Hot water immersion induces an acute cytokine response in cervical spinal cord injury.

PURPOSE: The dysfunctional sympathetic nervous system in individuals with cervical spinal cord injury (CSCI) impairs adrenergic responses and may, therefore, contribute to the blunted post-exercise cytokine response. The purpose of this study was to investigate an alternative way to exercise to induce an acute cytokine response by passive core temperature elevation in CSCI. METHODS: Seven male participants with a motor complete CSCI and 8 male able-bodied controls were immersed for 60 min in water set at a temperature 2 °C above the individuals' resting oesophageal temperature. Blood was collected pre, post, and every hour up to 4 h post-immersion. RESULTS: Hot water immersion resulted in an IL-6 plasma concentration mean increase of 133 ± 144 % in both groups (P = 0.001). On a group level, IL-6 plasma concentrations were 68 ± 38 % higher in CSCI (P = 0.06). In both groups, IL-8 increased by 14 ± 11 % (P = 0.02) and IL-1ra by 18 ± 17 % (P = 0.05). Catecholamine plasma concentrations were significantly reduced in CSCI (P < 0.05) and did not increase following immersion. CONCLUSIONS: Passive elevation of core temperature acutely elevates IL-6, IL-8 and IL-1ra in CSCI despite a blunted adrenergic response, which is in contrast to earlier exercise interventions in CSCI. The present study lays the foundation for future studies to explore water immersion as an alternative to exercise to induce an acute cytokine response in CSCI.

Increase in interleukin-6 immediately after wheelchair basketball games in persons with spinal cord injury: preliminary report.

STUDY DESIGN: Case series. OBJECTIVES: To investigate the effects of wheelchair basketball game on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and blood cell counts in persons with spinal cord injury (SCI). SETTING: The 2009 Mei-shin League of Wheelchair Basketball Games held at Wakayama, Japan. PARTICIPANTS: Five wheelchair basketball players with SCI voluntarily participated in this study. INTERVENTIONS: Blood samples were taken approximately 1 h before the player warm-up for the game and immediately after the game. MAIN OUTCOME MEASURES: IL-6, TNF-α, CRP and blood cell count were measured. RESULTS: Plasma IL-6 level and number of monocytes were significantly increased after the game, compared with pre-game measurements (P<0.05). No changes were observed in other measurements. There was a significant relationship between increased IL-6 levels and accumulated play duration. CONCLUSION: The lack of change in TNF-α and CRP levels suggested that the exercise-induced rise in IL-6 was not related to exercise-induced inflammatory response. Furthermore, the associated increase in the number of monocytes did not correlate with exercise-induced IL-6 changes, negating monocytes as the source of IL-6.

Consistent lack of CD34-positive stromal cells in the stroma of malignant breast lesions.

To examine the distribution of CD34-positive and ASMA-positive stromal cells in various breast lesions, we performed immunohistochemical assays (using a streptavidin-biotin immunoperoxidase technique) of tissue specimens, obtained by excisional biopsy and partial or total mastectomy, from 62 patients with breast lesions. Specimens were obtained from 64 lesions as follows: fibrocystic disease (n=12), intraductal papilloma (n=4), fibroadenoma (n=17), invasive lobular carcinoma (n=6), invasive ductal carcinoma (n=20) and invasive micropapillary carcinoma (n=5). In normal breast tissue (controls), CD34-positive spindle cells were abundant in the intralobular stroma, but no ASMA-positive stromal cells were identified except myoepithelial cells. Small to large numbers of CD34-positive cells were observed in the stroma of 29 of 33 benign diseases. In all invasive carcinomas (lobular, ductal and micropapillary), no CD34-positive stromal cells were observed in the stroma. In the stroma of benign lesions, the number of ASMA-positive stromal cells was various, but the stroma of all invasive breast cancers contained ASMA-positive stromal cells. The present results indicate that disappearance of CD34-positive stromal cells consistently occurs in the stroma of invasive carcinoma of the breast, irrespective of histological type and may be associated with the presence of ASMA-positive stromal cells.

A primary amelanotic melanoma of the vagina, diagnosed by immunohistochemical staining with HMB-45, which recurred as a pigmented melanoma.

Usually, malignant melanoma is readily diagnosed by the presence of melanin granules. Although amelanotic melanoma contains a few melanin granules, it is often difficult to differentiate from non-epithelial malignant tumours. This report describes a case of amelanotic melanoma of the vagina, which was originally suspected to be a non-epithelial malignant tumour, but was subsequently correctly diagnosed by immunohistochemical staining with the HMB-45 antibody and for the S-100 protein. A light grey tumour with superficial ulceration was located in the upper third of the vagina. The patient was treated with irradiation followed by chemotherapy. Subsequently, the tumour disappeared and cytology was negative; thus, she achieved complete remission. However, 20 months after complete remission, the tumour recurred locally: the site had a grossly black appearance, which was pathognomonic for a malignant melanoma. Thus, HMB-45 and S-100 protein immunohistochemistry confirmed the diagnosis of amelanotic melanoma.

Synchronous independent bifocal orthotopic thymomas. A case report.

A case of synchronous multiple thymomas is reported. The patient was an 81-year-old woman with 2 separate thymomas in the anterior mediastinum. A histological study revealed that both thymomas consisted of dense lymphocyte infiltration in the stroma and a small number of polygonal epithelial tumor cells with clear nuclei and distinct nucleoli. Immunohistochemical staining using the antibodies to 2 antigens, bcl-2, and MIB-1 showed identical staining patterns. In spite of these findings, we considered their origin to be synchronous multicentric development rather than intra-thymic metastasis, based on the non-invasive nature of these tumors.

Weber-Christian disease presenting with ocular manifestations.

A Japanese patient with Weber-Christian disease (WCD) presenting with ocular symptoms is reported. Panniculitis in the retrobulbar fat was diagnosed according to the histological findings from biopsy specimens, and improved over a month under steroid administration. Only three patients showing ocular manifestations have previously been reported. Panniculitis was in the late stage and a medium dose of prednisolone was effective in this patient. A biopsy of the orbital fat was useful for diagnosis. However, it is important to recognise that the stage of inflammation varies according to the fat tissue involved by WCD.

[Consideration of the prognostic factors influencing survival after lung metastasectomy of renal cell carcinoma].

From 1989 to 2002, 9 patients with metastatic renal cell carcinoma to lung underwent lung resections for curative removal of metastatic disease in our department. Disease free interval (DFI), number and size of metastases resected (at first metastasectomy), and number of metastasized regional lymph nodes were studied after resection of pulmonary metastases. DFI were 0 to 60 months with mean value of 23 months. At first operation, single metastases accounted for 4 cases and multiple lesions more than 2 metastases accounted for 5 cases with mean value of 2.1. Maximal diameter of metastases was 10 to 50 mm with mean value of 24 mm. Regional lymph nodes metastases were demonstrated only 1 patient in 2 of No. 12 lymph nodes adjacent to metastases. At subsequent relapse, 1 patient had second-stage metastasectomy, 2 patients went on to a third phase. Four patients were lost, 2 are under treatment for newly relapsed lesions, and 3 are now free of metastases. Analysis was performed by Cox proportional hazards model of survival using these factors. Though lacking the statistical significance, only maximal diameter of metastases was prone to have influencing factor on prognosis. Survival was not related to DFI between 0 to 21 months and more than 21 months and numerous lung metastases between single metastasis and with 2 or more. In general, estimated survival rate of these patients according to Kaplan-Meier was 0% at 67 months. Considering the above results, surgical treatment for patients with metastatic renal cell carcinoma to lung should be planned carefully.

High molecular weight caldesmon positive stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions.

AIMS: To investigate the smooth muscle nature of the spindle stromal cells in the capsule of thyroid tumours and tumour-like lesions. METHODS: Immunostaining for high molecular weight caldesmon (HCD), a highly specific marker for smooth muscle differentiation, was performed in 70 primary thyroid tumours and tumour-like lesions (21 hyperplastic nodules, 29 follicular adenomas, five minimally invasive follicular carcinomas, six widely invasive follicular carcinomas, and nine encapsulated papillary carcinomas). RESULTS: HCD positive stromal cells (HCD+ cells) were detected in the capsule of 20 of the 21 hyperplastic nodules, and all of the 29 follicular adenomas and five minimally invasive follicular carcinomas, whereas HCD+ cells were seen in the capsule of only four of the six widely invasive follicular carcinomas and no HCD+ cells were seen in the capsule of the nine encapsulated papillary carcinomas examined. CONCLUSIONS: The presence of HCD+ cells in the capsule is characteristic of thyroid follicular tumours and tumour-like lesions. The stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions are different from those of encapsulated papillary carcinoma.

[The usefulness of induction chemotherapy in cases with tumors showing border-line pathological aspects between thymoma and thymic carcinoma].

We present 2 surgically treated cases with thymoma classified as Masaoka stage III and IV a (type B 3 thymoma), which showed the border-line pathological aspects between the thymoma and thymic carcinoma. Induction chemotherapy [CAV-PVP (cyclophosphamide, adriamycin, vincristine sulfate, etoposide) therapy in one case and ADOC (adriamycin, cisplatin, vincristine sulfate, cyclophosphamide) therapy in another case] preluded their surgical resection resulted in reduction of the tumor's size moderately or severely. After achievement of induction chemotherapy, these tumors were resected with the midsternotomy approach, along with resection of the right upper lobe and the left brachiocephalic vein replacing the expanded pdytetrafluoroethylene (ePTFE) graft following mediastinal lymphnodes dissection in one case and leaving the tumor tissue around the pulmonary trunk in another case. Postoperative irradiation of 40 Gy in one case and 60 Gy in another case were performed in the mediastinal regions. From pathological aspects especially in second case, though the specimen by preoperative needle biopsy stained positive for bcl-2 and strong immunoreactivity (20%) for MIB-1, specimens excised operatively after induction chemotherapy showed negative staining for bcl-2 and little staining (lower than 5%) for MIB-1. This fact indicates that the induction chemotherapy makes the tumor less malignant, in other words, from the face of thymic carcinoma to the face of thymoma. Induction chemotherapy performed for the purpose of reducing the tumor size was very advantage in these 2 cases with type B 3 thymoma.

Intracystic carcinoma of the male breast: report of a case.

We experienced a very rare case of male intracystic breast carcinoma. A 66-year-old man presented at our hospital because of a palpable mass in his right breast. The imaging diagnosis was an intracystic carcinoma with hemorrhagic fluid and two mural nodules. Modified radical mastectomy was performed under general anesthesia. The pathological examination revealed the intracystic papillary carcinoma with foci of microinvasion. The findings of power Doppler ultrasonography and dynamic magnetic resonance imaging were very useful for the differential diagnosis of our case.

Iron deposition in renal biopsy specimens from patients with kidney diseases.

This study was performed to investigate the correlation between clinical parameters and grading of iron deposition in renal biopsy specimens from 102 patients with various kidney diseases. Iron deposition in renal tissues was detected by Berlin blue staining. The extent of iron staining was semiquantitatively graded as negative (Fe(-)), grade 0, or positive (Fe(+)), including faint, grade 1; moderate, grade 2; or severe, grade 3, by light microscopy. Thirty-four of 102 patients (33%) showed positive iron staining. Fe(+) patients had various renal diseases, mainly consisting of 12 patients with immunoglobulin A nephropathy and 5 patients with benign nephrosclerosis. Mean arterial pressure (MAP), serum creatinine (sCr) levels, incidence of hematuria, and urinary N-acetylbeta-D-glucosaminidase (u-NAG) levels in Fe(+) patients were significantly greater than those in Fe(-) patients, and u-NAG levels correlated positively with the extent of iron deposition. Study patients were tentatively divided into two groups according to the extent of iron deposition: group A, patients with grades 2 and 3 staining, and group B, patients with grades 0 and 1 staining. In group A, MAP, sCr level, urinary protein excretion, and the incidence of hematuria were significantly greater than in group B. Our results suggest that the amount of iron deposition in renal tissue may contribute to the progression of chronic renal disease and may be an early and sensitive indicator of renal damage in certain renal diseases.

Salivary duct carcinoma: cytologic characteristics and application of androgen receptor immunostaining for diagnosis.

BACKGROUND: Although there have been several reports of cytologic features for salivary duct carcinoma (SDC), it still can be difficult to diagnose patients with these tumor accurately at the time of fine-needle aspiration (FNA). Review of the literature indicates that, immunohistochemically, SDC expresses androgen receptor (AR) in the majority of patients. The authors investigated the cytologic characteristics and utility of AR immunostaining on cytologic smears for the diagnosis of patients with SDC. METHODS: FNA and imprint smears from four patients with SDC were stained with Papanicolaou and periodic acid-Schiff (PAS). Immunostaining for AR on paraffin sections and imprint smears of SDC was performed, including 51 benign and other malignant salivary gland tumors. RESULTS: The smears were cellular and contained three-dimensional clusters, flat sheets, and scattered epithelial cells with necrotic backgrounds. A cribriform architectural pattern was noted in many of the tumor sheets. The tumor cells were large polygonal, spindle, and round to oval, and had abundant, finely granular, or vacuolated cytoplasm. Intracytoplasmic vacuoles were PAS negative. The nuclei were hyperchromatic, medium to large in size, round to oval in shape, and often had prominent nucleoli. All SDC tumors expressed AR. Two patients with carcinoma in (pleomorphic adenoma) showed a focal, comedo carcinoma pattern in which AR positive nuclei were observed. Other salivary gland tumors were completely negative for AR. CONCLUSIONS: The cytologic features of high-grade adenocarcinoma with a variety of cell morphologies, flat sheets of tumor cells with a cribriform pattern, and necrotic backgrounds are characteristic findings in patients with SDC. Immunostaining for AR on cytologic smears is useful for the diagnosis of these patients.

Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain.

The epidermal growth factor receptor plays crucial roles throughout the development of multicellular organisms, and inappropriate activation of the receptor is associated with neoplastic transformation of many cell types. The receptor is thought to be activated by ligand-induced homodimerisation. Here, however, we show by chemical cross-linking and sucrose density-gradient centrifugation that in the absence of bound ligand the receptor has an ability to form a dimer and exists as a preformed dimer on the cell surface. We also analysed the receptor dimerisation by inserting cysteine residues at strategic positions about the putative alpha-helix axis of the extracellular juxtamembrane region. The mutant receptors spontaneously formed disulphide bridges and transformed NIH3T3 cells in the absence of ligand, depending upon the positions of the cysteine residue inserted. Kinetic analyses of the disulphide bonding indicate that EGF binding induces flexible rotation or twist of the juxtamembrane region of the receptor in the plane parallel with the lipid bilayer. The binding of an ATP competitor to the intracellular domain also induced similar flexible rotation of the juxtamembrane region. All the disulphide-bonded dimers had flexible ligand-binding domains with the same biphasic affinities for EGF as the wild-type. These results demonstrate that ligand binding to the flexible extracellular domains of the receptor dimer induce rotation or twist of the juxtamembrane regions, hence the transmembrane domains, and dissociate the dimeric, inactive form of the intracellular domains. The flexible rotation of the intracellular domains may be necessary for the intrinsic catalytic kinase to become accessible to the multiple tyrosine residues present in the regulatory domain and various substrates, and may be a common property of many cell-surface receptors, such as the insulin receptor.

Malignant phyllodes tumor of the breast with expression of osteonectin and vinculin.

Phyllodes tumor is a very rare neoplasm which accounts for 2.5% of all fibroepithelial lesions of the breast. The mesenchymal component of a malignant phyllodes tumor frequently contains heterologous components. We report a case of malignant phyllodes tumor. The patient was a 40-year-old woman with a lump on the left breast. Histological examination revealed the lump to be a malignant phyllodes tumor with foci of liposarcomatous differentiation. The mesenchymal tumor cells, including those in the liposarcomatous components, were found to express vimentin, osteonectin and vinculin. However, they showed no immunoreaction to CAM 5.2, desmin, alpha-smooth muscle actin (ASMA), neuron-specific enolase (NSE) nor S-100. Ultrastructurally, the mesenchymal tumor cells were found to have abundant cytoplasmic organelles, but there was no evidence showing their differentiation to myofibroblasts. Further studies will be necessary to elucidate the significance of vinculin and osteonectin expression in malignant phyllodes tumor.

[A case of rheumatoid arthritis associated with minimal change nephrotic syndrome].

A 55-year-old Japanese woman has been treated with various kinds of anti-rheumatic drugs under a diagnosis of rheumatoid arthritis(RA) for 18 years of disease duration. She persistently had right elbow joint pain and swelling and X-ray showed bone erosion on humerus. Thus, the synovectomy was performed with typical histopathology of RA on April 1999. On the end of February 2000, she had suddenly fatigue and anasarca with profound proteinuria of nephrotic syndrome. The renal biopsy showed minimal change glomerulopathy and no cellular infiltration in interstitial tissue by light microscopy and partial fusion of foot process by electron microscopy. Renal function was sustained normally. All of anti-rheumatic drugs including D-penicillamine(D-Pc) except NSAID were stopped and she was treated with bed rest, diet therapy, diuretics and albumin infusion without steroid therapy. Edema and proteinuria gradually disappeared. Membranous and amyloid nephropathy in RA patients associated with nephrotic syndrome are found in high incidence in literature. In low incidence, MCNS is associated with NSAID or D-Pc induced nephropathy in RA. In our case, nephrotic syndrome disappeared in 6 weeks without discontinuation of NSAID and application of steroid therapy. Thus, MCNS might be co-incidentally associated with RA.

Pleural effusion cytology in a case of cytophagic histiocytic panniculitis (subcutaneous panniculitic T-cell lymphoma). A case report.

BACKGROUND: Cytophagic histiocytic panniculitis (CHP) presents with subcutaneous panniculitis associated with hemophagocytic syndrome. Many cases of CHP are now being classified as a natural disease progression of subcutaneous panniculitic T-cell lymphoma (SPTL). There have been no cytologic reports dealing with pleural aspirates in cases of CHP or SPTL. CASE: A pleural aspirate obtained from a 19-year-old female revealed lymphoma cells and hemophagocytic histiocytes. A skin biopsy specimen showed the presence of CD8-positive lymphoma cells in fat lobules associated with cytologically benign histiocytes with erythrophagocytosis and lymphophagocytosis. CONCLUSION: Hemophagocytic histiocytes were seen in the pleural effusion from a patient with SPTL.

Vinculin: its possible use as a marker of normal collecting ducts and renal neoplasms with collecting duct system phenotype.

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

[A case of ANCA positive idiopathic crescentic glomerulonephritis initiated with fever and liver dysfunction].

We studied a case of a 63 year old Japanese man who presented in October, 1994 with general fatigue, low grade fever, micro hematuria and leukocytosis, elevated CRP as well as liver dysfunction. A liver biopsy at that time revealed mild cholangiolitis. Six months later he was admitted because of weight loss, protein urea, and renal failure. At that time he was positive for antineutrophil cytoplasmic antibody(ANCA) with perinuclear staining patter(p-ANCA) done by indirect immunofluorescence. He was also positive for anti-myeloperoxidase antibody(MPO-ANCA) done by ELISA. A renal biopsy showed idiopathic crescentic glomerulonephritis with pauci-immune type(ICGN). Despite therapy with steroids and cyclophosphamide, which improved his subjective symptoms, his renal failure accelerated necessitating hemodialysis which he has been on for over four years. In conclusion, this patient has a rare case of ICGN that presented with liver dysfunction similar to autoimmune hepatitis. Since ANCA has been known to be associated with systemic vasculitides as well as chronic inflammatory diseases(e.g. ICGN, microscopic polyarteritis nodosa, ulcerative colitis or autoimmune liver diseases), both the crescent formation in this patient's glomeruli and cholangiolitis in his liver may have shared the common etiology related to ANCA.