Biomedical subjects
S Kondo
Publications and source records attributed to S Kondo.
Case of retroperitoneal dedifferentiated mixed-type liposarcoma: comparison of proliferative activity in specimens from four operations.
In a case of retroperitoneal dedifferentiated mixed-type liposarcoma, a dedifferentiated component was observed in the so-called mixed-type liposarcoma consisting of well-differentiated and myxoid components. The proliferative activity was compared among the different components of the tumor by immunohistochemical study using the proliferating cell nuclear antigen (PCNA) and MIB-1 monoclonal antibodies. The dedifferentiated component showed higher positivity than the well-differentiated and myxoid components, and tumor progression was most advanced in the dedifferentiated component. In the chronological examination of each component, the labeling indices of PCNA and MIB-1 were significantly higher at the third recurrence than in the primary lesion in all types, indicating that the proliferative activity of the tumor cells increased gradually. Considering the surgical treatment of liposarcoma, an extended resection encompassing normal adjacent tissues is required in cases containing the dedifferentiated component in comparison to the cases containing only well-differentiated or myxoid components.
Treatment strategy for mucin-producing intrahepatic cholangiocarcinoma: value of percutaneous transhepatic biliary drainage and cholangioscopy.
Intrahepatic cholangiocarcinomas that secrete macroscopically excessive mucin into the biliary system are rare, and few of the previously reported cases have achieved a curative resection. We defined these tumors as "mucin-producing intrahepatic cholangiocarcinomas" and clarify the optimal preoperative and surgical management for them. Eleven patients with mucin-producing intrahepatic cholangiocarcinomas underwent surgical resection in our department. The clinical, radiologic, surgical, and pathologic findings were studied. The clinical presentation of the 11 patients included repeated abdominal pain, jaundice, and fever. Conventional cholangiographies, such as percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography, could not offer precise information about tumor location and extension because of abundant mucin in the biliary system. Using percutaneous transhepatic biliary drainage (PTBD) and percutaneous transhepatic cholangioscopy (PTCS), we were able to drain the mucin and determine precisely the cancer extension into intrahepatic segmental bile ducts. Based on these findings, various types of liver resection with or without extrahepatic bile duct resection were planned, and 10 patients obtained curative resection. The cumulative 5-year survival rate after curative resection was 78%. In patients with mucin-producing intrahepatic cholangiocarcinoma, PTBD and PTCS are important for evaluating the cancer extension. Rational surgery based on accurate preoperative diagnosis improved the prognosis of patients with this disease.
Macroscopic classification and preoperative diagnosis of intrahepatic cholangiocarcinoma in Japan.
We reviewed the records of 64 patients with resected intrahepatic cholangiocarcinoma (ICC) according to the macroscopic classification proposed by the Liver Cancer Study Group of Japan, in which ICC is classified into three types based on the macroscopic appearance of the cut sur-face of the tumor: mass-forming, periductal-infiltrating, and intraductal growth types. There were 24 patients with the periductal-infiltrating type, 28 with the mass-forming type, and 12 with the intraductal growth type. The mass-forming type essentially showed expansive growth irrespective of hilar invasion. The periductal-infiltrating type of tumor exhibited diffuse infiltration along the portal pedicle, and preoperative planning of the resection procedure was similar to that for primary bile duct carcinoma of the hepatic confluence. Vascular resection and reconstruction was required in some patients with advanced disease. In the intraductal growth type of tumor, precise determination of tumor extent was difficult because of the ambiguity caused by abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Percutaneous transhepatic cholangioscopy provided the most reliable information for designing the operative procedure. The macroscopic classification is useful for preoperative diagnosis of tumor extent and for planning the surgical procedure.
Persistent oxidative stress in human colorectal carcinoma, but not in adenoma.
Few studies have been conducted focusing on a potential role of reactive oxygen species in tumor cell metabolism. Here we studied human colorectal adenocarcinomas and adenomas to determine whether oxidative stress is imposed on cancer cells in vivo and used specific antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE)-modified proteins, and 3-nitro-L-tyrosine (3-NT) to determine whether there is an association between oxidative stress and cellular proliferation. Higher levels of oxidative modifications in DNA and proteins were observed in carcinoma cells, but not in adenoma cells, than in the corresponding nontumorous epithelial cells by immunohistochemistry as well as high-performance liquid chromatography (HPLC)-based 8-OHdG determination. The fraction of proliferating cell nuclear antigen-positive cells was proportionally associated in adenocarcinomas with the staining intensities of 8-OHdG and 3-NT. Furthermore, Western blot analysis of the proteins extracted from carcinoma cells revealed several specific proteins modified by HNE or peroxynitrite. Thus we concluded that colorectal carcinoma, but not adenoma cells, are exposed to more oxidative stress than their corresponding nontumorous epithelial cells, regardless of clinical stage and histology, and further that the oxidative stress in carcinoma cells might stimulate cellular proliferation.
Detecting expression of keratins 8/18 in human HaCaT keratinocytes.
Differences in treatment solution affect the efficiency of keratin extraction in cultured human squamous cell carcinomas, malignant melanomas, and melanocytes. Using an aqueous solution that is excellent for cultured cells, we focused this study on the expression of keratin subunits in the spontaneously immortalized human keratinocyte cell line HaCaT. We extracted several keratin (K) subunits, namely K4, K7, K8, K15, K17, and K18, and ATP synthase alpha-chain, in addition to those previously reported by Boukamp et al. (J Cell Biol 1988;106:761-771) in human HaCaT keratinocytes. In particular, K8 and K18 subunits, which are related to tumorigenesis, may be very important subunits within the specificities of immortalized HaCaT cells. Vimentin, which is frequently co-expressed in cultured epithelial cell lines, was not expressed.
jumonji gene is essential for the neurulation and cardiac development of mouse embryos with a C3H/He background.
The recessive mutant mouse jumonji (jmj), obtained by a gene trap strategy, shows neural tube defects in approximately half of homozygous embryos with a BALB/cA and 129/Ola mixed background, but no neural tube defects with BALB/cA, C57BL/6J, and DBA/2J backgrounds. Here, we show that neural tube and cardiac defects are observed in all embryos with a C3H/HeJ background. In addition, abnormal groove formation and prominent flexure are observed on the neural plate with full penetrance, suggesting that abnormal groove formation leads to neural tube defects. We found morphogenetic abnormalities in the bulbus cordis (future outflow tract and the right ventricle) of homozygous embryo hearts. Moreover, myocytes in the ventricular trabeculae show hyperplasia with cells filling the ventricles. Together with the observation that the jmj gene is expressed in the neural epithelium of the head neural plate and in myocytes in the bulbus cordis and trabeculae, the results show that the jmj gene plays essential roles in the normal development of the neural plate, morphogenesis of bulbus cordis, and proliferation of trabecular myocytes on a C3H/He background.
Zebrafish leopard gene as a component of the putative reaction-diffusion system.
It has been suggested, on a theoretical basis, that a reaction-diffusion (RD) mechanism underlies pigment pattern formation in animals, but as yet, there is no molecular evidence for the putative mechanism. Mutations in the zebrafish gene, leopard, change the pattern from stripes to spots. Interestingly each allele gives a characteristic pattern, which varies in spot size, density and connectivity. That mutations in a single gene can generate such a variety of patterns can be understood using a RD model. All the pattern variations of leopard mutants can be generated in a simulation by changing a parameter value that corresponds to the reaction kinetics in a putative RD system. Substituting an intermediate value of the parameter makes the patterns similar to the heterozygous fish. These results suggest that the leopard gene product is a component of the putative RD mechanism.
A second peak of egg excretion in Strongyloides ratti-infected rats: its origin and biological meaning.
In Strongyloides ratti-infected rats, 2 peaks of egg excretion were observed; a large one with maximum egg production on days 7-8 of infection and a small more inconspicuous one around day 25. The second peak, which had been ignored in most studies, was produced by adults in the caecum and the colon. The adults were larger in length and had more embryonated eggs in the uterus compared with adults in the small intestine at day 25 post-infection. It is suggested that parasitic adults once expelled from the small intestine resettle and recover in the large intestine. Filter paper faecal culture carried out for 9 days at different days post-infection revealed that the total number of infective larvae that developed during the second peak was twice the number that developed during the first peak, despite the fact that total egg output during the second peak was less than one twentieth of the first peak. The results suggest that the small second peak was as important as the first one in the transmission of S. ratti.
Keratin subunit expression in human cultured melanocytes and mouse neural crest cells without formation of filamentous structures.
The synthesis of keratin is considered to occur in epithelial and epidermal cells. Previous studies have not reported on keratin synthesis within melanocytes that derive from neural crest cells. Epithelial and neural crest cells originally develop from ectodermal tissue. We previously reported that the expression of keratin is a universal phenomenon seen in cultured melanoma cell lines, as demonstrated by two-dimensional polyacrylamide gel electrophoresis, western blot, and electron microscopy analyses. To further investigate the specificity of keratin function in melanocytic cells, we first examined the presence of keratin proteins in cultured human melanocytes, and unexpectedly found keratin subunits in melanocytes by the above-mentioned procedures. The keratin (K) subunits were composed of K1, K5, K8, K10, K14, K16, and K18, together with vimentin. Neural crest cells, which contain immature embryonic melanocytes developing from ectoderm, already expressed keratins; however, under electron microscopy, the expressed keratin did not form filamentous structures. Although the ATP synthase alpha-chain, which is expressed universally in cultured epidermal tumor cell lines, was also expressed in cultured melanocytes and neural crest cells, a novel malignant melanoma-related protein (MMRP) was absent in melanocytes and neural crest cells. We concluded that keratin subunits are present in both cells, but do not construct keratin filaments.
The roles of keratinocyte-derived cytokines in the epidermis and their possible responses to UVA-irradiation.
Skin is the largest organ, covering the entire body surface. Keratinocytes (KC) are its major component. The KC, by making keratin protein, function as a protective barrier against exogenous stimuli. As KC have been demonstrated to produce various kinds of cytokines, skin plays an important role in immunologic and inflammatory responses of the body. Cytokines affect other cells and organs, mediating cellular growth and differentiation as well as inflammation and immune reactions. Thus, cytokines maintain the cellular and intercellular homeostasis. Dysregulation and abnormal production of cytokines are detected in various skin diseases. Evidence is accumulating to show the significant contribution of cytokines to the pathogenesis or severity of certain diseases. In this report, the effects of KC-derived cytokines on various components in the skin are briefly summarized. We further demonstrate that ultraviolet (UV) light has a distinct effect on the production and secretion of cytokines from KC, depending upon its wavelength. Although some KC-derived cytokines were induced both by UVA and by UVB, suggesting augmentative effects of UVA on UVB-induced cutaneous responses such as sunburn and suntan, other cytokines, including IL-10 and IL-12, were found to be differentially regulated by UVA and UVB. UVA (less than 20 kJ per m2) was found to induce IL-12 but not IL-10 in normal human KC. Our results suggest an antagonistic effect of UVA against UVB, indicating the contribution of UV irradiation to the balance between Th1 and Th2 cytokines in the in situ skin.
Osteoporosis in a patient with recessive dystrophic epidermolysis bullosa.
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Hepatoid adenocarcinoma of the pancreas.
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Progressive bronchial obstruction associated with toxic epidermal necrolysis.
Toxic epidermal necrolysis (TEN) is an acute life-threatening condition, characterized by erosion of the mucous membranes, extensive detachment of the epidermis, and severe constitutional symptoms. Pulmonary complications of TEN are reported as rare, but are one of the most common causes of death. Our report focuses on an unusual case of toxic epidermal necrolysis which showed multiple bronchial obliteration during the chronic phase of the disease. Biopsied tissue of the obliterated bronchi demonstrated non-specific granulation. To improve the obliterated ventilatory function, we tried to reopen the bronchial obliteration using a balloon catheter under the guidance of fibreoptic bronchoscopy, however rapid restenosis of the bronchi ensued.
Dermatomyositis associated with testicular tumour with elevation of serum lactate dehydrogenase (LDH) isoenzyme-1.
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Integrins and the cytoskeleton: focal adhesion kinase and paxillin.
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Visualization of the interaction between blood vessels and podocytes in the mouse embryonic glomerulus using a barium-infusion method for scanning electron microscopy.
The present study revealed three dimensionally the formation of epithelial cells and vascular capillaries in glomeruli of the kidney of the mouse embryo. Barium sulphate was infused through the umbilical vessel of 16.5-17.5-day embryos and the backscattered electron (BSE) image and the secondary electron (SE) image of the identical area of glomeruli were obtained by scanning electron microscopy (SEM). The BSE images directly showed the vascular structure of the glomerulus, while the SE images showed a developmental process of podocytes from epithelial cells. Podocytes were more closely located to the vascular capillary than other epithelial cells. These findings were compared with those obtained in the resin cast model of glomeruli. Thus, the metal infusion-SEM method described here can trace the process of formation of urine filtration barrier in the mouse embryonic glomerulus.
Identification of an androgen receptor within the uterus of the domestic fowl.
Cytosolic and nuclear fractions of the uterus (shell gland) of the hen's oviduct were found to contain a specific [17alpha-methyl-3H]-methyltrienolone ([3H]R1881; a synthetic androgen) binding component having properties of an androgen receptor; i.e., binding specificity, high affinity, and limited capacity. The value of the equilibrium dissociation constant (Kd) was of the order of 10(-9), and did not differ between laying and nonlaying hens. The maximum binding capacity (Bmax) per gram of tissue of both fractions was greater in laying hens than in nonlaying hens. When 5alpha-dihydrotestosterone was administered exogenously, the Bmax of the cytosolic fraction decreased and that of the nuclear fraction increased without any change in Kd. The specific binding in both fractions was at an increased level from 4 to 11 h before oviposition, suggesting that androgen binding may be related to certain events during an early stage of shell formation in the uterus of laying hens.