Search PubMed⌕ Search

Biomedical subjects

K Hizawa

Publications and source records attributed to K Hizawa.

At least 73 records · Page 4Linked to original sources

Immunohistochemical localization of activin A and follistatin in human tissues.

We immunohistochemically investigated the localization of activin A and follistatin in various human tissues with specific antibodies to recombinant human (rh-) activin A and rh-follistatin. Specific immunostaining of activin A was detected in Leydig and Sertoli cells of the testis. In the ovary, granulosa cells of mature follicle and luteal cells of the corpus luteum stained for activin A. Immunoreactive activin A was present in somatotrophs of the pituitary gland and insulin-positive B cells of the pancreatic islets. Immunoreactivity for activin A was also found in thyroid follicular cells, adrenocortical cells, neuronal cells of the cerebrum and monocytoid cells in the bone marrow. Follistatin, an activin-binding protein, was immunostained in the same tissues as activin A. These findings indicated that activin A and follistatin are widely distributed in human tissues, suggesting that activin plays important roles as a common regulator in various tissues under the control of co-existing follistatin.

Activins↗

Use of endosonographic evaluation of colorectal tumor depth in determining the appropriateness of endoscopic mucosal resection.

OBJECTIVES: To determine the efficacy with which endoscopic ultrasonography (EUS) is able to differentiate between mucosal and submucosal invasion for application of endoscopic resection. METHODS: We prospectively analyzed 60 patients who were diagnosed with early cancer by conventional EUS with regard to the accuracy of mucosal neoplasia as a function of gender, age, location, size, endoscopic configuration, histological diagnosis, and method of resection. RESULTS: Forty lesions interpreted as mucosal by EUS were shown histologically to include 32 lesions in the mucosa and eight in the submucosa or deeper, whereas 20 tumors interpreted as invasive cancer included six lesions in the mucosa and 14 in the submucosa or deeper. The accuracy of mucosal neoplasia (AMN) detection was 77% (true-positive and true-negative mucosal neoplasias divided by all lesions). Assessment of pure cancers without adenomatous components produced a significantly lower AMN (59%, p = 0.03) than the assessment of pure adenomas (95%) or cancers in adenomas (87%). However, there were no significant differences in the EUS assessment of intramucosal neoplasia as a function of sex, age, endoscopic configuration, size, location, or treatment. CONCLUSIONS: We conclude that conventional EUS interpretation alone cannot determine the appropriate treatment for early colorectal cancer.

Case-Control Studies↗

Primary jejunal malignant mixed tumor in a patient with von Recklinghausen neurofibromatosis.

A rare case of primary jejunal malignant mixed tumor arising in a 49-64-old Japanese male with von Recklinghausen's disease is reported. The patient, who had a past history of partial gastrectomy due to duodenal ulcer, was admitted with a complaint of epigastric pain. Upper gastrointestinal examinations showed a huge polypoid tumor located in the efferent loop of the gastrojejunostomy site. Because the tumor was strongly suggestive of leiomyosarcoma on histological examination of biopsy specimens, laparotomy was performed. The resected tumor measuring 10 X 7 X 7 cm was composed of adenocarcinoma admixed with various sarcomatous components, including rhabdomyosarcoma, osteosarcoma, and other sarcomas. Immunohistochemical analysis also supported this diagnosis. The features of this tumor closely resembled malignant mixed mullerian tumor of heterologous type that develops in female genital organs. It is well known that patients with von Recklinghausen neurofibromatosis have an increased incidence of mesenchymal tumors and malignant neoplasias, and therefore, it seems that there is a possible relationship between the histogenesis of this peculiar tumor and the genetic abnormality in this patient.

Humans↗

Fibrosarcoma of the toe: a destructive lesion of the distal phalanx.

A rare case of well differentiated fibrosarcoma occurring in the left second toe is described in a 12-year-old boy who presented with a destructive lesion that had almost totally destroyed the distal phalanx, except for the epiphysis. Amputated specimens showed microscopic evidence of proliferation of uniform spindle cells arranged in both fascicles and a characteristic herringbone pattern with a small number of mitotic figures. This tumor did not show any specific immunoreactivity except for vimentin and had basic ultrastructural characteristics of fibroblasts and myofibroblasts. The tumor was treated by amputation at the middle phalanx level and had not recurred 3 years later. From the presenting radiographic features, some benign neoplasms and reactive lesions were considered in the differential diagnosis. Only results from the pathologic examination were useful in reaching a correct diagnosis.

Amputation, Surgical↗

Prognostic implication of the p53 protein and Ki-67 antigen immunohistochemistry in malignant fibrous histiocytoma.

BACKGROUND: Mounting evidence indicates that p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an unfavorable prognosis for patients with some types of carcinoma. The prognostic significance of p53 overexpression in malignant fibrous histiocytomas (MFHs) of soft tissue has not yet been elucidated. METHODS: Expressions of p53 protein and Ki-67 antigen in 54 primary MFHs of soft tissue were investigated immunohistochemically and indexed quantitatively by counting the number of immunoreactive nuclei versus the total neoplastic nuclei in the representative fields of each tumor to evaluate their prognostic implications and interrelations with other clinicopathologic parameters. RESULTS: The percentages (labeling indices [LIs]) of p53 and Ki-67-immunoreactive nuclei versus the total neoplastic nuclei were 0.1-93.2% (mean +/- standard deviation [SD], 40.6% +/- 21.8%) and 5.3-90.8% (mean +/- SD, 42.7% +/- 29.4%), respectively. The Ki-67 LI correlated with histologic grade (P = 0.01498), primary tumor size (P = 0.04985), disease free interval (reverse correlation, P = 0.00776), and recurrence and metastasis (P = 0.00360). The p53 LI correlated with primary tumor size (P = 0.00431) but did not show any significant correlation with histologic grade, Ki-67 LI, primary tumor size, disease free interval, or recurrence and metastasis. Other significant correlations included histologic grade and disease free interval (P = 0.00010), primary tumor size and disease free interval (reverse correlation, P = 0.00869), histologic grade and recurrence (P = 0.02714), and primary tumor size and primary tumor location (P = 0.00028). In the grouped survival analysis, patients with recurrence or metastasis or with tumors of larger size (> or = 7 cm), high histologic grade, or higher Ki-67 LI (> or = 25%) had a significantly reduced survival (P < 0.05). The different p53 immunohistochemical expression and the different histologic types did not reflect different cumulative survival (P > 0.05). Regression analysis revealed that the primary tumor size and histologic grade, but not Ki-67 or p53 LIs, were independent statistical variables for prognostication. CONCLUSIONS: These results indicate that (1) primary tumor size and histologic grade are two important prognostic factors, (2) Ki-67 LI should be used in adjunct with other main prognostic factors for patients with MFHs, and (3) nuclear p53 overexpression in MFHs of soft tissue is a comparatively common event that has no prognostic implication.

Adult↗

Endoscopic evaluation of gastric inflammatory fibroid polyp.

Clinical and endoscopic manifestations of 18 gastric inflammatory fibroid polyps (IFP) in 16 patients who underwent endoscopic or surgical removal were retrospectively analyzed. All of the lesions were located within the pyloric antrum, and the sizes varied from 0.8 to 7.0 cm. On endoscopy, six polyps which measured 1.0 cm or less uniformly seemed to be sessile or intramural tumors, whereas four of the nine polyps between 1.1 and 2.0 cm in size were additionally accompanied by a central depression. The remaining three, which measured more than 2.0 cm, showed characteristic polypoid growth with ulcerations. Three polyps more than 1.0 cm in size occasionally prolapsed into the duodenal bulb. Three patients with these prolapsing polyps and two with polyps accompanied by ulcerations experienced abdominal pain, nausea, or severe anemia. Two polyps (11%) were precisely diagnosed as IFP by means of conventional forceps biopsy. Histological examinations revealed that all of the polyps proliferated within the submucosa. Therefore, this type of polyp may be subject to endoscopic removal to enable a precise diagnosis and treatment.

Adult↗

Possible neoplastic transformation within gastric hyperplastic polyp. Application of endoscopic polypectomy.

A total of 263 gastric hyperplastic polyps, which had been removed endoscopically from 202 patients, were clinicopathologically analyzed. Among these polyps, there were nine polyps with neoplastic components (3.4%), corresponding to adenoma in five lesions and mucosal adenocarcinoma in four lesions. Comparing the neoplastic transformed polyps with the pure hyperplastic polyps, there was no significant difference according to age, gender, location, gross appearance, or size. However, the transformed polyps which were located in the lower third of the stomach were larger in size (mean, 20.8 mm) and were more likely to be found among older patients (mean, 75.8 years) than were the pure hyperplastic polyps (mean size and age: 14.5 mm and 61.8 years). These results may indicate the possibility of a different carcinogenesis belonging to gastric hyperplastic polyps by location, and this finding seems to be significant in the application of endoscopic polypectomy.

Adenocarcinoma, Mucinous↗

Differentiation and proliferative activity in benign and malignant cartilage tumors of bone.

To assess the histological grade in benign and malignant cartilage tumors of bone by more objective methods, we examined the differentiation and proliferative activity of tumor cells in six enchondromas, five chondroblastomas, and 13 chondrosarcomas immunohistochemically. A variable number of cells in all tumors showed S-100 protein and vimentin immunoreactivity. In fully differentiated cartilage of enchondromas and low grade chondrosarcomas, tenascin, which is an extracellular matrix glycoprotein, was present in small amounts or absent but was increased at the periphery of tumor lobules and even in the matrix throughout the high grade chondrosarcomas. Higher rate and intensity of proliferating cell nuclear antigen (PCNA) reactivity were found in chondrosarcomas, especially in spindle-shaped cells of high grade tumors, than in enchondromas. The distribution of PCNA-positive cells almost corresponded to the regions with tenascin reactivity. One tumor of high grade chondrosarcoma showed p53 protein immunoreactivity. Aberrant expression of cytokeratin was observed in four chondroblastomas. The expression of desmin was identified in relatively large proportions of enchondromas and chondrosarcomas, regardless of their benign or malignant nature and histological grade. Smooth muscle or muscle-specific actins also were present in a smaller number of tumors. Based on these findings, it is concluded that unusual staining characteristics were present, in addition to those of a chondroblastic nature, in the cartilage tumors of bone. Tenascin and PCNA positivity of various degrees in all chondroblastomas may suggest that they are chondrogenic tumors having a relatively high proliferative activity, albeit their benign clinical course. Proliferative activity of tumor cells in enchondromas and chondrosarcomas correlated well with their histological grade. Tenascin may play a role in promoting tumor cell proliferation of cartilagenous neoplasms and, on the other hand, the alterations of extracellular matrix involving tenascin synthesis seem to be a result of tumor development.

Adolescent↗

Aneurysmal fibrous histiocytoma of the skin. A histological, immunohistochemical, and ultrastructural study.

We present two cases of aneurysmal fibrous histiocytoma of the skin on the lower extremities of a 41-year-old man and a 23-year-old woman. Both the tumors appeared clinically as cutaneous nodules with a recent history of rapid growth and showed microscopically a unique formation of blood-filled tissue spaces and a storiform proliferation of histiocyte-like and fibroblast-like cells in a capillary-rich stroma. Such clinical and histologic features fit the original description of this entity. Immunohistochemically the tumor cells of both cases were immunoreactive for factor XIIIa, Mac 387, and vimentin and gave negative results for factor VIII-related antigen, desmin, actin, and S-100 protein. Ultrastructurally the tumors were composed mainly of siderosome-containing histiocyte-like cells, fibroblast-like cells, and intermediate cells and lacked prominent proliferation of endothelial cells. Thus, the ultrastructural findings agreed with the immunophenotypes expressed by the tumor cells, supporting the fibrohistiocytic origin of this lesion. In view of the recent rapid growth, the presence of hemorrhagic pseudocysts, the extravasation of erythrocytes, and the high vascularity of the present tumors, we emphasize the importance of distinguishing this lesion from angiomatoid fibrous histiocytoma and cutaneous malignancies of mesenchymal origin.

Actins↗

A clinicopathologic study of small flat colorectal carcinoma.

BACKGROUND: Recent studies have noted that small flat carcinomas do exist in the human colon, but their clinicopathologic features have not been fully delineated. METHODS: A clinicopathologic study of 62 flat colorectal carcinomas (FCC) and 80 polypoid colorectal carcinomas (PCC) was performed. FCC were defined for the study as colorectal adenocarcinomas confined to the mucosa or submucosa, macroscopically characterized as slightly elevated, often nearly flat, and sometimes with central shallow depressions. RESULTS: In intramucosal and submucosal invasive carcinomas, the mean size of FCCs was significantly smaller than that of PCCs, (P < 0.001). When compared with PCCs, FCCs were found more often in the proximal colon, less frequently well differentiated, and had fewer adenomatous remnants. In submucosal invasive cases, FCCs showed more frequent deep invasion (67 versus 32%, P < 0.05) and lymphovascular permeation (41% versus 16%, P < 0.05) compared with PCCs. CONCLUSIONS: These results suggest that FCCs are characterized by frequent deep invasion with lymphovascular permeation even when small, and that they may be more prevalent away from the rectosigmoid area.

Adenocarcinoma↗

Preventive effect of immunosuppressive agents against indomethacin-induced small intestinal ulcers in rats.

The mechanism of nonsteroidal antiinflammatory drug-induced intestinal ulcers is not clearly understood. To evaluate whether immunosuppressants have a preventive effect against indomethacin-induced gastrointestinal damage, we investigated the effects of prednisolone, cyclosporin, and the newly developed immunosuppressant FK-506 in intracolonically indomethacin-treated rats: 24 mg/kg of indomethacin, administered intracolonically for two days, caused gastric ulcers and two types of small intestinal ulcers (longitudinal ulcers and scattered small ulcers). Pretreatment with intraperitoneal immunosuppressants reduced the size of gastric ulcers. Both cyclosporin (10 mg/kg) and FK-506 (1 mg/kg, 2 mg/kg) treatments significantly reduced the incidence and the length of the longitudinal ulcers of the small intestine when compared to the vehicle-treated controls, whereas prednisolone (20 mg/kg) did not show any preventive effect. Furthermore, the number of small scattered ulcers of the small intestine was significantly reduced by the high dose of FK-506 (2 mg/kg), but not by cyclosporin or prednisolone. These findings indicate that immunosuppressants have protective and antiinflammatory effects in indomethacin-induced gastroenteropathy, suggesting that cytokines may be important mediators in the pathogenesis of enteropathy induced by nonsteroidal antiinflammatory drugs.

Animals↗

Gastrointestinal manifestations of Cowden's disease. Report of four cases.

Four patients with an established diagnosis of Cowden's disease underwent barium meal study, upper gastrointestinal endoscopy, barium enema examination, and colonoscopy. In three, the esophagus was affected by small protrusions, which were diagnosed as glycogenic acanthosis. Numerous hyperplastic polyps were found in the stomach in three patients, and in one an inflammatory fibroid polyp was also detected. Either lymphangiectasia or lymphoid polyps were found in the duodenum in two patients. In all patients, the colon showed polyps that varied in histology and included adenoma, hamartomatous polyp, and ganglioneurofibroma. In addition, jejunal lymphangiomas were found in one of the three patients in whom the small intestine could be precisely evaluated. These findings suggest that the gastrointestinal involvement in Cowden's disease is characterized by various benign lesions, especially esophageal glycogenic acanthosis, numerous gastric hyperplastic polyps, and multiple hamartomatous polyps in the rectosigmoid colon. Detection of these gastrointestinal manifestations may lead to early diagnosis of this potentially malignant disease.

Adult↗

Gastrointestinal involvement in tuberous sclerosis. Two case reports.

Two patients with tuberous sclerosis had multiple semispherical polyps in the large intestine, predominantly in the rectosigmoid colon. These were hamartomas with an excess of smooth muscle fibers in the stroma. In addition, the 21-year-old man had multiple tiny protrusions in the esophagus and oral fibroepithelial polyps. In the 31-year-old woman, who had pulmonary lymphangiomyomatosis with positive estrogen and progesterone receptors, hamartomatous gastric polyps, colonic leiomyoma, and adenomatous rectal polyps were also identified. Our findings suggest that gastrointestinal polyposis may be one of the phenotypes of tuberous sclerosis complex, possibly linking this disease with other hereditary polyposis syndromes.

Adult↗

Ossifying fibromyxoid tumor of soft parts: a morphological and immunohistochemical study.

A case is presented of ossifying fibromyxoid tumor of soft parts (OFMTSP) which occurred in the left cheek of a 59 year old Chinese woman. Histologically, the tumor was located in the subcutis with a fibrous pseudocapsule that contained discontinuous rims of mature trabecular bone. The tumor cells were small, round to ovoid with a uniform, round nucleus and a pale or slightly eosinophilic cytoplasm. Most of the cells were arranged in a random manner, some in a vague lace-like pattern. Mitotic figures were extremely rare. The stroma appeared fibromyxoid with scattered foci of mucinous lakes. Immunohistochemically, most of the neoplastic cells displayed immunoreactivities for S-100 protein, S-100 protein alpha, vimentin and alpha-smooth muscle actin; many tumor cells were positive for desmin. The tumor also showed stromal immunoreactivity for type IV collagen and was negative for cytokeratins, epithelial membrane antigen, glial fibrillary acidic protein, neurofilaments, muscle-specific actin, Leu-7, myelin-basic protein, osteocalcin and melanoma-specific antigen. The immunophenotypes expressed by the present OFMTSP seem to reflect two lineages of neoplastic cell differentiation, that is of nerve sheath and of smooth muscle; at the present stage, it is premature to diagnose this lesion as either nerve sheath or smooth muscle tumor.

Cheek↗

Mechanism of pain and cytoskeletal properties in angioleiomyomas: an immunohistochemical study.

Angioleiomyoma is a solitary subcutaneous tumor characterized by pain in about half of patients with this tumor, and the pathogenesis of this pain has been a cause of much debate. To clarify the mechanism of pain and cytoskeletal property of tumor cells, 50 angioleiomyomas were studied clinicopathologically and immunohistochemically. The tumors occurred preferentially on the extremities, particularly the lower leg (46%), and the female to male ratio was 1.9:1. They were classified into three histological subtypes: (i) solid (30 cases); (ii) venous (15 cases); and (iii) cavernous (five cases). The pain and/or tenderness were present in 26 out of 49 patients (52%), in which small nerve fibers immunoreactive for S-100 protein and PGP9.5 were identified within the capsule of 20 tumors (77%) and the tumor stroma of 18 (69%), irrespective of the histological subtypes. In 24 patients where the pain was absent or unknown, nerves were observed within the capsule of 19 tumors (79%) and tumor parenchyma of 10 (42%). Many cells in all 50 tumors were positive for alpha-smooth muscle actin, and a relatively large number of cells in many tumors were positive for vimentin, desmin and collagen type IV. Also, cytokeratin (CAM5.2) reactivity was scattered in a few cells of four tumors. From these findings, the peculiar pain of angioleiomyomas could be mediated by the nerve fibers especially located within the tumor parenchyma. Although the expression of intermediate filaments in angioleiomyomas was heterogeneous, the overall cytoskeletal features were of smooth muscle cell differentiation.

Adolescent↗

Effects of diet on experimentally induced intestinal ulcers in rats: morphology and tissue leukotrienes.

The effects of dietary pretreatment on longitudinal ulcers of the intestine induced by indomethacin given intracolonically were investigated in rats. The rats were pretreated with either standard diet or liquid meals. Intracolonic indomethacin (24 mg/kg/day) given for two days produced longitudinal ulcers and small scattered ulcers in the small intestine in the control rats that were receiving standard pelleted formula. Three days pretreatment with one of two types of liquid meals, low residual diet (LRD) or elemental diet (ED), significantly reduced the incidence (3% in ED group and 0% in the LRD group) and the length of the longitudinal ulcers in the small intestine. The caecum was affected in each dietary pretreatment group (67% in controls, 80% in LRD group, and 69% in ED group). Colonic ulcers that were located in a longitudinal fashion were found in 42% of LRD group, while these ulcers were less frequently found in the ED group (13%) and controls (0%). Development of ulcers in the caecum and in the colon of rats in ED and LRD groups was more delayed than that of small intestinal ulcers of control rats. In another experiment, pretreatment by ED significantly increased colonic tissue leukotriene B4 concentration when compared with that of controls. These findings suggest that the site of experimental enteropathy induced by indomethacin given intracolonically can be modified by dietary pretreatment. This animal model can be available for investigating differences in the pathophysiology of enteropathy according to the site of involvement.

Animals↗