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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 739 records · Page 41Linked to original sources

Effects of 17 beta-estradiol and R5020 on glucose-6-phosphate dehydrogenase activity in MCF-7 human breast cancer cells: a cytochemical assay.

Although increasing levels of glucose-6-phosphate dehydrogenase (G6PD) have been widely reported in human breast tumor tissue, the effects of 17 beta-estradiol and progesterone on this key enzyme of cellular growth processes have not been well documented. Cellular heterogeneity of breast tumor tissue, coupled with the low sensitivity of classical biochemical assays of G6PD, are the main sources of difficulties in these studies. In the present report, the effects of estradiol and a progesterone analogue (R5020) on G6PD activity were studied using the MCF-7 cell line and a cytochemical assay of G6PD activity. Our results show that: (a) this assay can be used to perform quantitative measurements of G6PD on individual cells using small number of cells (20-30); and (b) both estradiol (10(-8)-10(-5) M) and R5020 (10(-9)-10(-5) M) stimulate the G6PD activity in dividing MCF-7 cells. Maximal stimulation (20-30%) was obtained after 24 h of treatment. This combination of MCF-7 cells and cytochemical assay is suitable for further studies on the effects of estradiol and R5020 stimulation of G6PD activity in breast tumors.

Breast Neoplasms↗

Photoregulation process of sorghum leaf phosphoenolpyruvate carboxylase: study with monoclonal antibodies.

Monoclonal antibodies were produced against the G isozyme subunit of PEP carboxylase (PEPC) from Sorghum leaves by the hybridoma technique. More than 400 antibodies-producing hybridomas to PEPC were produced from the fusion of spleen cells from immunized mice with NS1 myeloma cells. By using an ELISA, three hybridomas (91-G, 83-G, 49-EG) were selected. Monoclonal antibodies were subsequently characterized in a Western experiment; Mabs 83-G and 91-G were found to be highly specific to the G isozyme whereas Mab 49-EG recognized both forms (E and G isozymes) of the enzyme. Addition of Mabs to the enzyme preparation did not modify its catalytic activity nor its activation by glycine. Use of these probes provided direct and definite evidence of the specific enhancing effect of light on the G form and on its corresponding mRNA.

Antibodies, Monoclonal↗

Endocrine and metabolic effects of simple hysterectomy.

A survey of 60 women who had undergone simple hysterectomy with preservation of ovaries revealed a high prevalence of menopausal flushes. Only 5 (8%) had menopausal concentrations of gonadotropins and estradiol. This is similar to the prevalence of natural menopause in population of comparable age. Of the remaining 55 women, 28 (47% of the total) had normal gonadotrophins and estradiol concentrations although they complained of hot flushes; these levels were not significantly different from those in 27 women who did not flush. The "flushers" did, however, have significantly diminished bone mineral index and higher serum uric acid concentrations than the "non-flushers". Flushes disappeared in those women who took estrogen replacement therapy. These data show that although full-blown menopause does not increase in frequency following simple hysterectomy, a subtle diminution in estrogenisation is frequent. This hypo-estrogenisation is sufficient to cause: (a) hot flushes; (b) demineralisation of the skeleton and (c) an elevation in serum uric acid concentrations. There may be a case for estrogen therapy in all women who develop hot flushes following simple hysterectomy.

Adult↗

Hereditary occurrence of anterior sacral meningocele: report of ten cases.

Anterior sacral meningocele is a rare and often occult disorder that is important to diagnose. It usually occurs sporadically, and familial case reports are rare. This report describes ten documented cases of anterior sacral meningocele in one family. Spanning five generations, it is the largest such series ever reported. In most cases, computerized tomography (CT) was employed to make the diagnosis. There was a high incidence of associated anomalies. The mode of transmission appears to be autosomal dominant with variable penetrance, similar to several other reported series.

Adolescent↗

Photocontrol of sorghum leaf phosphoenolpyruvate carboxylase : characterization of messenger RNA and of photoreceptor.

The mechanism underlying the light effect on phosphoenolpyruvate carboxylase (PEPC) from the C(4) plant sorghum (Sorghum vulgare Pers., var Tamaran) leaves was investigated. Following exposure to light a new isozyme of PEPC, specific for the green leaf and responsible for primary CO(2) fixation in photosynthesis, was established. Northern blot experiments revealed the presence of PEPC mRNA showing a molecular weight of 3.4 kilobases. During the greening process, concomitant to enzyme activity, PEPC protein and PEPC messenger RNA amounts increased considerably. This photoresponse was shown to be under phytochrome control.

Journal Article↗

Effect of acupuncture on experimentally induced itch.

The effect of acupuncture on experimentally induced itch was studied in 10 healthy volunteers. Itching was induced by intradermal injections of histamine on the upper arm. 'Placebo-acupuncture', acupuncture and electro-acupuncture at 2 Hz or 80 Hz were applied over the injection site, proximal to the injection site (in the same dermatome) or extrasegmentally (ipsilateral to the injected arm) for a period of 5 min following induction of itch. In addition, the effect of a 5 min period and a 20 min period of stimulation of the skin area prior to the induction of itch were studied. The same periods of stimulation were also applied to extrasegmental points prior to the induction of itch on the arm. Acupuncture and 2 Hz and 80 Hz electro-acupuncture significantly reduced subjective itch intensity when applied intrasegmentally. No significant effects were obtained when stimulation was applied extrasegmentally. The results suggest that acupuncture or electro-acupuncture could be tried in clinical conditions associated with pruritus.

Acupuncture Therapy↗

Enprostil and ranitidine: comparative efficacy and safety in patients with duodenal ulcer.

This randomised, double-blind, double-dummy, multiclinic study of duodenal ulcer healing compared the efficacy and safety of enprostil with ranitidine. The six week trial admitted 164 patients with endoscopically demonstrated duodenal ulcer. Ratings of symptoms and adverse events were collated from patients' daily diaries, and endoscopy was repeated to verify healing after four weeks and, if appropriate, after six weeks. Medication used was enprostil (35 micrograms capsule) or ranitidine hydrochloride (150 mg tablet) with matching placebos twice daily. After six weeks, 81% of patients treated with enprostil and 95% of those treated with ranitidine had healed ulcers, a statistically significant difference (p = 0.007). There were no differences between treatment groups for the number of days until the daytime ulcer pain completely ceased. Night-time ulcer pain ceased significantly earlier in the group receiving ranitidine (p = 0.019) and was less severe during the week before the last visit (p = 0.001); daytime pain for ranitidine users was also less severe (p = 0.020) during this week. Mild to moderate adverse experiences were reported by 44% of enprostil and 35% of ranitidine patients. There were no severe adverse events. In conclusion, both enprostil and ranitidine were found to be safe and effective in the treatment of duodenal ulcer. However, the ranitidine regimen used in this trial produced better results than the enprostil regimen.

Clinical Trials as Topic↗

Serum 1,25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major.

In view of the claim that low 25-hydroxyvitamin D (25-OHD) concentrations may contribute to the pathogenesis of bone disease in patients with beta thalassaemia major and iron overload, we have assessed the concentrations of 25-OHD, 1 alpha,25 dihydroxyvitamin D (1 alpha,25(OH)2D), parathyroid hormone, and osteocalcin in such patients. 25-OHD concentrations were significantly lower in patients with thalassaemia major and iron overload than in controls and in some patients were subnormal or undetectable. 1 alpha,25(OH)2D concentrations were, however, normal in all patients and were similar to those in controls. Serum parathyroid hormone and plasma calcium concentrations were also normal and not significantly different from those in controls. Although 25-OHD concentrations increased significantly between January and June, there was no change in 1 alpha,25(OH)2D concentrations. 25-OHD concentrations remained lower than control values, even in June. Parathyroid hormone concentrations fell, but not significantly, between January and June, but calcium concentrations did not alter. Osteocalcin concentrations were normal in all patients except one, who had extremely low concentrations of this protein. The concentration of osteocalcin was not related to 25-OHD or 1 alpha,25(OH)2D concentrations. Thus normal calcium homeostasis is maintained in patients with thalassaemia major despite low or low-normal 25-OHD concentrations; this is probably achieved through the maintenance of normal 1 alpha,25(OH)2D concentrations, which were indistinguishable from those in controls. Normal 1 alpha,25(OH)2D, parathyroid hormone, and osteocalcin concentrations argue against an important role for vitamin D deficiency in the pathogenesis of thalassemia bone disease.

Adolescent↗

Calcium, vitamin D and parathyroid hormone relationships in pregnant Caucasian and Asian women and their neonates.

Plasma calcium, serum 25 hydroxyvitamin D [25(OH)D], 1,25 dihydroxyvitamin D[1,25(OH)2D] and parathyroid hormone (PTH) have been measured in pregnant and newborn Caucasians and Asians. Calcium and 25(OH)D concentrations were lower in Caucasian than in Asian women at all four stages (three trimesters and during labour) of pregnancy. PTH concentrations were greater in Asian than in Caucasian women during the three trimesters, but not at labour, and increased in both groups through pregnancy, without a concomitant change in plasma calcium concentrations. There was a significant inverse correlation between calcium and PTH, as well as 25(OH)D and PTH, concentrations. These data demonstrate the presence of progressive 'hyperparathyroidism' during pregnancy in Caucasian and Asian women. The higher PTH concentrations in Asian women may reflect the necessity of maintaining adequate plasma calcium concentrations through PTH-induced osteolysis in the face of vitamin D deficiency. Relative hyperparathyroidism in Asians may contribute to net loss of calcium from the skeleton and osteopenia in Asian women. Calcium, 25(OH)D and 1,25(OH)2D concentrations were lower, and those of PTH higher, in Asian newborns compared with Caucasian newborns. Serum 1,25(OH)2D concentrations in the Asian newborn, though lower than respective maternal levels, were comparable with normal adult levels, indicating that 1,25(OH)2D biosynthesis is stimulated in the Asian newborn to compensate for the low serum 25(OH)D concentrations.

Alkaline Phosphatase↗

Sudden hearing loss and acquired immunodeficiency syndrome.

We have presented a case of a male homosexual with documented acquired immune deficiency syndrome in whom sudden sensorineural hearing loss developed after a series of opportunistic infections and before a massive intracerebral hemorrhage. Two major possible causes of his hearing loss are (1) actual involvement of spiral ganglion or acoustic division of the eighth cranial nerve by HTLV III virus, or (2) cryptococcal meningitis. He ultimately died after a series of neurological complications developed. These complications, which are common in patients with AIDS, include progressive dementia, obtundation, and coma. As the number of patients with AIDS in our society increases over the next 5 years, it will become more important for the otolaryngologist to recognize the complications of this disease that involve the ear, nose, throat, head, and neck. Sudden sensorineural hearing loss is one of these complications. The acquired immune deficiency syndrome, at this point, might best be treated by an approach of preventive medicine. However, such an approach would have far-reaching social and political implications--perhaps more so than in other venereally spread diseases. In the interim, the otolaryngologist-head and neck specialist is required to recognize AIDS as it manifests itself in the head and neck. In this case, sudden-onset sensorineural hearing loss was the otolaryngologic presentation of the AIDS.

Acquired Immunodeficiency Syndrome↗

Impaired carboxylation of osteocalcin in warfarin-treated patients.

The total circulating osteocalcin and ratio of inactive (noncarboxylated; GLU) to active (carboxylated; GLA) form of circulating osteocalcin were measured in patients receiving long term warfarin treatment (n = 20), age-matched control patients not receiving warfarin treatment (n = 10), and normal subjects before and after the administration of 30 mg warfarin (n = 7). There was no significant difference in the total osteocalcin concentrations between the control patients and the patients receiving long term warfarin treatment, and it did not significantly change after warfarin ingestion in the normal subjects. The GLU/GLA ratio was significantly increased (P less than 0.002) in the patients receiving long term warfarin treatment compared with that in the control patients. There was a significant increase (P less than 0.01) in the GLU/GLA ratio after warfarin ingestion in the normal subjects. This study demonstrates that osteocalcin carboxylation in humans is a vitamin K-dependent process and that circulating osteocalcin is structurally altered by warfarin administration. This finding has pathophysiological implications for the fetal warfarin embryopathy syndrome, bone disease associated with chronic liver diseases, and possibly for osteoporosis, in which vitamin K deficiency has been implicated.

1-Carboxyglutamic Acid↗

Hyperparathyroidism and low serum osteocalcin despite vitamin D replacement in primary biliary cirrhosis.

Thirty-six patients with primary biliary cirrhosis (PBC) receiving calcium and calciferol supplements (100,000 IU monthly by im injection) were investigated for their calcium, vitamin D, PTH, and osteocalcin status. The corrected plasma calcium concentrations in PBC patients were significantly greater than those in normal subjects. While the mean serum 25-hydroxycholecalciferol and 1,25-dihydroxyvitamin D concentrations in these patients were similar to those in normal subjects, the mean serum PTH concentration was significantly greater, and it was supranormal in 11 patients. Three patients had elevated corrected calcium concentrations; 1 of them had a concomitant increase in ionized calcium and a supranormal PTH level, and another had a high normal PTH. Ionized calcium concentrations were normal in the rest. Serum osteocalcin concentrations were significantly lower in the patients compared with those in normal subjects. These results indicate that PTH concentrations are frequently elevated in PBC patients despite adequate vitamin D supplementation and normal or even supranormal plasma calcium concentrations. Nonsuppression of PTH concentrations and autonomy of PTH secretion suggest that vitamin D deficiency and secondary hyperparathyroidism in such patients probably occur much earlier in the natural history of this disease than is currently realized. Persistent nonsuppressible hypersecretion of PTH probably contributes to the bone disease of primary biliary cirrhosis. The low osteocalcin concentrations probably reflect diminished osteoblastic activity, which may also contribute to osteopenia in these patients.

Adult↗

Oocyte maturity and human follicular fluid prostanoids, gonadotropins, and prolactin after administration of clomiphene and pergonal.

Follicular fluid (FF) and oocytes were obtained from 130 follicles of 52 women in whom ovulation was induced with human menopausal gonadotropin (Pergonal) and clomiphene citrate. Follicular aspiration was performed 36 h after an ovulatory injection of hCG. The concentrations of LH, FSH, PRL, and the prostanoids prostaglandin E2 (PGE2), PGF2 alpha, PGI2 (as 6-oxo-PGF2 alpha), and thromboxane A2 (as TXB2) in the FF were measured by RIA and related to the degree of maturation of the oocyte-corona-cumulus complex mass (OCCC). FF obtained from follicles with immature OCCC contained significantly lower concentrations of all four prostanoids (median concentrations, picograms per mL: PGE2, 88; PGF2 alpha, 85; 6-oxo-PGF1 alpha, 40; TXB2, 50) than those with intermediate OCCC (PGE2, 175; PGF2 alpha, 325; 6-oxo-PGF1 alpha, 130; TXB2, 65) and mature OCCC (PGE2, 425; PGF2 alpha, 860; 6-oxo-PGF1 alpha, 235; TXB2, 78; all P less than 0.01). There were no significant differences between the maturity of the complexes and the concentrations of LH, FSH, or PRL. There were significant correlations between the FF concentrations of LH and FSH and those of all of the prostanoids, but not with PRL, concentrations. These results indicate that the synthesis of prostanoids in the human Graafian follicles may be modulated by gonadotropins and consolidates the view that prostanoids may play a role in human oocyte maturation and ovulation.

6-Ketoprostaglandin F1 alpha↗

Structural studies of T200 glycoprotein and the IL-2 receptor.

Immunological analysis of the cell surface of hematopoietic cells has led to the identification of many different cell membrane molecules, some of which have well-defined functions as receptors. In general, however, the role of most lymphocyte cell surface molecules remains ill-defined even in cases in which antibody inhibition studies have given some insight into the biological processes in which they participate. Here we describe molecular and biochemical studies of T200 glycoprotein (leukocyte-common antigen) and the IL-2 receptor which illustrate the kinds of approaches that can be currently used to characterize individual molecules. T200 glycoprotein is a large Mr glycoprotein found exclusively on leukocytes. However, the exact Mr varies in a cell-type-specific fashion and this property is conserved between different species. Comparison of the rat, mouse and human cDNA sequences show that the large cytoplasmic portion of the molecule is well-conserved, approximately 90%, whereas the exterior portion is only about 50% homologous. Cell-type-specific differences in the primary sequence of the molecule have been identified in the N-terminal portion of the molecules. In contrast to T200, the function of the IL-2 receptor is well-known. The interaction of IL-2 with its receptor provides a growth signal that determines the magnitude and duration of T-cell responses. Limited proteolysis studies provide the first direct biochemical evidence that the external region of the IL-2 receptor consists of two independent domains. 125I-labeled IL-2 has been chemically crosslinked to the receptor and proteolytic cleavage of the crosslinked product indicates that IL-2 is selectively bound to the N-terminal domain of the receptor.

Animals↗

[Biological criteria for the evaluation of prophylactic treatment with a low molecular weight heparin (Kabi 2165)].

Efficacy of a low molecular weight heparin (Kabi 2165) was compared with that of non-fractionated heparin in the prevention of abdominal surgery postoperative venous thrombosis by means of a double-blind randomized trial in 79 patients. Determination of D. dimers in these patients allowed assessment of specificity of this assay for detection of postoperative venous thrombosis.

Abdomen↗

Subdural empyema.

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Adolescent↗

Renal-metabolic consequences of antihypertensive therapy with diltiazem versus hydrochlorothiazide.

Twenty-seven patients with mild to moderate essential hypertension were randomized to receive therapy with either hydrochlorothiazide or diltiazem. After a placebo run-in period of 2 weeks, patients received increasing doses of either drug for 14 weeks. Those in whom hypertension was effectively controlled continued for 26 weeks of total treatment. Those not controlled, i.e. blood pressure greater than 140/90 mm Hg or less than 10 mm Hg reduction of pressure, were unblinded and crossed over to therapy with both drugs. Eleven of 14 patients (79%) were effectively treated with diltiazem alone, and 8 of 13 patients (62%) were effectively treated with hydrochlorothiazide alone. Supine blood pressures fell from 152 +/- 5/97 +/- 1 to 142 +/- 4/87 +/- 3 mm Hg in the 11 patients treated with diltiazem, from 152 +/- 2/99 +/- 1 to 134 +/- 3/88 +/- 2 mm Hg in the 8 patients treated with hydrochlorothiazide, and from 151 +/- 4/104 +/- 3 to 140 +/- 5/92 +/- 1 mm Hg in the 8 patients who received both drugs (p less than 0.01 for each group). Diltiazem patients had significant increases in alkaline phosphatase and urinary magnesium. Hydrochlorothiazide patients had increases in serum uric acid, serum globulin, CO2 content, and plasma renin activity. Serum potassium, serum chloride, urinary osmolality, and urinary calcium decreased after treatment with hydrochlorothiazide. Patients receiving both drugs had increases in serum glucose, serum BUN, serum uric acid, serum globulin, and CO2 content. These patients had decreased serum chloride and urinary calcium. Diltiazem monotherapy was comparable to hydrochlorothiazide in efficacy of lowering blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗