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Biomedical subjects

Z H Chakmakjian

Publications and source records attributed to Z H Chakmakjian.

At least 19 recordsLinked to original sources

Steroid receptors in benign mastectomy tissue.

Estrogen and progesterone receptors (ERs and PRs, respectively) were measured in both cancerous and noncancerous components of 104 modified radical mastectomy specimens. In addition, ER and PR levels were determined for 14 benign breast specimens obtained by reduction mammoplasty. The receptor levels were measured by scatchard method. Each of these groups--cancerous, corresponding noncancerous, and mammoplasty specimens--were divided into subgroups according to their receptor levels. Fourteen of the 104 noncancerous specimens were found to be ER positive (ER+). Most cases of ER+ noncancerous tissue (13 of 14 cases) were associated with ER+ tumors. The reverse was not true because only 13 of 64 cases of the ER+ tumors were associated with positive ER in their noncancerous counterparts. Comparable results were obtained for PR. The average ER-PR level of the noncancerous mastectomy tissue was significantly higher than that of the mammoplasty specimens despite the similar histologic findings in both groups.

Breast Diseases↗

Bioavailability of progesterone with different modes of administration.

The bioavailability of micronized progesterone (P) was studied by measuring sequential serum P concentrations after a single bolus of 50-200 mg P given sublingually, orally (capsule and tablet), vaginally and rectally (suppositories) during the follicular phase in a group of normally menstruating women. When compared to other modes of P administration, the area under the curve during the first eight hours was twice as high with the rectal route. With 50 and 100 mg P given sublingually and 100 and 200 mg ingested as tablets, peak levels and area under the curve were twice as high with the higher dosage. The response was more sustained with the higher dosage. All subjects exhibited a significant increase in serum P levels over baseline that persisted for at least eight hours. P levels were still increased over baseline at 24 hours in all subjects after the administration of 100-mg vaginal and rectal suppositories and 200-mg tablets. These findings are in general agreement with previous reports showing that luteal phase serum P concentrations can be reached easily with non-parenteral modes of administering micronized P and that oral P administration could become an attractive alternative to the currently used oral mode of administering synthetic progestins.

Absorption↗

A method for the determination of sex hormone binding globulin in human serum.

A simple and rapid method for serum sex hormone binding globulin (SHBG) was developed. Sera from pregnant women were pooled and the SHBG concentration was measured by Rosner's method. This pool was diluted with charcoal-treated and heated serum to give standards ranging in concentrations from 26.8-0.8 micrograms/L. Two sets of tubes containing dihydrotestosterone (DHT), assay and control tubes, were prepared. Diluted standards and unknowns were added to assay and control tubes along with tritiated DHT. Following incubation, cold saturated ammonium sulfate was added to each tube, mixed, centrifuged and the supernatant counted. Mean SHBG concentration (microgram/L +/- SEM) in normal men was 3.6 +/- 0.4, normal women 11.4 +/- 2.2, pregnant women 58 +/- 2.6, obese women 3.3 +/- 1.0, hirsute women 2.9 +/- 0.2, hypothyroid women 7.3 +/- 1.0, and hyperthyroid women 26.0 +/- 1.6. These results correlate well with previous reports. This method is fast, convenient, and up to 40 samples can be analyzed in one assay.

Buffers↗

Androgen excess in cystic acne.

We measured hormone levels in 59 women and 32 men with longstanding cystic acne resistant to conventional therapy. Affected women had higher serum levels of dehydroepiandrosterone sulfate, testosterone, and luteinizing hormone and lower levels of sex-hormone-binding globulin than controls. Affected men had higher levels of serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone and lower levels of sex-hormone-binding globulin than controls. To lower dehydroepiandrosterone sulfate, dexamethasone was given to men, and dexamethasone or an oral contraceptive pill, Demulen (or both), was given to women. Of the patients treated for six months, 97 per cent of the women and 81 per cent of the men had resolution or marked improvement in their acne. The dose of dexamethasone required to reduce dehydroepiandrosterone sulfate levels was low, rarely exceeding the equivalent of 20 mg of hydrocortisone per day. We conclude that most patients with therapeutically resistant cystic acne have androgen excess and that lowering elevated dehydroepiandrosterone sulfate results in improvement or remission of acne in most instances.

17-alpha-Hydroxyprogesterone↗

A critical assessment of therapy for the premenstrual tension syndrome.

Various kinds of therapy have been used for the symptoms of premenstrual tension (PMT): sex steroid hormones, vitamins, prolactin inhibitors, hormones and factors associated with fluid retention and psychiatric/behavioral regimens. Clinical trials with natural progesterone, synthetic progestogens, androgens, estrogens, contraceptive pills, pyridoxine (vitamin B6), dopamine agonists, diuretics, psychoactive drugs and psychotherapy have given conflicting results. All these treatments are based on some underlying notion of etiology. Since the etiology of PMT is still obscure, it is not surprising that as yet there is no single treatment that is universally accepted as effective. It is essential that future trials be well controlled and double blind and that they include large numbers of participants keeping daily records of symptoms during the control and experimental cycles.

Androgens↗

A fast and convenient method for determining estrogen receptor using rabbit uterus as a standard.

A fast and convenient method is described for the determination of estrogen receptors (ERs). This method involves the use of rabbit uterus as a standard. ER content of the rabbit uterus powder was determined using the conventional methods, i.e., Scatchard plot and sucrose density gradient methods. The rabbit uterus cytosol was serially diluted to give a range of protein concentrations from 1 to 0.062 mg/ml. A standard curve was thus generated with the corresponding ER concentrations, and this curve was used for the determination of ERs in breast tumors. The method involved incubating the standards with 125I-estradiol and subsequent removal of the free radiolabeled estradiol using dextran-coated charcoal. A parallel sample was also incubated with diethylstilbestrol. A standard curve was obtained between the 125I-estradiol percentage of binding and the corresponding ER concentration. Tumor cytosols were also treated in a similar manner, and the receptor content was determined from the standard curve. Excellent correlation was obtained between this method and other conventional methods. This method is simpler and less time consuming, and up to ten tumors can be analyzed at one time. It is especially useful when limited amounts of tumor tissue are available, as a concentration of only 1 mg of protein per ml is required.

Animals↗

Stability of estrogen- and progesterone-receptor concentrations in human uterus tissue.

Homogeneous control specimens for estrogen receptor (ER) and progesterone receptor (PR) assays were prepared from freshly collected human uterus. After removal of the connective tissue, the specimen was washed with isotonic saline, cut into small pieces, quickly frozen in liquid nitrogen, and stored at -70 degrees C until analyzed. Cytosol prepared from this specimen was lyophilized and stored at -70 degrees C. A single step of reconstitution, with glycerol (100 mL/L) in water, is sufficient to prepare a control. Two specimens prepared this way were found to be reasonably stable for 20 months (first specimen, mean +/- SD: ER = 22.1 +/- 2.9 fmol/mg, PR = 136.5 +/- 26.9 fmol/mg; second specimen: ER = 107.2 +/- 11.7 fmol/mg, PR = 922 +/- 71.6 fmol/mg). Another specimen, prepared similarly but not frozen in liquid nitrogen soon after collection, was less stable; its ER and PR concentrations deteriorated faster.

Cytosol↗

Coexistent multiple myeloma and primary hyperparathyroidism.

A patient with multiple myeloma and hypercalcemia responded to cytotoxic chemotherapy. However, hypercalcemia persisted. Because of the absence of lytic bone lesions, the presence of a low serum phosphate level, and a family history of possible primary hyperparathyroidism, the patient was evaluated for this disorder. Serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were elevated. Exploration of the neck disclosed two enlarged parathyroid glands (1,850 mg and 210 mg), which were excised. After surgery, the patient's serum calcium levels remained normal for one year. Progressive myeloma bone disease developed that eventually resulted in recurrent hypercalcemia and death. Autopsy revealed only evidence of myeloma.

Bone Neoplasms↗

Ovarian and adrenal contributions to peripheral androgens in hirsute women.

Serum levels of testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), 17-hydroxyprogesterone (17-P), and cortisol (F) were measured in 33 hirsute women. Ten were hirsute and eumenorrheic (H-E), and 23 were hirsute and oligomenorrheic or amenorrheic (H-OA). Daily morning blood samples were obtained for 6 consecutive days. Dexamethasone (Dex), 2 mg/day was administered starting after venipuncture on the second day and continuing for 5 days. Human chorionic gonadotropin (hCG) was administered intramuscularly on the afternoon of the fourth and fifth days. The mean levels of all steroids measured under basal conditions in the hirsute women as a group were significantly elevated when compared to nonhirsute premenopausal women. Dehydroepiandrosterone-sulfate was the only steroid which showed significantly different mean levels between the two groups of hirsute women, being higher in the H-OA patients. Individual hirsute patients showed an elevated serum 17-P level as the most consistent finding; it was present in 90% of the patients in both groups. Significantly more H-E patients showed Dex-suppressible DHT (90% vs 40%; P less than 0.05) and A (70% vs 25%; P less than 0.05) than did H-OA patients. Dex-suppressibility of 17-P was observed in only 20% of the H-E and 15% of H-OA patients. A positive response to hCG was observed in all patients for serum 17-P and in about half or less of the patients for the other steroids. These dynamic tests of adrenal suppression and ovarian stimulation suggest that the ovary may be the main source of 17-P overproduction in both groups of patients. Although 17-P has been previously postulated to have androgenic activity, it is not yet known whether this steroid has a causal relationship to hirsutism.

Adrenal Glands↗

Peripheral steroid levels in a patient with virilizing adrenal adenoma.

The peripheral levels of pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), progesterone (P), 17-hydroxyprogesterone (17-P), testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), estrone (E1), estradiol-17beta (E2), and cortisol (F) were measured prior to and 1 1/2 and 9 months after removal of a right adrenal "compact cell" adenoma in an amenorrheic patient with a virilizing adrenal adenoma, under the following conditions: 1) control for 2 days, 2) dexamethasone, 0.5 mg, every 6 hours for 2 days, and 3) dexamethasone, 2 mg, every 6 hours for 2 days. Except for E1, E2, and F, the control levels of all steroids measured were elevated, markedly so for delta5-P, 17-delta5-P, DHEA, A, and DHEA-S. Dexamethasone treatment had no detectable effect on the steroid levels. Following removal of the adrenal adenoma, the levels of all steroids returned to normal. The patient became eumenorrheic, with marked improvement of her hirsutism and virilization.

17-alpha-Hydroxypregnenolone↗