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Biomedical subjects

J Martel

Publications and source records attributed to J Martel.

At least 55 records · Page 3Linked to original sources
PubMed1995

Accuracy of teleradiology in skeletal disorders: solitary bone lesions and fractures.

To evaluate the diagnostic accuracy of digitized film radiography and digital teleradiology for detecting bone fractures and for studying solitary bone lesions, we examined 633 single radiographs from 373 patients (159 with solitary bone lesions, 123 with fractures and 91 without pathology). Radiographs were digitized using a commercial teleradiology workstation and transmitted to a local hospital over a standard telephone line. Images were reviewed by two groups of three experienced radiologists. Receiver operating characteristic (ROC) curves were analysed for conventional films, digitized images and transmitted teleradiology images. No significant differences were found among readers for the evaluation of bone fractures and solitary bone lesions. Teleradiology systems permit remote expert consultation, and telediagnosis therefore is a powerful tool in telemedicine.

Bone Diseases↗
PubMed1994

X-linked hypophosphatemic Gy mice: renal tubular maximum for phosphate vs. brush-border transport after low-P diet.

We examined the effect of the X-linked hypophosphatemic Gy mutation on the maximal renal tubular reabsorption of phosphate (TmP) and compared the effects of phosphate deprivation on both TmP and Na(+)-dependent phosphate transport in renal brush-border membrane vesicles (BBMV). Adult female normal and Gy mice were fed a control (1.0% P) or low-phosphate (0.03% P) diet for 5 days. For TmP measurement, anesthetized mice were infused intravenously with [3H]inulin and increasing increments of phosphate (0, 0.27, 0.54, and 1.08 mumol/min). TmP was significantly reduced in Gy mice on the control diet. Normal mice responded to the low-phosphate diet by raising their TmP [2.35 +/- 0.12 (n = 9) vs. 3.71 +/- 0.16 (n = 9) mumol/ml glomerular filtrate, mean +/- SE, P < 0.001], whereas in Gy mice, the change was not significant [1.46 +/- 0.10 (n = 10) vs. 1.70 +/- 0.11 (n = 10)]. In contrast, Gy mice did respond to phosphate restriction by increasing the initial-rate Na(+)-dependent phosphate transport in the renal BBMV [314 +/- 11 (n = 5) vs. 1,105 +/- 157 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01] as did normal mice [583 +/- 64 (n = 5) vs. 1,692 +/- 203 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01]. In conclusion, the adaptive increase in Na(+)-phosphate cotransport in the brush-border membrane of the proximal tubule is not sufficient for the overall increase in TmP in the whole kidney in response to dietary phosphate deprivation.

Absorption↗
PubMed1994

Renal Na(+)-phosphate cotransport in murine X-linked hypophosphatemic rickets. Molecular characterization.

The X-linked Hyp mouse is characterized by a specific defect in proximal tubular phosphate (Pi) reabsorption that is associated with a decrease in Vmax of the high affinity Na(+)-Pi cotransport system in the renal brush border membrane. To understand the mechanism for Vmax reduction, we examined the effect of the Hyp mutation on renal expression of Na(+)-Pi cotransporter mRNA and protein. Northern hybridization of renal RNA with a rat, renal-specific Na(+)-Pi cotransporter cDNA probe (NaPi-2) (Magagnin et al. 1993. Proc. Natl. Acad. Sci. USA. 90:5979-5983.) demonstrated a reduction in a 2.6-kb transcript in kidneys of Hyp mice relative to normal littermates (NaPi-2/beta-actin mRNA = 57 +/- 6% of normal in Hyp mice, n = 6, P < 0.01). Na(+)-Pi cotransport, but not Na(+)-sulfate cotransport, was approximately 50% lower in Xenopus oocytes injected with renal mRNA extracted from Hyp mice when compared with that from normal mice. Hybrid depletion experiments documented that the mRNA-dependent expression of Na(+)-Pi cotransport in oocytes was related to NaPi-2. Western analysis demonstrated that NaPi-2 protein is also significantly reduced in brush border membranes of Hyp mice when compared to normals. The present data demonstrate that the specific reduction in renal Na(+)-Pi cotransport in brush border membranes of Hyp mice can be ascribed to a proportionate decrease in the abundance of Na(+)-Pi cotransporter mRNA and protein.

Animals↗
PubMed1994

Increased renal 25-hydroxyvitamin D3-24-hydroxylase messenger ribonucleic acid and immunoreactive protein in phosphate-deprived Hyp mice: a mechanism for accelerated 1,25-dihydroxyvitamin D3 catabolism in X-linked hypophosphatemic rickets.

X-Linked Hyp mice exhibit rachitic bone disease, hypophosphatemia, impaired renal phosphate reabsorption, and abnormal regulation of renal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism. We demonstrated that phosphate deprivation of Hyp mice, but not normal littermates, elicits a dramatic fall in serum 1,25-(OH)2D levels and an increase in renal 1,25-(OH)2D3 catabolism that can be ascribed to an increase in the activity of renal mitochondrial 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway. The present study was undertaken to elucidate the mechanism for the increase in renal 24-hydroxylase activity in phosphate-deprived Hyp mice. Phosphate deprivation of Hyp mice resulted in a 3-fold increase in the maximum velocity for 24-hydroxylase (n = 5; P < 0.001) accompanied by an increase in 24-hydroxylase immunoreactive protein relative to the level of ornithine aminotransferase. Phosphate deprivation of Hyp mice also elicited a 3-fold increase in renal 24-hydroxylase mRNA abundance relative to that of beta-actin mRNA (n = 7; P < 0.001). The increase in 24-hydroxylase mRNA was specific to the kidney and was evident as early as 1 day of the low phosphate diet. Phosphate deprivation had no effect on renal 24-hydroxylase immunoreactive protein or mRNA in normal littermates. In contrast to the abnormal 24-hydroxylase response to dietary phosphate, Hyp mice exhibited an appropriate increase in renal 24-hydroxylase mRNA and catalytic activity in response to increasing doses of 1,25-(OH)2D3. The present results demonstrate that elevated renal 24-hydroxylase activity in phosphate-deprived Hyp mice can be ascribed to an increase in the abundance of 24-hydroxylase mRNA and protein and suggest that inappropriate regulation of 1,25-(OH)2D3 catabolism in Hyp mice occurs at the pretranslational level.

Animals↗
PubMed1994

Usefulness of sequential urinary follicle-stimulating hormone and luteinizing hormone measurements in the diagnosis of adolescent hypogonadotropism in males.

FSH and/or LH deficiency in the second decade of life remains difficult to diagnose with testing at a single point in time because of the partial lack of hormone as well as the dynamic and inherently variable aspects of the pubertal process. A longitudinal study of gonadotropin excretion, therefore, was carried out in 78 normal boys and 157 male patients, aged 10-28 yr, with relative or absolute deficiencies of FSH and/or LH. Seven hundred and fifty-five timed urine samples were extracted with acetone, concentrated, and subjected to RIA. The results from patient groups with multiple tropic hormone deficiencies or isolated gonadotropin deficiency were clearly different from those of normal boys and individuals with constitutional delay in puberty. However, multiple samples obtained over a 2-yr period and, in selected cases, until the late teenage years may be required to diagnose gonadotropin deficiency in some patients, even using stringent predictive modeling criteria.

Adolescent↗
PubMed1994

Stromal spindle cells contain aromatase in human breast tumors.

In situ synthesis of estrogens by breast cancer tissue provides a potential explanation for the high concentrations of estradiol in mammary neoplasms in postmenopausal women. A major metabolic pathway for estrogen biosynthesis is the conversion of androstenedione to estrone via the enzyme aromatase. Biochemical studies have demonstrated aromatase in tumor tissue, but at relatively low and not clearly biologically significant levels. The present study tested the hypothesis that tumor levels of aromatase, albeit low, could be biologically important if present in high concentrations in focal clusters of specific cell types. A pilot study used an immunohistochemical method in frozen sections of fresh breast tumors as an optimal means to detect aromatase. Twelve of 18 tumors contained aromatase-positive cells, some with highly intense staining. A follow-up study then attempted to precisely define the types of cells containing aromatase and correlate the immunohistochemical findings with biochemical aromatase activity. A modified H-score (histological scoring system) was used to semiquantitate the amount of aromatase staining in tumor epithelial, stromal spindle, stromal inflammatory, and normal breast epithelial cells. We found that immunohistochemical staining for aromatase predominated in stromal spindle cells with a median H-score of 13, whereas tumor epithelial, stromal inflammatory, and normal breast elements contained lesser amounts (median H-scores of 4.8, 0.03, and 0.5, respectively). The H-score for stromal spindle cells, but not those for other cell types, correlated highly with the biochemical aromatase assay (P < 0.01). Using a cut-off parameter estimated by a sensitivity/specificity (receiver operating curve) analysis, 62% of tumors were classified as aromatase positive based on stromal spindle cell staining. A similar number were also positive by biochemical assay, with concordance between the two methods of 77%. These observations provide substantial evidence for the presence of aromatase in human breast tumors, particularly in stromal spindle cells, and support the biological importance of aromatase for in situ production of estradiol.

Aromatase↗
PubMed1993

Microtubules are not an essential component of phytohemagglutinin-dependent signal transduction in Jurkat T lymphocytes.

We have used two disruptors of the cytoskeleton microtubular network (colchicine and vinblastine) to investigate the role of microtubules in Phaseolus vulgaris phytohemagglutinin (PHA) signal transduction in Jurkat T cells. Both drugs decreased but did not abolish the PHA-dependent Ca2+ response of Jurkat cells. Neither colchicine nor vinblastine had any major effects on the PHA-dependent turnover of the mono-, di-, tri-, and tetra-substituted phosphorylated derivatives of D-myo-inositol or the cellular distribution of protein kinase C (PKC) activity. However, both microtubule disruptors increased interleukin-2 (IL-2) production. Whereas vinblastine enhanced IL-2 production approximately twofold at all the concentrations tested (0.1, 1.0, and 10 microM), colchicine did so only at a 10 microM concentration. When a combination of PHA and 12-O-tetradecanoyl-13-O-acetyl phorbol (TPA) was used, a small increase in IL-2 production was observed only in the presence of vinblastine (10 microM). In contrast to recent reports that microfilaments may be involved in the regulation of signal transduction, our data suggest that this is not the case for microtubules in PHA-dependent signal transduction in Jurkat T cells.

Animals↗
PubMed1993

Renal adaptation to phosphate deprivation: lessons from the X-linked Hyp mouse.

The X-linked Hyp mutation, a murine homologue of X-linked hypophosphatemia in humans, is characterized by renal defects in phosphate reabsorption and vitamin D metabolism. In addition, the renal adaptive response to phosphate deprivation in mutant Hyp mice differs from that of normal littermates. While Hyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodium-phosphate cotransport in vitro, the mutants fail to show an adaptive increase in maximal tubular reabsorption of phosphate per volume of glomerular filtrate (TmP/GFR) in vivo. Moreover, unlike their normal counterparts, Hyp mice respond to phosphate restriction with a fall in the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] that can be ascribed to increased renal 1,25(OH)2D catabolism. The dissociation between the adaptive brush-border membrane phosphate transport response and the TmP/GFR and vitamin D responses observed in Hyp mice is also apparent in X-linked Gy mice and hypophysectomized rats. Based on these findings and the notion that transport across the brush-border membrane reflects proximal tubular function, we suggest that the adaptive TmP/GFR response requires the participation of 1,25(OH)2D or a related metabolite and that a more distal segment of the nephron is the likely target for the 1,25(OH)2D-dependent increase in overall tubular phosphate conservation.

Adaptation, Physiological↗
PubMed1993

Effect of androstenedione on growth of untransfected and aromatase-transfected MCF-7 cells in culture.

Aromatase is present in human breast tumors and in breast cancer cell lines suggesting the possibility of in-situ estrogen production via the androstenedione to estrone and estradiol pathway. However, proof of the biologic relevance of aromatase in breast cancer tissue requires the demonstration that this enzyme mediates biologic effects on cell proliferation. Accordingly, we studied the effects of the aromatase substrate, androstenedione, on the rate of proliferation of wild-type and aromatase-transfected MCF-7 breast cancer cells. Androstenedione did not increase cell growth in wild-type MCF-7 cells which contained relatively low aromatase activity and produced 4-fold more estrone than estradiol. In contrast, aromatase-transfected cells contained higher amounts of aromatase, produced predominantly estradiol, and responded to androstenedione with enhanced growth. An aromatase inhibitor fadrozole hydrochloride, blocked the proliferative effects of androstenedione providing evidence for the role of aromatase in this process. As further evidence of the requirement for aromatase, cells transfected with the neomycin resistance expression plasmid but lacking the aromatase cDNA did not respond to androstenedione. These studies provide evidence that aromatase may have a biologic role for in-situ synthesis of estrogens in breast cancer tissue.

Analysis of Variance↗
PubMed1993

Na(+)-dependent sulfate transport in opossum kidney cells is DIDS sensitive.

Sulfate transport was examined in OK/E cells, a clonal subline of opossum kidney cells that express several differentiated functions of the proximal tubule. Extracellular Na+ stimulated [35S]sulfate uptake five- to sixfold. Hill analysis demonstrating the dependence of sulfate uptake on Na+ concentration yielded a Hill coefficient of 1.5 and a Michaelis constant (KNa+) of 23 mM. Na(+)-dependent sulfate uptake was increased by lowering the pH from 7.4 to 6.4, decreased by raising the pH to 8.4 and inhibited by a 10-fold molar excess of SO3(2-), S2O3(2-) and CrO4(2-), but not by phosphate. The Na(+)-mediated component of sulfate uptake was saturable and kinetic parameters were estimated [Michaelis constant (Km) = 2.4 +/- 0.2 mM and maximum velocity (Vmax) = 125 +/- 15 pmol.mg protein-1.min-1]. Omitting extracellular Cl- resulted in a significant increase in the affinity of the carrier for sulfate (Km = 0.5 mm), without changing Vmax, consistent with competitive inhibition by Cl-. Na(+)-dependent sulfate uptake in OK/E cells was also inhibited by HCO3- [half-maximal inhibitory concentration (IC50) = 7 mM], 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, IC50 = 0.9 microM), 0.5 mM picrylsulfonic acid and 0.1 mM ethacrynic acid, but not by 1 mM amiloride. Na(+)-dependent, DIDS-sensitive sulfate uptake was also expressed in the parental OK cell line and was not influenced by serum or 3,3',5-triiodo-L-thyronine. We conclude that Na(+)-dependent sulfate uptake in OK/E cells observes many of the features of Na(+)-sulfate cotransport in the renal brush-border membrane and provides a useful model to investigate the regulation of renal sulfate transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Synchronization of breast cancer cell proliferation in vivo by combined hormonal and polyamine manipulation.

Optimal synchronization of breast cancer cell proliferation by hormonal means may be limited by cellular heterogeneity in sensitivity to the multistep activation of growth following initial hormone binding to the receptor. We hypothesized that induced synchronous growth may be improved by combined manipulation of the polyamine (PA) pathway since we have previously shown that PAs are distal effectors of hormonal action on proliferation in breast cancer. To test our hypothesis, we induced an initial phase of hormone and PA depletion (castration plus administration of the PA synthesis inhibitor alpha-difluoromethylornithine) in rats bearing N-nitrosomethylurea induced mammary tumors. This was followed by transition phase of hormone repletion in the presence of alpha-difluoromethylornithine (to push the cells into the proliferative cascade up to the distal step controlled by PA) and finally a phase of hormone and PA repletion. Simultaneously, groups of rats were subjected to hormone/PA depletion/repletion individually. The effects of these manipulations on the labeling indices (LIs) of glandular, myoepithelial, and nonepithelial cells were estimated by autoradiography. The combined hormone/PA manipulation yielded the highest degree of synchronization with LIs of the glandular and myoepithelial cells being approximately 2-fold over intact control after only 2 or 3 days of combined repletion. In contrast, hormone treatment alone restored the LIs of glandular cells only to control levels and minimally influenced those of myoepithelial cells. PA manipulation alone failed to affect the LIs of any cell type. Although the rate of tumor regrowth was highest with the combination treatment, the absolute tumor volumes did not differ significantly at the end of the repletion phase between the three regimens. These results indicate that combined hormone/PA manipulation provides the best "therapeutic window" (LI/tumor volume) for implementation of kinetically based cytotoxic chemotherapy.

Animals↗
PubMed1992

Role of polyamines in the growth of hormone-responsive and -resistant human breast cancer cells in nude mice.

Recent in vitro data suggest that at least some hormone-independent breast cancer cells exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To address this issue under conditions of in vivo growth, we tested the antiproliferative effect of the polyamine synthetic inhibitor alpha-difluoromethyl-ornithine (DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth of established tumors to a similar extent in all cell lines, even though tumor regression was only observed with MCF-7 cells. DFMO, while inhibiting E2-supported MCF-7 breast cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines, while the spermine level was unaffected. Cellular putrescine levels were suppressed in MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7 or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors develop in some mice upon discontinuation of the drug. We conclude that the hormone-independent breast cancer cell lines tested do not exhibit increased polyamine biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice.

Animals↗
PubMed1992

The effects of TGF-alpha and 17 beta-estradiol on polyphosphoinositide metabolism in MCF-7 breast cancer cells.

The mechanism by which transforming growth factor-alpha (TGF-alpha) stimulates breast cancer cell proliferation is largely unknown. Furthermore, its potential role as an autocrine effector of estradiol-17 beta (E2)-stimulated growth of hormone-dependent mammary tumors remains controversial. Transient changes in phosphatidylinositol (PI) turnover have been demonstrated in several tissues in response to growth factors. In these experiments, we tested the effects of TGF-alpha and E2 on PI metabolism in three MCF-7 breast cancer cell sublines (MCF-7B, MCF-7I, and MCF-7J). Although TGF-alpha was mitogenic in MCF-7I and MCF-7J cells, PI hydrolysis was stimulated by the growth factor only in the MCF-7I cells. In addition, the TGF-alpha effect was relatively modest, ranging from 23% to 42%. E2 effects on PI turnover were tested in the MCF-7B cells, which were the most sensitive to the proliferative effect of the hormone. E2 did not stimulate PI hydrolysis, whether or not the cells were labelled in the presence of the hormone. On the other hand, E2 did seem to stimulate de novo synthesis of phosphatidylinositol and induce activation of PI kinases. These results demonstrate that TGF-alpha-stimulated PI hydrolysis is modest and cell type dependent. At least under certain conditions, PI metabolism is not involved in the proliferative effects of TGF-alpha (MCF-7J) or E2 (MCF-7B). The role of increased PI synthesis in E2-stimulated MCF-7 cell growth remains to be established.

Breast Neoplasms↗
PubMed1992

Oxytocin given in a pulsatile manner to the ewe at 120 to 140 days' gestational age increases fetal sheep plasma cortisol.

A single intravenous injection of oxytocin into pregnant sheep (123 to 144 days' gestational age) causes a bout of myometrial activity and an increase in fetal plasma corticotropin levels. We hypothesized that a sustained increased frequency of myometrial contractures accelerates the normal increase in fetal adrenal secretion in sheep in the last 3 weeks of gestation. To test this hypothesis, pulses of saline solution (group 1, 9 ewes and 10 fetuses) or oxytocin (group 2, 11 ewes and 12 fetuses) 600 or 960 microU/kg/min for 5 of every 30 minutes were infused into the maternal jugular vein for 6 days beginning at day 128 +/- 2 (mean +/- SD) days' gestational age. Total myometrial activity increased to 160% of baseline in group 2 by day 6. Myometrial activity did not change throughout the study in group 1. Maternal plasma cortisol concentrations did not rise during oxytocin infusion when compared with their own baselines (group 2) and were not different from concentrations in saline-infused ewes (group 1). By day 4 of oxytocin administration fetal plasma cortisol concentrations had risen significantly above baseline in group 2 (p less than 0.05). Fetal plasma cortisol concentrations did not rise in group 1. Corticotropin levels were not elevated in the fetal carotid arterial plasma of either group. A small but significant decrease occurred in fetal carotid arterial PO2 in group 2 by day 6 but not in group 1. In conclusion, increased myometrial activity produced by pulsed oxytocin is accompanied by increased fetal plasma cortisol concentrations, demonstrating that long-term alteration of myometrial activity affects fetal adrenal function over several days at this critical period of gestation.

Adrenocorticotropic Hormone↗
PubMed1987

Intraepikeratophakia.

A refractive keratoplasty technique has been devised where the donor lenticule is placed between Bowman's membrane and the epithelial layer. We have termed this operation "intraepikeratophakia." The technique is based on the same principles as keratophakia. The epithelium is removed surgically and reapproximated over the transplanted lenticule. Twenty-two patients underwent conventional epikeratophakia, and ten underwent intraepikeratophakia. Of the 32 patients in this study, three required removal of the donor lenticule. All of these patients were in the epikeratophakia group, and all failures were secondary to poor reepithelialization of the lenticule. Of the ten patients who underwent intraepikeratophakia, nine had complete reepithelialization by the second postoperative day. On the average, these patients required 77% less time to reepithelialize completely compared with epikeratophakia patients. Patients in the intraepikeratophakia group were also more comfortable throughout their postoperative course probably as a result of the faster rate of reepithelialization. Intraepikeratophakia offers definite advantages over epikeratophakia and is a viable alternative to patients requiring refractive keratoplasty.

Aphakia↗
PubMed1986

Transfusion-related sepsis after prolonged platelet storage.

The antecubital fossa venipuncture site in frequent blood donors can become scarred or "dimpled" and colonized with surface and deep bacteria that are not sterilized by standard iodophor preparation techniques. These microorganisms can be introduced into blood or platelets at the time of donation. Recent advances that permit the prolonged storage of platelets at room temperature before transfusion allow proliferation of these contaminating bacteria, particularly gram-positive microorganisms. Documented are three episodes of platelet contamination with gram-positive organisms and four cases of sepsis in recipients of these platelets, which were obtained through the "dimpled" site of a single donor and stored for at least 80 hours at 22 degrees C before transfusion. In contrast, platelets harvested from this donor's "dimpled" site and stored for not more than 50 hours were transfused to 25 patients without complication. Therefore, the extended storage of platelets at 22 degrees C prior to transfusion demands strict awareness of any possible sources of extrinsic contamination, since gram-positive bacteria can proliferate under these conditions and result in infectious complications in recipients.

Adult↗