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Biomedical subjects

I King

Publications and source records attributed to I King.

54 records · Page 3Linked to original sources
PubMed1989

Antagonistic effects of retinoic acid and hydrocortisone on terminal differentiation of human squamous carcinoma cells.

Differentiation of SqCC/Y1, a human malignant squamous carcinoma, can be modulated by the presence of both corticosteroids and retinoids. To evaluate the regulation of the differentiation of epidermal cells by these agents, we have employed delipidized serum from which glucocorticoids and retinoids were removed. Thirty percent of SqCC/Y1 cells spontaneously expressed the terminally differentiated phenotype after 6 d in culture, as measured by the capacity to form detergent-insoluble cornified envelopes. Exposure of SqCC/Y1 cells to hydrocortisone at concentrations of 30, 100 and 300 nM produced a 25, 100, and 175%, increase, respectively, in the number of differentiated cells over untreated control cultures. Exposure of cells to retinoic acid at levels of from 3 to 300 nM caused a 24 to 85% decrease in the quantity of differentiated cells. Simultaneous treatment of SqCC/Y1 cells with hydrocortisone and retinoic acid resulted in mutual antagonism of cornified envelope formation. Treatment of SqCC/Y1 cells with a 1000-fold molar excess of retinoic acid did not directly alter the uptake of hydrocortisone, and a 100-fold molar excess did not directly inhibit the binding of the corticosteroid to its receptor. Pretreatment of cells for 48, 72, or 96 h with 100 nM retinoic acid decreased the binding of hydrocortisone to its receptor by only 20%, and only resulted in a small decrease in the total amount of hydrocortisone associated with cells 48 h after the addition of retinoic acid. These findings suggest that the antagonism between hydrocortisone and retinoic acid on the terminal differentiation of SqCC/Y1 is not expressed at the level of the corticosteroid receptor.

Carcinoma, Squamous Cell↗
PubMed1989

Immunofluorescent localization, by use of anti-idiotypic antibody, of monoclonal anti-progesterone antibody in the mouse uterus before implantation.

Mouse monoclonal anti-progesterone IgG1 antibody designated DB3 has an anti-fertility effect when injected into female mice shortly after mating. In BALB/c mice, pregnancy is blocked, probably as a result of progesterone withdrawal with inhibition of implantation. Rabbit polyclonal anti-idiotype raised against DB3 has been used in an indirect immunofluorescence method on frozen tissue sections to demonstrate the presence of DB3 on the surface of uterine luminal and glandular epithelia before implantation. DB3 was only detectable 30-60 h after a single parenteral injection (9 nmol antibody per mouse i.p. or i.v. at 32 h post coitum). Immunolocalization was both pregnancy-dependent and anti-progesterone antibody-specific, as it was not seen in pseudopregnant mice or mice treated with P3 (mouse myeloma IgG1 protein, using polyclonal anti-P3 anti-idiotype as a probe) or saline. The immunofluorescent reaction was completely blocked by addition of DB3 idiotype in vitro. The results indicate that anti-progesterone antibody binds to an antigen associated with luminal and glandular epithelia which may locally inhibit the uterine uptake of progesterone and disrupt the process of implantation.

Animals↗
PubMed1988

Anti-idiotypic antibody used for the localization of parenterally administered monoclonal anti-progesterone antibody in mice.

Affinity-purified rabbit and sheep anti-idiotypic antisera raised against mouse monoclonal anti-progesterone IgG1 antibody (DB3) or mouse myeloma IgG1 protein P3 (MOPC 21) showed high binding specificities to the respective idiotypes used for immunization as determined by RIA or ELISA. They have been used in an indirect immunofluorescent method to demonstrate the localization of parenterally administered idiotypes in pregnant or pseudopregnant BALB/c mouse frozen tissue preparations, at known stages post coitum after a single intraperitoneal or intravenous injection of DB3 or P3. DB3 was visualized on the surface of uterine luminal and glandular epithelia of pregnant mice 36 h after treatment; the localization was DB3-specific as it was not seen in mice treated with P3 (using sheep anti-P3 anti-idiotype as a probe) or saline. The fluorescent staining reaction in oviduct was weak and only appeared on the surface of the oviducal serosa (peritoneal side). Both DB3 and P3 were also localized in liver (granules of Kupffer cells), kidney (glomerular basement membrane), spleen (on the membrane surface of mononuclear cells in the white pulp), and peritoneal exudate cells (on the membrane surface). Staining could be completely blocked by the addition of the free idiotypes against which the anti-idiotypes were made but not by the unrelated idiotype. Anti-idiotypic labelling in vivo is more specific and selective than anti-whole immunoglobulin labelling.

Animals↗
PubMed1986

Transcriptional regulation of the transferrin receptor in differentiating HL-60 leukemic cells.

HL-60 promyelocytic leukemia cells were induced to differentiate along the granulocytic pathway by treatment with dimethylsulfoxide. A significant decrease in transferrin receptor specific mRNA was seen as early as 4 hr after exposure to inducer. Relative to untreated controls, transcript levels decreased 5-fold within 24 hr of exposure to dimethylsulfoxide and remained depressed throughout a 6-day treatment period. Reductions in receptor transcripts preceded the loss of surface receptor which in turn preceded the expression of the differentiated phenotype. The findings demonstrate that differentiation-associated regulation of the transferrin receptor can occur at the transcriptional level.

Cell Differentiation↗
PubMed1986

A sensitive method to quantify the terminal differentiation of cultured epidermal cells.

Terminal differentiation of normal and malignant keratinocytes is routinely determined by the ability of these cells to form cornified envelopes after incubation with a calcium ionophore. We have used the human squamous cell carcinoma, SqCC/Y1, to quantify cellular differentiation by the formation of detergent-insoluble protein. The methodology developed employs the metabolic labeling of detergent-insoluble cellular protein with [35S]methionine in the presence of a calcium ionophore. The ratio of filter-retainable radioactivity to that of total cellular protein was shown to be closely correlated to the results obtained by measuring the number of envelope-competent cells when cells were induced to enter a pathway of terminal differentiation in culture by serum deprivation or by treatment with hydrocortisone, and during the inhibition of maturation by either retinoic acid (RA) or epidermal growth factor (EGF). This way of measuring the degree of terminal differentiation of epidermal cells is a relatively simple one that readily allows the simultaneous measurement of multiple samples.

Blood↗
PubMed1983

Tissue distribution of exogenous amino acids during transport across the vascularly perfused anuran small intestine.

Microdensitometric analysis of autoradiographs has been used to measure the distribution and intracellular concentration of L-leucine and L-lysine during transport across the vascularly perfused small intestine of Rana pipiens. L-leucine was not accumulated in the mucosal epithelium to a concentration higher than that in the lumen under steady-state conditions, whereas L-lysine was concentrated on average three- to four-fold. 2. At the end of 30 min loading, the majority of both amino acids were found in the mucosal epithelium and the villous core, although significant amounts were also present in the muscle. Lysine showed a gradient of accumulation within the mucosal epithelium along the length of the villous folds, the highest concentrations being achieved in the cells near the tip. Leucine showed no such gradient under steady-state conditions. 3. Superfusion of the mucosal surface of the tissue with leucine for only 3 min did reveal a gradient for uptake into the mucosal epithelium, although it was still not as steep as that seen for lysine. 4. The presence of leucine in the vascular bed while lysine was perfused through the lumen significantly lowered the concentration of lysine in the mucosal epithelium and villous core and eliminated the concentration gradient in the mucosal epithelium seen along the villous fold. 5. When leucine was perfused on its own through the vascular bed, the uptake into the muscle was greatly increased compared to when the amino acid was presented from the lumen. At the same time, the uptake into the mucosal epithelium was reduced by 45%. 6. Analysis of the tissue content of leucine after loading for 30 min from the lumen and then washing out the amino acid for 15 min showed that the mucosal epithelium, villous core and muscle had contributed 74%, 17% and 9% respectively to the total amino acid lost from the tissue. 7. These results are discussed with regard to the significance of the exit mechanisms for these amino acids and the validity of previous compartmental analyses made under similar conditions.

Animals↗
PubMed1980

Plasma zinc in psoriatic in-patients treated with local zinc applications.

Zinc is a major component of many local skin applications. An investigation into its systemic absorption in thirty-one psoriatic hospital in-patients is reported. Plasma zinc, copper and whole blood delta-aminolaevulinic acid dehydratase were followed before and during in-patient treatment over 14 days. No significant alteration in these parameters was detected. Significantly reduced plasma zinc levels were found in the patients compared to a matched control population.

Administration, Topical↗
PubMedDate not supplied

Evaluation of the acute and subchronic toxic effects in mice, rats, and monkeys of the genetically engineered and Escherichia coli cytosine deaminase gene-incorporated Salmonella strain, TAPET-CD, being developed as an antitumor agent.

TAPET-CD, a genetically engineered Salmonella strain with chromosomal-incorporated cytosine deaminase (CD) gene, has been shown to selectively accumulate tumors, suppress tumor growth, and convert 5-fluorocytosine (5-FC, an antifungal agent) to the antitumor agent 5-fluorouracil (5-FU) in animals. The current studies investigated the safety of TAPET-CD, and TAPET-CD/5-FC combination, in animals. In C57BL/6 mice (n = 10 females/dose), the maximum nonlethal dose of TAPET-CD (intravenous [IV] bolus) was 1 x 10(6) colony-forming units (cfu)/mouse, or > 10,000 x that of wild-type Salmonella. In Sprague-Dawley rats (n = 4/sex/group), after treatment with 4 weekly cycles of TAPET-CD (an IV injection/cycle at 1 x 10(5), 3 x 10(5), 1 x 10(6), 3 x 10(6), or 1 x 10(7) cfu/rat on day 1) and 5-FC (per os twice daily [PO b.i.d.], 250 mg/kg on days 2-7/cycle), clinical signs and mortality were evaluated daily, body weight and clinical pathology weekly, and gross necropsy on day 29. No treatment-related toxicity, although occasional and mild clinical signs (e.g., dehydration), increased hepatic enzyme/function values and white blood cells, splenic enlargement, and bilateral red discoloration of the kidneys, were observed. In cynolmogus monkeys, Experiment 1 involved treatment with TAPET-CD (IV injection at 1 x 10(9) cfu/monkey). Clinical signs and mortality were evaluated daily, body weight weekly, and gross necropsy on days 2, 7, and 31 (1/sex/time point). Experiment 2 involved treatment with TAPET-CD (IV injection at 1 x 10(9) and 1 x 10(10) cfu/monkey in Groups 1 to 3 and Groups 4 to 6, respectively) on day 1 and 5-FC (PO b.i.d. at 250, 500, and 1000 mg/kg in Groups 1 to 3, and 500, 1500, and 0 mg/kg in Groups 4 to 6, respectively) on days 4 to 17 (n = 1/sex/group). Clinical signs and mortality were evaluated daily; body weight and clinical pathology on days 1, 2, 4, 14, and 18; body temperature on days 1, 4, and 18; ophthalmic examinations on days 3 and 17; and gross necropsy and histopathology on day 18. Experiment 1 indicated that TAPET-CD at 1 x 10(9) or 1 x 10(10) cfu/monkey was well tolerated, with only occasional mild clinical signs (i.e., emesis, vomiting, inappetance, loose/infrequent/absence of stool), increases in hepatic enzyme/function values, and splenic enlargement. Experiment 2 indicated that TAPET-CD/5-FC combination had a maximum tolerated dose (MTD) of 1 x 10(10) cfu/monkey for TAPET-CD and 500 mg/kg for 5-FC in monkeys. Supra-MTDs induced renal toxicity. In conclusion, TAPET-CD had a good safety profile (reflected by the extremely large amount of TAPET-CD needed to induce mortality or toxicity) in mice, rats, and monkeys. More adverse events were observed with TAPET-CD/5-FC combination when compared to TAPET-CD and these events were similar to the reported effects of 5-FU, suggesting the involvement of 5-FU.

Animals↗
PubMedDate not supplied

Conceptual frameworks. Putting the nursing focus into core curricula.

The growing movement toward specialty certification in nursing has resulted in an increased demand for continuing education that supports specific areas of specialty practice and certification status. In examining a number of the specialty practice core curricula documents, it is evident that there is a tendency to organize nursing content using the medical model as a framework. A method by which core curricula for specialty practice are organized and developed from a distinctly nursing perspective is needed. The authors suggest that conceptual frameworks, developed by nurses who are expert in a specific clinical practice area, are a practical method for the development of such curricula.

Certification↗
PubMedDate not supplied

The effect of structured and unstructured pre-operative teaching: a replication.

This study conducted an approximate replication of the Lindeman and Van Aernam study (1971) on a sample of 49 patients from a large metropolitan hospital. Factors controlled in this study that were not present in the original study included sample restrictions to patients of three surgeons with similar techniques and to patients having lower or upper abdominal surgery. Structured pre-operative teaching was conducted primarily by the principle investigator and associate and a check list was used to indicate that the patients could perform the deep breathing, coughing, and exercises. For this sample, using p = .05, structured pre-operative instruction improved significantly the ability of the patients to deep breathe and cough post-operatively as measured by pulmonary function tests. Hypothesis I was supported. Structured pre-operative instruction did not reduce significantly the mean length of hospital stay and hypothesis II was not supported.

Adult↗
PubMedDate not supplied

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Adaptation, Physiological↗