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Biomedical subjects

J Alaghband-Zadeh

Publications and source records attributed to J Alaghband-Zadeh.

At least 19 recordsLinked to original sources

Cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating/Na-K-ATPase-inhibiting activity of plasma and hypothalamus in reduced renal mass hypertension.

Plasma from normal humans and rats on a high sodium intake, and from patients and rats suffering from hereditary hypertension has an increased cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating/Na-K-ATPase inhibiting activity. The hypothalamic content of this activity is also increased by a high sodium intake and in the spontaneously hypertensive rat (SHR). Using cytochemical techniques, the ability of plasma and the hypothalamus of reduced renal mass hypertensive rats to stimulate G6PD activity and to inhibit Na-K-ATPase was measured. The mean G6PD-stimulating capacity of the plasma from the hypertensive and normotensive groups of rats was 351 +/- 67 and 11.42 +/- 1.98 G6PD-stimulating units/mL respectively (P less than .001). The time courses of the ability of plasma from a hypertensive and a normotensive rat to inhibit fresh tissue Na-K-ATPase after 2, 4, 6, and 8 min of exposure demonstrated that the hypertensive rat plasma had a greater capacity to inhibit Na-K-ATPase. The mean G6PD-stimulating capacity of the hypothalamus from the hypertensive and normotensive groups of rats was 252,263 +/- 147,958 X 10(3) and 6.38 +/- 2.35 X 10(3) G6PD-stimulating units per hypothalamus, respectively (P less than .01). It is proposed that the raised concentration of cytochemically detectable G6PD-stimulating/Na-K-ATPase-inhibiting substance in both genetic and nongenetic forms of hypertension may be a manifestation of a communal hypertensinogenic mechanism. Thus, the raised plasma concentration would have a direct peripheral vascular constricting effect and the high hypothalamic concentration would be responsible for a central nervous hypertensinogenic effect.

Animals

Are patients with low serum thyroid stimulating hormone and normal total thyroxine hyperthyroid? Usefulness of 99mTc pertechnetate uptake.

The records of 107 patients who had had thyroid 99m Tc pertechnetate uptake measured, were reviewed. In patients with normal serum thyroxine (T4) and thyroid stimulating hormone (TSH), 35 of 36 with normal uptake and three with high uptake were clinically euthyroid. In patients with high serum T4 and low TSH, seven had normal and 29 had high uptake and all were clinically hyperthyroid. In patients with normal serum T4 and low TSH, 10 of 11 with high uptake were clinically hyperthyroid whereas only two of 18 with normal uptake were. The sensitivity, specificity and positive predictive value of pertechnetate uptake measurements were 83%, 94%, and 91%, respectively. The measurement of pertechnetate uptake is a rapid investigation and may help in the interpretation of patients with undetectable serum TSH found in the presence of normal serum T4.

Adult

Insulin-like growth factor binding proteins in follicular fluid from normal dominant and cohort follicles, polycystic and multicystic ovaries.

There is now considerable evidence that the insulin-like growth factors (IGFs) play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP-1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP-1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP-1 levels correlated with FF-volume (r = 0.58, P less than 0.001) and with paired serum levels (r = 0.63, P less than 0.001). In post-LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP-1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF-binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.

Adult

Follicular fluid concentrations of insulin-like growth factor 1, epidermal growth factor, transforming growth factor-alpha and sex-steroids in volume matched normal and polycystic human follicles.

Thirty-three samples of follicular fluid (FF) were collected from 14 patients with the polycystic ovary (PCO) syndrome and matched for FF-volume with small follicles collected from subjects with normal ovaries. The median (range) FF concentration of insulin-like growth factor 1 (IGF1) in the group with PCO, 0.42 (0.13-1.20) U/ml was significantly higher than that of the controls, 0.33 (0.04-0.59) U/ml. All samples tested had less than 1 ng/ml of FF-epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). The patients with PCO syndrome (PCOS) had similar FF-testosterone (T) and FF-progesterone (P) concentrations to volume matched controls, but significantly higher levels of FF-androstenedione (AD) and lower FF-oestradiol (E2). These results suggest that the granulosa cells within the polycystic follicle have a functional defect in their aromatase enzyme complex.

Adult

Oestrogen receptors in colorectal carcinoma.

The oestrogen receptor content of colorectal adenocarcinoma was investigated using an established ligand binding biochemical assay and two more recently introduced techniques using specific monoclonal antibodies (Abbott ER-EIA and ER-ICA assay kits). Twenty nine tumours were investigated by the ligand binding assay. Only one (3.4%) tumour gave a weakly positive result (11 fmol/mg cytosol protein); the rest were all negative. Where sufficient tissue was available, the receptors were also determined by a quantitative immunoassay in 18 patients and an immunohistochemical method in 13 patients. The results were similarly all negative. It is concluded that most colorectal carcinomas, irrespective of sex, are oestrogen receptor negative, and it is thus unlikely that hormonal manipulation would have an influence on the course of the disease.

Adenocarcinoma

Immunohistological study of oestrogen receptors in breast carcinomas that are biochemically receptor negative.

The reliability of an immunohistological method, applied to paraffin wax sections, was assessed for determination of oestrogen receptor content of biochemically oestrogen receptor negative breast carcinomata. Sixty consecutive tumours with oestrogen receptor concentrations of less than 10 fmol/mg cytosol protein, as estimated by dextran-coated charcoal biochemical assay, were examined. Paraffin wax sections were treated with DNAse before applying a peroxidase-anti-peroxidase method using ER-ICA monoclonal antibodies. Fifty one cases (85%) were negative, six (10%) weakly positive, and three (5%) were moderately positive. No strongly positive cases were seen. It is suggested that cases with weakly positive staining, especially when localised to a small area, should be regarded as negative. On the other hand, as the three moderately stained cases included two small tubular carcinomas and an invasive ductal carcinoma with high progesterone receptor concentrations, it is more likely that the biochemical assay in these cases represented false negative results due to sampling error or inclusion of fibrous or other non-neoplastic tissue in the assayed samples. It is concluded that the immunohistological method used here is fairly reliable and would be especially valuable for determination of oestrogen receptor content in small, mammographically detected tumours from which no tissue would be available for biochemical assay or frozen section examination.

Adenocarcinoma

Bone resorption and circulating PTH-like bioactivity in an animal model of hypercalcaemia of malignancy.

An in vivo model of humoral hypercalcaemia of malignancy has been used to examine the role of circulating PTH-like bioactivity in the development of bone resorption and hypercalcaemia. After inoculation of cells from a renal carcinoma cell line into nude mice, circulating PTH-like bioactivity as measured by the sensitive renal and metatarsal cytochemical bioassays for PTH was elevated in only 18% and 53% of the mice respectively. Bone resorption was elevated in all the mice investigated irrespective of the level of PTH-like bioactivity. Thus, in this model, while the circulating PTH-like moiety is more potent when acting on bone, it did not correlate with the degree of bone resorption suggesting that it may not be the sole cause of the hypercalcaemia.

Animals

The role of chronic anovulation in the polycystic ovary syndrome: normalization of sex-hormone-binding globulin levels after clomiphene-induced ovulation.

A group of anovulatory patients with polycystic ovaries (PCO) was given clomiphene citrate and compared with three control groups: normal women having spontaneous, ovulatory cycles, patients with PCO having spontaneous, regular, ovulatory cycles, and anovulatory patients without PCO. Comparisons were made at precise points of the menstrual cycle (taking the day of ovulation as day 0), using ultrasound estimates of mean follicular diameter, uterine volume, and endometrial thickness, and biochemical measurements of LH, FSH, oestradiol (E2), testosterone (T), progesterone (P) and sex-hormone-binding globulin (SHBG). Before clomiphene treatment, the anovulatory patients with PCO had significantly lower levels of SHBG and higher follicular phase concentrations of LH than all three control groups. After two cycles of clomiphene-induced ovulation, the serum LH concentration fell significantly and levels of SHBG increased significantly to levels similar to those found in spontaneously ovulating women with normal ovaries. It is likely that the loss of the usual considerable rise in E2 in both the follicular and luteal phases of ovulatory cycles is the main reason for the low SHBG found in the PCO syndrome. The loss of the normal P-induced gonadotrophin suppression may be a factor in allowing LH levels to rise.

Adolescent

Is the polycystic ovary a cause of infertility in the ovulatory woman?

Ovulatory women with polycystic ovaries (PCO) were compared with ovulatory women with normal ovaries, using high-resolution ultrasound and biochemical parameters to compare precise points in the menstrual cycle taking the day of ovulation as day 0. The PCO group had higher median follicular phase LH (days 'menses', -5, -3), FSH (days -5, -3) testosterone (days -3, -2) and free androgen index (days -5, -3, -1) than the controls. Women with PCO had a longer follicular phase and larger follicles. These results suggest that abnormal secretion of LH and free testosterone may contribute to the subfertility of women with PCO, possibly by premature activation of the oocyte or by interfering with folliculogenesis.

Adult

The diagnosis of polycystic ovaries in subfertile women.

Laparoscopy was used to identify the polycystic ovary (PCO) in a group of subfertile women. A third were found to have PCO. These patients had higher levels of luteinizing hormone (LH), testosterone (T) and a higher free androgen index (FAI) than those with normal ovaries. Only 15% of patients with laparoscopic evidence of PCO were obese, hirsute and oligomenorrhoeic. Within the PCO group, hirsutism was strongly associated with obesity and a high FAI. A group of subfertile women with PCO and regular cycles was found who had no other identifiable cause for their infertility. These women had higher follicular phase concentrations of LH and higher FAI than ovulatory women with normal ovaries.

Adult

Insulin-like growth factor 1 as an intra-ovarian hormone--an integrated hypothesis and review.

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least 2 samples of clear follicular fluid (FF) collected in the late follicular phase. Dominant follicles contained significantly higher concentrations of insulin-like growth factor-1 (IGF1), oestradiol (E2), progesterone (P) and lower androstenedione (AD) than their matched cohorts. After the luteinizing hormone (LH) surge, a significant increase in dominant FF-IGF1 and FF-P occurred. Log FF-E2 and log FF-P were correlated with both FF-IGF1 and FF volume. Log FF-AD was negatively correlated with FF-volume, FF-E2 and FF-P (but not FF-IGF1). The cohort concentration of FF-IGF1 was correlated with serum IGF1. These results support the hypothesis that IGF1 has a central role in the selection of the dominant follicle.

Adult

Oestrogen receptors in mucinous carcinoma of the breast: an immunohistological study using paraffin wax sections.

An immunohistological method (Shintaku-Said method) for the demonstration of oestrogen receptors in routinely processed paraffin wax embedded tissue was applied to 19 cases of mucinous carcinoma of the breast. Seventeen (89%) tumours showed variable degrees of positivity and two were negative. In eight cases the receptors were also assayed biochemically using a dextran-coated charcoal method, and the results of the two methods showed good correlation. No difference in the distribution of positive and negative cases was noted between pure and mixed mucinous tumours, and in the latter group the pattern of staining of the mucinous elements was similar to that seen in the solid elements. It is concluded that the major advantage of this method is its ability to offer for study the distribution of the receptors in individual cells and specific histological structures. The results also indicate that most mucinous carcinomas of the breast are oestrogen receptor positive, irrespective of whether they are pure or mixed type.

Adenocarcinoma, Mucinous

The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume.

Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.

Adult

Mammary duct ectasia and pituitary adenomas.

Mammary duct ectasia developed in three postmenopausal patients who had had pituitary chromophobe adenomas. The first patient had bilateral duct ectasia that developed 8 and 11 years after hypophysectomy. The second patient, who also had bilateral ectasia, had a prolactin-producing pituitary adenoma for which bromocriptine was prescribed. The ectasia developed in one breast before commencing bromocriptine therapy, and in the other breast 2 years later. The third patient also had a prolactin-producing pituitary adenoma. Unilateral duct ectasia developed while bromocriptine was taken. The ectasia in all patients was very marked and affected all excised ducts. Cholesterol granulomas were sometimes very extensive. These cases suggest a relationship between certain hypothalamic/pituitary disorders, possibly related to prolactin secretion and the development of mammary duct ectasia in postmenopausal patients.

Adenoma, Chromophobe

A comparison of follicular fluid levels of insulin-like growth factor-1 in normal dominant and cohort follicles, polycystic and multicystic ovaries.

Fourteen ovulatory patients undergoing diagnostic laparoscopy had at least two samples of clear follicular fluid (FF) collected in the late follicular phase. The cohort concentrations of Insulin-like Growth Factor-1 (IGF1) were significantly correlated with serum IGF1 and dominant follicles contained significantly higher concentrations of IGF1 and oestradiol (E2) than their cohorts. After the LH surge, a further significant increase in dominant FF-IGF1 occurred. FF-(log)E2 was significantly correlated with both FF-IGF1 and FF volume. Nine women with the polycystic ovary syndrome (PCOS) and one patient with multicystic ovaries (MCO) associated with weight-loss related amenorrhoea also had follicular aspiration performed. The mean (SD) FF-IGF1 in the PCOS group, 0.42 (0.15) U/ml, was not significantly different from that of the cohorts in the control group, 0.39 (0.13) U/ml. The patient with MCO had both serum and FF-IGF1 concentrations less than 10th centile. These results support the hypothesis that IGF1 has a paracrine (and possibly endocrine) role in the regulation of ovarian function in the human female.

Adult

What are the ultrasound and biochemical features of impending ovulation?

Thirty-two ovulatory women had serial ultrasound measurements of uterine volume, endometrial thickness and leading follicular diameter compared with serum oestradiol, testosterone and sex-hormone binding globulin. Follicular diameter, endometrial thickness and uterine volume were significantly correlated with serum oestradiol. The day before ovulation was characterized by maximal values for oestradiol, testosterone, luteinizing hormone, endometrial thickness, uterine volume and leading follicular diameter. Leading follicular diameter and endometrial thickness in particular, appear to be useful parameters to indicate impending ovulation.

Endometrium

Elevated free androgen index as an indicator of polycystic ovaries in oligomenorrhoea without obesity or hirsuties.

A group of oligomenorrhoeic women without obesity or hirsuties was investigated with high-resolution ultrasound, laparoscopy and biochemical parameters. In this series, polycystic ovaries (PCO), as defined by ultrasound and laparoscopy, are a common cause of oligomenorrhoea in women without the classic symptoms, and were strongly associated with an elevated free androgen index (FAI). Despite an elevated FAI, these women were not hirsute, It would seem reasonable to include a FAI in the investigation of the oligomenorrhoeic woman, along with the more 'standard' tests, such as thyroid function and a prolactin level.

Adult