Hypertrophy of the extra-articular tendon of the long head of biceps correlates with the location and size of a rotator cuff tear.

AIMS: The aim of this study was to assess hypertrophy of the extra-articular tendon of the long head of biceps (LHB) in patients with a rotator cuff tear. PATIENTS AND METHODS: The study involved 638 shoulders in 334 patients (175 men, 159 women, mean age 62.6 years; 25 to 81) with unilateral symptomatic rotator cuff tears. The cross-sectional area (CSA) of the LHB tendon in the bicipital groove was measured pre-operatively in both shoulders using ultrasound. There were 154 asymptomatic rotator cuff tears in the contralateral shoulder. Comparisons were made between those with a symptomatic tear, an asymptomatic tear and those with no rotator cuff tear. In the affected shoulders, the CSAs were compared in relation to the location and size of the rotator cuff tear. RESULTS: The mean CSA was 21.0 mm2 (4 to 71) in those with a symptomatic rotator cuff tear, 19.9 mm2 (4 to 75) in those with an asymptomatic rotator cuff tear and 14.1 mm2 (5 to 43) in those with no rotator cuff tear. The mean CSA in patients with both symptomatic and asymptomatic rotator cuff tears was significantly larger than in those with no rotator cuff tear (p < 0.001). In the affected shoulders, there were significant differences between patients with more than a medium sized posterosuperior cuff tear and those with an antero-superior cuff tear. CONCLUSION: Regardless of the symptoms, there was significant hypertrophy of the extra-articular LHB tendon in patients with a rotator cuff tear. The values were significantly related to the size of the tear. Cite this article: Bone Joint J 2017;99-B:806-11.

Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders.

OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

Minimal change oesophagitis: a disease with characteristic differences to erosive oesophagitis.

BACKGROUND: The majority of gastro-oesophageal reflux disease (GERD) seems to be non-erosive reflux disease. Nonerosive reflux disease includes minimal change oesophagitis (whitish or reddish, oedematous change and erosion that is not regarded as mucosal break) and no endoscopic abnormalities. AIM: To investigate the accurate proportion of those with minimal change oesophagitis and to clarify its characteristics. In addition, we evaluated the effect of famotidine (40 mg/day) in those with minimal change. METHODS: Prospective endoscopic assessment was performed for consecutive 606 out-patients. Of the 582 patients suitable for analysis, 347 were non-treated. The latter were divided into those with erosive GERD or minimal change, and their endoscopic findings and characteristics were compared. RESULTS: Among 347 non-treated patients, 88 (25%) had erosive GERD and 249 (72%) had minimal change. Compared with patients who have erosive GERD and those with minimal change, the latter were less likely to have hiatal hernia or bile reflux, but more likely to have gastric atrophy. Symptomatic patients (n = 55) with minimal change oesophagitis were more likely to have hiatal hernia than those who were asymptomatic (n= 194). Most patients preferred taking famotidine on-demand, during a 4-week follow-up period. CONCLUSIONS: Most non-erosive reflux disease can be classified as minimal change oesophagitis, and that have different characteristics from erosive GERD. On-demand famotidine may be a suitable alternative treatment for patients with minimal change disease.

A human case of gnathostomiasis nipponica confirmed indirectly by finding infective larvae in leftover largemouth bass meat.

A human case of creeping eruption due to Gnathostoma nipponicum was confirmed indirectly by finding infective advanced third-stage larvae in leftover largemouth bass meat. This is the first report indicating that the largemouth bass (Micropterus salmoides) serves as a source of G. nipponicum infection in humans.

Interleukin-5 transgenic mice show augmented resistance to Angiostrongylus costaricensis infection.

To determine the possible role of eosinophils in Angiostrongylus costaricensis infection, both interleukin-5 (IL-5) transgenic (Tg) and non-transgenic (non-Tg) C3H/HeN mice were infected with A. costaricensis third-stage larvae. IL-5 Tg mice demonstrated greater resistance than non-Tg mice to A. costaricensis, as shown by lower adult worm recovery, smaller adults, fewer eggs in the intestinal wall and fewer larvae passed in the feces. Both mice showed similar antigen-specific IgA and IgGI antibody responses, although IgA was more prominent than IgG1. Egg deposition and inflammatory responses in the intestinal walls were milder in IL-5 Tg mice than in non-Tg mice. The eggs with developed larvae, deposited in the intestinal walls of IL-5 Tg mice, were surrounded by numerous degranulating eosinophils and sometimes with Splendore-Hoeppli deposits. The data suggest that eosinophils are involved in the resistance of the mouse during primary infection with A. costaricensis.

Eosinophils in the cerebrospinal fluid of mice infected with Angiostrongylus cantonensis are resistant to apoptosis.

Interleukin-5 (IL-5) transgenic mice were used to assess the immunological features of CSF eosinophils from mice infected with Angiostrongylus cantonensis. CSF eosinophils were hypodense by day 14 post infection (p.i.). CSF eosinophils survived longer in vitro than peritoneal eosinophils collected from cadmium sulphate (CdSO(4)) -treated normal IL-5 transgenic mice. Apoptosis was measured by Annexin V binding and the presence of a distinct laddering pattern of DNA fragmentation on agarose electrophoresis. Regardless of the presence or absence of Actinomycin D, CSF eosinophils collected from IL-5 transgenic mice from days 15-36 p.i. exhibited less apoptosis than peritoneal eosinophils collected from uninfected IL-5 transgenic mice. CSF eosinophils collected from A. cantonensis infected C57BL/6 mice at days 15-34 p.i. showed elongation of survival time and less apoptosis during in vitro cultivation. Reduced apoptosis was noted only in CSF eosinophils, but not in peritoneal eosinophils recovered from the same infected IL-5 transgenic mice. CPP32/Caspase 3 activity of cultured peritoneal eosinophils from both infected and uninfected IL-5 transgenic mice was higher than that of cultured CSF eosinophils. Stimulation with A23187 readily induced apoptosis of peritoneal eosinophils, but not CSF eosinophils or peritoneal eosinophils cultured with mouse recombinant IL-5. The latter cells were morphologically identical to hypodense eosinophils. RT-PCR analysis indicated that bcl-2 and bcl-x(L) mRNA expression was higher in CSF eosinophils compared with peritoneal eosinophils and this expression in the latter cells was upregulated after culture with mouse recombinant IL-5. These results suggest that CSF eosinophils, shifting to hypodense status through an accumulation from peripheral blood, are resistant to apoptosis. These changes may explain the long-lasting, helminthotoxic and neurotoxic actions of CSF eosinophils in A. cantonensis infection.

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Infection with the helminth parasite Schistosoma mansoni is associated with a pathogenic granulomatous response to parasite eggs. Multiple cell types constitute the granuloma with eosinophils achieving numerical dominance. We hypothesize that eosinophil dominance is achieved by selective apoptosis in lymphocytes. We report here that lymphocytes from both the spleens and granulomas of S. mansoni-infected mice undergo apoptosis. We also show that granuloma lymphocytes are more susceptible to Fas-FasL-mediated apoptosis than spleen lymphocytes and this apoptosis may be related to antigen concentration. Conversely, eosinophils from the granuloma and spleens of S. mansoni-infected mice are resistant to apoptosis in vivo and are protected in vitro from Fas-FasL-mediated apoptosis by the absence of FasL expression in the presence of Fas expression. Finally, the apoptotic regulatory molecules Bcl-2, Bcl-xL, and Bax, do not appear to play a significant role in the regulation of eosinophil apoptosis in the schistosome granuloma.

Identification of the prelinitis condition in gastric cancer and analysis of TGF-beta, TGF-beta RII and pS2 expression.

In the present study, we performed an immunohistochemical examination of the expression of transforming growth factor-beta (TGF-beta), TGF-beta type II receptor (TGF-beta RII) and a trefoil peptide, pS2, in the several types of gastric cancer. The TGF-beta:TGF-beta RII ratios of IIc-like type and Ménétrier type closely resembled that of linitis type. pS2 was intensely expressed in cytoplasm of the superficial and foveolar epithelium, as well as in scirrhous type gastric cancers which retained the gastric or intestinal phenotype. However, pS2 expression was significantly (p < 0.05) reduced in linitis type gastric cancers (1 of 6; 17%) when compared with other scirrhous types of gastric cancers (13 of 22; 59%). A decrease in the TGF-beta:TGF-beta RII ratios in linitis type, IIc-like type and Ménétrier type gastric cancers may be associated with the fibrosis seen in these types of cancer. Furthermore, reduction of pS2 expression in linitis type gastric cancer may represent a dedifferentiation of the cancer from gastric or intestinal phenotype. Judging by the expression patterns of TGF-beta, TGF-beta RII and pS2, it is possible that IIc-like type and Ménétrier type gastric cancers are precursor lesions of linitis type gastric cancer.

SCID mice show a similar susceptibility to Angiostrongylus cantonensis as do wild-type mice of the C.B-17 strain.

C.B-17-SCID/SCID (SCID) mice infected with Angiostrongylus cantonensis yielded a high percentage of worm recovery and did not show any body weight loss until day 24 postinfection. Unexpectedly, C.B-17-+/+(+/+) mice also produced a similar worm burden containing well-developed worms. This is probably attributable to the observation that +/+ mice failed to induce eosinophilia in cerebrospinal fluid (CSF) despite their production of antigen-specific IgA and IgGI; +/+ mice have defective bone-marrow eosinopoiesis, which in turn results in reduced blood and CSF eosinophilia. Interleukin 5 (IL-5) production in +/+ mice is similar to that in BALB/c and C57BL/6 mice. However, bone-marrow eosinopoiesis in response to IL-5 is markedly suppressed in +/+ mice. This is probably associated with impaired expression of common beta-chain mRNA in bone-marrow cells of +/+ mice, which leads to the failure of bone-marrow eosinopoiesis. Hence, +/+ mice may serve as a useful model for the elucidation of eosinophil production in the mouse and for determination of the relationship between parasite infection and the eosinophil.

[Prognostic factors of hepatocellular carcinoma: analysis by the proportional hazard model].

Five hundred fifty patients hospitalized to our hospital during 1990 to 1999 were studied. Subjects consisted of 413 males and 102 females and mean age was 62.1 years. Association with HBV infection, HCV infection and both infection was 11.1%, 78.4% and 2.5% respectively. According to the criteria based in Liver Cancer Study of Japan, 5 year survival rate in clinical stage I, II, III was 42.3%, 38.8% and 17.5%. Tumor morphology was nodular type in 78.9%, massive type in 9.1% and diffuse type in 10.5% of cases. Portal tumor thrombus and distal metastasis were observed in 19.9% and 6.3% of all cases. The 1-, 3- and 5-year survival rate in patients received any therapy was 80.8%, 44.6% and 28.7%, respectively. Analysis by the proportional hazard model showed that HBV infection, advanced clinical stage, multiple tumors, a tumor diameter in excess of 5 cm and AFP positivity were shown as significant factors on poor prognosis.

Immunolocalisation of PIVKA-II in paraffin-embedded specimens of hepatocellular carcinoma.

AIMS/BACKGROUND: Although serum PIVKA-II has been widely used as a tumor marker for hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II, and detection of tissue PIVKA-II in paraffin-embedded tissue specimens of HCC is also considered difficult. METHODS: Paraffin-embedded HCC tissues obtained at autopsy from 22 patients were subjected to immunohistochemical staining using the antibody MU-3 (Eisai Co., Ltd.) after microwave antigen retrieval. RESULTS: PIVKA-II was mainly detected in the cytoplasm of HCC cells. The intensity of tissue PIVKA-II staining was not correlated with serum PIVKA-II levels or with the histotogical differentiation of HCC. However PIVKA-II staining tended to be more intense in tissue from patients with portal tumor thrombus, distant metastases, or a longer duration of HCC. CONCLUSION: This method of immunohistochemical staining is easy and simple to use and may be helpful for detecting tissue PIVKA-II in paraffin-embedded HCC specimens.

[Positivity rate of TTV-DNA in patients with acute liver injury of undetermined etiology].

To elucidate a role of TTV infection in patients with acute liver injury, TTV-DNA in the sera from 97 patients with acute liver injury of various etiology were determined according to Okamoto's method. Out of 77 patients with acute liver injury of determined etiology, 31 patients(40.3%) showed TTV-DNA positive, and out of 15 patients with acute liver injury of undetermined etiology, 8 patients(53.3%) showed TTV-DNA positive. These results suggested no evident role of TTV in patients with acute liver injury was shown. Further study including genotype and quantitative determination of TTV-DNA and antibody assay is needed.

Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro.

BACKGROUND: Polaprezinc has been shown to exert an anti-oxidant property in a tube experiment, protect gastric mucosa from experimental ulcerations in vivo, and accelerate the healing of gastric ulcer in humans. AIM: To examine a possible protective effect of polaprezinc on oxidant-mediated injury in primary monolayer cultures of rat gastric fundic mucosa. METHODS: Cytotoxicity was quantified by measuring 51Cr release. Whether or not polaprezinc exerts an antioxidant property was investigated by determining the effect of this agent on hydrogen peroxide (H2O2)-induced injury. The effects of polaprezinc on superoxide (O2-. ) generation as well as on ethanol (EtOH)-induced injury were also examined. Generation of O2-. was assessed by the reduction in cytochrome c. RESULTS: H2O2 caused a time- and dose-dependent increase in 51Cr release. The dose-response curve of 51Cr release by H2O2 shifted to the right in the presence of polaprezinc. Polaprezinc, at submillimolar concentrations, prevented H2O2-induced 51Cr release. EtOH also caused a dose-dependent increase in 51Cr release, which was prevented by the addition of polaprezinc. The incubation of cells with EtOH caused an increase in cytochrome c reduction, as the concentrations of EtOH increased. Polaprezinc inhibited EtOH-induced cytochrome c reduction. Protection by polaprezinc was microscopically associated with the prevention of monolayer disruption. CONCLUSIONS: Polaprezinc is antioxidative and directly protects gastric mucosal cells from noxious agents through its antioxidant properties in vitro. This finding may provide the theoretical basis for the usage of an antiulcer drug with antioxidant properties for the treatment of gastric inflammation, such as that induced by ethanol.

Activated eosinophils are the major source of Th2-associated cytokines in the schistosome granuloma.

Eosinophils are a numerically dominant cell population within the schistosome granuloma. These granuloma eosinophils can produce a variety of cytokines, including IL-2, IL-4, IL-5, and IFN-gamma. Therefore, eosinophils may play a key role in the determination of the unique cytokine microenvironment within the granuloma milieu. These studies investigated the potential role of eosinophils in the regulation of granuloma immunopathology. We have characterized spleen- and granuloma-derived eosinophils based on cellular activation and cytokine production during the development of murine schistosomiasis. Based on the criteria of hypodensity and CD69 expression, granuloma eosinophils were highly activated and very homogeneous at 7 and 11 wk postinfection. Splenic eosinophils were also activated at 7 wk postinfection, but were much more heterogeneous than their granuloma counterparts. By 11 wk postinfection, few hypodense splenic eosinophils were observed. Eosinophils represented the majority of cytokine-producing cells in the granuloma and were a dominant source of IL-4. Eosinophils also produced IL-2, IL-5, and IFN-gamma, using the criteria of mRNA in situ hybridization and intracellular cytokine staining by FACS. Granuloma eosinophil activation and cytokine production were greatest at the time of maximum granuloma formation, i.e., 10-12 wk after initial cercarial exposure. Therefore, locally activated eosinophils, not Th2 lymphocytes, produce the majority of Th2 cytokines in the granuloma milieu and may be important determinators of immunopathology in schistosomiasis.

A case of late onset primary hyperoxaluria type I (PH-I) presented with black liver.

A 63-year-old woman who had received hemodialysis therapy since she fell acute on chronic renal failure 4 years ago presented with multiple joint pain. Nephrocalcinosis was not detected by abdominal X-ray when hemodialysis therapy was initiated. Laboratory testing showed azotemia, anemia, hypoproteinemia and mild liver dysfunction but no liver cirrhosis. Biopsied bone tissue demonstrated numerous calcium oxalate crystal depositions. Laparoscopy revealed black liver in macroscopic view. Histological studies showed numerous lipofuscin-like dark brown granules were deposited in hepatocytes. The activity of alanine : glyoxylate aminotransferase (AGT) was less than 0.1 U/g in biopsied patient's liver tissue. Generally, clinical symptoms demonstrated by Japanese primary hyperoxaluria type I (PH-I) patients are milder than those of European patients. Some PH-I patients may successfully avoid urinary tract calcification unless they fall into oliguria by some other causes. The lipofuscin granules are most likely the source of the dark color. Massive deposition of the lipofuscin granules indicated that the duration of the liver metabolic abnormality had lasted for long time. Thus, black liver may be related to a mild form of PH-I.

The schistosome granuloma: characterization of lymphocyte migration, activation, and cytokine production.

Granuloma formation and its regulation are dependent on lymphocytes. Therefore, we compared the characteristics of lymphocytes derived from the spleens and granulomas of Schistosoma mansoni-infected mice during the course of their disease. We examined lymphocyte cell cycle kinetics, migration, expression of activation Ags (CD69 and IL-2R), cytokine production (IL-2, IL-4, IFN-gamma), and apoptosis. Lymphocytes in the G2/M phase of the cell cycle and high levels of lymphocyte intracellular IL-2 were found in the spleen but not in the granuloma. Cell trafficking experiments showed Ag-specific recruitment of schistosomal egg Ag (SEA)-reactive lymphoblasts into granulomas in vivo, as well as recruitment to, residence within, and egress from granulomas in vitro. Granuloma-derived lymphocytes were more highly activated than splenic lymphocytes based on higher levels of CD69 and IL-2R expression. While the granuloma microenvironment was rich in Th2 cytokines, during peak granuloma formation, the lymphocytes per se from the spleen and granuloma did not exhibit a dominant Th1 or Th2 cytokine profile, producing low but similar levels of IL-4 and IFN-gamma. The discrepancy between high IL-2R expression and low levels of IL-2 protein production by granuloma lymphocytes was associated with increased apoptosis in the granuloma compared with the spleen. These findings support the hypothesis that granulomas may play a role in the regulation of systemic pathology in schistosomiasis by adversely affecting the survival of SEA-reactive, immunopathogenic T lymphocytes.