Search PubMed⌕ Search

Biomedical subjects

J R Goodlad

Publications and source records attributed to J R Goodlad.

34 records · Page 2Linked to original sources

Activation of nuclear factor kappa B in Crohn's disease.

OBJECTIVES AND DESIGN: The location and degree of activation of nuclear factor kappa (NFkappaB), a primary transcription factor that plays a regulating role in immune and inflammatory responses, was determined in Crohn's disease using full thickness specimens of bowel collected at surgery. MATERIALS AND METHODS: Resected specimens of inflamed and non-inflamed bowel were collected from thirteen patients with Crohn's disease and non-inflamed bowel from eleven control subjects. Prepared frozen sections were immunostained using a monoclonal antibody to the activated form of the p65 subunit of NFkappaB and the number of positive staining cells counted using a Lennox graticule. RESULTS: The number of cells positive for activated NFkappaB was significantly increased (p = 0.001 ) in all layers of inflamed Crohn's disease bowel, compared to non-inflamed bowel from controls. There was also a significant increase ( p = 0.009) in the number of positive cells, when compared to non-inflamed bowel from control subjects, in the submucosa of non-inflamed areas of Crohn's disease bowel. Cells positive for activated NFkappaB were provisionally identified by morphological criteria as mostly macrophages with some lymphocytes. There was no activation in endothelia. CONCLUSION: NFkappaB is activated within large mononuclear cells in all layers of inflamed areas of the bowel in Crohn's disease and may represent key events in the inflammatory process. Increased activation in the submucosa of non-inflamed Crohn's disease bowel provides further evidence of early immunological activation in macroscopically and microscopically uninvolved areas and an underlying abnormal immune system in Crohn's disease.

Adolescent↗

Ancient hematoma: a unifying concept for a post-traumatic lesion mimicking an aggressive soft tissue neoplasm.

We describe the clinicopathologic features of four cases of ancient hematoma occurring in the tensor fascia lata and perifascial tissue that clinically and radiologically mimicked aggressive soft tissue neoplasms. The lesions arose in three men and one woman, aged between 31 and 61 years. In three cases, an injury to the affected site had been noted 18 months, 19 years, and 20 years beforehand, respectively. At presentation, these deep-seated and enlarging lesions were highly suggestive of soft tissue sarcomas. Three lesions were treated by excision of an intramuscular or perifascial mass; in one case, repeated incomplete excisions were performed. Grossly, in three cases a well-circumscribed, fusiform mass with a soft cystic center and a fibrous pseudocapsule was described. Histologically, blood clot, fibrin, and predominant amorphous debris were seen in the central cavities; in three cases, the fibrous pseudocapsule contained clumped, eosinophilic, amorphous debris surrounded by a prominent xanthogranulomatous inflammatory infiltrate with numerous, multinucleated, foreign body-type, giant cells. Additionally, cholesterol clefts, areas of hemorrhage and dystrophic calcification, hemosiderin deposits, and cellular scar tissue were seen. Follow-up information revealed no evidence of recurrence or secondary infection in the three cases treated by local or wide excision; in the case in which incomplete excision was performed, continuous symptomatic growth was noted. Pathologic features of ancient hematomas are similar, if not identical, to those hematomas described previously as calcific myonecrosis, chronic expanding hematoma or posttraumatic cyst of soft tissues; we propose instead the term ancient hematoma. The reason for the commonly very long delay between the initiating trauma and presentation is uncertain.

Adult↗

Mesenteric vasculitis associated with Sézary syndrome.

A 71 year old lady with Sézary syndrome presented with chronic diarrhoea and cramping abdominal pains. A small bowel meal x ray examination showed two mid-ileal strictures. At laparotomy the small intestine was found to be sub-acutely obstructed and resection of a 15 cm ileal stricture and stricturoplasty of a second, 10 cm stricture were performed. Histological examination of the stricture revealed a mesenteric vasculitis with secondary ischaemic changes in the small bowel wall. Mesenteric vasculitis causing small bowel stricture may be associated with Sézary syndrome.

Aged↗

Surgical resection of primary soft-tissue sarcoma. Incidence of residual tumour in 95 patients needing re-excision after local resection.

We reviewed retrospectively 236 consecutive patients seen in our soft-tissue sarcoma clinic. Of these, 95 had had a primary soft-tissue sarcoma excised elsewhere, but with histologically inadequate resection margins. All these patients had a secondary and wider re-excision. The tissues removed at the secondary re-excision were examined histologically for the presence of residual tumour. Definite tumour tissue was found in 29 of 55 lower-limb specimens, 16 of 25 upper-limb, 7 of 10 trunk and 4 of 5 head and neck specimens. In 31 cases some residual tumour was visible macroscopically, and in 56 of the 95 patients (59%) the primary tumour had been incompletely excised. Our results indicated that surgical assessment of the adequacy of excision is very inaccurate and that most local recurrences are the consequence of inadequate primary surgery. The large number of patients who had inadequate initial treatment emphasises the need for a co-ordinated multidisciplinary approach to the management of patients with soft-tissue sarcoma.

Adolescent↗

Germinal-center cell proliferation in response to T-independent antigens: a stathmokinetic, morphometric and immunohistochemical study in vivo.

Although the nature of the germinal center reaction during responses to T-dependent antigens has been well documented, much less is known regarding the relationship between germinal centers and T-independent antigens. In this study, germinal-center cell proliferation was determined at specific time points in spleens of C3H/HeN mice following immunization with either the type-1, T-independent antigen dinitrophenol-lipopolysaccharide (DNP-LPS), or the type-2, T-independent antigen DNP-Ficoll. A stathmokinetic technique was employed to assess proliferation in terms of germinal center cell birth rate and morphometry was used to measure actual growth and regression of the germinal center cell population. An estimate of the absolute rate of germinal-center (GC) cell proliferation was derived from these two values. In addition, immunohistochemistry was performed to correlate changes in GC cell proliferation with the presence or absence of antigen within GC. Following immunization with both antigens, there was an initial reduction of proliferation within pre-existing germinal centers which manifested as either GC dissociation (DNP-LPS) or a suppression of birth rates (DNP-Ficoll). This was followed by a period of increased GC cell proliferation in animals immunized with DNP-LPS, but not in those exposed to DNP-Ficoll. GC cell proliferation was then measured in mice treated with cyclosporin A from 1 day before to 2 days after immunization with DNP-LPS. In these animals, the expected increase in GC cell birth rates did not take place. Immunohistochemistry showed that DNP-Ficoll and DNP-LPS were present in GC from 1 day after immunization until the end of the experiment on day 7. Treatment with cyclosporin A did not affect the deposition of DNP-LPS in GC. These results show that only some T-independent antigens are able to stimulate GC cell proliferation, and we propose that this is related to their ability to recruit precursors of GC B cells into the GC reaction. In addition, the results indicate that GC proliferation seen in response to a so-called T-independent antigen is at least partly driven by T cell-derived cytokines.

Animals↗

Regulation of murine germinal centre cell proliferation in vivo: a stathmokinetic study examining the effect of differently timed doses of cyclosporin A.

Although studies have identified factors which affect germinal centre cell proliferation in vitro, their relative contributions in vivo remain largely undetermined. In this study, the proliferative rate of germinal centre cells was measured in sheep red blood cell-immunized C3H/HeN mice exposed to variously timed doses of cyclosporin A. Germinal centre (GC) cell proliferation was measured by a stathmokinetic technique to determine GC cell birth rates at specific time points after immunization. Changes in total GC volume were determined by morphometry in order to assess actual growth and regression of the GC cell population. An estimate of the absolute rate of GC cell proliferation was derived from these two values. Following exposure to antigen, there was an initial inhibition of proliferation within pre-existing germinal centres, followed by a rapid rise, then a sustained phase of increased GC cell proliferation. By comparing the effects of the different cyclosporin A treatment regimes, it was possible to deduce that the initial inhibition of proliferation was mediated by a T-cell-derived cytokine, as was the final sustained phase of the proliferative response. The intervening rise in GC cell proliferation, however, was attributable to a contact-dependent signalling mechanism.

Animals↗

Recent developments in soft tissue tumors.

This article reviews the clinicopathological features of several recently described soft tissue tumours, namely ossifying fibromyxoid tumour, angiomyofibroblastoma, epithelioid angiosarcoma, retiform haemangioendothelioma, intra-abdominal desmoplastic small cell tumour, spindle cell liposarcoma and low grade fibromyxoid sarcoma. Conceptual changes are also discussed. These include the relationship between Ewing's sarcoma and peripheral primitive neuroectodermal tumour, the proposed use of the term atypical lipoma for a subset of well differentiated liposarcomas, and the occurrence at a wide variety of sites of inflammatory myofibroblastic lesions of uncertain biological potential. In addition, advances in the study of soft tissue lesions at the molecular and cytogenetic levels are outlined, with particular emphasis on the recent identification of tumour-specific karyotypic abnormalities in a wide variety of sarcomas.

Humans↗

Low grade fibromyxoid sarcoma: clinicopathological analysis of eleven new cases in support of a distinct entity.

Low grade fibromyxoid sarcoma is a recently recognized, uncommon soft tissue neoplasm with a tendency to develop in deep soft tissue of young adults. Diagnostic criteria have not been well defined and this tumour has not been widely accepted as a distinct entity. Eleven new cases are reported here for which reproducible histological features are described and in which the immunohistochemical profile of the tumour cells is documented for the first time. Ten of the eleven patients were male and the majority were young or middle-aged adults (median age 45 years). All except one of the tumours were situated in deep soft tissue. Lower limb (four cases) and chest wall (three cases) were the commonest primary sites; one case each arose in the groin, buttock, axilla and retroperitoneum. Follow-up (median duration 6 years) was available in nine patients. Six developed local recurrence and in five cases recurrences were multiple. Pulmonary metastasis occurred in one patient. All tumours were characterized by the presence of bland spindle cells, showing a mainly whorled or focally linear arrangement, set in alternating areas with a fibrous or myxoid stroma. Tumour cells were small, spindle to stellate, with poorly defined, palely eosinophilic cytoplasm and hyperchromatic ovoid nuclei. Most tumour cells showed strong staining with antibodies to vimentin, while occasional cells stained positively for actin, desmin and cytokeratin, in keeping with focal myofibroblastic differentiation. Ultrastructural examination in one case revealed features of fibroblasts. Careful consideration of the morphological and immunohistochemical features of these tumours permits a positive diagnosis of low grade fibromyxoid sarcoma and allows its distinction from a number of other benign and malignant soft tissue neoplasms.

Adolescent↗

Increased epidermal cell proliferation in normal human skin in vivo following local administration of interferon-gamma.

Recombinant human interferon-gamma was administered intradermally (10 micrograms in 0.1 ml) to healthy adult human volunteers from day 1 to day 3, and epidermal cell proliferation was measured on whole skin biopsies at day 6. Three independent parameters were assessed, namely, a) epidermal keratin-16 expression, b) keratinocyte proliferating cell nuclear antigen expression, and c) keratinocyte silver nucleolar organizer region counts. Significantly increased scores for each parameter were observed after interferon-gamma injection (P < 0.01 in each case) compared to site-matched controls. Keratin-16 expression was confined to suprabasal epidermis, whereas proliferating cell nuclear antigen and silver nucleolar organizer region counts were particularly elevated in the basal epidermis. Taken together with previous findings, these studies indicate both proinflammatory and growth regulatory roles for interferon-gamma in human skin. These data are likely to be of particular importance to pathophysiological mechanisms of psoriasis and related cutaneous inflammatory diseases.

Adult↗

A comparison of proliferating cell nuclear antigen (PCNA) immunostaining, nucleolar organizer region (AgNOR) staining, and histological grading in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours are lesions in which it is difficult to predict clinical outcome from the histological appearances. Sixty cases were studied using three different methods of assessing aspects of cellular proliferation; these were (i) immunostaining for proliferating cell nuclear antigen (PCNA), (ii) interphase nucleolar organizer region staining (AgNORs), and (iii) a histological grading system based on mitotic counts. Both PCNA immunostaining and AgNOR counts were found to correlate well with histological grading and all three methods independently showed good correlations with survival. This suggests that these proliferation-associated markers may be used as additional features to support histological grading in this relatively uncommon group of tumours.

Antigens, Neoplasm↗

Primary biphasic synovial sarcoma of the orbit.

Synovial sarcoma is one of the most common soft tissue malignancies of adolescents and young adults. Despite its name, it is no longer thought to be histogenetically derived from the synovium. What seems to be the first case of synovial sarcoma to arise in the orbit presented in a 21 year old woman as a slowly enlarging subconjunctival mass. Although this tumour was typically biphasic, the monophasic spindle cell variant arising at this site could easily be confused with less aggressive orbital connective tissue neoplasms.

Adult↗

Nucleolar ultrastructure in low- and high-grade non-Hodgkin's lymphomas.

Transmission electron microscopy was used to study the ultrastructure of nucleoli in seven high- and seven low-grade non-Hodgkin's lymphomas. Nucleoli with a single large fibrillar centre were predominantly seen in the low-grade group, while the majority of nucleoli in high-grade lesions contained several small fibrillar centres of approximately equal size. A third type of nucleolar appearance was identified, with a large central fibrillar centre surrounded by numerous small 'satellite' fibrillar centres. This nucleolar configuration was the least common but was more often seen in low-grade than in high-grade lymphomas. The mean fibrillar centre cross-sectional area was determined for each group and measured 278,800 nm2 for low-grade non-Hodgkin's lymphomas and 62,507 nm2 for high-grade lymphomas (P less than 0.001). These results show that fibrillar centre size and morphology correlates with grade of non-Hodgkin's lymphoma and may reflect differences in ribosomal deoxyribonucleic acid transcription.

Cell Nucleolus↗

Malignant peripheral nerve sheath tumour with annulate lamellae mimicking pleomorphic malignant fibrous histiocytoma.

The nature and nosologic status of malignant fibrous histiocytoma (MFH), or at least its most common pleomorphic variant, are a matter of controversy and it is possible that this entity represents the shared morphologic phenotype of a range of other dedifferentiated neoplasms. An unusual case of malignant peripheral nerve sheath tumour which very closely mimicked pleomorphic MFH is presented. Its true nature was only disclosed by ultrastructural examination. A further interesting and previously unreported feature in tumours of this type was the presence of annulate lamellae in many of the tumour cells. This case adds weight to the assertion that the light microscopic features of pleomorphic MFH may not be specific.

Aged↗

Solitary fibrous tumour arising at unusual sites: analysis of a series.

Solitary fibrous tumours ('pleural fibromas') are well-recognized in the pleura, but their rare occurrence at other sites has only become appreciated in recent years, as a consequence of which extrapleural examples often go unrecognized or misdiagnosed. Eight cases (three peritoneal, two retroperitoneal, two intrapulmonary and one mediastinal) are presented herein. All but one presented in adulthood, and three were asymptomatic chance findings. Size ranged from 0.8 to 26 cm in maximum diameter. To date, none has behaved in an aggressive fashion. Histologically, these lesions are entirely comparable to their pleural counterparts, and accurate diagnosis is largely dependent on appreciation of their potential extrapleural location. Immunohistochemistry in seven cases favoured myofibroblastic/fibroblastic differentiation, in keeping with the putative submesothelial origin of these lesions.

Actins↗