Possible induction of [Met]enkephalin-Arg6-Gly7-Leu8 immunoreactivity in neurons of the rat superior colliculus following eye enucleation

The distribution of [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL)-immunoreactive (-IR) neurons and its modification after enucleation have been investigated in the rat superior colliculus. In normal rats and on the ipsilateral side of monocular-enucleated rats, small sized vertically elongated fusiform-shaped weakly immunostained neurons were dispersed throughout the sublamina of the stratum griseum superficiale (SGS). In bilaterally enucleated rats and on the contralateral side of monocular-enucleated rats, many small strongly immunoreactive MEAGL-containing neurons, projecting processes horizontally or obliquely toward the surface, appeared in the deepest part of the SGS and the superficial part of the stratum opticum (SO), in contrast to the disappearance of the fusiform-shaped weakly stained neurons in the SGS. MEAGL-IR fibers increased in density throughout the sublamina of the SGS, being densest in the deep SGS, accompanying their increase in the neighboring SO. Sporadically found MEAGL-IR neurons in the deep SO and the stratum griseum intermediale did not show the detectable change of immunoreactivity. These results indicate that enkephalin biosynthesis is undergone by different type of neurons in the normal and the ocular-derived superior colliculus, and suggest that some neurons in the adult superior colliculus have a potentiality to express the peptidergic phenotype.     

Possible involvement of keratinocyte growth factor and its receptor in enhanced epithelial-cell proliferation and acquired recurrence of middle-ear cholesteatoma

Middle-ear cholesteatoma is characterized by enhanced proliferation of epithelial cells and granular tissue formation. However, the molecular mechanism underlying these pathological changes is largely unknown. Keratinocyte growth factor (KGF) is a mesenchymal cell-derived paracrine growth factor that specifically stimulates epithelial cell proliferation. In the present study, we investigated the possible involvement of KGF and its receptor, KGFR, in the pathogenesis of cholesteatoma using in situ hybridization and immunohistochemistry, respectively. We examined 56 cholesteatoma specimens, and 8 normal skin areas as control. KGF and KGFR expression was examined by immunohistochemistry using rabbit anti-human KGF and anti-human KGFR polyclonal antisera raised in our laboratories against synthetic peptides corresponding to parts of human KGF and KGFR, respectively. KGF protein and mRNA were detected exclusively in stromal fibroblasts and infiltrating T lymphocytes in 80% of cholesteatoma cases, whereas KGFR protein and mRNA were localized in the epithelium in 72% of cases. Assessment of the proliferative activity of cholesteatoma using the labeling index for Ki-67 showed a significantly higher Ki-67 labeling index (66%) in KGF+/KGFR+ cases than other cases. There was a significant correlation between KGF+/KGFR+ expression and recurrence. Our results indicate the possible involvement of both KGF and KGFR in enhanced epithelial cell proliferative activity and recurrence of cholesteatoma.     

A human vitelline component in embryonal carcinoma of the testis

The correlation between increased serum alpha-fetoprotein (AFP) and a human vitelline component of 5 testicular embryonal carcinomas (1 was one histological type, 4 were more than one histological type) with no histological features specific for yolk sac tumor (YST) or endodermal sinus tumor (EST) was presented. In all 5 cases, distinct cells simulating the human yolk sac endodermal cell (HYSEC) with eosinophilic-granular or clear-vacuolated cytoplasm were found. These cells contained PAS positive, diastase resistant eosinophilic hyaline globules (EHG) which were positive for AFP. In the embryoid body, the same cells with positive AFP as the HYSEC were also seen. Electron microscopic investigation of these cells revealed basement membrane-like materials which were observed in organoid structure of YST. Positive AFP in these cells showed no binding to Concanavalin A (Con A), which was similar to AFP in YST. It was suggested that testicular embryonal carcinoma with higher serum AFP showing no histological features specific for YST had a vitelline component simulating the HYSEC and produced an increased serum AFP. Immunohistochemical staining for AFP of embryonal carcinoma with higher serum AFP is useful for detecting a human vitelline component and is important to guess the survival for the patient.     

Pineal malignant rhabdoid tumor with chondroid formation in an adult

A pineal tumour in a 27-year-old male is presented with the characteristic histological features of a pineal malignant rhabdoid tumor (MRT) with chondroid formation. Occasionally, tumor cells contained a single well-demarcated hyaline globular inclusion within the cytoplasm adjacent to the nucleus. The stroma of these tumors tends to be densely hyalinized and become chondroid. Immunohistochemical staining was positive for vimentin, epithelial membrane antigen, chromogranin A, synaptophysin, neuron-specific enolase, S-100 protein, and muscle actin. Despite surgery and radiochemotherapy, the tumor recurred in the pineal region and metastasized to the lower lobe of right lung. The patient died 2 years after the initial diagnosis. This is the second published case of central nervous system-MRT appearing in an adult. The clinical and pathological features of pineal MRT in this patient are presented.     

A HUMAN VITELLINE COMPONENT IN EMBRYONAL CARCINOMA OF THE TESTIS

The correlation between increased serum alpha-fetoprotein (AFP) and a human vitelline component of 5 testicular embryonal carcinomas (1 was one histological type, 4 were more than one histological type) with no histological features specific for yolk sac tumor (YST) or endodermal sinus tumor (EST) was presented. In all 5 cases, distinct cells simulating the human yolk sac endodermal cell (HYSEC) with eosinophilic-granular or clear-vacuolated cytoplasm were found. These cells contained PAS positive, diastase resistant eosinophilic hyaline globules (EHG) which were positive for AFP. In the embryoid body, the same cells with positive AFP as the HYSEC were also seen. Electron microscopic investigation of these cells revealed basement membrane-like materials which were observed in organoid structure of YST. Positive AFP in these cells showed no binding to Concanavalin A (Con A), which was similar to AFP in YST. It was suggested that testicular embryonal carcinoma with higher serum AFP showing no histological features specific for YST had a vitelline component simulating the HYSEC and produced an increased serum AFP. Immunohistochemical staining for AFP of embryonal carcinoma with higher serum AFP is useful for detecting a human vitelline component and is important to guess the survival for the patient.     

Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine tracheomalacia: a preliminary report

We investigated whether saber sheath-type tracheomalacia could be treated by the slow release of bone morphogenetic protein (BMP)-2 from a gelatin sponge. A 1 cm gap was made in the middle portion of each of 10 consecutive tracheal cartilage rings in the canine cervix (control group, n = 3), then a gelatin sponge containing 12 microg of BMP-2 solution was implanted in the gap (12 microg group, n = 3). In another group (120 microg + P group, n = 3), the implanted gelatin sponge contained 120 microg of BMP-2 solution, and the gap was covered with periosteum. All of the control dogs developed saber sheath-type tracheomalacia, whereas tracheomalacia was not observed in the 12 microg and 120 microg + P groups. In the 12 microg group, fibrous cartilage was observed at the ends of the cartilage stumps. In the 120 microg + P group, newly formed bone and cartilage were observed to form a bridge between the cartilage stumps. The regeneration of cartilage or bone induced by the slow release of BMP-2 from a gelatin sponge might be useful for treatment of tracheomalacia.     

Mechanical properties of dilated human ascending aorta

Dilation of the ascending aorta, associated with Marfan Syndrome, bicuspid aortic valve, or advanced age, may lead to aortic dissection and rupture. Mathematical models can be used to assess the relative importance of increased wall stresses and decreased strength in these mechanical failures. To obtain needed inputs for such models, mechanical properties of dilated human ascending aorta were measured in vitro. Specimens for opening angle, biaxial elastic, and uniaxial circumferential strength tests were cut from excised tissue obtained from 54 patients (age 18–81 years) undergoing elective aortic graft replacement surgery. Opening angle was significantly greater in patients older than 50 years (262°±76°, n=21) compared to younger patients (202°±70°, n=13 All biaxial elastic specimens n=40 exhibited nonlinear stress-strain behavior. Rapid increases in circumferential and axial stresses occurred at lower strains in the older patient group than in the younger. Mean strength was significantly lower in older patients (1.35±0.37 MPa, n=14) than younger (2.04 ± 0.46 MPa, n=11, age <50 years). These changes in mechanical properties suggest that age may influence the risk of aortic dissection or rupture of dilated ascending aorta. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8719Hh     

Reduced expression of tissue inhibitor of metalloproteinase (TIMP)-2 in gestational trophoblastic diseases

To elucidate the involvement of type IV collagenases [matrix metalloproteinase (MMP)-2 and MMP-9] and their tissue inhibitors (TIMP-1 and TIMP-2) in the development of gestational trophoblastic disease (GTD), we quantified their levels in hydatidiform mole and choriocarcinoma tissues using specific enzyme-linked immunosorbent assays, and the results were compared with those from normal first trimester placenta. Levels of pro-MMP-2 were increased in hydatidiform mole, and they were further elevated in choriocarcinoma. Levels of pro-MMP-9 in choriocarcinoma and those of TIMP-1 in both hydatidiform mole and choriocarcinoma were also increased. In contrast, TIMP-2 levels were markedly decreased in both hydatidiform mole and choriocarcinoma. Similar results were obtained by the tissue culture of first trimester placenta and hydatidiform mole. Gelatin zymography indicated that the levels of both pro- and activated forms of MMP-2 and MMP-9 were higher in hydatidiform mole and choriocarcinoma. The decreased expression of TIMP-2 in hydatidiform mole and choriocarcinoma was confirmed by Western blot, Northern blot and immunohistochemistry, with the decrease being more pronounced in choriocarcinoma. Taken together, the present study shows that both TIMP-2 mRNA and protein levels are markedly decreased in GTD and the imbalance of MMP-TIMP production, shifted toward greater MMP activity, may be involved in the pathogenesis of GTD.     

High TT virus load as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease

The TT virus (TTV) load was estimated in sera obtained from 237 patients with hepatitis C virus (HCV)-related chronic liver disease including 42 patients with hepatocellular carcinoma (HCC), by real-time detection PCR using primers and a probe derived from the well-conserved untranslated region of the TTV genome, which can detect all known TTV genotypes. Of the 237 patients studied, 18 (8%) were negative for TTV DNA, 87 (37%) had low TTV viremia (1.3 x 10(2)-9.9 x 10(3) copies/ml), and 132 (56%) had high TTV viremia (1.0 x 10(4)-2.1 x 10(6) copies/ml). Various features were compared between the patients with high TTV load (n = 132) and those with no TTV viremia or low viral load (n = 105). High TTV viremia (> or =10(4) copies/ml) was significantly associated with higher age (P < 0.05), past history of blood transfusion (P < 0.001), complication of cirrhosis (P < 0.05) or HCC (P < 0.0005), lower HCV RNA titer (P < 0.05), and lower platelet count (P < 0.01). On multivariate logistic regression analysis, high TTV viral load was a significant risk factor for HCC (P < 0.05), independent from known risk factors such as complication of liver cirrhosis (P < 0.0001) and high age (> or =65 years, P < 0.05), among all 237 patients. Furthermore, high TTV viral load was an independent risk factor for HCC among the 90 cirrhotic patients (P < 0.05). These results suggest that a high TTV viral load is associated independently with the complication of HCC and may have prognostic significance in patients with HCV-related chronic liver disease, although whether high TTV viremia mediates the progression of HCV-related chronic liver disease remains to be defined.     

The inferior supernumerary renal arteries: A classification into three types

Among cases that had multiple renal arteries on one side, an inferior supernumerary renal artery was found in 24/270 cases (ca. 9%) on the right and in 19/270 cases (ca. 7%) on the left, together with the usual renal artery. We have noticed that there are correlations between their levels of origin from the aorta and their positional relation to the ureter and the inferior vena cava (IVC). An inferior supernumerary renal artery (InfRA) of lower origin passes in front of the IVC and behind the ureter. An InfRA of middle origin passes in front of both the IVC and the ureter. An InfRA of upper origin passes behind the IVC and in front of the ureter or renal pelvis. In addition there was a tendency for the lower origin type to have an ureteric branch, while the middle and upper origin types had a gonadal branch. These findings suggest that different derivations lead to the inferior supernumerary renal arteries.