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M D O'Hara

Publications and source records attributed to M D O'Hara.

At least 19 recordsLinked to original sources
PubMed1999

The role of laminin-1 in the modulation of radiation damage in endothelial cells and differentiation.

Microvascular dysfunction due to endothelial damage is often associated with the ionizing radiation used during cancer therapy. This radiation-induced capillary injury is a major factor in the inhibition of new vessel growth (angiogenesis) and in disease states such as radiation-induced pneumonitis and nephropathy. Many studies have examined the effects of radiation on endothelial cell function; however, little is known regarding the role the basement membrane plays in radiation-induced endothelial cell damage and angiogenesis. Therefore, we examined the effects of gamma radiation on aortic explants, and in vitro on three endothelial cell types (of artery, vein and capillary origin) irradiated with or without the basement membrane glycoprotein laminin-1. As expected, irradiation inhibited angiogenic sprouting of the aortic explants, endothelial cell proliferation, attachment, migration and differentiation in vitro in a dose-dependent manner. However, the effect of radiation on several of these processes in angiogenesis was reduced when the cells were irradiated on laminin-1. To further evaluate the effects of radiation on endothelial cells, we examined the expression of the vascular endothelial cell growth factor (VEGF) kinase domain region receptor in endothelial cells irradiated in the presence and absence of laminin-1. In endothelial cells irradiated on laminin-1, KDR expression increased 2.5-fold over control levels. Therefore, although radiation has a dose-dependent inhibitory effect on processes associated with angiogenesis in vitro, the presence of the basement membrane glycoprotein laminin-1 during irradiation decreases these effects.

Animals↗
PubMed1998

Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta.

Marrow stromal cells from wild-type mice were infused into transgenic mice that had a phenotype of fragile bones resembling osteogenesis imperfecta because they expressed a human minigene for type I collagen. In mice that were irradiated with potentially lethal levels (700 cGy) or sublethal levels (350 cGy), DNA from the donor marrow stromal cells was detected consistently in marrow, bone, cartilage, and lung either 1 or 2.5 mo after the infusions. The DNA also was detected but less frequently in the spleen, brain, and skin. There was a small but statistically significant increase in both collagen content and mineral content of bone 1 mo after the infusion. Similar results were obtained with infusion of relatively large amounts of wild-type whole marrow cells into the transgenic mice. In experiments in which male marrow stromal cells were infused into a female osteogenesis imperfecta-transgenic mouse, fluorescense in situ hybridization assays for the Y chromosome indicated that, after 2.5 mo, donor male cells accounted for 4-19% of the fibroblasts or fibroblast-like cells obtained in primary cultures of the lung, calvaria, cartilage, long bone, tail, and skin. In a parallel experiment in which whole marrow cells from a male mouse were infused into a female immunodeficient rag-2 mouse, donor male cells accounted for 4-6% of the fibroblasts or fibroblast-like cells in primary cultures. The results support previous suggestions that marrow stromal cells or related cells in marrow serve as a source for continual renewal of cells in a number of nonhematopoietic tissues.

Animals↗
PubMed1998

A regional audit of perinatal and infant autopsies in Northern Ireland.

OBJECTIVE: To investigate the rate and quality of perinatal/infant autopsies and their contribution to the final diagnosis. METHODS: The anonymised reports of autopsies performed on 174 of the 367 cases reported to the Northern Ireland Regional Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) coordinator in 1993 were reviewed. They were scored using a modification of the CESDI Pathology Audit Form 93 and, based on the score obtained, ascrined to one of three groups: good, adequate or inadequate. Based on the information obtained, they were also assessed as providing diagnostic, confirmatory, additional or no diagnostic data. The pre-autopsy clinical extended Wigglesworth classification was compared with that based on autopsy findings. RESULTS: The autopsy rate was 47.4% and included 18 late fetal losses, 70 stillbirths, 57 neonatal deaths and 29 post neonatal deaths. The Regional Paediatric Pathology Centre performed 34.5% of the autopsies. Of the total number of autopsies, 46.6% failed to reach an adequate standard. Only 4.9% of the inadequate autopsies were performed in the Regional Centre. The Wigglesworth classification was altered in 20.7% of cases following autopsy. The autopsy findings of 49 cases were diagnostic, 75 confirmatory, 23 yielded additional information and 27 were useful in only a negative sense. CONCLUSION: The autopsy rate for this region is well below the recommended level of 75%. With the exception of the Regional Centre, the quality of the perinatal/infant autopsy did not reach the standard suggested in the CESDI Pathology Audit form 93. Despite this the autopsy yielded valuable diagnostic, confirmatory or additional findings in 84.5% and resulted in alteration to the pre-autopsy Wigglesworth classification in 20.7%.

Autopsy↗
PubMed1998

Cytokeratin positive T cell malignant lymphoma.

A high grade T cell malignant lymphoma is described in which weak staining of tumour cells for leucocyte common antigen and T cell markers coexisted with strong positive cytoplasmic staining with the anticytokeratin marker CAM 5.2. This is the first report of non-CD30 positive T cell lymphoma showing cytokeratin positivity. On ultrastructural examination there was no evidence of epithelial differentiation or of accumulation of cytokeratin-type intermediate filaments. The case adds to the range of malignant lymphomas which can, on rare occasions, show cytokeratin positivity. Pathologists should be aware of this potential diagnostic pitfall if inappropriate investigations and therapeutic regimens are to be avoided.

Aged↗
PubMed1996

Infantile haemangiopericytoma of the hand.

Infantile haemangiopericytomas (IHP) are rare subcutaneous tumours arising from pericytes. Clinically they are difficult to diagnose and pathologically they appear to be locally invasive, but they have a better prognosis than adult haemangiopericytomas. We report a case of IHP affecting the hand of a 7-week-old child that required urgent treatment.

Hand↗
PubMed1996

Paraganglioma: an unusual tumour of the parathyroid gland.

A case of paraganglioma arising within a parathyroid gland is reported. The lesion was an incidental finding in a block dissection of neck performed for squamous carcinoma of the pharynx. A well-circumscribed lesion, exhibiting the characteristic pathological features of a paraganglioma, was embedded within the right inferior parathyroid gland. Due to its location, the chief histological differential diagnosis was an unusual variant of parathyroid adenoma. Immunohistochemistry and electron microscopy assisted in reaching a diagnosis. This, as far as we are aware, is the first reported case of a paraganglioma of the parathyroid gland.

Aged↗
PubMed1995

Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice.

Cells from transgenic mice expressing a human mini-gene for collagen I were used as markers to follow the fate of mesenchymal precursor cells from marrow that were partially enriched by adherence to plastic, expanded in culture, and then injected into irradiated mice. Sensitive PCR assays for the marker collagen I gene indicated that few of the donor cells were present in the recipient mice after 1 week, but 1-5 months later, the donor cells accounted for 1.5-12% of the cells in bone, cartilage, and lung in addition to marrow and spleen. A PCR in situ assay on lung indicated that the donor cells diffusely populated the parenchyma, and reverse transcription-PCR assays indicated that the marker collagen I gene was expressed in a tissue-specific manner. The results, therefore, demonstrated that mesenchymal precursor cells from marrow that are expanded in culture can serve as long-lasting precursors for mesenchymal cells in bone, cartilage, and lung. They suggest that cells may be particularly attractive targets for gene therapy ex vivo.

Animals↗
PubMed1995

Thermal response and hyperthermic radiosensitization of scid mouse bone marrow CFU-C.

PURPOSE: Scid mice are severely immunodeficient as a result of a defective recombinase system. Mice with the scid mutation have been shown to have an increased sensitivity to ionizing radiation, presumably as a result of an inability to repair DNA damage. Little is known of the impact of this mutation on the thermal response and on hyperthermic radiosensitization. This investigation established the thermal response (42-44 degrees C), patterns of thermotolerance development, and the impact of hyperthermia (60 min at 40 degrees C or 42 degrees C) on the radiation response of bone marrow colony forming unit-culture cells (CFU-C) in scid mice. METHODS AND MATERIALS: Anesthetized scid mice (pentobarbital, 90 mg/kg) were killed by cervical dislocation and the nucleated marrow obtained from both tibia and femora by passing 2 ml of cold McCoy's 5A medium supplemented with 15% fetal bovine serum through each bone. Single cell suspensions of nucleated marrow were heated in 12 x 75 mm sterile tissue culture tubes at a concentration of approximately 5 x 10(6) cells/ml. Radiation, when used, was delivered immediately prior to hyperthermia by a 137Cs irradiator (dose rate of 1.20 Gy/min). Colony forming unit-culture were cultured in semisolid agar in the presence of colony stimulating factor (conditioned medium from L929 cells) for 7 days. RESULTS: The slope of the radiation dose-response curve for CFU-C in scid mice was biphasic, the Dos (+/- SE) were 0.29 +/- 0.03 Gy and 1.09 +/- 0.20 Gy, respectively. The Dos of the radiation dose-response curve for wild type marrow from CB-17 and Balb/c mice were 1.28 +/- 0.05 Gy and 1.47 +/- 0.15 Gy, respectively. The Dos of the hyperthermia dose-response curves for scid mice were 75 +/- 5, 10 +/- 1.4, and 4 +/- 0.2 min, respectively, for temperatures of 42 degrees, 43 degrees, and 44 degrees C. Thermotolerance development at 37 degrees C increased to a maximum at approximately 240 min after acute hyperthermia (15 min at 44 degrees C) and thereafter, decreased to control levels within 15 h. Thermotolerance did not develop in scid CFU-C during chronic hyperthermia at temperatures < 42.5 degrees C. Hyperthermia (60 min at 40 degrees or 42 degrees C) immediately after ionizing radiation did not significantly alter the terminal slope of the radiation dose-response curve of scid CFU-C (Do = 1.28 +/- 0.08 Gy). By contrast, hyperthermia following radiation of wild type CFU-C resulted in a decrease in the Do from 1.47 +/- 0.05 Gy (Balb/c, rad only) to 1.31 +/- 0.08 or 1.06 +/- 0.18 Gy for 60 min at 40 degrees or 42 degrees C, respectively. CONCLUSION: These results show that the thermal response and the pattern of thermotolerance development of scid CFU-C were similar to that of wild type Balb/c CFU-C, but that hyperthermia given immediately after ionizing radiation did not alter the radiation response of scid CFU-C. The scid mutation does not increase hyperthermic sensitivity or change the pattern of thermotolerance development of scid mouse CFU-C, implying that the scid mutation is not involved with thermal response, but does render the already radiation-sensitive scid cells incapable of thermal radiosensitization.

Animals↗
PubMed1994

Varicella zoster gastritis in a bone marrow transplant recipient.

A case is reported of a patient who had previously undergone autologous bone marrow transplantation for recurrent Hodgkin's disease. The patient developed a generalised vesicular skin eruption. The clinical diagnosis was of disseminated shingles. Herpes viral particles were identified within the vesicular fluid by electron microscopy and using a specific monoclonal antibody to varicella zoster virus (VZV), positive immunofluorescence was detected in scrapings from the base of a vesicle. Gastroscopy and biopsy were performed because of severe abdominal pain and vomiting. The histological features were of non-specific active inflammation. Despite the histological absence of viral inclusions electron microscopy of the gastric biopsy revealed the presence of intranuclear herpes viral particles with a diameter of 90-100 nm. VZV specific DNA was detected by the polymerase chain reaction in the gastric biopsy extract. The patient was treated with acyclovir and made a full recovery.

Adult↗
PubMed1994

Influence of biological response modifiers: measurement of tumor blood flow and temperature.

Human recombinant interferon-alpha-2b (IFN) is known to inhibit growth of both normal and tumor cells and to stimulate immune effector cell function. We have previously shown that IFN and other biological response modifiers augment accumulation of radiolabeled antibodies in tumors. This investigation demonstrates that 30 min post i.m. administration of IFN significantly (p < 0.01) enhances tumor perfusion in tumor-bearing mice and persists for a much longer time than in normal tissue, which, in part, may contribute to the enhanced tumor uptake of radiolabeled monoclonal antibodies within 1.5 h of their administration. Histological examinations of tumors obtained from animals receiving IFN 72 h previously did not show changes in inflammatory cells. Our investigation shows that laser Doppler flowmetry and color Doppler imaging can provide an excellent means of measuring tumor perfusion changes in small living animals where radioactive tracers cannot be used.

Animals↗
PubMed1992

Dynamic hepatic scintigraphy in the screening of psoriatic patients for methotrexate-induced hepatotoxicity.

We report the use of dynamic hepatic scintigraphy in the assessment of the hepatic status of psoriatic patients before and during methotrexate therapy. Eighty-seven paired dynamic scans and percutaneous liver biopsies were performed in 63 patients. The liver biopsies were graded according to Warin et al. with fibrosis of grade 2 or worse being a strong indication for withdrawal of methotrexate. The sensitivity of dynamic hepatic scintigraphy in detecting fibrosis of grade 2 or worse was 83.3% and the specificity was 81.5%. The predictive value of a normal scan for fibrosis of grade 0-1 was high (98.5%) although the predictive value of an abnormal scan for fibrosis of grade 2 or worse was low (25%). Dynamic hepatic scintigraphy may therefore offer a means to reduce the number of liver biopsies necessary in patients receiving methotrexate for psoriasis.

Adult↗
PubMed1992

Ileal haemangiopericytoma and von Recklinghausen's disease.

Haemangiopericytoma is an uncommon tumour of vascular pericytes which usually arises in deep subcutaneous tissues or the retroperitoneum. There are few reports in the English literature of haemangiopericytoma arising in the ileum. Von Recklinghausen's disease, a condition of autosomal dominant inheritance with a prevalence of 1 in 3000, is often associated with tumours of neural origin. Tumours of non-neural origin also occur in Von Recklinghausen's disease but haemangiopericytoma has not been described. We report on a patient with Von Recklinghausen's disease presenting with massive haemorrhage from an ileal haemangiopericytoma.

Hemangiopericytoma↗
PubMed1991

Histological changes following submucosal Teflon injection in the bladder.

Histological examination following subureteric Teflon injection was carried out on 32 ureters and four granulomatous polyps. When the Teflon was correctly placed in the submucosa it remained circumscribed and reflux was more likely to be corrected. If the Teflon was placed more deeply it became diffuse, caused a giant cell reaction, and was less likely to correct the reflux. The granulomatous polyps may represent a reaction to leakage of Teflon from the injection site.

Foreign-Body Reaction↗
PubMed1991

Congestive heart failure due to aortic incompetence with intestinal infarction due to endarteritis obliterans.

A 27-year-old man with congestive heart failure due to aortic incompetence and subsequent intestinal infarction was found at laparotomy to have extensive necrosis of the bowel due to proliferative endarteritis. Symptoms resolved following treatment with prednisolone and cyclophosphamide, and replacement of the aortic valve. The sub-total occlusion produced by endarteritis obliterans may lead to acute end-organ infarction if cardiac output is reduced.

Adult↗
PubMed1991

The thermal response and development of thermotolerance of the bone marrow stromal progenitor CFU-F.

The effect of hyperthermia on the murine bone marrow stromal progenitor (fibroblast colony-forming unit, CFU-F) was evaluated and its ability to develop thermotolerance demonstrated. CFU-F were obtained from nucleated marrow of Balb/c mice and heated in vitro in alpha minimum essential medium plus 15% fetal bovine serum. Thermotolerance development was tested two ways. 1) The development of thermotolerance during prolonged hyperthermia was observed with a "step-up" heating protocol (i.e., cells were incubated at 41 degrees C and at regular intervals challenged with 15 min at 44 degrees C). 2) The development of thermotolerance at 37 degrees C after a short exposure to a high temperature (greater than or equal to 43 degrees C) was observed with a split treatment protocol that consisted of two 15-min treatments of 44 degrees C separated with time at 37 degrees C. The inverse of the slopes of the hyperthermia dose-response relationships (Do +/- SE) for CFU-F were 118 +/- 14, 53 +/- 7, 23 +/- 0.6, 11 +/- 0.3, 7 +/- 0.3, and 5 +/- 0.5 min for exposures of 41.5 degrees, 42 degrees, 42.5 degrees, 43 degrees, 43.5 degrees, and 44 degrees C, respectively. The plot of the slopes of the heat "dose-response" relationships versus the inverse of the absolute temperature (Arrhenius plot) yields a change in slope at approximately 43 degrees C, and the inactivation enthalpies (slopes above and below the inflection point at 43 degrees C) were 606 +/- 100 kJ/mol (145 +/- 24 kcal/mol) and 1372 +/- 29 kJ/mol (328 +/- 7 kcal/mol) above and below 43 degrees C, respectively. The maximum thermotolerance ratio (TTR, surviving fraction after maximum thermotolerance development to surviving fraction of normotolerant CFU-F) at 37 degrees C after an acute thermal exposure to 15 min at 44 degrees C occurred after 12 h, with a half time of 60 min and a TTR of 41. The maximum TTR during prolonged hyperthermia at 41 degrees C was 2.4 by approximately 50 min. These results show that CFU-F are as sensitive as committed hematopoietic precursors (e.g., granulocyte-macrophage colony-forming units, CFU-GM) to hyperthermia over a wide range of thermal exposures and are capable of thermotolerance development during prolonged hyperthermic exposures and at 37 degrees C after short exposures. We conclude that at least one of the stromal elements of normal marrow may be compromised during whole-body or regional clinical hyperthermia protocols.

Animals↗