diverse tissues. Our data indicate that this is not the case, at least so far as thyroid and gastric autoimmune diseases are concerned. This observation increases the likelihood that the real explanation for such clustering concerns sharing of idiotypic determinants by the different pathogenic clones involved or by their precursors.

Anemia, Pernicious↗
PubMed1983

Clinical pharmacology of the anticancer polypeptide neocarzinostatin.

The clinical pharmacology of the anticancer polypeptide neocarzinostatin was studied in 16 patients with disseminated neoplasia using a radioimmunoassay technique. Patients who received 2,400-3,600 U of the drug per square meter BSA by rapid IV infusion had triphasic plasma decay curves. For eight patients with normal hepatic and renal function, neocarzinostatin mean plasma half-lives were 0.14, 0.50, and 7.7 h. The mean plasma drug clearance was 32.4 ml/min/m2 and the apparent volume of distribution 19.3 l/m2. Two patients with liver dysfunction had shorter terminal plasma half-lives and greater drug clearance, while two with renal disease exhibited prolonged plasma half-lives and reduced drug clearances. The mean cumulative urinary excretion of neocarzinostatin was 69.1% of the administered dose at 72 h in three patients with normal hepatic and renal function. One patient with liver disease excreted 90.4%, while a patient with renal disease excreted only 58.1% of the dose in 24 h. In one patient with marked liver disease, biliary excretion accounted for 0.1% of the administered dose in 72 h. Cerebrospinal fluid concentrations of neocarzinostatin studied in two patients showed a CSF penetration of about 16% the plasma concentration at 1-5 h; concentrations persisted for 19 h in one patient with an Omayha reservoir. Neocarzinostatin was rapidly cleared from the plasma and eliminated in the urine. Dosage reductions of 50% are recommended for patients with impaired renal function, while no reduction or escalated doses could be tolerated by patients with liver disease. The pharmacologic data suggest a continuous IV infusion may be a more toxic but perhaps more effective schedule of administration.

Adult↗
PubMed1983

Differentiation of a squamous carcinoma cell line in culture and tumourigenicity in immunologically incompetent mice.

The process of differentiation in keratinocytes is accompanied by specific membrane and cytoplasmic changes. Using simple tissue culture techniques a well differentiated squamous carcinoma cell line is shown to exhibit in vitro keratinization with the formation of a multilayered structure and shedding of cells with a cornified envelope. The cell line produces tumours when xenografted into mice which are well differentiated and indistinguishable at the light and electron microscope level from the original surgical biopsy. It is concluded that the tumour will provide a suitable model for detailed in vitro and in vivo studies to compare both biological and pathological features of normal keratinocytes and their malignant counterparts.

Animals↗
PubMed1983

Growth in agar and tumor formation in immunologically incompetent mice as criteria for keratinocyte transformation.

Established cell lines from 8 human squamous cell carcinomas (SCC) together with normal human keratinocytes, have been investigated for their ability to grow in soft agar and as xenografts when injected as a single cell suspension into immunologically incompetent mice. One of 8 SCC lines formed colonies with efficiencies greater than 1% in soft agar, and only 2 formed progressively growing tumors when injected into animals. It is concluded that these 2 criteria are not reliable markers of malignant transformation in squamous epithelia unless cytological criteria are also applied.

Agar↗
PubMed1983

Gastric duplication presenting as a double esophagus.

Duplications of the stomach are infrequent and, when present, usually become clinically manifest as an abdominal mass. Other clinical presentations have rarely been described. This report illustrates the case of a patient who presented with occult blood loss and radiographic evidence of esophageal duplication. A technetium scan demonstrated gastric duplication with mediastinal extension. Operative management and a review of the literature are described.

Diagnosis, Differential↗
PubMed1983

Body composition comparison in two elite female wheelchair athletes.

It was the purpose of this study to determine body composition by two methods in two excellent female athletes. One sportswoman (SRH) was national wheelchair marathon champion in 1977 in 3 hours, 40 minutes on the Boston course. She still competes internationally and has won three gold medals and set three world records in the last Olympiad for the handicapped in 1980. The second woman athlete (LSJ) competes in wheelchair basketball and track on a national level. Body density was determined by the standard underwater weighing procedure and residual volume determination. A second method to calculate cellular body mass was the measure of potassium 40 (40K) activity by whole body scintillation counter. The characteristics of these athletes are listed as follows: (formula; see text) The results show that both methods of determining adiposity produce results differing by only one percentage point. It is important to determine body composition in these wheelchair athletes since their cellular body mass is decreased because of their disability.

Adipose Tissue↗