bluuebunny/crossref_metadata_2025 huggingface dataset:
Why classify basal cell carcinomas?
Authors: Rippey
Published: March 2003

Basal cell carcinoma of the skin is the commonest form of cancer in the white population. A simple pathological classification is presented and recommended for general use to aid clinicians in their management of cases. Basal cell carcinoma can be classified as nodular, infiltrative, superficial apparently multifocal and mixed in terms of the histological growth pattern. These patterns can be related to the likelihood of complete excision and, if excision is incomplete, to the frequency of recurrence.
Familial mediterranean fever and acute myocardial infarction secondary to coronary vasculitis
Authors: Serrano R , Martínez M A , Andrés A , Morales J M , Samartin R
Published: March 2003

Aims

We report a case study to elucidate the pathogenesis of polyarteritis nodosa (PAN) type vasculitis, a rare complication of familial mediterranean fever (FMF).

Methods and results

A woman with amyloidosis complicating FMF underwent a cadaveric renal transplantation and 5 years later suffered an acute myocardial infarction secondary to an isolated coronary vasculitis.

Conclusions

The histopathological findings of the vasculitis were not in keeping with PAN. We postulated that the pathogenesis of vasculitis in FMF is different from that of the classic PAN and might be similar to the mechanism of the serosal inflammation.
Immunohistochemical assessment of p170 provides prognostic information in endometrial carcinoma
Authors: Bonatz  , Lüttes  , Hamann  , Mettler  , Jonat  , Parwaresch
Published: March 2003

Aims

To determine the significance of proliferative activity (PA) in endometrial carcinomas, we analysed the expression of cell cycle‐related antigens in routinely processed tissue.

Methods and results

Serial sections of 164 endometrial carcinoma specimens were immunostained with the monoclonal antibodies (MoAb) Ki‐S4 (specificity for p170) and Ki‐S5 (specificity for p320/350). The Ki‐S4 PA (median value 18.3%) and Ki‐S5 PA (median value 25.0%) in endometrial carcinomas showed a significant correlation (r = 0.89, P < 0.001). A significantly lower median value of Ki‐S4 and Ki‐S5 immunoreactivity was ascertained in endometrial carcinomas stage I vs. > I (P < 0.05), in tumours with myometrial invasion ≤ 50% vs. > 50% (P < 0.03), and in grade 1 vs. grade 2 and 3 tumours (P < 0.001). Univariate analysis showed that age, FIGO stage and grade, histopathological subtype, myometrial invasion, Ki‐S4 and Ki‐S5 PA provided prognostic information on the adjusted overall survival, whereas FIGO stage (P = 0.002) and Ki‐S4 PA (P = 0.008) were independent prognosticators for adjusted overall survival in multivariate analysis.

Conclusions

The association with established prognosticators for endometrial carcinomas, and the results of uni‐ and multivariate analysis indicates that the additional evaluation of Ki‐S4 PA is useful for classifying patients into subgroups with low and high risk of relapse which might help individualizing the therapeutic strategy in endometrial cancer patients.
Primary CD30‐positive cutaneous T‐cell lymphomas and lymphomatoid papulosis frequently express cytotoxic proteins
Authors: Boulland  , Wechsler  , Bagot  , Pulford  , Kanavaros  , Gaulard
Published: March 2003

Aims

To analyse the relationship between expression of cytotoxic proteins, histopathology and the CD30 status in primary cutaneous T‐cell disorders, we investigated the expression of TIA‐1, granzyme B and perforin in CD30 negative and CD30 positive cutaneous T‐cell lymphomas (CTCL) and lymphomatoid papulosis (LP).

Methods and results

We studied 26 cases of CTCL and 12 cases of LP for the expression of TIA‐1, granzyme B and perforin which are granule‐associated proteins of cytotoxic lymphocytes involved in the mechanism of apoptosis. We showed that most cases (10/13) of CD30 negative pleomorphic lymphomas expressed cytotoxic proteins only in scattered, apparently reactive lymphocytes, the exception being one CD8+ CTCL and two γδ subcutaneous ‘panniculitis‐like’ T‐cell lymphomas. We also showed that at least one cytotoxic protein was expressed in a proportion of neoplastic cells in 77% (10/13) of CD30+ T‐cell lymphomas (3/4 pleomorphic and 7/9 anaplastic) and in a proportion of atypical cells in 75% (9/12) of LP.

Conclusions

Our findings show a strong correlation between the CD30 phenotype and the expression of cytotoxic proteins in primary CTCL. In addition, these results provide further evidence for an overlap between lymphomatoid papulosis and cutaneous CD30+ pleomorphic and anaplastic lymphomas. These entities, which belong to the spectrum of CD30 positive cutaneous T‐cell lymphoproliferations, appear to be derived from cytotoxic cells.
Malignant angiomyolipoma of the liver: a hitherto unreported variant
Authors: Dalle  , Sciot  , De Vos  , Aerts  , Van Damme  , Desmet  , Roskams
Published: March 2003

Aims

After their original recognition in the kidney, angiomyolipomas (AMLs) have been reported in the liver for more than 20 years. In the kidney, five cases of malignant AML have been reported. We report the first case of malignant hepatic AML.

Methods and results

A 70‐year‐old female patient presented with abdominal discomfort. Clinical examination revealed a palpable liver. CT scan showed a polymorphous hypervascular lesion in the right liver lobe. A biopsy was taken and resulted initially in a differential diagnosis between a hepatocellular carcinoma, a metastatic tumour (possibly of renal origin) and angiomyolipoma (AML). After immunohistochemistry, a hepatic AML was suggested, given the immunoreactivity for HMB45/NKIC‐3. The mass was resected 5 years later because of relapsing abscess formation. Gross examination of the resection specimen showed a focally encapsulated brown mass with focal necrosis. Microscopic examination showed a tumour growing in sheets, separated by sinusoidal‐like vessels. Most of the tumour cells had a large, polygonal, clear cytoplasm, often with eosinophilic condensation around the nucleus. There was prominent vascular invasion. Immunohistochemistry (reactivity for HMB‐45, NKIC‐3, S100 and alpha smooth muscle actin, negativity for cytokeratin and vimentin) and electron microscopy confirmed the diagnosis of monomorphic epithelioid AML with prominent vascular invasion. Seven months after tumour resection, the patient died of recurrent disease.

Conclusions

This case highlights the importance of immunohistochemistry and electron microscopy in diagnosing this type of tumour. Possibly, in the past, malignant AML of the liver has been misdiagnosed as HCC.
A reassessment of primary thyroid lymphoma: high‐grade MALT‐type lymphoma as a distinct subtype of diffuse large B‐cell lymphoma
Authors: Skacel M , Ross C W , Hsi E D
Published: March 2003

Aims

Primary lymphoma of the thyroid gland (PTL) is a relatively rare disease. During an 18‐year period, 53 cases of primary non‐Hodgkin's lymphoma involving this extranodal site were seen at our institutions. The aims of this study were to evaluate the spectrum of PTLs using current lymphoma classification concepts and immunocytochemical markers, determine whether features of MALT‐type lymphoma were evident in PTL, and if there was any clinical significance of such a finding.

Methods and results

The cases were retrospectively studied clinically, histologically and immunohistochemically. The tumours were classified according to the Revised European–American Lymphoma Classification of lymphoid malignancies (REAL classification). Thirty‐eight patients were females, 15 were males and mean age at diagnosis was 66.3 years (range 38–90). Three cases were low‐grade marginal zone lymphomas (low‐grade MALT‐type lymphomas). There were 45 diffuse large B‐cell lymphomas (DLBCL) of which there were 27 DLBCL‐NOS and 18 high‐grade MALT‐type lymphomas. Within the diffuse large B‐cell lymphoma (DLBCL) category, cases were subdivided into those without (DLBCL‐NOS) and those with features of ‘high‐grade’ MALT‐type lymphoma based on presence of a low‐grade component or large cell lymphoepithelial lesions (HG MALT‐type lymphoma). In addition there were three follicle centre lymphomas, one anaplastic large cell lymphoma and one peripheral T‐cell lymphoma. Twenty cases were stage IE, 18 stage IIE, and four stage IV. All patients with low‐grade MALT‐type lymphoma are alive without disease. The 5‐year survivals for DLBCL‐NOS and HG MALT‐type lymphoma were 75% and 25%, respectively. Univariate analysis (log rank) among the DLBCLs showed stage (P < 0.001) and subtype (P = 0.005) were associated with survival. Stage was associated with type of DLBCL, 65% of DLBCL‐NOS being stage IE compared to 20% of HG MALT‐type lymphomas.

Conclusions

We conclude that primary thyroid lymphomas occur most commonly in elderly women and are frequently present in clinical stage IE and IIE. Low‐grade MALT‐type lymphomas are relatively uncommon but appear to have a favourable prognosis. DLBCL is the most common lymphoma and features of MALT can be seen in over one‐third of cases. As a group, HG MALT‐type lymphomas had a worse outcome than DLBCL‐NOS, primarily due to higher clinical stage at diagnosis. These two subtypes of DLBCL appear to be distinct clinical and histological entities.
Distribution of apoptotic cells and expression of apoptosis‐related proteins along the intrahepatic biliary tree in normal and non‐biliary diseased liver
Authors: Harada K , Iwata M , Kono N , Koda W , Shimonishi T , Nakanuma Y
Published: March 2003

Aims

The cell kinetics and homeostasis of biliary epithelial cells may be maintained differently along the biliary tree. In this study, the role of apoptosis in the maintenance and homeostasis of the intrahepatic biliary tree was evaluated.

Methods and results

By counting apoptotic biliary cells and by immunostaining apoptosis‐related proteins in normal liver, fatty liver, and those with acute viral hepatitis, chronic viral hepatitis, and hepatitis virus‐related cirrhosis, it was found that the larger the intrahepatic bile ducts became, the more biliary epithelial cells underwent apoptosis. bcl‐2, an inhibitor of apoptosis, was diffusely expressed in the interlobular bile ducts, but rarely detectable in the large and septal bile ducts. bcl‐XL and mcl‐1, inhibitors of apoptosis, and bax, a promoter of apoptosis, were diffusely expressed along the intrahepatic biliary tree. CD95, a direct inducer of apoptosis, was present in the large and septal bile ducts, but rarely in the interlobular bile ducts.

Conclusion

The ratio of bax to bcl‐2, as well as the expression of CD95 which differed at the interlobular versus large and septal bile ducts, may be responsible for the unique distribution of apoptotic biliary cells and involved in the homeostasis of the intrahepatic biliary tree.
Cutaneous perineurioma: a poorly recognized tumour often misdiagnosed as epithelioid histiocytoma
Authors: Robson A M , Calonje E
Published: March 2003

Aims

Eleven cases of cutaneous perineurioma were studied to further characterize the histological features of this entity.

Methods and results

The histological and immunocytochemical features of 11 cases of cutaneous perineurioma were studied and detailed by two pathologists. Clinical data were obtained from the referring clinician. Seven patients were female and four were male with ages ranging from 19 to 67 years (median 41 years). Six lesions arose on the leg. Macroscopically lesions ranged from 4 mm to 14 mm in maximum diameter (median 7 mm). Diagnostic histological features included a nonencapsulated but sharply demarcated tumour with a dumbbell architecture. The tumour cells were spindle‐shaped with delicate inconspicuous cytoplasm and arranged in sheets, whorls or with a vague fascicular pattern. Epithelioid cells with moderate amounts of eosinophilic cytoplasm were frequently admixed with the spindle cells. One tumour had trabeculae of cells embedded within a dense collagenous stroma as described in sclerosing perineurioma. One case displayed a prominent myxoid stroma. Three further cases contained small foci of fibrosis or myxoid change suggesting a morphological spectrum exists in cutaneous perineurioma. Mitoses were exceptionally rare and necrosis and significant cytonuclear pleomorphism was not found. All tumours were epithelial membrane antigen (EMA) positive. Six cases showed focal positivity for factor XIIIa. Follow‐up ranged from 5 months to 6 years (median 1 years). No tumour recurred or metastasized.

Conclusions

The histological appearance of this tumour is broader than hitherto realized. Several cases in this series were misdiagnosed histologically and cutaneous perineuriomas may be more common than currently appreciated.
Sequential changes in localization of repair‐related proteins (heat shock protein 70, ubiquitin and vascular endothelial growth factor) in the different stages of myocardial infarction
Authors: Ishikawa Y , Akasaka Y , Ishii T , Itoh K , Masuda T , Zhang L , Kiguchi H
Published: March 2003

: The myocardium expresses vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP70), and ubiquitin immediately after the onset of cardiac ischaemia. This study demonstrated the sequential changes in localization of these proteins, in addition to fibronectin and troponin T (TnT), in human hearts with myocardial infarction (MI).

: Myocardial tissues from 40 autopsied MI cases were immunostained with the five antibodies against VEGF, HSP70, ubiquitin, fibronectin and TnT. Fibronectin was recognized only in the cardiomyocytes with infarction. Although TnT, HSP70, ubiquitin and VEGF were detected in the affected myocardium in the early stages, their expression in cardiomyocytes around infarcted foci were more intense. The cardiomyocytes with coagulative myocytolysis were positive for fibronectin, but negative or weakly positive for TnT, HSP70, ubiquitin and VEGF. In contrast, the cardiomyocytes with colliquative myocytolysis were strongly positive for TnT, HSP70, ubiquitin and VEGF, but negative for fibronectin.

: Immunostaining using antibodies to fibronectin, TnT, HSP70, ubiquitin and VEGF is useful for the discrimination between infarcted myocytes and ischaemia‐damaged myocytes in the human heart with MI at autopsy.
Evaluation of DNA topoisomerase IIα expression provides independent prognostic information in non‐Hodgkin's lymphomas
Authors: Korkolopoulou P , Angelopoulou M , Siakantari M , Mitropoulos F , Vassilakopoulos T , Zorzos H , Rassidakis G , Androulaki A , Patsouris E , Kittas C , Davaris P , Pangalis G A
Published: March 2003

In view of the dual role that DNA topoisomerase IIa (TopoIIa) plays as a cell proliferation marker and as a possible indicator of chemosensitivity, we investigated its expression in non‐Hodgkin's lymphomas (NHL) in relation to conventional clinicopathological parameters, cell proliferation (as defined by Ki67 immunoreactivity), response to therapy and patient outcome.

Formalin‐fixed paraffin‐embedded tissues from 153 patients with NHL were immunohistochemically stained for TopoIIα. Patients were followed up until death (n = 63) or for an average of 68 months (median 64 months, n = 90). The percentage of TopoIIα positive cells (TopoIIα LI) increased with grade (P < 0.001), extranodal location (P = 0.05) and Ki67 LI (P = 0.01, r = 0.673). In most cases (58%), Ki67 LI exceeded TopoIIα LI (TopoIIα/Ki67 < 1), especially within the indolent group (P < 0.001). TopoIIαLI, Ki67LI and TopoIIα/Ki67 ratio were all adversely related to overall survival in univariate analysis, though their significance was not maintained after adjustment for grade. In multivariate analysis high TopoIIα/Ki67 ratio and high TopoIIα LI independently predicted shortened overall and post‐relapse survival, respectively. Most importantly, low TopoIIα/Ki67 ratio was the only independent predictor of diminished disease‐free survival. However, there was no relationship between TopoIIα expression and response.

Our results suggest that evaluation of TopoIIα expression and TopoIIα/Ki67 ratio as cell proliferation markers provides independent prognostic information in relation to post‐relapse and overall survival. Furthermore, TopoIIα/Ki67 ratio appears to play a key role in the identification of patients prone to early relapse.
The utility of cytokeratin subsets in distinguishing Barrett's‐related oesophageal adenocarcinoma from gastric adenocarcinoma
Authors: Ormsby A H , Goldblum J R , Rice T W , Richter J E , Gramlich T L
Published: March 2003

Aims: Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barrett's‐related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co‐ordinate CK7 and 20 expression in the distinction of Barrett's‐related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia.

Methods and results: CK7 and 20 immunostaining was performed on randomly selected surgical resection specimens from patients with Barrett's‐related oesophageal adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14) arising in a background of intestinal metaplasia. A CK7+ CK20‐ immunophenotype was demonstrated in 27 of 30 (90%) patients with Barrett's‐related oesophageal adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The sensitivity, specificity and positive predictive value of a CK7+/20– immunophenotype for a diagnosis of Barrett's‐related oesophageal adenocarcinoma was 90%, 79%, and 90%, respectively.

Conclusions: A CK7+/20– tumour immunophenotype is associated with Barrett's‐related oesophageal adenocarcinoma and may be useful in accurate tumour classification, thus facilitating improving epidemiological evaluation of tumours at the oesophagogastric junction.
Lipomembranous fat necrosis in three cases of testicular torsion
Authors: Nistal M , González‐Peramato P , Paniagua R
Published: March 2003

Lipomembranous fat necrosis in three cases of testicular torsion

Aims: To describe for the first time a lesion termed lipomembranous fat necrosis (LFN) in three patients with spermatic cord torsion.

Methods and results: We reviewed 386 testes and their epididymides and spermatic cords which had been removed for testicular infarction. For the three cases showing LFN, a battery of histochemical tests (including periodic acid–Schiff (PAS), orcein, Sudan black and Perls stains) was applied and clinical histories and laboratory data were also investigated. Findings were similar in the three specimens. The testes showed a central group of necrotic seminiferous tubules which were surrounded by granulation tissue consisting of macrophages, multinucleated giant cells, lymphocytes, plasma cells and fibrous connective tissue at the periphery of the lesion. The spermatic cord showed thrombosed veins surrounded by fat necrosis showing cystic cavities which were bounded by wavy hyaline membranes. These stained with Sudan black, PAS (before and after diastase digestion) and orcein and presented yellowish‐green autofluorescence.

Conclusions: Lipomembranous fat necrosis of the spermatic cord is a distinctive entity which seems to be related to spermatic cord torsion and the differential diagnosis of which should be established with regard to the presence of parasites, sclerosing lipogranuloma and granuloma evoked by rupture of a testicular prosthesis.
Cytokeratin expression and epithelial differentiation in Warthin’s tumour and its metaplastic (infarcted) variant
Authors: Schwerer M J , Kraft K , Baczako K , Maier H
Published: March 2003

Cytokeratin expression and epithelial differentiation in Warthin’s tumour and its metaplastic (infarcted) variant

Aims: Warthin’s tumour is characterized by a bilayered columnar epithelium. Transformation into metaplastic (infarcted) Warthin’s tumour includes squamous metaplasia of the epithelium along with regressive changes in the stroma. Misinterpretation of metaplastic Warthin’s tumour for malignancy is a serious diagnostic pitfall. This study assesses the utility of cytokeratin expression in Warthin’s tumour and its metaplastic variant.

Methods and results: Twenty‐six cases of Warthin’s tumour, among them eight metaplastic Warthin’s tumours, were investigated employing immunohistochemistry. Both Warthin’s tumour and its metaplastic variant regularly expressed cytokeratins (CK) 7, 8, 18, and 19. Staining results with antibodies to CK10, 10/13, 1/2/10/11, and 20 were negative in all specimens. Immunoreactivity for CK 5/14 and 17 was restricted to basal cells in Warthin’s tumour, but involved basal as well as surface cells in metaplastic Warthin’s tumour.

Conclusions: Warthin’s tumour and its metaplastic (infarcted) variant both express CK 7, 8, 18, and 19, which are typical for columnar differentiation. Cytokeratins typical of squamous differentiation are absent from Warthin’s tumour and its metaplastic variant, irrespective of the squamous morphology of the epithelium in metaplastic Warthin’s tumour. The expression of CK 5/14 and 17, which are typical of regenerative cells, is restricted to basal cells in Warthin’s tumour, but is expressed also in surface cells in metaplastic Warthin’s tumour.
Adenomatous polyposis coli (APC), β‐catenin, and cadherin are expressed in human bone and cartilage
Authors: Monaghan H , Bubb V J , Sirimujalin R , Millward‐Sadler S J , Salter D M
Published: March 2003

Adenomatous polyposis coli (APC), β‐catenin, and cadherin are expressed in human bone and cartilage

Aims: Members of the cadherin and catenin families are involved in chondrogenesis and catenin gene mutations have been detected in malignant tumours of bone. This study was undertaken to assess in detail expression of cadherin, β‐catenin and the associated tumour suppressor gene product APC in bone and cartilage at different stages of human skeletal maturity and in non‐neoplastic and neoplastic osteoarticular disease.

Methods and results: Immunohistochemical staining of formalin‐fixed paraffin‐embedded normal and osteoarthritic adult articular cartilage, fetal growth plate and a series of tumours of bone and cartilage was undertaken with a panel of antibodies against APC, β‐catenin, and pan‐cadherin. This study demonstrated expression of APC, β‐catenin and cadherin in normal and diseased bone and cartilage. APC was present both in osteoblasts and osteoclasts but not in osteocytes. Although only weak APC staining of occasional growth plate hypertrophic chondrocytes and normal articular chondrocytes was seen, APC staining was increased in osteoarthritic articular cartilage. β‐catenin and pan‐cadherin staining was strongly positive in osteoclasts and osteoblasts, with expression being lost when bone cells differentiated into osteocytes. Expression of APC, β‐catenin and pan‐cadherin in bone tumours was similar to that of non‐neoplastic adult tissues.

Conclusions: These findings suggest previously unrecognized roles for APC in regulation of function of chondrocytes, osteoblasts and osteoclasts and support the view that catenin–cadherin interactions are important in regulation of bone cell activity. Abnormalities of expression or function of these molecules may be important in formation of bone tumours and their clinical behaviour.
Pigmented spindle cell carcinoid tumour of the thymus with ectopic adrenocorticotropic hormone secretion: report of a rare variant and differential diagnosis of mediastinal spindle cell neoplasms
Authors: Kuo T‐t
Published: March 2003

Pigmented spindle cell carcinoid tumour of the thymus with ectopic adrenocorticotropic hormone secretion: report of a rare variant and differential diagnosis of mediastinal spindle cell neoplasms

Aims: A variety of histological variants of thymic carcinoid tumour have been described. A rare case of pigmented spindle cell carcinoid tumour of the thymus is documented and compared with the reported cases of thymic pigmented carcinoid tumour in the literature, with a discussion of the differential diagnosis of spindle cell tumours of the mediastinum.

Methods and results: A thymic tumour with ectopic adrenocorticotropic hormone (ACTH) secretion was resected from a 24‐year‐old man suffering from Cushing's syndrome. Histological, immunohistochemical, and ultrastructural studies revealed an ACTH‐producing spindle cell carcinoid tumour harbouring pigmented melanocytes. Among four thymic pigmented carcinoid tumours reported before, only one was similar to the present case by being also an ACTH‐secreting pigmented spindle cell thymic carcinoid tumour. The clinicopathological features of this tumour distinguish it from a spindle cell thymoma, spindle cell thymic carcinoma, and other mediastinal spindle cell tumours.

Conclusions: This case illustrates an extremely rare variant of thymic carcinoid tumour exhibiting a spindle cell morphology and harbouring pigmented melanocytes. Awareness of this histological variant is important in the differential diagnosis of spindle cell tumours of the mediastinum.
Duodenal wall cysts may be derived from a ductal component of ectopic pancreatic tissue
Authors: Suda K , Takase M , Shiono S , Yamasaki S , Nobukawa B , Kasamaki S , Arakawa A , Suzuki F
Published: March 2003

Aims: To clarify the mechanism of origin of duodenal wall cysts in patients with chronic pancreatitis, developing into duodenal stenosis.

Methods and results: Specimens from 12 pancreatoduodenectomized patients with chronic pancreatitis and 51 controls were studied histopathologically and immunohistochemically. Variously shaped cystic lesions, averaging about 15 mm in diameter, were found in the duodenum in six of the 12 patients with chronic pancreatitis, but were not observed in the controls. Each case had an average of two cysts, which were located mainly in the muscularis propria of the duodenum with or without submucosal or extraduodenal–peripancreatic extensions. The inner part of the cyst wall consisted of a moderate rim of granulation tissue, with both myofibroblasts and smooth muscle proliferation in the tissue surrounding the cyst and the submucosal layer of the duodenum, occasionally accompanied by an epithelial lining. A ductal structure in the muscularis propria of the duodenum, possibly a ductal component of ectopic pancreatic tissue, was found in five of the six cases. Some of these structures showed cystic changes. Three of the six patients had accompanying duodenal stenosis.

Conclusions: Duodenal wall cysts occur mainly in the muscularis propria of the duodenum associated with both myofibroblasts and smooth muscle proliferation, and may result in duodenal stenosis. These cysts may be derived from a ductal component of ectopic pancreatic tissue.
The development and evaluation of the UK national telepathology network
Authors: Bamford W M , Rogers N , Kassam M , Rashbass J , Furness P N
Published: March 2003

Aims:  As technology advances and costs fall, it may be anticipated that soon every histopathologist will expect to be able to exchange electronic images with colleagues. Arguing that the value of a network increases as more people are connected, we sought to install a simple, low‐cost telepathology system into any histopathology laboratory which requested it within the UK.

Methods and results:  We assumed that laboratories had microscopes, computers and internet access. We offered low‐cost video cameras, video input cards, software and training to any histopathology department requesting installation, limited only by resources supplied by the UK government. We also established central servers and a website with ‘help’ files. After 1 year we studied system use and pathologists' opinions by circulating a questionnaire. Installations were completed in 35 laboratories; there are currently 66 registered users of the system, with 16 identified ‘experts’ covering most organ systems. Serious difficulties were caused by institutional firewalls and reluctance of local information technology (IT) staff to make changes to facilitate the installation or to help resolve subsequent network problems. After installation, many of the telepathology systems remain unused. Concerns were expressed about image quality, though mainly by pathologists who had not used the system for diagnostic work. The system remains available, but the level of use is low.

Conclusions:  This project has not achieved its aims. The reasons are complex, but mainly relate to human attitudes. Pathologists with excessive workloads were reluctant to use time to learn new skills which were not directed to reducing workload. IT staff did not perceive the project as part of their routine work. There were also numerous technological problems, but although image quality was cited by many, it was not a complaint of those who actively used the system. These problems have not been encountered by previous projects which involved small groups of committed enthusiasts.
Distal Vβ promoters transcribe novel T‐cell receptor‐β transcripts in early development
Authors: SUTTON  , VU  , WILKINSON
Published: March 2003

The transcriptional activation of germline T‐cell receptor (TCR) and immunoglobulin (Ig) genes has been proposed to promote the rearrangement of these genes. Here we report the identification of distal TCR promoters (PDs), located upstream of the previously characterized promoters in the mouse Vβ5.1 and Vβ8.1 gene segments, that are active in germline TCR genes in fetal thymus and liver in vivo. We also identified an immature T‐cell clone, SL12.4, that expresses both endogenous and transfected PDs in a regulated manner in vitro. We propose that the transcription of these distal promoters in germline TCR genes may be important for inducing TCR gene rearrangements during T‐cell development. Northern blot, RNase protection and reverse transcription–polymerase chain reaction (RT–PCR) analyses demonstrated that PDs are also transcribed from fully rearranged TCR genes in adult thymus, lymph node, and spleen. Although the functional significance of this expression is not known, our sequence analysis of the 5′ leader in PD‐derived Vβ5.1 and Vβ8.1 transcripts revealed the presence of several open reading frames (ORFs) that may encode novel polypeptides or regulate the efficiency of TCRβ translation.
CD8+ T cells inhibit immunoglobulin E synthesis in low responder SJL/J mice
Authors: YANG  , CAO  , MOHAPATRA
Published: March 2003

In an effort to examine the basis for low IgE responsiveness of SJL/J strain mice, we analysed the profiles of cytokines, such as interleukin‐2 (IL‐2), IL‐4 and interferon‐γ (IFN‐γ), in SJL/J and A.SW/SnJ mice following immunization. Splenocytes of ovalbumin (OVA) ‐immunized SJL/J mice, secreted significantly higher levels of IL‐4 and lower levels of IFN‐γ than those of A.SW/SnJ mice. A time–course analysis of cytokine expression in in vitro cultures of spleen cells indicated that the levels of IL‐4 and IL‐2 remained persistently high throughout in the cultures of SJL/J splenocytes as opposed to those of A.SW/SnJ. Depletion of CD4+ T cells in vivo suppressed the production of IL‐2, IL‐4 and IFN‐γ suggesting that CD4 T cells are the producers of most cytokines in both SJL/J and A.SW/SnJ mice. Depletion of CD8+ T cells in vivo not only induced productive ε transcript but also enhanced IgE production in SJL/J mice. Moreover, CD8 depletion in SJL/J mice led to decreased production of IFN‐γ, resulting in a net decrease in the ratio of IFN‐γ to IL‐4. A similar shift in the IFN‐γ/IL‐4 ratio was found in splenocytes of SJL/J mice following irradiation, which is known to enhance IgE synthesis in these mice. Taken together, it is concluded that low IgE responsiveness in SJL/J mice is not due to a defect in IL‐4 production per se. Increased IFN‐γ production by the CD8+ T cells inhibits class switch and suppresses IgE antibody production in SJL/J mice.
Proliferation of CD3+ B220− single‐positive normal T cells was suppressed in B‐cell‐deficient lpr mice
Authors: AKASHI  , NAGAFUCHI  , ANZAI  , KITAMURA  , WANG  , TANIUCHI  , NIHO  , WATANABE
Published: March 2003

It is known that lpr mice develop systemic lymphadenopathy and lupus erythematosus‐like autoimmune disease that are associated with the accumulation of CD4− CD8− (double‐negative; DN) CD3+ B220+ abnormal T cells as well as normal mature CD4+ or CD8+ single‐positive (SP) CD3+ T cells. In order to clarify the role of B cells in the lymphoproliferation and autoimmunity of lpr mice, we created B‐cell‐deficient C57BL/6 (B6) lpr mice (B6lpr/lprμMT/μMT) by crossing B6lpr/lpr mice with B6μMT/μMT mice in which the B‐cell development was arrested at pre‐B stage owing to a targeted disruption of the immunoglobulin μ heavy‐chain gene locus. In the B‐cell‐deficient B6‐lpr mice, both lymphadenopathy and splenomegaly were markedly suppressed. Although the accumulation of both CD3+ B220− SP normal T cells and CD3+ B220+ DN abnormal T cells was inhibited in the B‐cell‐deficient lpr mice, the decrease in numbers of CD3+ B220− SP normal T cells occurred more strikingly than that of the CD3+ B220+ DN abnormal T cells. Glomerulonephritis did not develop in the B‐cell‐deficient lpr mice over 40 weeks. The present results indicate that the B cells thus play a crucial role in the extensive proliferation of normal CD3+ B220− mature SP T cells rather than the accumulation of abnormal DN T cells.
Comparative cytokine gene expression: regulation and release by human mast cells
Authors: MÖLLER  , HENZ  , GRÜTZKAU  , LIPPERT  , ARAGANE  , SCHWARZ  , KRÜGER‐KRASAGAKES
Published: March 2003

Since data on the ability of human mast cells to produce various cytokines are scanty, we examined the mRNA expression, its modulation and the resulting protein expression of a number of well‐characterized cytokines, using semi‐quantitative reverse transcription‐polymerase chain reaction of cell extracts and enzyme‐linked immunosorbent assays for analysis of cell supernatants. One million cells/ml of the human mast cell line HMC‐1 were stimulated with 25 ng/ml phorbol myristate acetate (PMA), 5×10−7 m calcium ionophore A 23187 (ionophore) or both stimuli combined for various time periods. Constitutive expression in unstimulated cells was found for interleukin‐1β (IL‐1β) ‐3, ‐4, ‐8, tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β (TGF‐β). Maximal mRNA up‐regulation was observed by 2–4 hr, with a second peak for TNF‐α at 24 hr. After a 4‐hr stimulation, IL‐13 expression was detectable as well, whereas for IL‐12, only the p35 but not the p40 chain was found, and IL‐2, ‐5, ‐7 and interferon‐γ (IFN‐γ) were not expressed at all. Large quantities of IL‐8, TNF‐α, granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and IL‐3 were secreted time‐dependently over a 72‐hr period, with lower levels of IL‐1β, ‐6, ‐10 and TGF‐β and no detectable IL‐2, ‐4 and IFN‐γ protein. When IL‐6 and IL‐8 expression was compared in more detail, IL‐6 mRNA was found to be up‐regulated only with ionophore but not PMA, whereas both stimuli alone or combined increased IL‐8 mRNA expression. Preincubation with cycloheximide inhibited IL‐6 but not IL‐8 transcription, and incubation of stimulated cells with actinomycin D stabilized IL‐8 and also IL‐6 mRNA. These data suggest a selective regulation of distinct cytokines in human mast cells at the transcriptional and post‐transcriptional levels. Furthermore, the spectrum of cytokines produced by HMC‐1 cells supports the well‐recognized role of mast cells in immediate‐type hypersensitivity reactions as well as their potential colony‐stimulating and tissue‐remodelling abilities.
CD4+ T cells, but not CD8+ T cells, are required for the development of experimental autoimmune gastritis
Authors: DE SILVA  , VAN DRIEL  , LA GRUTA  , TOH  , GLEESON
Published: March 2003

Murine autoimmune gastritis, induced by neonatal thymectomy, is characterized by a mononuclear infiltrate within the gastric mucosa, loss of parietal and zymogenic cells and circulating autoantibodies to the gastric H/K ATPase. The infiltrate contains both CD4+ and CD8+ T cells. Here we have investigated the roles of CD4+ and CD8+ T cells in the development of gastritis by in vivo treatment with depleting rat anti‐CD4 and anti‐CD8 monoclonal antibodies. Depletion of CD4+ T cells decreased the incidence of gastric mononuclear infiltrates from 63% (5/8), observed in normal rat immunoglobulin G (IgG)‐injected mice, to 8% (1/12) and also abolished the production of antigastric autoantibodies. In contrast, depletion of CD8+ T cells did not reduce the incidence of gastritis. The absence of CD8+ T cells in the infiltrate of the stomach of anti‐CD8+‐treated mice was confirmed by immunocytochemistry. These results argue that neonatal thymectomy‐induced autoimmune gastritis is mediated by CD4+ T cells and that CD8+ T cells do not play a significant role in the development of the gastric lesion.
Multiple signals regulate the intracellular trafficking of HLA‐DM in B‐lymphoblastoid cells
Authors: COPIER  , POTTER  , SACKS  , KELLY
Published: March 2003

Peptide loading by major histocompatibility complex (MHC) class II molecules occurs in the endocytic pathway and is critically dependent upon the function of the class II‐related molecule human leucocyte antigen‐DM (HLA‐DM). We have previously shown that a tyrosine‐based lysosomal targeting signal present in the cytoplasmic tail of DMB has the capacity to target HLA‐DM to peptide‐loading compartments in HeLa cells. Here we investigate the importance of this signal in directing HLA‐DM to processing compartments in professional antigen‐presenting cells. We reconstituted a DMB‐negative B‐lymphoblastoid cell line with native or targeting‐deficient DMB and show that in the absence of its tyrosine signal, DMB‐Y230A is as efficient as the wild‐type molecule in inducing MHC class II SDS stable dimer formation; restoring expression of the conformation‐dependent DR3 epitope 16:23; the removal of CLIP; and accessing lysosomal peptide‐loading compartments. By transient transfection in HeLa cells we show that Ii is able to compensate for loss of DMB‐encoded targeting information. These data imply that in cells expressing physiological levels of class II, Ii and DM, there is sufficient association with Ii to direct the majority of DM into the endocytic pathway. Thus MHC class II and HLA‐DM may follow similar intracellular trafficking pathways on route to antigen‐processing compartments.
Imm_unohistochemical investigation of the tissue distribution of mannan‐binding lectin in non‐infected and virus‐infected chickens
Authors: NIELSEN  , JØRGENSEN  , HEDEMAND  , JENSENIUS  , KOCH  , LAURSEN
Published: March 2003

This paper describes the results of imm_uno‐histochemical staining for chicken mannan‐binding lectin (MBL) in formalin‐fixed tissue sections from non‐infected chickens, and from chickens infected with infectious laryngotracheitis virus (ILTV) or infectious bursal disease virus (IBDV). In the non‐infected chickens, MBL was detected in the cytoplasm of a few hepatocytes and in the germinal centres of the caecal tonsils, whereas sections of kidney, heart muscle, spleen, cerebrum, thymus, adrenal gland, bursa of Fabricius, bone marrow and trachea were without staining. In the ILTV‐infected chickens, an intense staining reaction for MBL was detected in the cytoplasm of all hepatocytes and on the surface of, and inside, ILTV‐infected cells. Also in the IBDV‐infected chickens, an intense staining reaction for MBL was detected in the cytoplasm of all hepatocytes. No staining was seen in the follicles of the bursa of Fabricius, but MBL was present in non‐identified cells in the interstitium, and in the cytoplasm of macrophage‐like cells, located peripheral to the ellipsoid of the spleen. These findings indicate the liver as the primary site of MBL synthesis, and points to up‐regulation as a result of the viral infections. The location outside the liver could indicate a role of MBL in the imm_une defence.
Bolus injection of aqueous antigen leads to a high density of T‐cell‐receptor ligand in the spleen, transient T‐cell activation and anergy induction
Authors: SWITZER  , WALLNER  , BRINER  , SUNSHINE  , BOURQUE  , LUQMAN
Published: March 2003

In vivo anergy can be modelled by administration of soluble peptide to T‐cell receptor (TCR) transgenic mice specific for the moth cytochrome c peptide 88–103 (MCCp). Two weeks after initial peptide treatment, T cells were present in normal numbers but were unresponsive to antigen stimulation in vitro. Only bolus injections of peptide, either subcutaneous or intravenous, were effective at inducing tolerance, while slowly released antigen administered via mini‐osmotic pump failed to result in anergy. Examination of T cells soon after bolus peptide administration revealed that anergy induction was preceded by a transient hyperactivation of T cells in vivo. Within 2 hr of peptide treatment, interleukin‐2 was detectable in the plasma of the transgenic mice. Interestingly, only bolus injections of peptide led to high levels of T‐cell activation, while adjuvant emulsified and pump‐administered peptide resulted in very low stimulation in vivo. When the dose of bolus‐injected peptide used for tolerization was titrated, the extent of anergy induction directly correlated with the intensity of early T‐cell activation. Indirect measurements of TCR‐ligand density on the surface of antigen‐presenting cells following peptide administration revealed that aqueous peptide delivered via bolus injection generated a large number of major histocompatibility complex–peptide complexes, while pump‐delivered and adjuvant‐emulsified peptide did not. These data suggest that high levels of TCR ligand are required for in vivo T‐cell hyperactivation and induction of anergy.
T cell‐ and perforin‐dependent depletion of B cells in vivo by staphylococcal enterotoxin A
Authors: SUNDSTEDT  , GRUNDSTRÖM  , DOHLSTEN
Published: March 2003

Bacterial superantigens bind to major histocompatibility complex (MHC) class II and subsequently activate both CD4+ and CD8+ T lymphocytes expressing certain T‐cell receptor (TCR)‐Vβ chains. In response to superantigen exposure these subsets proliferate, produce large amounts of proinflammatory cytokines and in addition CD8+ cytotoxic T lymphocytes (CTL) are induced. Previous studies in vitro have shown that these CTL effectively lyse MHC class II‐expressing cells presenting the proper superantigen. However, it is unknown whether superantigens induce a similar response towards MHC class II+ antigen‐presenting cells in vivo. In this study we demonstrate that administration of repeated injections of the superantigen staphylococcal enterotoxin A (SEA) to TCR‐Vβ3 transgenic mice results in a loss of MHC class II‐expressing cells in the spleen. Analysis of different MHC class II+ subsets revealed a selective depletion of CD19+ B cells, while F4/80+ macrophages increased in number. Depletion of T cells with anti‐CD4 or anti‐CD8 monoclonal antibody indicated that CD8+ T cells were crucial for SEA‐induced cytotoxicity in vivo. Repeated injections of SEA to perforin‐deficient mice resulted in significantly less B‐cell depletion compared with control mice. This suggests that superantigen‐activated CD8+ T cells lyse MHC class II+ antigen‐presenting cells in a perforin‐dependent manner in vivo. It is suggested that this represents a novel bacterial immune escape mechanism, which may particularly impair local humoral immune responses.
Rapid recruitment of macrophages in interleukin‐12‐mediated tumour regression
Authors: HA  , LEE  , KIM  , SHIN  , SUNG
Published: March 2003

In order to study the mechanism of interleukin‐12 (IL‐12) antitumour activity, RH7777 rat hepatoma cells were engineered to express mouse IL‐12 (mIL‐12) (RH7777/mIL‐12) under the tight control of doxycycline (dox). The production of the mIL‐12 protein was regulated by the concentration of dox that was present in the culture medium. RH7777/mIL‐12 cells appeared to have the same tumorigenic activity as did parental RH7777 cells, when subcutaneously injected into syngeneic rat (BUF/N) in the absence of dox. However, the tumorigenicity of RH7777/mIL‐12, but not RH7777, cells were significantly decreased when dox was administrated to the animals. In addition, established tumours of RH7777/mIL‐12 cells gradually disappeared upon the induction of mIL‐12 by dox. To elucidate the kinetic profile of immune cells involved in the mIL‐12‐induced tumour regression, both histological and immunohistochemical analyses were performed 1, 3 and 14 days after the dox treatment on rats bearing tumours that were approximately 0·5 cm in diameter. Tumour‐infiltrating macrophages began to appear at the tumour site one day after dox treatment. As time elapsed, the number of tumour infiltrates including CD4+, CD8+, natural killer (NK) cells and macrophages gradually increased. In particular, CD8+ and NK cells constituted the major population of the tumour‐infiltrated cells. Furthermore, it was found that resting peritoneal macrophages (PM) from rats were chemoattracted in response to mIL‐12. The effects of mIL‐12 on PM chemotaxis were reproducibly observed in concentrations as low as 0·1 ng/ml. These findings suggest that IL‐12 can directly recruit macrophages into tumour sites which, in turn, leads to a broad and intense immunological response against tumour.
Tissue distribution of the guinea‐pig decay‐accelerating factor
Authors: NISHIKAWA  , MATSUO  , TAMAI  , OKADA  , OKADA
Published: March 2003

MCA44 is a monoclonal antibody (mAb) to guinea‐pig decay‐accelerating factor (DAF) and, using this mAb, tissue distribution of guinea‐pig DAF was studied by immunofluorescence. Guinea‐pig DAF was found to be expressed not only on the vascular endothelium but also on different types of cells, such as the tubular epithelium of the kidney, epidermal cells of the skin and synovial lining cells. As there was no significant reduction in staining intensity with MCA44 following treatment with phosphatidylinositol‐specific phospholipase C, many guinea‐pig DAF molecules expressed in these tissues may be of the transmembrane form.
Cytokine gene expression in skin of susceptible guinea‐pig infected with Treponema pallidum
Authors: WICHER  , SCAROZZA  , RAMSINGH  , WICHER
Published: March 2003

Using a semi‐quantitative multiplex reverse transcription–polymerase chain reaction assay, we examined cytokine mRNA expression for interleukin‐1α (IL‐1α), IL‐2, IL‐10, IL‐12p40, tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β (TGF‐β) in skin samples obtained from C4‐deficient (C4D) guinea‐pigs inoculated intradermally with virulent Treponema pallidum (VTP). Controls included unmanipulated animals, guinea‐pigs injected with T. pallidum‐free rabbit inflammatory testicular fluid (ITF) alone, or mixed with heat‐killed organisms (HKTP). The expression of IL‐1α, IL‐12p40, and TNF‐α mRNA [T helper type 1 (Th1)] remained within the normal range in both infected and control animals throughout the experimental period. However, a significant increase (P<0·05) in IL‐10 mRNA (Th2) was found exclusively in the VTP‐inoculated animals from 3 to 30 days post‐infection. Another unique characteristic of the inflammatory response in infected guinea‐pigs was the appearance, between 11 and 30 days post‐inoculation, of a substantial number of eosinophils in addition to infiltrating mononuclear cells. The results showed a local Th2 response which is consistent with an inadequate immune response. This is reflected by the lengthy and incomplete clearance of the pathogen from the local site of entry and the chronic infection of distant organs.