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Biomedical subjects

J Knight

Publications and source records attributed to J Knight.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Metomidate, etomidate and fentanyl as injectable anaesthetic agents in mice.

Light surgical anaesthesia lasting 12-15 min was produced by metomidate at 50 mg/kg and by etomidate at 30 mg/kg after intraperitoneal injection. Full surgical anaesthesia lasting about 160 min was achieved after subcutaneous injection of a metomidate-fentanyl mixture (60 mg/kg: 0.06 mg/kg) and this proved superior to etomidate-fentanyl given subcutaneously or intraperitoneally. It was concluded that metomidate-fentanyl is superior to pentobarbitone and tribromoethanol as an injectable anaesthetic for mice.

Anesthesia, General↗

Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative diseases by clinical, virological, and immunopathological studies.

Multiple methods, pedigree analysis, clinical evaluation, and Epstein-Barr virus (EBV)-specific serology, EBV DNA hybridization of tissues to probe for viral genome, staining of touch imprints for EBV nuclear-associated antigen, establishment of spontaneous infected B-cell lines from peripheral blood or tissues, examination of peripheral blood smears, and hematopathology studies, were used to study seven patients with the X-linked lymphoproliferative syndrome and seven additional patients with life-threatening EBV-associated diseases. These studies demonstrated EBV in the tissues of all 14 patients and immunodeficient antibody responses to EBV were documented. This virus can produce various life-threatening lymphoproliferative diseases in a variety of immunodeficient patients.

Adolescent↗

Sigmoidoscopic reduction of sigmoid volvulus.

Twenty-six patients were treated for a volvulus of the sigmoid colon between January, 1971, and June, 1979. Eight patients had an emergency resection and, although there was a high postoperative morbidity, there were no deaths in this group. An attempt to decompress the volvulus by means of a rigid sigmoidoscope was made in 18 patients. This was successful in 14 patients. Six of these patients suffered a recurrence, and perforation occurred in four patients, three of whom subsequently died. Because of the high risk of perforation, care should be taken with this procedure.

Aged↗