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Biomedical subjects

N Davies

Publications and source records attributed to N Davies.

At least 19 recordsLinked to original sources
PubMed1996

Antitumour activity of S-p-bromobenzylglutathione cyclopentyl diester in vitro and in vivo. Inhibition of glyoxalase I and induction of apoptosis.

The glyoxalase I inhibitor diester, S-p-bromobenzyl-glutathione cyclopentyl diester (BrBzGSHCp2), inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The median growth inhibitory concentration GC50 value of BrBzGSHCp2 was 4.23 +/- 0.001 microM (n = 21), and the median toxic concentration TC50 value was 8.86 +/- 0.01 microM (n = 21). BrBzGSHCp2 inhibited DNA synthesis in the third hr of incubation: the median inhibitory concentration IC50 value was 6.11 +/- 0.02 microM (n = 8). Incubation of HL60 cells with 10 microM BrBzGSHCp2 delivered the diester into cells: de-esterification of the diester there in lead to formation of the S-p-bromobenzylglutathione, inhibition of glyoxalase I activity in situ, increase in the methylglyoxal concentration after 1 hr, and induction of apoptosis after 6 hr. BrBzGSHCp2 (50-200 mg/kg) also inhibited the growth of murine adenocarcinoma 15A in vivo. Glyoxalase I inhibitor diesters may, therefore, inhibit tumour growth by inducing the accumulation of methylglyoxal in tumour cells, and induction of apoptosis.

Adenocarcinoma↗
PubMed1996

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers.

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.

Adult↗
PubMed1996

Therapeutic potential of octreotide in the treatment of liver metastases.

Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.

Animals↗
PubMed1995

Octreotide inhibits the growth and development of three types of experimental liver metastases.

A study was performed to assess the effects of octreotide on the growth and development of liver metastases in rats. Tumour was induced by intraportal injection of three tumorigenic cell lines (the fibrosarcoma HSN and colonic adenocarcinomas K12/Tr and WB2054M) in syngeneic rats. Octreotide treatment (2 micrograms subcutaneously for 3 or 4 weeks) was started 18 h and 1 week after tumour induction; a delay in treatment of 1 week allowed micrometastases to develop. Treatment with octreotide significantly (P < 0.001) reduced the median hepatic replacement of liver by tumour compared with that of control rats given saline (controls: HSN 76.4 per cent, K12/Tr 17.5 per cent, WB2054M 43.9 per cent; octreotide treatment delayed 18 h: HSN 2.7 per cent, K12/Tr 0.6 per cent, WB2054M 1.3 per cent; octreotide treatment delayed 1 week: HSN 9.3 per cent, K12/Tr 2.5 per cent, WB2054M 2.3 per cent). These results clearly indicate that octreotide significantly inhibits the growth and development of experimental liver metastases. Further studies are required both to delineate the mechanism of action and to investigate these effects in a clinical setting.

Animals↗
PubMed1995

Hyperactivation may assist human spermatozoa to detach from intimate association with the endosalpinx.

The behaviour of human spermatozoa was observed during incubation with epithelial cells isolated from the isthmic and ampullary sections of human uterine (Fallopian) tubes. During incubation, spermatozoa were observed to bind to the epithelial cells of the tube (the endosalpinx), and individual spermatozoa attached and detached at intervals. The kinematic characteristics of spermatozoa during these behaviour patterns were determined. The results showed that detached spermatozoa typically had an increased curvilinear velocity and amplitude of lateral head displacement, accompanied by a decrease in their linearity. Significantly (P < 0.01) more of the detaching spermatozoa were hyperactivated than were spermatozoa prior to attachment for both isthmic (35.3 +/- 5.5 versus 4.0 +/- 3.3%; mean +/- SEM) and ampullary (26.0 +/- 7.0 versus 2.0 +/- 1.4%) regions. Incubation with epithelial cells from either region produced no differences in any category of sperm behaviour. Furthermore, there was no significant difference between regions in the amount of time spermatozoa spent bound (33.6 +/- 12.9 and 20.6 +/- 3.0 s for isthmic and ampullary tissue respectively). These results support the hypothesis that hyperactivation may assist spermatozoa in breaking connections with epithelial cells.

Cell Adhesion↗
PubMed1995

Effect of octreotide infusion on hepatic and tumour blood flow in two experimental models of liver metastases.

OBJECTIVE: To investigate the effects of octreotide infusion on hepatic and tumour blood flow in rats with experimentally induced liver tumours. DESIGN: Blood flow was determined in tumour-bearing rats using a dual reference microsphere technique before and after intravenous infusion of octreotide. METHODS: Tumours were induced in syngeneic rats by intraportal injection of K12-Tr and WB2054-M adenocarcinoma cells. Hepatic arterial and portal venous inflow, tumour blood flow and systemic arterial pressure were determined before and after octreotide infusion (0.05 microgram/min). RESULTS: In rats with K12-Tr tumours there was no change in tumour blood flow, hepatic arterial flow or portal venous inflow after octreotide infusion. In contrast, in rats with WB2054-M tumours, octreotide infusion resulted in a significant reduction in the blood flow to the hepatic tumour (from 0.37 to 0.135 ml/min/g) but had no effect on hepatic artery or portal venous inflow. CONCLUSION: The reduction in blood flow to tumours derived from WB2054-M cells could, at least in part, explain the inhibitory effect of octreotide on the growth and development of these tumours. However, octreotide had no effect on blood flow to tumours derived from K12-Tr cells, suggesting that the analogue must inhibit tumour growth by other mechanisms.

Adenocarcinoma↗
PubMed1995

The prevalence of respiratory symptoms in South Australian preschool children. I. Geographic location.

OBJECTIVE: This study was designed to ascertain the prevalence of respiratory symptoms in South Australian preschool children and to investigate the relationship between prevalence rates and geographic location. METHODOLOGY: Data were collected from 14,124 families with a child aged 4 years 3 months to 5 years of age. This sample represents 73% of the State preschool population of that age. At the time of a routine preschool health check, parents completed a questionnaire regarding their child's respiratory health and place of residence (postcode). RESULTS: Results showed that the prevalence rates were as follows: (i) ever having chest wheezing 38.6%; (ii) chest wheezing within the preceding 12 months 25.2%; (iii) ever having asthma 22.5%; (iv) ever having a dry cough at night 33.7%; (v) ever having bronchitis or cough with sputum 55.3%; (vi) ever having hay fever 29.7%; (vii) prone to excessive head colds 32.6%; and (viii) ever having eczema 18.8%. Over 38% of parents claimed that winter was the season for the most frequent or severe attacks of wheezing and 31.7% claimed no seasonal difference. Winter was the season most associated with episodes of bronchitis (50.9%), with no seasonal difference in episodes for 29.8% of children. Prevalence rates differed by geographic location within South Australia and within the Adelaide metropolitan region. CONCLUSION: This population-based survey shows that over 22% of South Australian 4 to 5 year old preschool children have had (or continue to have) asthma. The study also documented the geographic distribution of respiratory symptom prevalence within South Australia.

Asthma↗
PubMed1995

The prevalence of respiratory symptoms in South Australian preschool children. II. Factors associated with indoor air quality.

OBJECTIVE: This study investigated the relationship between indoor air quality and the prevalence of respiratory symptoms in South Australian preschool children. METHODOLOGY: Data were collected from 14,124 families with a child aged 4 years 3 months to 5 years of age. This sample represents 73% of the targeted State preschool population. At the time of a routine preschool health check, parents completed a questionnaire regarding: their child's respiratory health and place of residence (postcode), parental smoking, type of fuel used for cooking and heating and method used for home cooling. RESULTS: For preschool children residing in the greater Adelaide region, logistic regression analyses found that having a natural gas stove compared to an electric stove was significantly associated with increased prevalence rates for: (i) asthma (odds ratio [OR] 1.24); (ii) wheezing in the preceding 12 months (OR 1.16); excessive colds (OR 1.14); and hay fever (OR 1.13). The use of a liquid petroleum gas stove compared to an electric stove was not associated with any respiratory symptoms. The use of a flueless gas heater compared to other forms of heating was significantly associated with increased prevalence rates for dry cough (OR 1.26), ever having wheezed (OR 1.15) and wheezing in the preceding 12 months (OR 1.18). The use of a wood fire/heater compared to other forms of heating was significantly associated with a reduced prevalence rate for dry cough (OR 0.84) and ever having wheezed (OR 0.82). Parental smoking was significantly associated with increased prevalence rates for bronchitis (OR 1.21) and ever having wheezed (OR 1.24). The form of home cooling used was not associated with prevalence rates, after accounting for geographic location. Socio-economic status (postcode level) was not generally associated with prevalence rates. CONCLUSIONS: These results suggest that respiratory symptom prevalence is related to the fuel used for cooking and heating and parental smoking. Prospective investigation regarding indoor air quality and respiratory symptoms is required.

Air Conditioning↗
PubMed1995

Octreotide, the reticuloendothelial system, and experimental liver tumour.

The inhibitory effect of octreotide on the growth of liver tumour is probably mediated (at least in part) by stimulation of the hepatic reticuloendothelial system (RES) activity. This study therefore investigated the effect of octreotide on the hepatic and splenic RES (assessed by the uptake of technetium 99m labelled albumin colloid, 99mTc-AC) in normal and tumour bearing rats and in animals treated with gadolinium chloride. The effects of gadolinium chloride and octreotide alone or in combination on the growth of liver tumour were also studied. Octreotide significantly stimulates both hepatic and splenic uptake of 99mTc-AC in normal rats and tumour bearing rats. In controls, the uptake of 99mTc-AC was significantly reduced by gadolinium chloride and was not changed by octreotide. RES blockade with gadolinium chloride significantly increased (p < 0.001) tumour growth compared with controls (hepatic replacement 42%; 95% confidence intervals (CI), 27.6 to 56.4 v 16.7%, 95% CI, 11.1 to 21.3%) whereas octreotide significantly inhibited (p < 0.001) the percentage hepatic replacement by tumour (0.7%; 95% CI, 0 to 2.3 v 16.7%; 95% CI, 11.1 to 21.3). This study highlights the importance of the RES in the development of liver tumour. Furthermore, octreotide inhibited the growth of liver tumour in rats with RES blockade, albeit to a lesser degree than in normal animals. These findings suggest that octreotide inhibits the growth of hepatic tumour by mechanisms other than stimulation of RES activity.

Animals↗
PubMed1995

Opsite skin closure in day case paediatric surgery: is a subcuticular suture necessary?

Opsite skin closure without skin suture was compared with subcuticular Vicryl in a randomized trial in children undergoing day-case surgery for hernia, hydrocele or undescended testis. Ninety-nine groin closures were randomized, 47 to Opsite and 52 to subcuticular Vicryl. There was no difference in the duration of operation or in the cosmetic appearance of the wounds. Complications were all minor and similar in both groups. Opsite alone is suitable as a skin closure for the groin wounds in children.

Adolescent↗
PubMed1993

Reticuloendothelial stimulation: levamisole compared.

PURPOSE: Levamisole in combination with 5-fluorouracil is an effective adjuvant for the treatment of resected Dukes stage C colon cancer. Since the mechanism of action of levamisole is not known, we have investigated its effects on hepatic and splenic reticuloendothelial system (RES) activity in the rat and compared the effect of levamisole with other known RES stimulators. METHODS: The hepatic and splenic uptake of an intravenous dose of technetium-99m-sulfur colloid has been used to measure RES activity in rats treated with levamisole, glucan, zymosan, chlormethiazole, octreotide, and saline. RESULTS: Levamisole significantly increased the hepatic uptake of technetium-99m-sulfur colloid and is comparable in its effect to the other RES stimulators. In contrast, levamisole has no effect on splenic RES activity. CONCLUSION: RES function is considered to be a potentially important factor in the development of liver metastases, and the stimulatory effect of levamisole on the hepatic RES may partly explain its efficacy as an adjuvant treatment in colon cancer.

Animals↗
PubMed1993

Anti-müllerian hormone in early human development.

Anti-müllerian hormone (AMH) is a glycoprotein produced by immature Sertoli cells and responsible for the regression of müllerian ducts in male fetuses. The ontogeny of the hormone in early human development was investigated. While no detectable AMH could be found in female fetal serum, in males, the mean +/- S.E.M. AMH serum concentration was 40.5 +/- 3.9 ng/ml from 19 to 30 weeks (n = 13), and 28.4 +/- 6.1 ng/ml from 30 weeks to term (n = 9). The latter value is significantly different from the mean AMH concentration in serum from boys aged 2 months to 2 years (43.1 +/- 3.7), suggesting that AMH production is sluggish during the perinatal period. The serum AMH concentration of a 46,XX male fetus was in the normal range for males. Using in situ hybridization, AMH transcripts were detected in the testicular tissue of all fetuses from 8 weeks onwards, but not in fetal ovaries nor in the yet undifferentiated gonadal tissue of a 7-week-old fetus bearing male-determining DNA sequences. Together, these data indicate that AMH is a reliable marker for the presence of functional testicular tissue and, as such, may be helpful for the diagnosis of fetal sex, particularly in the presence of sex chromosome abnormalities.

Amniotic Fluid↗
PubMed1993

Transforming growth factor alpha is trophic to pancreatic cancer in vivo.

Pancreatic cancer cell lines overexpress epidermal growth factor (EGF) receptors and also have the capacity to produce transforming growth factor alpha (TGF alpha), the alternate agonist of the EGF receptor. The purpose of this study was to determine if TGF alpha had a trophic effect on the growth of pancreatic cancer in vivo. Syrian golden hamsters were inoculated with 50,000 H2T hamster ductal pancreatic cancer cells. The hamsters were then randomised to three equal groups: the groups received either saline (control), EGF, or TGF alpha, each by intraperitoneal injection, three times a day. Treatment continued for seven weeks, and each week the hamsters were weighed and tumour areas were measured. The hamsters were then killed, and the tumours were excised, weighed, and extracted for assay of DNA content as a measure of cellularity. From week four onwards both EGF and TGF alpha significantly stimulated tumour growth. Although tumour weights were not significantly different, tumour DNA content had nearly doubled after exposure to both EGF and TGF alpha. It is concluded that like EGF, TGF alpha can stimulate pancreatic cancer growth in vivo, and this may in part explain the aggressive nature of these cancers in clinical practice.

Animals↗
PubMed1991

Histone-DNA contacts in the 167 bp 2-turn core particle.

The histone-DNA contacts in the 167 bp 2-turn core particle have been compared with those in the 146 bp 1.75-turn core particle by the methodology developed by Mirzabekov and his colleagues. The contacts in the 167 bp 2-turn core particle retain the essential features of those in the 146 bp 1.75-turn core particle but contacts for histones H3 and H2A were found in the 10 bp extension that discriminates the two particles. In addition the contact for histone H2A near the dyad axis was far more pronounced in the case of the 146 bp core particle.

DNA↗