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Biomedical subjects

J Hardy

Publications and source records attributed to J Hardy.

At least 343 records · Page 19Linked to original sources
PubMed1989

Lack of diurnal variation in plasma levels of androstenedione, testosterone, estrone and estradiol in postmenopausal women.

Plasma 4-en-androstenedione, testosterone, estradiol and estrone were measured during the day in six healthy postmenopausal women and in six breast cancer patients, three of whom received treatment with glucocorticoids. Blood samples were obtained at 8 a.m., 10 a.m., 12 noon, 4 p.m., 8 p.m. and 12 midnight. There was a considerable variation in plasma levels of all steroids during the day; for 4-en-androstenedione the mean within patient coefficient variation was 61.4%, for testosterone it was 28.9%, for estrone it was 17.8% and for estradiol it was 29.2%. While the plasma levels for all steroids tended to be higher in the morning than in the evening, the changes were not statistically significant (Friedman's test: P greater than 0.10). We conclude that although a moderate diurnal variation in the plasma level of these steroids may occur, it is of a moderate magnitude compared to variations due to other causes.

Androstenedione↗
PubMed1989

Antibodies in serum of patients with Alzheimer's disease cause immunolysis of cholinergic nerve terminals from the rat cerebral cortex.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged↗
PubMed1989

Phase I clinical investigation of amonafide.

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.

Adenine↗
PubMed1988

Regional distribution of pre- and postsynaptic glutamatergic function in Alzheimer's disease.

Ca2+/Cl- -independent L-[3H]glutamate- and sodium-dependent D-[3H]aspartate binding assays were used to assess the integrity of N-methyl-D-aspartate (NMDA) receptors and glutamate uptake sites in a number of areas from control and Alzheimer's diseased brain. NMDA receptor densities were unchanged in all areas tested. In contrast, significant reductions in the number of glutamate terminals were seen in the hippocampus of the Alzheimer's samples. A smaller reduction was seen in the caudate nucleus but this failed to reach significance. No such reductions were seen in either the frontal or parietal cortices.

Aged↗
PubMed1988

Change in nicotinic receptor subtypes in temporal cortex of Alzheimer brains.

Competition experiments using (-)-[3H]nicotine and unlabelled nicotine revealed both high and low affinity nicotinic binding sites in temporal cortex of control and Alzheimer (AD/SDAT) brains. A significant reduction in the proportion of high affinity nicotinic binding sites (-20%) and a parallel increase in the proportion of low affinity nicotinic binding sites was obtained in AD/SDAT brain cortex compared to control brain. Moreover, a marked decrease was observed in the affinity of the low affinity nicotinic binding sites in AD/SDAT.

Aged↗
PubMed1988

Presynaptic and postsynaptic glutamatergic function in Alzheimer's disease.

Sodium dependent D-aspartate and Ca2+/Cl-independent L-glutamate binding assays were used to assess the integrity of glutamate uptake sites and postsynaptic NMDA receptor levels in control and Alzheimer's disease temporal cortex. The number of glutamate uptake sites was significantly and substantially reduced in accordance with previous findings. However, NMDA receptor levels were unchanged. This finding suggests that glutamatergic presynaptic elements are severely reduced in Alzheimer's disease, whilst postsynaptic elements remain intact.

Aged↗
PubMed1988

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data presented support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged↗
PubMed1988

Mixed growth hormone and prolactin-secreting human pituitary adenomas: a pathologic, immunocytochemical, ultrastructural, and immunoelectron microscopic study.

A study of 30 adenomas from patients with signs of growth hormone (GH) and prolactin (PRL) hypersecretion revealed the presence of mammosomatotroph cells (MSC) containing both hormones in all cases. Although the number of immunostained cells varied from case to case, in 14 of 25 tumors, all stained cells were MSC. Nine tumors had the ultrastructural appearance of densely granulated growth hormone adenomas, while 11 cases resembled sparsely granulated growth hormone adenomas with frequent fibrous bodies. Exocytosis was present in six of these 11 cases, a feature unusual for pure growth hormone adenomas. Nine tumors consisted of a mixture of cells with the morphology of GH and PRL cells. In the four cases examined, immunoelectron microscopy using double immunolabeling with protein A-gold particles revealed the presence of secretory granules containing both hormones in some tumor cells recognized as mammosomatotroph cells.

Adenoma↗
PubMed1988

Microadenomas of the human pituitary and their vascularization.

During 100 autopsies of patients who had no previous endocrinological problem, selective injections of the pituitary arterial systems were performed. Pituitary glands were examined from 60 male and 40 female patients with an average age of 68 years. Detailed histological and immunocytological studies using peroxidase-antiperoxidase techniques for prolactin (PRL), adrenocorticocotropic hormone (ACTH), follicle-stimulating hormone, thyroid-stimulating hormone, and growth hormone were used. Thirty-three microadenomas were found in 27 patients; 22 were single, 4 were double, and 1 was triple. Fourteen were nonreactive to immunostaining, 10 were reactive to PRL, and 9 were reactive to ACTH. Their diameters ranged between 0.5 and 5.0 mm, and they were located mainly in the lateral wings and the peripheral zone of the anterior pituitary gland. Microvascular study revealed that 22 microadenomas (66%) had direct extraportal arterial supplies. Because the hypothalamic factors are transported to the anterior lobe through the portal vessels, this study suggests that the formation of microadenomas occurs most frequently outside the hypothalamic-hypophyseal portal system and further supports the hypothesis that pituitary adenomas may arise de novo without the influence of hypothalamic factors.

Adenoma↗
PubMed1988

Defective dopaminergic regulation of prolactin secretion in patients with hyperprolactinemia.

In order to evaluate the dopaminergic control of the lactotroph, we examined the plasma prolactin response to metoclopramide (a dopamine receptor blocker, 10 mg iv bolus) and to dopamine (1 microgram/Kg/min iv infusion for 120 min) in 52 hyperprolactinemic female patients and 19 healthy volunteer women. Three diagnostic categories were included: "idiopathic" hyperprolactinemia (21), microadenoma (24), and macroadenoma (7). Patients from all groups showed a marked blunting of the prolactin response to metoclopramide as compared to the prolactin rise in normal women (p less than 0.001). However, normal responses were observed in 8 patients with idiopathic hyperprolactinemia and in one patient with adenoma. The magnitude of the prolactin response to metoclopramide (percent of baseline level) correlated negatively with the level of basal prolactin in each group except for macroadenoma patients. Dopamine infusion significantly (p = 0.015) reduced the mean plasma prolactin levels in hyperprolactinemic patients and normal women. However, patients with idiopathic hyperprolactinemia were hyposensitive to dopamine (p less than 0.05). Furthermore, microadenoma patients were less responsive to dopamine suppression than were the patients with macroadenoma (p less than 0.05). The results indicate the presence of a relative resistance to dopamine in patients with idiopathic hyperprolactinemia and in patients with microadenoma. They also suggest that in these patients, the decrease in prolactin response to metoclopramide may be explained by the relative refractoriness to endogenous dopamine.

Adenoma↗