Patients with follicular non-Hodgkin's lymphoma (NHL) generally have an indolent clinical course and respond well to standard chemotherapeutic regimens. However, the response duration is rather short. There has been no therapeutic regimen superior to CHOP chemotherapy for aggressive NHL in past 20 years. Novel therapeutic strategies are necessary for these types of B-cell lymphomas which express CD20 antigen on the surface of tumor cells. Chimeric human/mouse anti-CD20 monoclonal antibody, rituximab, has a powerful therapeutic activity with minimal adverse reaction in B-cell lymphoma through complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC) and apoptotic mechanisms. The combination of rituximab and CHOP chemotherapy produced a high response rate (95%) in patients with indolent B-cell NHL and prolonged the progression-free and overall survivals in patients with diffuse large-B-cell lymphoma. Confirmation of CD20 expression of tumor cells is essential to predict the response to rituximab in B-cell lymphoma.
To study the protein expression of sex hormone receptors in relation to failure of the testicular descent (cryptorchidism), cryptorchid rats were obtained with administrating flutamide, an androgen antagonist, to pregnant rats. Immunolocalization of the androgen receptor (AR) and estrogen receptors α (ER α) and β (ERβ) was examined in the gubernaculum and cremaster muscle in cryptorchid rats. Testicular descent was normally completed by 4 weeks of age in rats. In control rat fetuses, AR and ERβ were expressed at high levels in fetal gubernaculum but were downregulated after birth. ERα was undetectable in fetal gubernaculum, but its protein expression was upregulated after birth. Similar results were found in the cremaster muscle. These results suggest that expression of AR, ERα and ERβ is developmentally regulated in the gubernaculum and cremaster muscle during the period of testicular descent. In cryptorchid rats, however, remarkable levels of expression of ERα and ERβ were detected in the gubernaculum at 2 weeks after birth. These strong expressions of ERα and ERβ decreased to control levels at 4 weeks. Immunoexpression of AR in cryptorchid rats after birth was the same level as that of control rats. These results indicate that flutamide significantly affects the expression of ERs, but AR expression less intensely. It is assumed that sex hormone receptors have an important role during the period of testicular descent.
Examination of the mesenteric arteries of experimental hypertensive rats revealed leukocyte adhesion to the endothelium, leukocyte infiltration, deposition of fibrinoid substance in the intima, and severe medial smooth muscle cell injury. After injecting hypertensive rats with nitroblue tetrazolium (NBT), formazan deposits which were reaction product that NBT was reduced by superoxide were observed in the endothelial and medial cells of uninjured arteries. Formazan deposition was observed in neutrophils in the lumen of the injured arteries, neutrophils adhering to their endothelium, and neutrophils that had infiltrated in the intima and media. Marked upregulation copper zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) expression was found in the endothelial cells of the arteries of hypertensive rats. Endothelial expression of inducible nitric oxide synthase (iNOS: NOS II) and endothelial nitric oxide synthase (eNOS: NOS III) was strong in the arteries of normotensive rats and decreased in the injured arteries of hypertensive rats, but slight iNOS upregulation was found in the endothelium of uninjured arteries. Deposition of 4-hydroxy-2-nonenal (4-HNE) was observed in the intima of the injured arteries of hypertensive rats. Conclusion: Hypertensive arterial disease is the result of hypertension-induced oxidative stress produced by neutrophils, endothelial cells, and medial smooth muscle cells as well as enzyme activity release by neutrophils activated by hypertension.
As one of the inlets to the mechanism of oral immunotolerance induced by pollen powder, the absorption of antigenic pollen proteins (PPs) through the healthy intestinal mucosa and their destinations were observed. Immunohistochemical observations of the organs of rats given PPs into the digestive tract revealed that PPs were adhered to the surface of the mucous epithelial cells of jejunum being taken into the cells by pinocytosis and then transferred to the blood capillaries, indicating that the antigenic PPs are absorbed through the normal intestinal epithelium keeping the antigenicity. One hour after the PPs administration the absorbed proteins were found in liver parenchymal cells and kidney convoluted tubules but not in spleen and lymphatic tissues. Three hours after administration the distinct positive reaction of PPs disappeared leaving only faint reaction in some liver parenchymal cells. The findings indicate that intestinal epithelial cells, liver parenchymal cells and or renal tubular cells will be closely related to the development of oral immunotolerance.
Maxillofacial growth and histochemical effects of long-term unilateral chewing caused by unilateral facial paralysis on the masseter muscle were studied in growing rabbits. The sample for this study consisted of a total of 20 young male Polish rabbits. The experimental group was comprised of 15 rabbits, which were subjected to dissection of the right facial nerve on the 21st day after birth, while the remaining 5 animals served as a control. The duration of the experimental period was 6 months. In the experimental group, the rabbits with facial abnormality on the paralyzed right side performed unilateral chewing only on the surgically unmanipulated side. Morphometric analysis showed facial asymmetry, with the maxillofacial region severely atrophied on the side that had undergone surgery. Both 4 weeks and 6 months after the operation, type 1 fibers of the masseter muscle on the denervated side, i.e., the non-chewing side, were significantly fewer in number and smaller than those on the unmanipulated side. However, type 2 fibers did not differ in size between sides. NADH-tetrazolium-reductase (NADH-TR) of the masseter was less reactive on the denervated side, reflecting a lower oxidative capacity. These results indicate that the alteration of the functional activities contributed to selective disuse atrophy of the type 1 fibers and a conversion from type 1 to type 2A fibers on the non-chewing side. In other words, the larger diameter and greater proportion of type 1 fibers of the masseter was indicative of work hypertrophy on the unmanipulated, chewing side. This study reveals that facial nerve dissection changes the maxillofacial growth and the histochemical features of the portion of the masseter muscle innervated by the trigeminal nerve, but not by the facial nerve.
Fiber type distributions, cross-sectional areas (CSAs), and succinate dehydrogenase (SDH) activities of the slow soleus (SOL) muscle and the deep (EDLd) and superficial (EDLs) regions of the fast extensor digitorum longus (EDL) muscle were determined in 10- and 20-week-old male spontaneously hypertensive rats (SHR) and compared with those in age-matched normotensive Wistar-Kyoto rats (WKY). There were no differences in the body weight or the SOL and EDL weight between WKY and SHR at 10 weeks of age, while the body weight and the SOL and EDL weight were lower in SHR than in WKY at 20 weeks of age. A higher percentage of type IIA and type IIC fibers and a lower percentage of type I fibers were observed in SOL of SHR at 10 weeks of age. A higher percentage of type IIB fibers and a lower percentage of type IIA fibers were observed in EDLd and EDLs of SHR at 10 weeks of age. In contrast, there were no differences in the fiber type distribution, except a higher percentage of type IIA fibers and a lower percentage of type I fibers in EDLd of SHR, in SOL, EDLd, or EDLs between WKY and SHR at 20 weeks of age. There were no differences in the CSA, except a smaller CSA of type IIC fibers in SOL of SHR, in SOL, EDLd, or EDLs between WKY and SHR at 10 weeks of age. In contrast, a smaller CSA of type I fibers was observed in SOL of SHR at 20 weeks of age. A smaller CSA of all types of fibers in EDLd and of type IIA fibers in EDLs was observed in SHR at 20 weeks of age. There were no differences in the SDH activity of fibers between WKY and SHR, irrespective of the age and fiber type. It is concluded that age-related differences in the fiber type distribution or CSA are observed in the skeletal muscles between SHR and WKY.
We previously established a seizure-sensitive strain of Mongolian gerbil, MGS/Idr, in which seizure-inducing stimuli often elicit repetitive backward jerks of the ears at the beginning of seizures, and found that unilateral application of (−)-bicuculline methiodide (BMI) to an area of the somatosensory cortex in this strain induced similar, but long-lasting, repetitive movements of the contralateral ear. In the present study, we have extended this observation by using immunohistochemistry to look for areas of the brain in which c-Fos protein, an immediate early gene product, appeared unilaterally following BMI application. At 4 hr after BMI application, the cerebral cortex under the application site showed intense c-Fos immunostaining. In addition, c-Fos immunoreactivity appeared in restricted areas of the ipsilateral thalamus, including the ventroposterior nucleus, posterior nucleus, and reticular nucleus. Control saline-treated gerbils did not show unilateral staining in the corresponding thalamic areas. These areas may form a network with the somatosensory cortex that is involved in the recurrent phenomena, as proposed for other areas of the cerebral cortex.
Tongue carcinoma is one of the most common malignant neoplasms in the oral cavity. To assess the role for angiogenesis in carcinogenesis of tongue carcinoma, we performed qualitative and quantitative analyses of vascular endothelial growth factor (VEGF) and two forms of the specific receptors (VEGFRs), Flt-1 and Flk-1, in rat tongue squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. In situ hybridization and immunohistochemistry revealed the colocalization of VEGF and VEGFRs mRNA signals and protein immunoreactivities, respectively in the cytoplasm of the normal epithelial cells, dysplastic cells, cancer cells, and vascular endothelial cells. Both the labeling indices of VEGF and VEGFRs in immunostained sections and the immunoreactive intensities on immunoblots for VEGF and VEGFRs disclosed a duration-dependent increase along with disease progression. An increase in the VEGF labeling index positively correlated with increases in the Ki-67 labeling index and blood vessel density. The present results suggest that angiogenesis is necessary for carcinogenesis, and that VEGF has relevance to the pathomechanism of tongue carcinoma via paracrine and autocrine mechanisms.
We estimated the proliferative activity of serous and mucous acinar cells in mixed-type salivary glands of sucking Mongolian gerbils, using immunohistochemistry with proliferating cell nuclear antigen (PCNA) and in vivo labeling of S-phase cells with the thymidine analog bromodeoxyuridine (BrdU). In both sublingual and Weber's (postlingual) salivary glands, acinar secretory cells showing immunoreactivity for anti-PCNA and anti-BrdU were restricted to serous-type cells that were also positive for a serous component, lysozyme. Some less-differentiated cells found in the serous demilunes or acini, which were negative for lysozyme, also showed proliferative activity, while mucous-type cells never did. These results suggest that in the histogenesis of the mixed gland endpieces, the serous-type cells include immature, differentiating cells, while the mucous-type cells consist of only mature, well-differentiated cells.