Biomedical subjects

K Mandai

Publications and source records attributed to K Mandai.

At least 37 records · Page 2Linked to original sources

PubMed1999

Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells.

BACKGROUND: We have recently identified a novel cell-cell adhesion system, named NAP system, which is localized at cadherin-based cell-cell adherens junctions (AJs). The NAP system is composed of at least nectin, afadin and ponsin. Nectin is an immunoglobulin-like cell adhesion molecule. Afadin is an actin filament-binding protein which associates nectin with the actin cytoskeleton. Ponsin is an afadin-binding protein which furthermore binds to vinculin and provides a possible linkage of nectin-afadin to cadherin-catenin through vinculin. We compared here the behaviour of the NAP and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells. RESULTS: At the early stage of the formation of the polarized junctional alignment in MTD-1 A cells, primordial spot-like junctions were formed at the tips of thin cellular protrusions radiating from adjacent cells. Nectin, afadin, ponsin, cadherin and catenin were simultaneously recruited to these junctions. As the cell polarization proceeded, the spot-like junctions were gradually fused to form belt-like AJs where all these proteins were concentrated. The disruption of cell-cell AJs in MDCK cells by culturing at a low Ca2+ concentration caused rapid endocytosis of cadherin, but not that of nectin or afadin. Addition of 12-O-tetradecanoylphorbol-13-acetate to the cells formed a tight junction-like structure where nectin and afadin, but not cadherin, accumulated. CONCLUSION: These results indicate that the NAP and cadherin-catenin systems show similar and differential behaviour during the formation and disruption of the polarized junctional alignment in epithelial cells.

Animals↗

PubMed1999

Undifferentiated carcinoma with lymphoid infiltration of the esophagus: a case report.

This paper reports a surgically treated case of undifferentiated carcinoma with lymphoid infiltration of the esophagus. Histologically, most of the tumor consisted of undifferentiated carcinoma (non-small cell type) with lymphoid infiltration and a small portion showed features of poorly differentiated squamous cell carcinoma. Carcinoma with lymphoid infiltration in the stomach, breast or nasopharynx has a good prognosis, but in the esophagus this histological type is extremely rare and its characterization is unclear. This is only the sixth report to date of undifferentiated carcinoma with lymphoid infiltration of the esophagus.

Aged↗

PubMed1998

Frabin, a novel FGD1-related actin filament-binding protein capable of changing cell shape and activating c-Jun N-terminal kinase.

We purified from rat brain a novel F-actin-binding protein with a Mr of about 105,000 (p105), which was estimated by SDS-polyacrylamide gel electrophoresis. We cloned its cDNA from a rat brain cDNA library and characterized it. p105 was a protein of 766 amino acids and showed a calculated Mr of 86,449. p105 consisted of one F-actin-binding domain at the N-terminal region, one Dbl homology domain and one pleckstrin homology domain at the middle region, and one cysteine-rich domain at the C-terminal region. This domain organization of p105 was similar to that of FGD1, which has been determined to be the genetic locus responsible for faciogenital dysplasia or Aarskog-Scott syndrome. We therefore named p105 frabin (FGD1-related F-actin-binding protein). Frabin bound along the sides of F-actin and showed F-actin-cross-linking activity. Overexpression of frabin in Swiss 3T3 cells and COS7 cells induced cell shape change and c-Jun N-terminal kinase activation, respectively, as described for FGD1. Because FGD1 has been shown to serve as a GDP/GTP exchange protein for Cdc42 small G protein, it is likely that frabin is a direct linker between Cdc42 and the actin cytoskeleton.

Actins↗

PubMed1998

Breast-Concerving Surgery Following Preoperative Radiotherapy to the Primary Breast Cancer of 3 cm or Larger: Histological Analysis of Size Reduction of the Tumors by Radiotherapy.

Fifteen women with primary breast cancer of 3 cm or larger were treated by radiotherapy of 5000 or 5100 cGy preoperatively for breast conservation. Among them, three responded completely to radiotherapy clinically, 6 did partially, and 6 showed minor response. Breast-concerving surgery was performed in all cases. Histologically one patient did not have cancer cells at surgery, while eight showed good response but had residual tumor, and the rest responded moderately. The histological margins were positive in six cases, of those three were positive due to an invasive component. Calculation of the size reduction of the primary tumor by radiotherapy at a histological level revealed that the invasive area of the tumors was 79.5% on average. There was a tendency, among well responding patients, to show a large reduction in size. However, the tumor cells tended to remain in the peripheral areas of the originally invasive areas. In summary, preoperative radiotherapy made the size of the primary tumors smaller in the majority of the cases clinically but the actual histological size reduction was relatively small in general. We conclude that preoperative radiotherapy is effective to extend the indications of conservative treatment in patients with a large primary breast cancer. However, care is required when we treat patients with a very large primary breast cancer conservatively.

Journal Article↗

PubMed1998

Circulating platelet-derived endothelial cell growth factor increases in hepatocellular carcinoma patients.

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that is expressed in various cancer tissues. Little is known regarding plasma PD-ECGF levels in patients with chronic liver disease such as chronic hepatitis (CH), cirrhosis, and hepatocellular carcinoma (HCC) with cirrhosis. The expression of PD-ECGF in HCC tissues also remains to be clarified. METHODS: Plasma PD-ECGF levels in patients with chronic liver disease were determined with an enzyme-linked immunoadsorbent assay system using the mouse monoclonal antibodies specific to PD-ECGF. These were cross-sectionally compared among groups of normal persons, CH, cirrhosis, and HCC patients. The HCC patients were classified into two groups based on TNM stage: early and advanced stage disease groups. PD-ECGF expressions in HCC tissues were immunohistologically examined. RESULTS: The plasma PD-ECGF levels from the normal individuals and those with CH, cirrhosis, and HCC specimens were 4.2+/-0.5, 4.3+/-0.6, 4.6+/-1.1, and 6.0 +/-2.5 U/mL, respectively. The plasma PD-ECGF concentration was highest in HCC (P < 0.05). No significant difference was found among the normal subjects, CH, and cirrhosis specimens. Plasma PD-ECGF concentrations were significantly higher in the advanced stage disease HCC group compared with the early stage disease group (6.75+/-2.62 U/mL vs. 4.19+/-0.34 U/mL) (P < 0.05). Immunohistochemical expression of PD-ECGF in HCC cells increased significantly compared with normal liver cells (P < 0.05). CONCLUSIONS: Circulating PD-ECGF plasma level might be a new tumor marker for progression in patients with HCC. Immunohistological findings correspond to elevation of the plasma PD-ECGF in HCC patients. It is possible that increased production of PD-ECGF in HCC cells causes abundant neovascularization.

Adult↗

PubMed1998

Two cases of intrapulmonary lymph node presenting as a peripheral nodular shadow: diagnostic differentiation from lung cancer.

We present two cases of intrapulmonary lymph node. The patients were a 44-year-old woman and a 71-year-old man each with a small peripheral nodule in the lung. On computed tomography (CT) scans, both nodules were spiculated. Since histological diagnosis could not be obtained by bronchoscopic examination or CT-guided needle biopsy, they underwent video-assisted thoracoscopic surgery. Histological examination of the resected material revealed that both nodules were composed of lymph node. Intrapulmonary lymph node has until recently been assigned no clinical significance; however, differential diagnosis of this lesion from lung cancers and other metastatic tumors is now clinically important.

Adult↗

PubMed1998

[Small cell carcinoma of the prostate: a case report].

A 57-year-old man was admitted with the chief complaint of macrohematuria. Digital rectal examination showed a slightly enlarged, irregular prostate with stony consistency. Serum levels of prostate specific antigen (PSA), neuron-specific enolase (NSE) and progastrin-releasing peptide (ProGRP) were elevated. Transurethral resection (TUR)-biopsy of the prostate revealed small cell carcinoma with poorly differentiated adenocarcinoma. Various radiological examinations revealed metastases to pelvic lymph nodes and liver. He was treated with chemoendocrine therapy consisting of cisplatin, etoposide, flutamide and luleinizing hormone-releasing hormone (LH-RH) agonist. The primary tumor and metastatic lesion decreased and serum PSA, NSE and ProGRP levels were decreased to normal ranges after 5 cycles of chemotherapy. After the 5-cycle chemotherapy, TUR-biopsy proved viable tumor cells. During the additional chemotherapy, tumor markers increased and 4 months later liver metastasis progressed. He died 13 months after diagnosis of small cell carcinoma of the prostate.

Carcinoma, Small Cell↗

PubMed1997

Neurabin: a novel neural tissue-specific actin filament-binding protein involved in neurite formation.

We purified from rat brain a novel actin filament (F-actin)-binding protein of approximately 180 kD (p180), which was specifically expressed in neural tissue. We named p180 neurabin (neural tissue-specific F-actin- binding protein). We moreover cloned the cDNA of neurabin from a rat brain cDNA library and characterized native and recombinant proteins. Neurabin was a protein of 1,095 amino acids with a calculated molecular mass of 122,729. Neurabin had one F-actin-binding domain at the NH2-terminal region, one PSD-95, DlgA, ZO-1-like domain at the middle region, a domain known to interact with transmembrane proteins, and domains predicted to form coiled-coil structures at the COOH-terminal region. Neurabin bound along the sides of F-actin and showed F-actin-cross-linking activity. Immunofluorescence microscopic analysis revealed that neurabin was highly concentrated in the synapse of the developed neurons. Neurabin was also concentrated in the lamellipodia of the growth cone during the development of neurons. Moreover, a study on suppression of endogenous neurabin in primary cultured rat hippocampal neurons by treatment with an antisense oligonucleotide showed that neurabin was involved in the neurite formation. Neurabin is a candidate for key molecules in the synapse formation and function.

Actins↗

PubMed1997

Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction.

A novel actin filament (F-actin)-binding protein with a molecular mass of approximately 205 kD (p205), which was concentrated at cadherin-based cell-to-cell adherens junction (AJ), was isolated and characterized. p205 was purified from rat brain and its cDNA was cloned from a rat brain cDNA library. p205 was a protein of 1,829 amino acids (aa) with a calculated molecular mass of 207,667 kD. p205 had one F-actin-binding domain at 1,631-1,829 aa residues and one PDZ domain at 1,016- 1,100 aa residues, a domain known to interact with transmembrane proteins. p205 was copurified from rat brain with another protein with a molecular mass of 190 kD (p190). p190 was a protein of 1,663 aa with a calculated molecular mass of 188,971 kD. p190 was a splicing variant of p205 having one PDZ domain at 1,009-1,093 aa residues but lacking the F-actin-binding domain. Homology search analysis revealed that the aa sequence of p190 showed 90% identity over the entire sequence with the product of the AF-6 gene, which was found to be fused to the ALL-1 gene, known to be involved in acute leukemia. p190 is likely to be a rat counterpart of human AF-6 protein. p205 bound along the sides of F-actin but hardly showed the F-actin-cross-linking activity. Northern and Western blot analyses showed that p205 was ubiquitously expressed in all the rat tissues examined, whereas p190 was specifically expressed in brain. Immunofluorescence and immunoelectron microscopic studies revealed that p205 was concentrated at cadherin-based cell-to-cell AJ of various tissues. We named p205 l-afadin (a large splicing variant of AF-6 protein localized at adherens junction) and p190 s-afadin (a small splicing variant of l-afadin). These results suggest that l-afadin serves as a linker of the actin cytoskeleton to the plasma membrane at cell-to-cell AJ.

Actins↗

PubMed1997

Angiosarcoma of the Breast: Report of Case and Autopsy Findings.

We report a case of angiosarcoma of the breast and the autopsy findings. The patient was a 35-year-old premenopausal woman who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant. The tumor was elastic and soft, smooth surfaced, well-difined and mobile. Dimpling sign or change of skin color were not observed. Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended surgery was recommended, but the patient refused additional therapy. Histological findings revealed a free surgical margin and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the cervical and thoracic vertabrae were observed and radiatioon therapy was performed. Sixteen months from onset, she died due to multi-organ failure as general metastases of angiosarcome. At autopsy, metastases to many organs including the digestive system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor. This case emphasized the diffculties in clinical diagnosis and treatment for the angiosarcoma of breast.

Journal Article↗

PubMed1997

Serum CD44 levels in patients with non-small cell lung cancer and their relationship with clinicopathological features.

Serum CD44 standard and CD44 variant 6 levels were measured in 45 non-small cell lung cancer (NSCLC) patients and 33 patients with benign lung disease by enzyme-linked immunosorbent assay (ELISA). Expression of CD44 variant 6 in trans-bronchial biopsy specimens from the NSCLC patients was studied by an immunoperoxidase method. CD44 standard and CD44 variant 6 levels in NSCLC patients were not significantly different from those in benign lung disease patients. However, serum CD44 variant 6 level in squamous cell carcinoma patients (226.8 +/- 152.7 ng/ml) was significantly higher than in patients with benign lung disease (154.8 +/- 46.4 ng/ml) (P = 0.011). Neither the serum level of CD44 standard nor that of CD44 variant 6 was correlated with disease Stage and metastasis. CD44 variant 6 expression was most frequently observed in squamous cell carcinoma (P = 0.00058); 15 (79%) of 19 squamous cell carcinoma cases were positive, as were five (22%) of 23 adenocarcinoma cases and two (67%) of three large cell carcinoma cases. Serum CD44 variant 6 levels were 217.1 +/- 143.1 and 156.1 +/- 48.8 ng/ml in patients with and without positive expression of CD44 variant 6, respectively (P = 0.020). Serum CD44 standard and CD44 variant 6 levels are not useful indicators of tumor burden and metastasis in patients with NSCLC. CD44 variant 6 expression might be associated with histological features of NSCLC.

Adenocarcinoma↗

PubMed1997

Measurement of serum p53 protein in patients with small cell lung cancer and results of its clinicopathological evaluation.

Serum p53 protein levels were measured in 36 patients with small cell lung cancer (SCLC) and 35 patients with benign lung diseases in order to evaluate the relationship of these levels to clinicopathological features of SCLC. Serum levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53 protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21 patients with limited disease, and lower than that in 15 patients with extensive disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not correlated with age, smoking index, or presence of cancer history for patients with SCLC. However, immunohistochemical examination disclosed a mild correlation between the expression of p53 protein by SCLC tumor and p53 protein serum level (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53 protein (> 2 S.D. above the mean for benign lung diseases). However, measurement of p53 protein serum level was not found to be clinically useful for detection of SCLC.

Age Factors↗

PubMed1997

Ischemic tolerance in hippocampal CA1 neurons studied using contralateral controls.

We induced ischemic tolerance unilaterally in gerbil hippocampus using the contralateral hippocampus as control. Ischemia for 2 min of right common carotid occlusion was reversible but sufficient to cause heat-shock protein 70 production in CA1 neurons. This pretreatment given four days prior to occlusion of both common carotids for 5 min, but not at longer preceding intervals, induced tolerance in right CA1 neurons. Neuroprotection was still evident two months after the 5 min occlusion. Adenosine triphosphate content and immunoreactive microtubule associate protein 2 in the hippocampus showed that the 5 min ischemic insult was essentially equal in both hemispheres. Repetitive pretreatments at two day intervals caused almost complete protection of CA1 neurons against subsequent 5 min ischemia, while a single pretreatment showed 80% protection. However, the increase in heat-shock protein 70 with repeated pretreatments was not significantly more than with one pretreatment. We concluded that true ischemic tolerance was induced by ischemic stress itself, was long-lasting, was not due to mitigation of subsequent ischemia, and was augmented by repetition without further increase of heat-shock protein 70.

Adenosine Triphosphate↗

PubMed1997

Small cell carcinoma of the esophagus: a case report.

This article reports a case of primary undifferentiated small cell carcinoma of the esophagus with lymph node metastasis which invaded the stomach wall. The patient was treated with chemotherapy alone, consisting of CDDP and VP-16. The patient had a complete response to chemotherapy, with no evidence of disease for nine months, after six courses of the regimen. Small cell carcinoma of the esophagus is an aggressive tumor with an extremely poor prognosis. Because its characteristics are similar to small cell carcinoma of the lung, small cell carcinoma of the esophagus should be treated by multi-drug chemotherapy including CDDP, with or without radiation as the first line treatment. This chemotherapy regimen may achieve a long disease-free survival time.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

[The clinical analysis of pediatric meningioma: 5 cases].

Five cases of pediatric meningioma were reported with special emphasis on the clinical features. These cases consisted of three boys and two girls between eight and fifteen years old. Two were falx meningioma, two were suprasellar, and one was petroclival. One falx meningioma was associated with Neurofibromatosis II, and a suprasellar case had no dural attachment, but had cystic component after recurrence. Histologically, there were three meningothelial, one transitional, and one fibrous meningioma. No malignant meningioma was found among any of the cases. Two cases received postoperative irradiation and had no recurrence. A falx meningioma with Neurofibromatosis II and a suprasellar with no dural attachment had evidence of recurrence. The latter suffered from severe neurological deficits after reoperation. It was suggested that irradiation against residual tumor should be considered. However, total removal should be carried out in pediatric cases of meningioma. The authors concluded that our cases had features intermediate between adult meningiomas and pediatric meningiomas because the majority of cases were senior children.

Adolescent↗

PubMed1997

Ischemic damage and subsequent proliferation of oligodendrocytes in focal cerebral ischemia.

In order to achieve a better understanding of the pathophysiology of ischemic white matter lesions, oligodendrocytic degeneration and subsequent proliferation were examined in the mouse model of middle cerebral artery occlusion. In situ hybridization histochemistry for proteolipid protein messenger RNA was employed as a sensitive and specific marker of oligodendrocytes, and immunohistochemistry for myelin basic protein was used as a compact myelin marker. Immunohistochemistry for microtubule-associated protein 2 and albumin was employed to monitor neuronal degeneration and the breakdown of the blood brain barrier, respectively. In the ischemic core of the caudoputamen, the immunoreactivity for microtubule-associated protein 2 disappeared and massive albumin extravasation occurred several hours after vessel occlusion, while proteolipid protein messenger RNA signals remained relatively strong at this time. The messenger RNA signals began to attenuate 12 h after ischemia and were hardly detectable 24 h after ischemia in the whole ischemic lesion. In situ end-labeling of fragmented DNA showed some cells with proteolipid protein messenger RNAs to have DNA fragmentation at this period. In contrast to proteolipid protein messenger RNA signals, the immunoreactivity for myelin basic protein was detected as long as five days after ischemia. An apparent increase in the cells possessing strong proteolipid protein messenger RNA signals was found five days after ischemia, mainly in the corpus callosum and the cortex bordering the infarcted areas. A double simultaneous procedure with in situ hybridization for proteolipid protein messenger RNA and immunohistochemistry for glial fibrillary acid protein or lectin histochemistry for macrophages/microglia showed proliferating oligodendrocytes to be co-localized with reactive astrocytes and macrophages/microglia. These findings show that oligodendrocytic damage occurred following ischemic neuronal damage and the breakdown of the blood brain barrier, but preceded the breakdown of myelin proteins in the ischemic lesion, that an apoptosis-like process was involved in ischemic oligodendrocytic death, and that surviving oligodendrocytes responded and proliferated in the outer border of the infarcted area.

Animals↗

PubMed1997

Total necrosis of hepatocellular carcinoma with a combination therapy of arterial infusion of chemotherapeutic lipiodol and transcatheter arterial embolization: report of 14 cases.

Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte, France) containing styrene maleic acid neocarzinostatin and transcatheter arterial embolization (L-TAE) has been an important conservative therapy for hepatocellular carcinoma (HCC). We examined the clinical and pathologic characteristics of 14 HCC cases that achieved total tumor necrosis in response to L-TAE. The HCCs of all cases were resected 45 +/- 17 days after L-TAE and were confirmed to be totally necrotic. Ultrasonography showed a mean tumor size of 2.5 +/- 1.0 cm, often with a halo formation around the tumor. Angiographically, neovascularity and clear tumor stains were observed in all cases. Computed tomography portography showed nodular perfusion defects in all the cases examined. There were portal invasions in two cases. On Lipiodol-computed tomography, Lipiodol was densely and homogeneously retained within the whole tumor. The number of tumors was single in all diagnostic images. Macroscopic view of HCCs were single nodular type in nine cases and single nodular type with extra growth in four cases. Clear capsular formation was seen in each HCC nodule. Soft x-rays were taken to observe the exact distribution of Lipiodol in the operative specimens. Microscopic intrahepatic metastases were found histologically in four cases. Histologic examination showed the trabecular pattern with broad blood spaces in which Lipiodol was positive with Sudan III staining. Necrosis was seen not only in the main tumor, but also in the capsular invasions and microscopic metastases with Lipiodol deposition. The characteristics of the cases with total tumor necrosis were as follows. Deposition of Lipiodol throughout the tumor was essential, and clinically the cases showed a single HCC tumor with a diameter of more than 5 cm and arterial hypervascularity. The pathologic findings included expansive growth with capsular formation and trabecular-type HCC with abundant blood spaces. These findings are important for evaluating the radical efficacy of L-TAE.

Aged↗

PubMed1997

[Histological effect of arterial embolization chemotherapy for metastatic liver tumors from colorectal cancer--report of cases of hepatectomy after arterial embolization chemotherapy].

To evaluate the histological effect of arterial embolization chemotherapy (AEC) for the metastatic liver tumors from colorectal cancer, 5 lesions were examined in 4 patients who were treated with surgery after AEC. In addition, to compare the histological changes of the metastatic liver tumors, we histologically examined 7 lesions in 5 patients who were treated with surgery alone as a historical control. For the patients with AEC, anti-cancer agents and lipiodol were administered by selected hepatic arterial infusion with fragments of sponzel. In a group of AEC, all metastatic liver tumors were detected after resection of the primary tumors. The range of tumor size in these lesions was from 2.5 to 4.2 cm in diameter. Otherwise, in a group of non-AEC, the size of tumors ranged from 2 to 5 cm in diameter. In angiography, tumor stainings were detected in 2 lesions, and in all lesions no accumulation of lipiodol was detected by CT scan. The overall response rate at the surgery was 7 to 33% (average 23%) in a group of AEC. In addition, in 2 lesions, about 60% of the lesions were necrotic tissues, and more than 90% of the tumor lesions in 3 lesions were histologically necrosis. Within these lesions, encapsulation of the metastatic tumors was observed in 3 lesions. Otherwise, in a group of non-AEC, 50-70% of the tumor lesions were histologically detected as necrosis, and in one lesion, encapsulation was observed. These evidences suggest the histological effect of AEC may be evaluated when more than 70% of tumor necrosis in lesions is observed. In conclusion, the treatment was effective in 3 cases and not effective in one case.

Adenocarcinoma↗