Biomedical subjects

F Hasegawa

Publications and source records attributed to F Hasegawa.

At least 19 recordsLinked to original sources

PubMed2003

Expression of smooth muscle markers in so called malignant fibrous histiocytomas.

AIMS: To obtain further information regarding the frequency and degree of positivity for smooth muscle markers in a large number of malignant fibrous histiocytomas (MFHs), as an aid to accurate diagnosis. METHOD: The immunohistochemical features of 100 MFHs were studied and the results were compared with those for 30 leiomyosarcomas. Eighteen cases of MFH with smooth muscle actin (SMA) positivity were examined ultrastructurally. RESULTS: Immunoreactivity for smooth muscle markers, such as desmin, SMA, muscle specific actin (MSA) and h-caldesmon (HCD), which is a specific marker for smooth muscle cells and their tumours, was found in 28, 30, 29, and 29 of 30 leiomyosarcomas. Immunoreactivity for desmin, SMA, MSA, and HCD was found in 17, 30, 14, and two of the MFHs. On electron microscopic examination, approximately half of the cases contained a varying proportion of myofibroblastic cells. The others had only fibroblastic or undifferentiated tumour cells. At least 30% of the cases were found to display features consistent with limited smooth muscle or myofibroblastic differentiation. CONCLUSION: A large subset of so called MFH in fact shows poorly differentiated smooth muscle or myofibroblastic features, and perhaps such tumours should be regarded as pleomorphic leiomyosarcomas and/or pleomorphic myofibroblastic sarcomas.

Actins↗

PubMed2001

Involvement of poly(ADP-ribose) polymerase in trophoblastic cell differentiation during tumorigenesis.

Poly(ADP-ribose) polymerase (Parp) monitors DNA strand breaks and poly(ADP-ribosyl)ates nuclear proteins using NAD as a substrate. The participation of Parp in DNA damage responses has been demonstrated by recent studies using Parp knockout mice. On the other hand, accumulated evidence has shown that Parp is involved in the regulation of gene expression and cell differentiation. In this study, the role of Parp in tumorigenesis and differentiation was studied with Parp-/- embryonic stem (ES) cells. When Parp+/+, Parp+/-, and Parp-/- ES cells were injected subcutaneously into nude mice, teratocarcinoma-like tumors developed from ES cells. However, only tumors derived from Parp-/- ES cells showed trophoblast giant cells (TGCs) containing single or multiple megalo-nuclei. These TGCs are located in a large blood-lake like hemorrhage. This example suggests that Parp is not essential for tumor formation, however, it is involved in trophoblastic cell differentiation and could consequently affect tumor phenotype.

Animals↗

PubMed2001

Restoration of epithelial cell polarity in a colorectal cancer cell line by suppression of beta-catenin/T-cell factor 4-mediated gene transactivation.

Beta-catenin acts as a transcriptional coactivator by forming a complex with T-cell factor/lymphoid enhancer factor (TCF/LEF) DNA-binding proteins. Aberrant transactivation of a certain set of target genes by beta-catenin and TCF4 complexes has been implicated in familial and sporadic colorectal tumorigenesis. A colorectal cancer cell line, DLD-1, becomes irregularly multilayered, when maintained confluent for 2-3 weeks, and forms numerous dome-like polypoid foci piled-up over the surface of cell sheets. By the use of a strict tetracycline-regulation system, we found that the continuous suppression of beta-catenin/TCF4-mediated gene transactivation by dominant-negative TCF4B (deltaN30) reduced these piled-up foci and restored a simple monolayer of polarized columnar cells resembling normal intestinal epithelium. The restoration of epithelial cell polarity was evident in two ways: (a) the formation of microvilli over the apical surface; and (b) the distribution of a tight junction protein, ZO-1, to the lateral plasma membrane. Retroviral expression of stabilized beta-catenin (deltaN89) induced the formation of similar piled-up foci in untransformed IEC6 intestinal epithelial cells. Sulindac, a nonsteroidal antiinflammatory drug effective against colorectal tumorigenesis in familial adenomatous polyposis syndrome, suppressed the formation of foci. The loss of epithelial cell polarity may be a critical cellular event driving beta-catenin/TCF4-mediated intestinal tumorigenesis.

Adenocarcinoma↗

PubMed2001

Establishment and characterization of three new rat renal cell carcinoma cell lines from N-ethyl-N-hydroxyethylnitrosamine-induced basophilic cell tumors.

Three new rat cell lines (designated as BP13, BP30 and BP36B), derived from rat basophilic-type renal cell carcinomas induced with N-ethyl-N-hydroxyethylnitrosamine, were established and characterized. Passaged up to 100 times in vitro for 3 years, each cell line forms epithelial monolayers with cell cycles for BP13, BP30 and BP36B of 29, 21 and 17 h, respectively. Positive glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltransferase (gamma-GT) activity in their cytoplasm, but negative succinate dehydrogenase (SD) and slightly positive carbonic anhydrase type II (CA) localization indicates an origin from proximal tubules. Ultrastructural examination showed the presence of variable numbers of mitochondria and many microvilli and intracellular junctions on the plasma membrane. BP13 and BP30 were found to be tetraploid and BP36B diploid. BP13 has one marker chromosome 15p+, and BP36B an isochromosome of 1q. Anchorage-independent growth and tumorigenicity in immunosuppressed nude mice of BP13 and BP36B, but not BP30, proved their neoplastic nature. These three cell lines should provide useful tools for studying the biological characteristics of renal cell tumors.

Animals↗

PubMed2001

Steroidal glycosides from the bulbs of Camassia leichtlinii and their cytotoxic activities.

Phytochemical analysis of the bulbs of Camassia leichtlinii (Liliaceae) resulted in the isolation of six new spirostanol saponins, a new furostanol saponin, a cholestane glucoside, and four known steroidal saponins. The structures of the new saponins were determined by detailed analysis of their spectral data, including two-dimensional NMR spectroscopy, and by the results of hydrolytic cleavage. Cytotoxic activities of the isolated compounds against human oral squamous cell carcinoma (HSC-2) cells and normal human gingival fibroblasts (HGF) are also reported.

Carbohydrate Sequence↗

PubMed2000

Dedifferentiated liposarcoma of retroperitoneum and mesentery: varied growth patterns and histological grades--a clinicopathologic study of 32 cases.

The purpose of this study was to obtain further information regarding cellular differentiation and proliferative characteristics of dedifferentiated liposarcoma (DDL) arising in the retroperitoneum and mesentery for accurate diagnosis and prognostic criteria. The patients included 20 men and 12 women, mean age, 60 years (range, 33 to 80 years). Twenty-seven tumors were located in the retroperitoneum and 5 in the mesentery. Tumor size ranged from 9 to 51 cm (mean, 24 cm). Follow-up was available on all patients and ranged from 4 to 243 months (mean, 64 months). Twenty-four (75%) patients developed local recurrences, 3 (9%) had distant metastasis, and 16 (50%) died of the disease. The predominant histology of dedifferentiation (DD) included fibrosarcoma or malignant fibrous histiocytoma (MFH) in 15 (47%), myxofibrosarcoma (myxoid MFH) in 5 (16%), mixed type in 10 (31%), and a whorling pattern in 2 (6%). Divergent differentiation, such as osseous, osteosarcomatous, chondrosarcomatous, and leiomyosarcomatous, was observed in 9 (28%). Immunoreactivity for vimentin, desmin, CD34, neurofilament, alpha-smooth muscle actin, p53, and MDM2 was observed in 32 (100%), 14 (44%), 8 (25%), 13 (41%), 14 (44%), 19 (59%), and 18 (56%) of DD areas, respectively. On the basis of a histological grading using MIB-1 (MIB-1 index range, 3% to 80%; mean, 27%) to replace mitosis counts (1 to 35/10 high-power fields [HPF]; mean, 13/10 HPF), 16 tumors each were classified as low-grade (grade 2) and high-grade (grade 3). The mixed type with poorly differentiated areas including scattered lipoblasts could be mistaken for myxoid liposarcoma but lacked the C/EBP-homologous protein-translocated in liposarcomat (CHOP-TLS) fusion genes specific for myxoid liposarcoma. Period to the first recurrence and histological grade using the MIB-1 index were associated with overall survival. Identification of DD areas, especially a poorly recognized variant of the mixed type, careful follow-up to detect early recurrence, and histological malignancy grading combined with proliferation indices are important in providing an accurate prognosis for all patients with retroperitoneal and mesenteric liposarcoma.

Adult↗

PubMed2000

Primary extracranial meningioma of the foot: a case report.

We present a rare case of primary extracranial meningioma in a 36-year-old man, who had a solitary multinodular mass located in the plantar muscle of the foot. The histology of specimens from simple excision was typical of meningioma, showing bland spindle cell proliferation with a whorl pattern. Immunohistochemical analysis demonstrated that the tumor cells showed diffuse and strong positivity for epithelial membrane antigen as well as moderate reactivity for cytokeratin and vimentin. Ultrastructurally, the tumor cells were characterized by thin bipolar cytoplasmic processes and joined by multiple small desmosomes. There were frequent pinocytotic vesicles and a distinct external lamina on the cell surface. These findings suggest that this primary ectopic meningioma, arising in the soft tissue, may have been derived from perineurial cells of the peripheral nerve, but was morphologically distinguishable from perineurioma. Primary extracranial meningioma should be included in the differential diagnosis of soft-tissue spindle cell tumors, especially those of peripheral nerve origin.

Adult↗

PubMed2000

Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases.

High-grade invasive ductal carcinomas (IDCs) of the breast with large, central acellular zones on their cut surfaces are usually associated with the myoepithelial immunophenotype of carcinoma cells, which includes the expression of S-100 protein, alpha-smooth muscle actin, and keratin 14. To clarify the clinical significance of these features of IDCs, the authors compared the incidence of the myoepithelial immunophenotype immunohistochemically, patient prognosis, and metastatic sites of the tumor between 20 high-grade IDCs with large, central acellular zones and 40 control high-grade IDCs without these zones. The myoepithelial immunophenotype was detected in 16 IDCs (80%) with large, central acellular zones but in only seven IDCs (18%) without. The risk ratio of metastasis, especially in the brain and lung, and death from cancer were significantly higher (p = 0.0096 and p = 0.030) for the 20 IDCs with large, central acellular zones than for those without by Cox's univariate analysis. Using Cox's multivariate analysis, large, central acellular zones in IDCs were an indicator of high risk of brain and lung metastases and of death by cancer independent of nodal status and tumor size. Examination of large, central acellular zones and myoepithelial immunophenotype in high-grade IDCs appears helpful in predicting patient prognosis and preferential metastatic sites of the tumors.

Actins↗

PubMed1999

Syncytiotrophoblastic giant cells in teratocarcinoma-like tumors derived from Parp-disrupted mouse embryonic stem cells.

The enzyme poly(ADP-ribose) polymerase (Parp) catalyzes poly(ADP-ribosyl)ation reaction and is involved in DNA repair and cell death induction upon DNA damages. Meanwhile, poly(ADP-ribosyl)ation of chromosome-associated proteins is suggested to be implicated in the regulation of gene expression and cellular differentiation, both of which are important in tumorigenesis. To investigate directly the role of Parp deficiency in tumorigenicity and differentiation of embryonic stem (ES) cells during tumor formation, studies were conducted by using wild-type J1 (Parp(+/+)) ES cells and Parp(+/-) and Parp(-/-) ES clones generated by disrupting Parp exon 1. These ES cells, irrespective of the Parp genotype, produced tumors phenotypically similar to teratocarcinoma when injected s.c. into nude mice. Remarkably, all tumors derived from Parp(-/-) clones contained syncytiotrophoblastic giant cells (STGCs), which possess single or multiple megalo-nuclei. The STGCs were present within large areas of intratumoral hemorrhage. In contrast, neither STGC nor hemorrhage was observed in tumors of both wild-type J1 cells and Parp(+/-) clones. Electron microscopic examination showed that the STGCs possess microvilli on the cell surface and contained secretory granules in the cytoplasm. Furthermore, the cytoplasms of STGCs were strongly stained with antibody against mouse prolactin, which could similarly stain trophoblasts in placenta. These morphological and histochemical features indicate that the STGCs in teratocarcinoma-like tumors derived from Parp(-/-) clones belong to the trophoblast cell lineage. Our findings thus suggest that differentiation of ES cells into STGCs was possibly induced by the lack of Parp during the development of teratocarcinoma.

Animals↗

PubMed1999

Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior.

The histological variability of solitary fibrous tumors may contribute to the difficulty in diagnosing these neoplasms, especially when they arise in extrathoracic sites. Like intrathoracic lesions, the behavior of extrathoracic solitary fibrous tumors is currently unpredictable because these types of tumor have only recently been recognized. This study therefore was undertaken to examine the clinical behavior and histological, immunohistochemical, and ultrastructural features of 24 extrathoracic solitary fibrous tumors with long-term follow-up. The patients comprised 10 men and 14 women, between 30 and 85 years of age (mean, 51 years). Ten tumors were located in the retroperitoneum or pelvis, 5 in the trunk, 4 in the extremities, 2 in the orbital region, and 1 each in the kidney, uterine cervix, and meninges. All of the tumors showed a classic morphological appearance, diffuse and strong immunoreactivity for both vimentin and CD34, and variable reactivity for bcl-2. All 7 cases examined ultrastructurally contained fibroblasts and myofibroblasts. Six tumors contained multinucleated giant cells, and in 4 cases these lined pseudovascular spaces with mononuclear cells, thus resembling giant cell angiofibroma and giant cell fibroblastoma. Other potentially similar spindle cell neoplasms mixed with adipose tissue, such as dendritic fibromyxolipoma, lipomatous hemangiopericytoma, cellular angiofibroma, and spindle cell lipoma, were considered in the differential diagnosis. One tumor displayed atypical histological features in the form of increased cellularity and nuclear pleomorphism, but this patient has remained free of disease for 14 years. Another 2 patients developed local recurrences at 6 months and 5 years, and a further patient developed pulmonary metastases that were diagnosed after 7 years. These tumors lacked any atypical histological features in the primary lesions. No patient has so far died of the disease. In conclusion, most extrathoracic solitary fibrous tumors appear to pursue a benign course, although, because some have the potential to recur or metastasize, careful long-term follow-up is necessary for all patients.

Abdominal Neoplasms↗

PubMed1996

Leiomyosarcoma of the vaginal wall causing difficulty in micturition: a case report.

A 52-year-old woman was admitted because of a vaginal-wall tumor adjacent to the external urethral orifice. The tumor had been causing disturbances in micturition for the past year. Magnetic resonance imaging and computed tomography images indicated a 6 x 3 cm solid mass in the anterior vaginal wall. The tumor was enucleated surgically through a median longitudinal incision of the anterior vaginal wall. Micturitional disturbances were rectified after surgery. Histologically, the tumor was a mixture of a high-cellularity area with a mitosis rate of 7 per 30 high-power fields, and a less cellular area without mitosis. Immunohistochemical staining was performed for both areas. The prognostic implications of the tumor are discussed.

Female↗

PubMed1996

Incomplete testicular feminization syndrome: studies on androgen receptor(AR) function, AR gene analysis, and aromatase activities at puberty and long-term observations of clinical and hormonal features from infancy to puberty.

A female infant with partial androgen insensitivity (PAIS) was first seen at 4 months of age with slight virilization of the genitalia and externally palpable testes. Sex chromosome was 46,XY. She received left orchidectomy and exploratory laparotomy at 2 yr of age. At exploratory laparotomy, neither a uterus nor fallopian tubes were found. The right testis was preserved by fixing it at the external inguinal ring expecting spontaneous pubertal maturation. After discharge, serum levels of LH, FSH, testosterone (T) and estradiol (E2) were measured annually, and the steroid responses to hCG stimulation were examined every two yr. At the age of 10 yr, she developed breasts and a very feminine body habitus. At 12 yr, she received a clitoroplasty and right orchidectomy. The fibroblast cultures were made from the genital skin whereby androgen receptor (AR) binding was assessed by radioreceptor assay using 3H-DHT as the ligand, and thermoinstability of AR was noted despite normal maximum binding (Bmax) and dissociation constant (Kd) at 22 degrees C. But another binding experiment with 3H-Mibolerone resulted in the lack of receptor binding. AR gene analysis with direct sequencing of coding exons of the gene revealed no abnormality of the AR gene. 5 alpha-reductase activity was normal. Aromatase activity appeared to be enhanced in the genital skin fibroblast (GSF) cells as well as in the testicular tissue. The results of these studies indicated that the patient had PAIS with impaired AR functions and increased aromatase activity. After the discharge, the patient has maintained feminine phenotype, receiving estrogen therapy with mestranol 0.02 mg/day po.

Aging↗

PubMed1994

[Application of antiandrogens on prostatic diseases].

Antiandrogen therapy for benign prostatic hyperplasia (BPH) and prostatic carcinoma has been introduced in clinical practice. Steroidal antiandrogens such as progestational agents suppress prostatic growth through pituitary gonadotropin suppression as well as by blocking intraprostatic androgen action. Although clinical efficacy of the therapy appears to be promising in some clinical trials, the side effect of sexual function disturbances remains to be solved especially in BPH patients. The new treatment modality for advanced prostatic carcinoma has been introduced; the total androgen blockade therapy, utilizing a pure antiandrogen (Flutamide) in combination with an LH-RH agonist, has been proposed by some authors, but the overall efficacy has not been established yet. Clinical trials for two pure antiandrogens (Flutamide and Casodex) are currently in progress in Japan.

Androgen Antagonists↗

PubMed1992

[A case of urinary bladder hernia].

A 77-year-old male visited our hospital complaining of swelling in the right scrotal and inguinal region, urinary urgency and difficulty of urination. Physical examination revealed an elastic soft mass in the right inguinal region toward the right scrotum. Rectal examination proved that the prostate was moderately enlarged. Cystogram and urethrography showed hernia of the bladder into the right scrotum and benign prostatic hyperplasia. Urodynamic studies demonstrated organic obstruction in the lower urinary tract. Transurethral resection of the prostate was done for benign prostatic hyperplasia. Later, surgical treatment for the bladder hernia was performed by replacing the bladder into the pelvic cavity and closing the hernial ring without resection of the bladder wall. The bladder hernia proved to be a para-peritoneal type. The postoperative course was uneventful. The previous reports of urinary bladder hernia are reviewed and the incidence, etiology, diagnosis the treatment are discussed.

Aged↗

PubMed1988

[A case of giant vesical calculus after ileocystostomy].

A 52-year-old female, who had undergone nephrectomy and ileocystostomy for right-renal tuberculosis and contracted bladder 19 years earlier was seen with anemia and metabolic acidosis. Radiographic findings demonstrated that the patient suffered from a giant vesical calculus. Cystolithotomy was performed and the removed calculus weighed 460 g. Of the 66 cases of giant vesical calculus weighing more than 200 g reported in our country only 7 were in females.

Anastomosis, Surgical↗

PubMed1988

[Retrograde nephrostomy for percutaneous nephrolithotomy].

Between June, 1985 and November, 1986, 25 patients at our institute underwent retrograde nephrostomy placement to provide percutaneous access to the kidney for percutaneous nephrolithotomy (PNL) of renal or upper ureteral calculi. Overall, retrograde nephrostomy was successfully completed through the desired calyx in 80% of the patients and calculi were successfully removed by the subsequent PNL. There were 5 failures primarily due to wrong indication and inexperience with the technique. The procedures had been done without significant complications in this series including unsuccessful cases. On the basis of our experiences, it is practically important for successful retrograde nephrostomy to fix the tip of the catheter firmly in the desired calyx until the puncture wire is advanced into the renal parenchyma. It is also important to aim the puncture wire at the skin in a favorable direction to avoid adjacent visceral penetration. Retrograde nephrostomy is a useful aid for percutaneous calculus removal particularly in patients with nondilated intrarenal collecting systems, because this new technique allows precise tract placement to the kidney required for efficient calculus manipulation with less risk than that associated with conventional percutaneous nephrostomy.

Adult↗

PubMed1985

[A case of ureteral disruption caused by a traffic accident].

Disruption of the ureter is very rarely caused by a blunt trauma, only 12 cases having been reported in Japan. A 20-year-old male suffered from a blunt abdominal trauma in a traffic accident. Although his urinalysis showed no abnormalities, a dull pain in the left flank region persisted for over a week after the injury. Under the suspicion of renal or ureteral injury, an excretory urogram (DIP) was conducted. The form of renal pelvis and calyces was almost normal on both sides, while extravasation of contrast medium was recognized around the lower pole of the left kidney. The retrograde pyelogram of the left side revealed that catheterization was possible up to 30 cm from the ureteral orifice, but the injected medium leaked into the retroperitoneal space making it impossible to visualize the left renal pelvis and calyces. An operation was performed under the diagnosis of left ureteral injury on the 19th day after trauma. The left ureter was completely disrupted 2 cm distally from the ureteropelvic junction. An end to end anastomosis of the ureter was done with 6-0 Dexon sutures. The DIP taken on the 25th day after the operation showed slight dilatation of the left pelvis and calyces. However, the renogram conducted 6 months after the operation demonstrated a normal pattern on both sides.

Accidents, Traffic↗

PubMed1981

[Studies on catabolism of ether lipids. -Solubilization of alkylglycerol monooxygenase from rat liver microsome (author's transl)].

The author has investigated the condition for solubilization of alkylglycerol monooxygenase from rat liver microsome. The solubilization of this enzyme has been done by using Triton X-100, because this enzyme is considered to be relatively stable in the presence of 0.5% Triton X-100. It is suggested that there are factors leading to decrement of enzyme activity during the procedure of DEAE-cellulose column chromatography. Since the enzyme activity is markedly stimulated by phosphatidyl choline or catalase in the enzyme system obtained by DEAE-cellulose chromatography, it is presumed that the enzyme activity is markedly reduced because of removing the H2O2-scavenging system as well as the lipids, which are necessary to activate or stabilize the enzyme, from the microsomal enzyme system. Key words: Alkyglycerol monoxygenase, Solubilization, Microsome.

Animals↗