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Biomedical subjects

T J Martin

Publications and source records attributed to T J Martin.

At least 91 records · Page 5Linked to original sources
PubMed1998

Pneumo-orbital cyst after orbital fracture repair.

PURPOSE: To report a case of a respiratory epithelial-lined, air-filled orbital cyst as a late complication of orbital fracture repair. METHOD: Case report. RESULTS: Recurrent episodes of diplopia and hyperophthalmia developed secondary to pneumatic inflation of a respiratory epithelial-lined orbital cyst 6 months after orbital fracture repair. This cyst remained in communication with an ethmoidal air cell and became inflated during pressurization of the ethmoid sinus. Removal of the cyst and orbital implant was curative. CONCLUSION: Air-filled, respiratory epithelial-lined orbital cyst is a rare cause of episodic diplopia and globe displacement after orbital trauma.

Accidents, Traffic↗
PubMed1998

Relative afferent pupillary defects in patients with Leber hereditary optic neuropathy and unilateral visual loss.

PURPOSE: It has been suggested that the pupillary light reaction is relatively preserved in the affected eyes of patients with Leber hereditary optic neuropathy (LHON). To test the hypothesis that visual-pupillomotor dissociation exists in LHON, we performed a retrospective study to evaluate the magnitude of the relative afferent pupillary defect (RAPD) in patients who had experienced monocular visual loss. We also compared the size of the measured RAPD with the size of the RAPD that would be expected on the basis of documented visual field loss. METHODS: We identified a cohort of patients with LHON and monocular visual loss, whose pupillary reactions had been quantified using neutral density filters. From a review of the case records, we determined whether an RAPD was present, as well as the magnitude of the documented RAPDs. We also calculated the expected size of the RAPD for each patient, using previously established templates that correlated the size of the RAPD with the degree of visual field loss. RESULTS: An RAPD was identified in all 10 patients in this study. There was no significant difference between the size of the measured and predicted RAPD, nor did the size of the RAPD correlate with visual acuity or the time interval between the onset of visual loss and evaluation. CONCLUSION: The results of this study do not support the hypothesis that visual-pupillomotor dissociation is a common feature of LHON.

Adolescent↗
PubMed1998

Training dose and session time as contextual determinants of heroin self-administration in rats.

In this study a rat self-administration model was used to examine the effects of training dose and time in the session on the dose-effect curve for heroin. Doses of heroin lower than 5.4 microg/inf maintained higher rates of drug intake in animals trained with 5.4 microg/inf compared to 18 microg/inf. Doses greater than 5.4 microg/inf maintained similar rates of intake in both groups of animals. The dose-response curve was shifted downward and to the right as the session progressed for animals trained with 5.4 microg/inf of heroin; however, the shift in the dose-intake curve over the session was less pronounced when the training dose was 18 microg/inf. Naltrexone and naltrindole were administered to animals in which responding was engendered with infusions of 5.4 microg of heroin to determine the effects of these antagonists in the context of time is the session. The potency of naltrexone decreased across the 4 h of the session with a time course that was consistent with literature reports on the elimination kinetics of naltrexone in rat brain. In contrast, there was not a significant interaction between naltrindole dose and session time. Therefore, the rates of heroin intake in rats are dependent not only upon the dose available for self-administration, but upon the session time and training dose as well.

Animals↗
PubMed1998

Localization of parathyroid hormone-related protein in osteoclasts by in situ hybridization and immunohistochemistry.

Using immunohistology with two specific antisera raised against N-terminal parathyroid hormone-related protein (PTHrP) and in situ hybridization (riboprobe to common coding exon), evidence is provided for the expression of PTHrP by mouse, rabbit, and human osteoclasts derived from several in vitro and in vivo sources. In cocultures of mouse bone marrow and calvarial cells treated with 1,25-dihydroxyvitamin D3, the generated osteoclasts expressed both PTHrP messenger RNA (mRNA) and protein. In addition, PTHrP was detected in the majority of actively resorbing osteoclasts in sections of newborn and adult mouse long bones. Using an in vivo intramembranous bone formation model in rabbits, expression of PTHrP mRNA and protein was demonstrated in osteoclasts at active bone resorption sites as well as in actively synthesizing osteoblasts and bone lining cells. Localization of PTHrP was also demonstrated in osteoclast-like cells of human giant cell tumors from bone. In some of these tumors, a small proportion of the multinucleated cells expressed tartrate resistant acid phosphatase (TRAP), but not PTHrP mRNA or protein. Finally, both mRNA and protein for PTHrP were expressed in osteoclasts in sections of bone or joints from patients with Paget's disease, rheumatoid arthritis, and osteoarthritis. These observations raise the possibility that PTHrP might participate in osteoclast function.

Animals↗
PubMed1998

Parathyroid hormone-related protein in lower vertebrates.

1. Parathyroid hormone-related protein (PTHrP) is an important mediator of humoral hypercalcaemia of malignancy in humans. Normal human subjects have very low levels of PTHrP in their circulation. 2. Parathyroid hormone-related protein has recently been demonstrated in high levels in the circulation and tissues of the sea bream and the dogfish, leading to the hypothesis that PTHrP may be a 'classical' hormone in fish. 3. Immunohistochemistry and in situ hybridization were performed to investigate the evolutionary history of PTHrP. Tissues were examined from a number of lower vertebrates, including lungfish, lamprey and several species of bony and cartilaginous fish. Parathyroid hormone-related protein was localized to the skin and to kidney tubules in all animals studied. In the developing lungfish, PTHrP was observed in the notochord, developing brain and skeletal muscle layers. These results suggest that PTHrP is of ancient origin and has a basic and fundamental function in vertebrates.

Animals↗
PubMed1998

A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro.

Both human and murine osteoclasts can be derived in vitro from hematopoietic cells or monocytes that are co-cultured with osteoblasts or marrow-derived stromal cells. The osteoclastogenic stimulus provided by murine osteoblasts and marrow-derived stromal cells is now known to be mediated by osteoclast differentiation factor (ODF), a membrane-bound tumor necrosis factor-related ligand. This study demonstrates that mouse spleen cells and monocytes form osteoclasts when cultured in the presence of macrophage-colony stimulating factor (M-CSF) and a soluble form of murine ODF (sODF). Numerous multinucleated osteoclasts expressing tartrate resistant acid phosphatase (TRAP) and calcitonin receptor (CTR) formed within 7 days of culture and engaged in extensive lacunar bone resorption. Osteoclast number and bone resorption area was dependent on sODF concentration. Long-term cultured human monocytes also formed bone resorbing osteoclasts in response to co-stimulation by sODF and M-CSF, although this required more than 11 days in culture. This human osteoclast differentiation was strongly inhibited by granulocyte-macrophage colony stimulating factor. This study further characterises murine osteoclast differentiation caused by sODF and M-CSF co-stimulation in vitro, and shows that the same co-stimulation causes human osteoclast differentiation to occur. We propose that this methodology can be employed to investigate the direct effects of cytokines and other factors on human osteoclast differentiation.

Acid Phosphatase↗
PubMed1998

Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells.

The osteoclastogenic factor of osteoblastic origin has recently been elucidated as a novel Tumor Necrosis Factor (TNF)-ligand family member, termed osteoclast differentiation factor (ODF). Using a semiquantitative RT-PCR approach, we sought to determine the mRNA expression of ODF and its decoy receptor, osteoprotegerin (OPG), in a selection of osteoblastic cell lines and in response to three factors representative of different signal transduction pathways, vitamin D receptor, protein kinase A or gp130. Each osteotropic agent, either 1,25-(OH)2D3, PTH or IL-11, promoted an increase in the ratio of ODF:OPG, with maximal stimulation occurring at 24 h, 4 h, and 8 h, respectively, and furthermore each was shown to act in a dose-dependent manner. This report establishes that osteoblastic cell lines incapable of supporting osteoclast formation have markedly reduced ODF expression and also illustrates the importance of the relative abundance of ODF compared with the levels of OPG for the induction of osteoclastogenesis.

Animals↗
PubMed1998

Expression of rat homeobox gene, rHOX, in developing and adult tissues in mice and regulation of its mRNA expression in osteoblasts by bone morphogenetic protein 2 and parathyroid hormone-related protein.

The rat homeobox gene, rHox, was cloned from a rat osteosarcoma cDNA library. Southwestern and gel mobility shift analyses showed that rHox binds to the promoter regions of collagen (alpha1)I and osteocalcin genes while transient transfection with rHox resulted in repression of their respective promoter activities. In situ hybridization studies showed that rHox mRNA was widely expressed in osteoblasts, chondrocytes, skeletal muscle, skin epidermis, and bronchial and intestinal epithelial cells, as well as cardiac muscle in embryonic and newborn mice. However in 3-month-old mice, rHox mRNA expression was restricted to osteoblasts, megakaryocytes, and myocardium. Bone morphogenetic protein 2, a growth factor that commits mesenchymal progenitor cells to differentiate into osteoblasts, down-regulated rHox mRNA expression by 40-50% in UMR 201, a rat preosteoblast cell line, in a time- and dose-dependent manner. In contrast, PTH-related protein (PTHrP), recently shown to be a negative regulator of chondrocyte differentiation, significantly enhanced rHox mRNA expression in UMR 106-06 osteoblastic cells by 3-fold at 24 h while at the same time down-regulating expression of pro-alpha1(I) collagen mRNA by 60%. Expression of rHox mRNA in calvarial osteoblasts derived from PTHrP -/- mice was approximately 15% of that observed in similar cells obtained from normal mice. In conclusion, current evidence suggests that rHox acts as a negative regulator of osteoblast differentiation. Furthermore, down-regulation of rHox mRNA by bone morphogenetic protein 2 and its up-regulation by PTHrP support a role of the homeodomain protein, rHox, in osteoblast differentiation.

Animals↗
PubMed1998

Parathyroid hormone-related protein mRNA and protein expression in multiple myeloma: a case report.

Multiple myeloma frequently leads to complications, such as osteolytic lesions, hypercalcemia, and pathological fractures. Increased bone resorption in myeloma is due to osteoclast activation. The nature of the osteoclast activator(s) remains unclear. We describe a case of multiple myeloma with marked hypercalcemia and skeletal complications that progressed rapidly despite chemotherapy. The patient had marked hypercalcemia at diagnosis (4.5 mmol/l), and elevated parathyroid hormone-related protein (PTHrP) levels were found in plasma. Analysis of the bone marrow trephine biopsy showed PTHrP gene transcription and protein in myeloma cells. These results provide strong evidence for the production of significant amounts of PTHrP by human myeloma cells. PTHrP has been measured as elevated in the plasma of patients with myeloma and might be an important contributor to the skeletal complications in this disease.

Aged↗
PubMed1998

The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study.

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either "low" or "high" trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean +/- SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (-0.50 +/- 0.05 and -0.21 +/- 0.08), spine-lateral (-0.28 +/- 0.06 and -0.19 +/- 0.10), femoral neck (-0.42 +/- 0.04 and -0.26 +/- 0.09), Ward's triangle (-0.44 +/- 0.04 and -0.28 +/- 0.08), trochanter (-0.44 +/- 0.05 and -0.32 +/- 0.08), total body (-0.46 +/- 0.06 and -0.32 +/- 0.08), ultradistal radius (-0.47 +/- 0.05 and -0.42 +/- 0.07), and midradius (-0.52 +/- 0.06 and -0.33 +/- 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score < -2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Absorptiometry, Photon↗
PubMed1998

Effect of antagonism of the parathyroid hormone (PTH)/PTH-related protein receptor on decidualization in rat uterus.

Parathyroid hormone-related protein (PTHrP) was detected at 32.8 +/- 3.9 pmol 1-1 in uterine luminal fluid from immature rats treated with oestradiol. As mRNA encoding PTHrP has previously been localized to implantation sites in pregnant rats, the role of luminal PTHrP during pregnancy was explored. Infusion of a parathyroid hormone (PTH)/PTHrP receptor antagonist, [Asn10,Leu11]PTHrP(7-34) amide, into the uterine lumen during pregnancy in rats resulted in excessive decidualization. This effect was also observed after intrauterine infusion of a monoclonal antibody raised against PTHrP. The effect of infusion of PTH/PTHrP receptor antagonist was dependent upon successful implantation, was dose-dependent and confined to the treated horn. A decrease in the number of apoptotic decidual cells in antagonist-infused uterine horns compared with vehicle or non-infused horns was detected immunohistochemically at day 13 of pregnancy, and this decrease is likely to contribute to the 'over-decidualization' observed. In pseudopregnant rats, infusion of PTH/PTHrP receptor antagonist into the uterine lumen resulted in an increase in uterine wet weight of the infused horn compared with the non-infused horn, indicating a direct effect on deciduoma formation. Thus, activation of the PTH/PTHrP receptor by locally produced PTHrP appears to be crucial for normal decidualization during pregnancy in rats.

Animals↗
PubMed1998

Interleukins in the control of osteoclast differentiation.

To maintain homeostasis of bone, the production of osteoblasts and osteoclasts is tightly regulated. At the local level, hormones and cytokines control formation of osteoclasts from hemopoietic precursors by acting upon osteoblastic-stromal cells and in some cases also upon cells of the immune system. Osteoblasts regulate osteoclast formation by providing physical support and cytokines such as M-CSF and IL-11, which promote osteoclast differentiation. Osteoblasts are also a source of IL-18, which limits osteoclast formation. The requirement of contact between osteoblasts and hemopoietic cells for successful osteoclast formation led to a concept of a membrane-anchored stromal cell molecule that programs osteoclast differentiation. This mechanism has been highlighted by the discovery of osteoprotegerin (OPG), a soluble tumor necrosis factor (TNF) family member that inhibits osteoclast formation. The ligand for OPG is a novel transmembrane TNF receptor superfamily member, the osteoclast differentiating factor (ODF). The recognition of the osteoprotegerin/osteoprotegerin-ligand axis will lead to new insights into the control of osteoclast differentiation by interleukins.

Animals↗
PubMed1998

Type I collagen influence on gene expression in UMR106-06 osteoblast-like cells is inhibited by genistein.

We have previously shown that an exogenous type I collagen matrix can regulate expression of mRNA for parathyroid hormone (PTH)-related protein (PTHrP) and its receptor, the PTH/PTHrP receptor, in the UMR106-06 osteogenic sarcoma cell line, which is considered to be representative of a relatively mature osteoblast phenotype. Consistent with those data, we show here that growth of UMR106-06 cells on type I collagen increased PTH/PTHrP receptor-binding capacity. Analysis of the binding data showed that the number of PTH/PTHrP receptors expressed by cells cultured on collagen was at least 2-fold greater than that of cells cultured on plastic. Expression of mRNA encoding alkaline phosphatase (ALP) and osteopontin (OP) was also upregulated in cells cultured on collagen, suggesting that interaction with collagen promotes the osteoblast phenotype in this cell line. Retinoic acid (RA), which has also been shown to promote osteoblastic differentiation, synergized with type I collagen to cause super-induction of OP mRNA. In contrast, RA abolished the collagen-induced increase in ALP mRNA and PTH/PTHrP receptor mRNA. The collagen-mediated increase in the expression of OP and PTH/PTHrP receptor mRNA, but not that of ALP, was perturbed by prior covalent modification of the collagen by non-enzymatic glycation. The collagen effects did not occur via interaction with RGD amino acid domains in type I collagen, but evidence was obtained for involvement of the DGEA amino acid cell-binding domain. The mechanism by which plating of UMR106-06 cells on a type I collagen substrate affects PTH/PTHrP receptor mRNA levels was investigated. Inhibition of cytoskeletal organization using cytochalasin D, and inhibitors of protein phosphatases, protein kinase C, phospholipase C and cyclooxygenase, did not abrogate the collagen-mediated effects. In contrast, treatment of cells with the protein tyrosine kinase inhibitor genistein, but not herbimycin A, dose-dependently abolished the collagen effects on the expression of PTH/PTHrP receptor, ALP and OP mRNA. These results show that a type I collagen substrate influences the expression of osteoblast-associated genes in a cell model of mature osteoblasts and suggests that this involves, at least in part, changes in intracellular tyrosine phosphorylation.

Alkaline Phosphatase↗
PubMed1998

Parathyroid-hormone-related protein in sarcoidosis.

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.

Adult↗
PubMed1997

Calcitonin receptors, bone sialoprotein and osteopontin are expressed in primary breast cancers.

Several human breast cancer cell lines express the calcitonin receptor (CTR), but this has not been demonstrated previously in clinical breast cancers. We examined 18 primary breast cancers by reverse transcription-PCR, for expression of CTR and of the bone proteins osteopontin (OPN) and bone sialoprotein (BSP). OPN and CTR were expressed by each of the tumours, and 7 (39%) additionally expressed an alternate form of CTR, whilst BSP was expressed by 13 tumours (72%). In situ hybridisation confirmed that expression of OPN and CTR was confined to the tumour cells. Expression of CTR, BSP and OPN may prove to be a useful marker for breast cancers, and their role in the homing of breast cancer cells to bone remains to be investigated.

Breast Neoplasms↗