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Biomedical subjects

D Kirk

Publications and source records attributed to D Kirk.

At least 127 records · Page 7Linked to original sources

Growth, DNA repair, sister chromatid exchange and chromosome studies in fibroblasts from Huntington's disease patients.

Fibroblast cultures from six unrelated Huntington's Disease (HD) patients and controls and one affected relative of an HD patient were used in studies of cell growth, DNA repair, sister chromatid exchange (SCE) and chromosome aberrations. There were no significant differences in background levels of SCEs or of chromosome aberrations between HD cultures and controls. Preliminary results using epidermal growth factor indicated that HD cells may have a lowered relative response to this polypeptide hormone. Cell growth studies showed no correlation between growth rate and HD. Increased cell saturation density was recorded in cell lines from four of the HD patients; the remaining three lines from affected individuals (two of them related) were indistinguishable from control cultures. This variation may reflect genetic heterogeneity in HD. An apparent deficiency in DNA repair capacity following UV irradiation in cultures from three HD patients was subsequently shown to be the result of the increased cell saturation densities in these cultures.

Adult↗

An electrophysiological study of the smooth muscle of the human colon.

Electrical recordings were made in vitro from preparations of human colonic smooth muscle from surgically resected specimens. The behaviour of the taenia consisted of regular spike action potentials based on a slow wave rhythm (22 +/- 5 c.p.m.), with tetanic contractions of the muscle. The actions of cholinergic drugs were studied and experiments performed to investigate the mechanism of the action potentials. The circular muscle produced clusters of spikes with solitary contractions. The differences between the two muscle layers may be of relevance to understanding the colonic electromyogram as recorded in vivo.

Acetylcholine↗

Modulation of growth of a human prostatic cancer cell line (PC-3) in agar culture by normal human lung fibroblasts.

The influence of normal human lung fibroblasts (NLF) on the clonal growth of human prostatic carcinoma cells (PC-3) in soft agar was studied. PC-3 growth was assessed by both colony-forming efficiency and clonal growth rate as estimated from increase in colony diameter. Effects of anchored NLF (proliferating cell monolayer) and nonanchored NLF (nonproliferating cells embedded in agar) on PC-3 growth were compared. Marked differences were observed. Anchored NLF inhibited whereas nonanchored NLF stimulated PC-3. Under suboptimal growth conditions (7% fetal bovine serum), PC-3 growth was stimulated about three-fold when NLF was added to the agar at a NLF:PC-3 seeding ratio of 60:1. Similar seeding ratios using anchored NLF cells caused a 98% inhibition of PC-3 growth. Control experiments with NLF-seeded coverslips on agar cultures ruled out medium depletion as a cause of the PC-3 inhibition. PC-3 inhibition was independent of NLF cell contact, required the continued presence of NLF cells, and was thus attributed to a diffusible, labile factor derived from anchored NLF monolayers. Kinetic analysis was used to determine the nature of the nonanchored NLF-fetal bovine serum interaction on stimulated PC-3 growth. Although the NLF factor was not a component of fetal bovine serum, it acted synergistically with it to stimulate PC-3 growth. It was concluded that there were strong correlations between (a) nonanchored NLF cells and PC-3 stimulation and (b) anchored NLF cells and PC-3 inhibition.

Agar↗

Non-reciprocal interactions in normal-neoplastic human cells. A quantitative, kinetic approach to cell interactions in vitro.

The mechanism of altered neoplastic growth has been investigated using a co-culture system for a kinetic study of normal-neoplastic human cell interactions in vitro. It was concluded that the cancer cells produced a growth factor for normal cells whereas normal cells produced both labile inhibitory and stable growth factors for cancer cells. Inhibition of the cancer cells was found to be proportional to normal cell growth rate. These heterologous growth interactions were potentiated through diffusable factors.

Blood↗

Normal human endometrium in cell culture. II. A microspectrophotometric study of polyploid nuclei in short-term primary epithelial cultures.

The growth of short-term primary cultures of endometrial epithelium has been studied using Feulgen microspectrophotometry. A gradual increase in the number of polyploid nuclei up to 64C has been observed and is associated with a decline in the growth capacity of the cultures. The specific mechanism(s) of this polyploidization is not known.

Cell Nucleus↗

Hibitane bladder irrigation in the prevention of catheter-associated urinary infection.

The effect of regular chlorhexidine bladder irrigations on catheter-induced urinary infection in patients admitted as urological emergencies was investigated. Excluding patients infected on admission the urine remained sterile throughout the period of catheterisation in 52% of those receiving chlorhexidine but in only 26% of a control group of patients.

Aged↗

Transitional cell carcinoma of the prostate.

Thirty-three cases of transitional cell carcinoma involving the prostate gland are reviewed. Four different types of involvement are described. The mortality of 66% was largely confined to those with primary prostatic transitional cell carcinoma and those in whom there was direct invasion of the prostate by a bladder tumour. The relationship of some of these lesions to urothelial carcinoma in situ is discussed.

Aged↗

Normal human endometrium in cell culture. I. Separation and characterization of epithelial and stromal components in vitro.

Separation of human endometrium into its epithelial and stromal components has been achieved through collagenase digestion and has permitted a study of these two cell populations under specific experimental culture conditions. The stromal cell populations showed a progesterone response, were easily handled in culture, and displayed a limited in vitro life span typical of human diploid fibroblasts. In contrast, epithelium only survived in short-term primary culture and showed no clear hormone response. High-density epithelial cultures remained viable for longer periods in culture. Comparisons between resurfacing endometrial epithelial cells in vivo and epithelial cells migrating from explants in vitro suggested that this initial epithelial migration in vitro was the counterpart of the repair response in vivo.

Cell Movement↗

Electrical activity of human colonic smooth muscle in vitro.

1. Extracellular and intracellular recordings were made of the electrical activity of isolated strips of human colonic smooth muscle, cut from sixty surgical specimens. 2. Strips of taenia were spontaneously active. The myogenic activity consisted in half the strips of intermittent periods of regular spike activity (frequency 22 +/- 5 (S.D.) c/min) accompanied by tetanic contractions; in the other half of the strips activity was continuous. In half the specimens, slow potentials were recorded between periods of spike activity. Slow potentials were not accompanied by contractions. 3. Spikes in taenia were abolished by verapamil. Spikes disappeared in low Ca and low Na solutions, but in low Na solution spikes could be stimulated by 15 mM-KCl. 4. ACh and physotigmine produced tetanic contractions in taenia. 5. Circular muscle was not spontaneously active within 1 h of incubation in the water bath, possibly due to inhibition by prostaglandins. 6. Circular muscle responded to ACh with irregular bursts of spikes associated with discrete contractions. Similar activity was seen after inhibition of prostaglandin synthesis with indomethacin. After treatment with tetrodotoxin, ACh produced regular spikes and tetanic contractions in circular muscle. 7. The possible relationships of these results to the myoelectrical activity of the human colon in vivo are discussed.

Acetylcholine↗

Anomalous cellular proliferation in vitro associated with Huntington's disease.

Detailed growth analyses of cultured skin fibroblasts from two patients with Huntington's Disease (HD) were compared with those from controls matched for age and sex. In contrast to control cells, HD fibroblasts plated more efficiently at the low seeding densities used. Subsequent exponential growth of HD cultures was more stable towards routine trypsinisation than that of controls. However, the most striking feature of HD cultures was their ability to grow to significantly higher cell saturation densities. Experiments with trypsinised and untrypsinised cultures imply an inherent alteration in the HD cell membrane.

Cell Division↗

The role of oxygen therapy in the healing of experimental skin wounds and colonic anastomosis.

A number of experimental studies have indicated that wound healing is adversely affected by hypoxia, and it has been suggested that healing can be improved by increasing inspired oxygen tensions. However, this hypothesis is based on observations on simulated wounds or tissue implants in experimental animals, and the clinical relevance of these observations is uncertain. The effects of oxygen therapy on the healing of skin wounds and colonic anastomoses were examined in rats. Sutured skin incisions and normal and ischaemic colonic anastomoses were studied in control animals breathing air and in test animals breathing 50 per cent oxygen. Wound healing was assessed by measurements of wound breaking strength, colonic bursting wall tension and wound collagen after 7 days' treatment with oxygen. There was no significant difference in the measurements in skin wounds or colonic anastomoses in test and control animals, and there was a similar incidence of anastomotic dehiscence in the ischaemic colon of test animals and controls. Oxygen therapy had no apparent effect on wound healing in this study, and it was concluded that further studies are required to determine whether or not there is a rational basis for the clinical use of oxygen therapy to help wound healing.

Animals↗

Effects of topically potent glucocorticoids on human diploid fibroblasts in vitro.

A wide range of concentrations of both cortisol and a topically more potent synthetic derivative, fluocinolone acetonide, was found not to inhibit the growth of cultured human skin fibroblasts; fluocinolone acetonide produced a slight increase in the growth rate. Both steroids had a transient stimulatory effect on fibroblasts, promoting an earlier entry into the period DNA synthesis (S) which was also accompanied by a substantial increase in the length of S.

Cell Division↗