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Biomedical subjects

M C White

Publications and source records attributed to M C White.

At least 109 records · Page 6Linked to original sources
PubMed1991

Interleukin 6 is secreted by breast fibroblasts and stimulates 17 beta-oestradiol oxidoreductase activity of MCF-7 cells: possible paracrine regulation of breast 17 beta-oestradiol levels.

Previous studies have demonstrated that cultured human breast fibroblasts secrete a high-molecular-weight polypeptide which stimulates the ability of human breast-cancer MCF-7 cells to convert oestrone (E1) to the biologically more active 17 beta-oestradiol (E2). This effect is mediated by an increase in reductive E2 oxidoreductase (EOR) activity. We have identified the fibroblast-derived stimulatory factor as interleukin 6 (IL6) or an immunologically related peptide. Human breast fibroblasts in culture secreted up to 10 ng IL6/ml medium during 24 hr of incubation. The effects of IL6 and breast fibroblast conditioned medium (CM) on reductive EOR activity of MCF-7 cells were similar; both CM and IL6 potently stimulated enzyme activity in a dose-dependent manner, and both exerted synergistic stimulatory effects in combination with E2. A polyclonal neutralizing antibody to IL6 completely abolished the reductive EOR-stimulating activity of CM. These results indicate that breast stromal fibroblasts may have a paracrine role in regulation of breast-cancer-tissue levels of E2, and that this effect is mediated by IL6 or a closely related peptide.

Breast↗
PubMed1990

LH and FSH secretion and responses to GnRH and TRH in patients with clinically functionless pituitary adenomas.

Serum concentrations of LH and FSH and their response to the separate administration of GnRH (100 micrograms i.v.) and TRH (200 micrograms i.v.) have been studied preoperatively in 12 patients with a clinically functionless pituitary adenoma, of whom nine (3F: 6M) were found to secrete gonadotrophins in vitro. In three patients with a gonadotrophin-secreting adenoma (GSA) the pulsatile release of LH and FSH was also assessed preoperatively. An elevated serum FSH was recorded in six of nine patients with a GSA, and was subnormal in one, whilst an elevated LH was recorded in only two and was subnormal in six. A doubling of LH occurred in only four of the nine patients after GnRH and in three of six after TRH. None of the three patients with a non-GSA was shown to have an aberrant response to GnRH or TRH. In patients with a GSA, pulsatile release of LH and FSH was usually asynchronous and neither hormone demonstrated any regular harmonic pattern. These data show that in patients with a GSA the serum FSH level is usually elevated but this is not invariable, and the LH may well be low. Pathological responses of LH are frequently found following the administration of either GnRH or TRH and these stimulation tests should be performed separately in patients presenting with a clinically 'non-functioning' pituitary tumour to assist in the preoperative diagnosis. The absence of normal LH and FSH pulsing also appears to be a feature of GS adenomas, and suggests that tumorous gonadotrophin secretion is not under physiological control by hypothalamic GnRH.

Adenoma↗
PubMed1990

Rapid pulses of luteinizing hormone during the ovarian cycle.

Luteinizing hormone has been shown to be secreted in a complex pattern of low-amplitude, high-frequency pulses superimposed on high-amplitude, low-frequency pulses. To test the hypothesis that the rapid, small pulses vary during the ovarian cycle, 16 normal women were studied on two occasions each, in the early and late follicular phases of one cycle or the luteal and following early follicular phase. Blood samples were taken every 1 min for 1 h. Statistical methods of time series analysis were applied to the data. There were significant amplitude differences between subjects at all stages of the cycle. We found no evidence to support the hypothesis that the frequency of the small rapid pulses varied during folliculogenesis. The results for the luteal phase, while less uniform, showed no consistent change. It is suggested that the rapid pulses may be related to function of the hypothalamic-pituitary axis rather than direct ovarian control.

Adolescent↗
PubMed1990

Analysis of regulation of the ilvGMEDA operon by using leader-attenuator-galK gene fusions.

Five of the genes for the biosynthesis of isoleucine and valine form the ilvGMEDA operon of Escherichia coli K-12. Expression of the operon responds to changes in the availability of isoleucine, leucine, and valine (ILV). Addition of an excess of all three amino acids results in reduced expression of the operon, whereas limitation for one of the three amino acids causes an increase in expression. The operon is preceded by a leader-attenuator which clearly regulates the increased expression that occurs due to reduced aminoacylation of tRNA. To assess the factors that result in the reduced expression of this operon upon the addition of ILV, a series of plasmids were constructed in which the ilv regulatory region was fused to galK. In response to addition of the amino acids, expression of the galK gene fused to the leader-attenuator decreased five- to sevenfold, instead of the twofold observed for the chromosomal operon. A deletion analysis with these plasmids indicated that the ILV-specific decrease in expression required an intact leader-attenuator but not ilvGp2 or the DNA that precedes this promoter. This conclusion was supported by both S1 nuclease analysis of transcription initiation and determination of galK mRNA levels by RNA-RNA hybridization.

Cloning, Molecular↗
PubMed1990

Administration of high-dose octreotide (Sandostatin) by continuous subcutaneous infusion for the treatment of acromegaly.

Patients with active acromegaly were treated with octreotide (SMS 201-995, Sandostatin; Sandoz Pharmaceuticals) given in high dosage by continuous subcutaneous administration (CSI). Serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations were rapidly and consistently reduced to the normal range and maintained for up to 14 weeks of study. Maximal inhibition of GH and IGF-1 secretion was obtained at a dose of 600 micrograms/24 h; all except 1 of the 7 patients were able to tolerate a higher dose of 1,600 micrograms/24 h. A single patient failed to show GH suppression at any dosage of octreotide. Computed tomographic evidence of tumour shrinkage was not demonstrated in these 7 patients, although in 2 patients subsequently studied by us definite tumour shrinkage was observed. These data show that the administration of octreotide by CSI is a highly satisfactory method for persistently lowering GH and IGF-1 concentrations in acromegalic patients sensitive to this drug.

Acromegaly↗
PubMed1989

Continuous infusion of octreotide in acromegaly.

15 patients with acromegaly were treated with continuous subcutaneous infusion of octreotide in increasing dose from 200 to 1600 micrograms per 24 h by 200 micrograms increments each week. Patients were studied during the initial 7 h of infusion, weekly at each dose level, then after 1 and 2 months at maximum dosage. 13 patients responded well, as judged by growth hormone (GH) suppression and return of insulin-like growth factor 1 to normal, although 1 patient withdrew due to adverse effects; 2 patients showed no significant reduction in GH. In the 12 responders GH level fell within the first 3 h of infusion at a mean plasma octreotide level of 0.76 (SE 0.26) micrograms/l, corresponding to 25 micrograms of infused drug. Optimum suppression of GH occurred at a dosage of 600 micrograms per 24 h, a plasma drug level of 3.5 (0.5) micrograms/l. A definite reduction in tumour size was seen on computerised tomographic scan in 2 patients. All responders noted subjective improvement in acromegalic symptoms. Adverse effects comprised gastrointestinal disturbances, which were transient and mild in 14 patients but severe in 1; biliary sludging occurred in 1 patient. No significant deterioration in carbohydrate tolerance was seen in the responders.

Acromegaly↗
PubMed1989

Octreotide.

Explore the source record for details and available documents.

Acromegaly↗
PubMed1989

A study of multiple causes of death in California: 1955 and 1980.

Multiple cause of death patterns in California for 1980 were compared to a similar study of deaths conducted in 1955. Primary underlying causes of death changed, mainly reflecting the emergence of respiratory cancer as a major cause of death in 1980. The number of causes reported per death increased from 1955 to 1980, in all age and sex groups. Diseases of the arteries and pneumonia, which are among the most common underlying causes of death, appeared more often on death certificates in both 1955 and 1980 as contributing causes than as underlying the death. Diabetes was studied in detail in the 1955 report, and comparisons were made in 1980 to show increases in the proportions of deaths with this disease and corresponding increases in its prevalence among the living population from the National Health Survey. Multiple cause of death data can provide further information on the prevalence of a fatal disease in a population and its relative role in contributing to mortality, and can also provide new information on diseases that contribute to deaths, which was not previously available in population-based studies of single cause of death.

Adult↗
PubMed1989

Luteinizing hormone in women is secreted in superimposed pulse patterns.

1. The pulsatile nature of luteinizing hormone (LH) secretion has recognized physiological and clinical importance, but because of the difficulties with statistical analysis of serial data the precise nature of this pulsed signal is poorly understood. Several groups have noted small-amplitude, high-frequency pulses superimposed on large slower pulses, but, using conventional methods of analysis, it is not possible to distinguish these from assay variation or to characterize them. 2. In an alternative approach we have applied the methods of time series analysis which identify the harmonic patterns within data. Twenty-four healthy women in the early follicular phase of the cycle had blood samples taken at intervals of 1, 5 or 10 min for up to 6 h. 3. We found that LH secretion consists of superimposed harmonics of varying amplitude which occur in frequency bands of about (a) 1-3 h and (b) 2-3 min. Investigations excluded a reproducible pulsatility in our LH assay, implying that the small fast pulses are physiological events. 4. We conclude that LH release is highly complex and that the methods of time series analysis permit identification and characterization of the multiple pulses.

Adult↗
PubMed1989

Testicular enlargement and elevated serum inhibin concentrations occur in patients with pituitary macroadenomas secreting follicle stimulating hormone.

We studied four male patients with pituitary macroadenomas. Before treatment all had high serum FSH concentrations, but LH and testosterone were normal or subnormal; all patients were found to have large testes. All had had normal sexual function, and three patients had fathered children. After pituitary surgery there were decreases in serum gonadotrophins and testosterone, which were accompanied by decreases in testicular volumes. hCG stimulation tests in two patients showed normal responses of testosterone and oestradiol, confirming normal Leydig cell function. Inhibin levels were increased in two patients studied when FSH levels were high, suggesting a defect in gonadal-pituitary feedback control. Later, as FSH concentrations decreased to normal, so did inhibin levels. Histology showed that increased testicular size was due to increased lengths of seminiferous tubules. The association of pituitary macroadenomas, large testes and increased serum inhibin has not been reported previously. Assessment of testicular size in patients with raised serum FSH is important, since enlarged testes suggest the likely pathogenesis is that of a pituitary gonadotrophinoma, rather than primary gonadal failure. Increased inhibin levels may then confirm this, and be a biochemical marker for these tumours.

Adenoma↗
PubMed1989

Osmoregulation of thirst and vasopressin secretion in Kallmann's syndrome.

It has been suggested that abnormalities of thirst and vasopressin secretion commonly coexist with Kallmann's syndrome. Out-patient plasma osmolality, plasma sodium and 24-hour urine volume were similar in 10 patients with Kallmann's syndrome and 10 matched controls. Six patients underwent dynamic testing of osmoregulation with hypertonic sodium chloride infusion. There were similar rises in plasma AVP concentration in patients (0.4 +/- 0.1-6.2 +/- 1.2 pmol/l, P less than 0.001) and controls (0.4 +/- 0.1-5.7 +/- 1.0 pmol/l P less than 0.001). Thirst ratings rose in similar fashion in patients (0.7 +/- 0.3-6.2 +/- 1.0 cm, P less than 0.001) and controls (1.0 +/- 0.3-7.2 +/- 0.5 cm. P less than 0.001). Drinking rapidly abolished thirst and lowered AVP concentrations in both groups before major changes in plasma osmolality occurred. Linear regression analysis defined similar osmotic thresholds for thirst onset and vasopressin release in the two groups, and there was no difference in the calculated sensitivity of the osmoreceptor/vasopressin secretory unit as defined by the slopes of the regression lines. We conclude that osmoregulation is normal in Kallmann's syndrome.

Adolescent↗
PubMed1989

LH in polycystic ovary syndrome: reproducibility and pulsatile secretion.

Serum concentrations of LH are increased in polycystic ovary syndrome (PCOS). We have investigated two aspects of LH secretion which have not previously been reported: its reproducibility within individuals and the pattern of superimposed pulses of LH secretion. In nine patients with PCOS the mean concentration of LH was calculated from 24 blood samples taken at 15-min intervals for 6 h on two or three occasions over 1 year. Results showed differences in mean LH between subjects but reproducible concentrations within subjects over that period. It has been shown that LH is secreted in a complicated pattern of superimposed pulses which can be characterized by using the statistical methods of time-series analysis. To evaluate these pulse patterns of LH we studied nine patients with PCOS and compared the results with those of 12 normal women in the early follicular phase of the ovarian cycle. Blood samples were taken at either 5-min intervals for 6 h of 1-min intervals for 1 h. Pulses were detected in both groups at frequencies of about 1 h and 2 to 3 min. There was no significant difference in the pulse frequencies between the patients and controls but the amplitude of both groups of pulses was increased in the PCOS patients.

Adult↗
PubMed1988

Measurements of respiratory illness among construction painters.

The prevalence of different measurements of respiratory illness among construction painters was examined and the relation between respiratory illness and employment as a painter assessed in a cross sectional study of current male members of two local affiliates of a large international union of painters. Respiratory illness was measured by questionnaire and spirometry. Longer employment as a painter was associated with increased prevalence of chronic obstructive disease and an interactive effect was observed for smoking and duration of employment as a painter. Multiple regression analysis showed a significant association between years worked as a painter and a decrement in FEV1 equal to about 11 ml for each year worked. This association was larger among painters who had smoked. The prevalence of chronic bronchitis was significantly associated with increased use of spray application methods.

Acute Disease↗
PubMed1988

Long-term effects of a gonadotrophin-releasing hormone agonist ([D-Ser(But)6]GnRH(1-9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro.

We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [D-Ser(But )6]GnRH(1-9) nonapeptide-ethylamide), on LH, FSH, alpha subunit and LH-beta subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/l resulted in a significant (P less than 0.05) stimulated release of FSH and alpha subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P less than 0.05) stimulated the release of alpha subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and alpha subunit concentrations were maintained, but secretion of LH, and LH-beta (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P less than 0.05) stimulation of alpha subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of the three adenomas studied. The mechanisms for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common alpha subunit.

Adenoma↗