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Biomedical subjects

K Karasawa

Publications and source records attributed to K Karasawa.

At least 37 records · Page 2Linked to original sources

Deficient platelet-activating factor and related enzymes in hemimegalencephaly.

Platelet-activating factor (PAF) may influence neuronal migration, and gyral anomaly in hemimegalencephaly is believed to result from a neuronal disorder. A 7-month-old girl with hemimegalencephaly presented with intractable seizures, for which graded hemispherectomy was performed. In the resected specimen, we could not detect PAF, and related enzyme activities were low. These results suggest a role of PAF in neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Molecular remission in adult T cell leukemia after autologous CD34+ peripheral blood stem cell transplantation.

This report describes a patient with acute-type adult T cell leukemia/lymphoma (ATLL) successfully treated by autologous CD34+ peripheral blood stem cell transplantation after fractionated total body irradiation and high-dose cytarabine and cyclophosphamide. A newly established inverse polymerase chain reaction method was used to demonstrate the disappearance of ATLL clonal cells. The patient achieved a sustained molecular remission after transplantation, but died from opportunistic infection 4 months after transplantation. Thus, autologous CD34+ peripheral blood stem cell transplantation is promising for this type of malignancy. However, a prudent clinical attitude toward immunological fragility after transplantation is needed for better outcome.

Antigens, CD34↗

Metabolism of oxidized phosphatidylcholines formed in oxidized low density lipoprotein by lecithin-cholesterol acyltransferase.

The possible involvement of lecithin-cholesterol acyltransferase (LCAT) in the metabolism of oxidized phosphatidylcholine (PC) in plasma was investigated. A variety of oxidized products are formed from PC following oxidation of low density lipoproteins (LDL). A significant increase in LDL oxidation levels in patients with familial LCAT deficiency (FLD) has been previously demonstrated by a sensitive sandwich ELISA for oxidized LDL using the monoclonal antibody DLH3 which recognizes oxidized products of PC. In the present study, we found that LCAT produces various metabolites from oxidized PC and that oxidized PC molecules in LDL particles serve as substrates. When the neutral lipid fraction was separated by TLC after the incubation of oxidized 1-palmitoyl-2-[1-14C]linoleoyl PC with human plasma, a number of radioactive bands were formed in addition to cholesteryl ester. These products were not formed from native 1-palmitoyl-2-[1-14C]linoleoyl PC. Plasma from FLD patients also failed to form the additional products from oxidized PC. The addition of dithio-bis(nitrobenzoate) (DTNB), an LCAT inhibitor, or the inactivation of LCAT activity by treating the plasma at 56 degrees C for 30 min abolished the generation of these products from oxidized PC. The activity was recovered in the high density lipoprotein (HDL) fraction but not in the LDL fraction separated from normal plasma. When 1-palmitoyl-2-[1-14C](9-oxononanoyl) PC and 1-stearoyl-2-[1-14C](5-oxovaleroyl)PC, PC oxidation products that contain short chain aldehydes, were incubated with human plasma, radioactive products in the neutral lipid fraction were observed on TLC. LDL containing oxidized PC was measured by sandwich ELISA using an anti-apolipoprotein B antibody and DLH3. The reconstituted oxidized PC-LDL particles were found to have lost their ability to bind DLH3 upon incubation with HDL, while the reactivity of the reconstituted oxidized PC-LDL remained unchanged in the presence of DTNB. These results suggest that LCAT is capable of metabolizing a variety of oxidized products of PC and preventing the accumulation of oxidized PC in circulating LDL particles.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

The Escherichia coli pldC gene encoding lysophospholipase L(1) is identical to the apeA and tesA genes encoding protease I and thioesterase I, respectively.

We deduced the amino acid sequence of Escherichia coli lysophospholipase L(1) by determining the nucleotide sequence of the pldC gene encoding this enzyme. The translated protein was found to contain 208 amino acid residues with a hydrophobic leader sequence of 26 amino acid residues. The molecular weight of the purified enzyme (20,500) was in good agreement with the predicted size (20,399) of the processed protein. A search involving a data bank showed that the nucleotide sequence of the pldC gene was identical to those of the apeA and tesA genes encoding protease I and thioesterase I, respectively. Consistent with the identity of the pldC gene with these two genes, the enzyme purified from E. coli overexpressing the pldC gene showed both protease I and thioesterase I activities.

Amino Acid Sequence↗

[Effectiveness of 3 ways method in intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].

We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.

Adult↗

High-dose conformal radiotherapy influenced the pattern of failure but did not improve survival in glioblastoma multiforme.

BACKGROUND AND PURPOSE: Although glioblastoma multiforme is clearly radiation-resistant, there is evidence of a dose-dependent response relationship. The purpose of the study was to evaluate the impact of higher dose by rotational multileaf collimator (MLC) conformal radiation therapy. MATERIALS AND METHODS: From 1984 to 1995, 38 consecutive cases with intracranial glioblastoma multiforme were treated using the rotational MLC conformal therapy. There were 25 men and 13 women with a median age of 47 years (12-73 years, mean 46.5 years). Median Karnofsky performance score was 80 (30-100, mean 78.2). Median tumor volume was 64 cc (8-800 cc, mean 110.3 cc). All underwent surgical intervention (only biopsy in 1, partial resection in 13, subtotal resection in 21, and gross total resection in 3). Radiation dose to was 60 to 80 Gy (median 68.5 Gy, mean 68.3 Gy) in 21 patients treated before 1990 and 90 Gy in the 17 patients thereafter. Biweekly i.v. chemotherapy was also administered for both arms. RESULTS: The 1-year, 2-year, 5-year, and 10-year overall survival rates were 75%, 42%, 20%, and 15%, respectively. Univariate analysis showed the initial tumor volume, residual tumor volume, and Karnofsky performance score were statistically significant factors for survival. Only the residual tumor volume was statistically significant by multivariate analysis. The 5-year survival rate of patients with residual tumors of 5 cc or less in volume was as good as 37%. Survival of the 90-Gy Group appeared inferior to that of the Low-Dose Group, though no statistical difference was seen (the 3-year survival was 40% vs. 22%). Local failure was observed in 16 of the 19 recurrences in the Low-Dose Group, whereas it was observed in only 4 of the 13 recurrences in the 90-Gy Group. The difference in pattern of failure was statistically significant. Two patients of the High-Dose Group developed radiation necrosis and one died of it. CONCLUSIONS: The high-dose conformal radiotherapy did not improve survival in the disease, but did change the pattern of failure.

Adolescent↗

Radiotherapy of bone metastases of a spinal meningeal hemangiopericytoma.

Hemangiopericytoma is a rare tumor arising from pericapillary cells or pericytes of Zimmerman, and can occur anywhere capillaries are found. We describe a patient with a meningeal hemangiopericytoma who was treated with primary surgical resection and experienced multiple bone metastases 20 years after the first treatment. This patient with multiple bone metastases was treated with multiple courses of irradiation and good palliation was achieved.

Adult↗

Relationship between fat distribution and lipid and apolipoprotein profiles in young teenagers.

The influence of obesity and fat distribution on serum levels of lipoprotein and apolipoprotein was investigated in 294 Japanese junior high school children (12-13 years of age). Serum levels of low-density lipoprotein cholesterol (LDLC) (P = 0.013), triglycerides (TG) (P = 0.0006), and apolipoprotein B (apoB) (P = 0.003), and the apoB/A-I ratio (P = 0.005) were significantly higher and serum levels of high-density lipoprotein cholesterol (HDLC) (P = 0.00003) and apoA-1(P = 0.003) were significantly lower in obese boys than in non-obese boys. The serum levels of TG (P = 0.013) and the apoB/A-I ratio (P = 0.011) were significantly higher and the serum levels of HDLC (P = 0.004) was significantly lower in obese girls than in non-obese girls. The LDLC/apoB ratio was lower in obese girls than in non-obese girls (P = 0.03). Obesity (> or = 20% of ideal weight) was strongly correlated with the serum levels of lipids and apolipoproteins in boys; this relationship was less clear in girls. The degree of obesity and the body mass index (BMI) were more strongly correlated with serum levels of lipids and apolipoproteins in boys than in girls. In boys, atherogenic lipoproteins and apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the thickness of the triceps skinfold, while in girls the anti-atherogenic lipoproteins and apolipoproteins, such as HDLC and apoA-I, showed a stronger correlation with both the triceps and the subscapular skinfold thicknesses. In girls the relationships between the BMI and the degree of obesity and the thickness of the subscapular skinfold (S) thickness were similar to the relationships between those parameters and the triceps skinfold (T) thickness. In boys, these parameters showed a stronger correlation with the subscapular skinfold thickness than with the triceps skinfold thickness. The correlation coefficients for the relationships between skinfold thickness and lipid and apolipoprotein levels were similar to the coefficients for the relationships between skinfold thicknesses and the severity of obesity and the BMI. The distribution of central-type fat accumulation, which is indicated by the thickness of the subscapular skinfold, the S/T ratio and S-T value, was inversely correlated with the HDLC level in both boys and girls. The degree of obesity was strongly correlated with the atherogenic lipoprotein profile in boys, in part because the subscapular skinfold thickness was strongly correlated with the degree of obesity and the BMI. In girls, the correlations between indices of central-type obesity and atherogenic lipid and apolipoprotein profiles were stronger than in boys. These data suggest that childhood obesity may be an early cardiovascular risk factor.

Adipose Tissue↗

Radiotherapy for osseous metastases from hepatocellular carcinoma: a retrospective study of 57 patients.

OBJECTIVE: We undertook to evaluate the therapeutic effects of radiotherapy in patients with bone metastases from hepatocellular carcinoma (HCC), identify prognostic factors, and find an optimum radiation schedule. METHODS: We retrospectively analyzed the clinical records of 57 patients (99 sites) with painful bone metastases from HCC from December 1978 to March 1997. Their ages ranged from 51 to 82 yr (mean, 62 yr), and the male:female ratio was 49:8. Among them, there were nine patients (16%) with metastases to other organs. Twenty patients (35%) had a solitary bone metastasis and 37 (65%) had multiple bone metastases. The total radiation dose ranged from 20 to 65 Gy (mean, 43 Gy) and that of the Time, Dose, and Fractionation Factor (TDF) values (per explanation given in text) ranged from 35.2 to 118.2 (mean, 73.2). RESULTS: Pain relief was obtained for 83.8% (83/99) of bone metastases from HCC. Those with a TDF value of > or = 77 (a TDF value of 77 is nearly equal to 48 Gy administered in fractions of 2 Gy each daily or 39 Gy administered in fractions of 3 Gy each daily), responded better than those with a TDF value of < 77 (p < 0.05). Overall, the median survival time from the start of radiotherapy was 179 days (6 months). Patients with a solitary bone metastasis and those without metastases to other organs had a better prognosis (p < 0.05 for both subgroups). CONCLUSIONS: Radiation therapy was effective for bone metastases from HCC, especially for those treated with a TDF value of > or = 77.

Aged↗

[Efficacy of intraoperative radiotherapy (IORT) for local recurrence of rectal cancer].

The efficacy of intraoperative radiotherapy (IORT) for the local recurrence of rectal cancer was evaluated. Operations were performed for a total of 43 patients with local recurrence of rectal cancer, and among them 13 cases received IORT. These patients were divided into two groups those with a suspicion of cancer remaining in the surgical margin macroscopically (EW+ group) or those with no such suspicion (EW- group). The length of pain relieving period and total survival between the IORT and no IORT groups in EW- patients showed no statistical difference. Though the same result was found in EW+ patients, in the patients whose area of positive surgical margin was less than 10 cm2 and given IORT, the pain relief period was prolonged compared with the no IORT patients such as 270 days v.s. 218 days. IORT did not show efficacy in terms of the survival period, but if the local remnant area was small, it was beneficial for the patients in terms of the pain period.

Adenocarcinoma↗

[Radiotherapy for locally advanced esophageal cancer].

The conventional treatment for patients with locally advanced esophageal cancer has been surgery or radiotherapy. The indication of the treatment depends on the location of the primary tumor, tumor stage, resectability of the lesion and operability of the patient. Radiotherapy is used in a case refusing surgery, medical contraindications to surgery, extensive locoregional disease or poor general condition. The survival rate by surgery alone or radiotherapy alone is poor. Thus, single modality therapy is not a standard treatment, but combined multimodal therapy including chemotherapy is a standard approach for locally advanced esophageal cancer. Further studies of optimization of multimodal therapies which are surgery and/or radiotherapy combined with chemotherapy are needed to improve the results in the treatment of esophageal cancer.

Brachytherapy↗

Changes in composition of newly synthesized sphingolipids of HeLa cells during the cell cycle -- suppression of sphingomyelin and higher-glycosphingolipid synthesis and accumulation of ceramide and glucosylceramide in mitotic cells.

Sphingolipid biosynthesis in synchronized HeLa cells was studied by pulse labeling with [14C]Ser or [14C]Gal and a simple TLC method. The major HeLa cell sphingolipids are ceramide (Cer), sphingomyelin, glucosylceramide (GlcCer), lactosylceramide (LacCer), globotriaosylceramide (Gb3Cer), N-acetylneuraminosylgangl iotriaosylceramide (GM2) and sialylparagloboside (G[M1-GlcNAc]). The sphingolipid biosynthetic profiles of HeLa cells in the G1, G1/S boundary, S and G2 phases were similar, but significant changes occurred during M phase, when incorporation of radioactivity into sphingomyelin, Gb3Cer and a mixture of GM2 and G(M1-GlcNAc) decreased, and those of Cer and GlcCer increased. These data indicate that transfer of phosphocholine and galactose to Cer and GlcCer, respectively, decreased in mitotic cells, resulting in accumulation of Cer and GlcCer. Analysis of LacCer synthase activity revealed that GlcCer accumulation was not due to reduced activity of this enzyme. The results suggest that Cer and GlcCer accumulation in mitotic cells resulted from suppression of sphingomyelin and LacCer synthesis, probably caused by vesiculation of membranous organelles, such as the endoplasmic reticulum and Golgi apparatus.

Autoradiography↗

Activated mast cells release extracellular type platelet-activating factor acetylhydrolase that contributes to autocrine inactivation of platelet-activating factor.

IgE-dependent and -independent activation of mouse bone marrow-derived mast cells (BMMC) elicited rapid and transient production of platelet-activating factor (PAF), which reached a maximal level by 2-5 min and was then degraded rapidly, returning to base-line levels by 10-20 min. Inactivation of PAF was preceded by the release of PAF acetylhydrolase (PAF-AH) activity, which reached a plateau by 3-5 min and paralleled the release of beta-hexosaminidase, a marker of mast cell exocytosis. Immunochemical and molecular biological studies revealed that the PAF-AH released from activated mast cells was identical to the plasma-type isoform. In support of the autocrine action of exocytosed PAF-AH, adding exogenous recombinant plasma-type PAF-AH markedly reduced PAF accumulation in activated BMMC. Furthermore, culture of BMMC with a combination of c-kit ligand, interleukin-1beta and interleukin-10 for > 24 h led to an increase in plasma-type PAF-AH expression, accompanied by a reduction in stimulus-initiated PAF production. Collectively, these results suggest that plasma-type PAF-AH released from activated mast cells sequesters proinflammatory PAF produced by these cells, thereby revealing an intriguing anti-inflammatory aspect of mast cells.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Nucleolar organizing regions in primary intracranial malignant lymphomas.

Twenty-two non-immunocompromised patients with primary intracranial malignant lymphomas were examined on surgical material by using an argyrophilic method for the demonstration of nucleolar organizer regions as Ag-NORs. The histopathological classifications of 22 patients included 3 small lymphocytic, 7 small cleaved, 9 large cell. 1 mixed large and small, and 2 small non-cleaved type. The numbers of Ag-NOR of malignant lymphoma patients varied from 1.36 to 5.02 (mean 3.46 +/- 0.25). The mean Ag-NOR numbers in the histopathological subtypes were small lymphocytic 1.63, small cleaved 3.18, large 4.21, mixed large and small 3.47, and small non-cleaved 3.78. The number of Ag-NORs in small lymphocytic type was significantly less than small cleaved or large cell type (p < 0.05). The small cleaved type also had a smaller Ag-NOR number than the large cell type (p < 0.05). Except for two patients who had postoperative deterioration, 20 patients received postoperative irradiation ranging from 36 to 54 Gy (median, 46 Gy). Sixteen patients had complete response to radiotherapy, and 4 had good partial response. Ten patients had tumor recurrence within the remission period of 3 months to 7 years and 10 months (median 4.8 months). Three patients with intracranial relapse at a remote site had a significantly longer remission period (mean 57.3 months) than 7 with local relapse (mean 6.29 months), p < 0.05. The mean Ag-NOR number of the short and long remission period were 3.13 +/- 0.34 and 3.8 +/- 0.80, respectively. No significant difference was found between these two groups. The survival period was 3.2 months to 12 years (median 20 months). The Ag-NOR numbers of survival period less than or more than 20 months were 3.62 +/- 0.40 and 3.27 +/- 0.37, respectively. The Ag-NOR numbers did not correlate with either the remission or the survival period. These results indicate that Ag-NOR numbers may correlate with the histopathologic types, but not with the prognosis of primary intracranial malignant lymphomas.

Adult↗

Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity.

Chondroitin sulfate dipalmitoylphosphatidylethanolamine (CS-PE), when immobilized onto substratum, inhibited the adhesion of B16F10 mouse melanoma cells to fibronectin-coated dishes (anti-adhesion activity). CS-PE showed the most potent anti-adhesion activity for the melanoma cells among various GAG-PEs. CS-PE also inhibited the adhesion of B16F10 cells to Matrigel and the invasion of the cells into Matrigel. In the in vivo system of experimental metastasis, administration of B16F10 cells with CS-PE into C57BL/6 mice significantly inhibited lung metastasis. The inhibition degree of CS or hyaluronic acid-PE was lower than CS-PE. CS-PE administered intravenously into mice before the injection of B16F10 cells also inhibited metastasis. Pretreatment of B16F10 cells with CS-PE caused some but a lower degree of inhibition. When CS-PE was injected intravenously into mice, more binding in the lung was found than when CS was injected. CS-PE but not CS inhibited the retention in the lung of fluorochrome-labeled B16F10 cells when injected intravenously into mice. Since there was no significant effect of CS-PE on the viability and growth of B16F10 cells, the results suggest that CS-PE immobilized onto the subendothelial matrix may prevent melanoma cells from adhering to the subendothelial substrata of lung capillaries and inhibit subsequent invasion processes of metastasis.

Animals↗

[Retrospective analysis of prognostic factors for survival and intracranial control in postoperative radiotherapy for metastatic brain tumor: examination of localized field irradiation].

To analyze the prognostic factors for postoperative radiotherapy of metastatic brain tumors, we retrospectively analyzed the clinical records of 127 cases that received more than 30 Gy of postoperative radiotherapy. The overall one-year survival rate (SR) was 48.2%, while the intracranial control rate (ICR) was 51.7%. Univariate analysis (UVA) revealed that female sex (p = 0.02), higher radiation dose (p = 0.05), and late onset (p = 0.05) were significantly favorable factors of SR. With multivariate analysis (MVA), the approving factors were higher radiation dose (p = 0.02), small number of metastases (p = 0.004), lesser extracranial metastasis (p = 0.02), and female sex (p = 0.02). In MVA, greater radiation dose (p = 0.004), lung cancer (p = 0.02), and late onset (p = 0.05) were found to be significantly good factors for ICR. Our unique method of localized field radiation as applied to well-resected and solitary metastatic tumors, was significantly correlated with better SR in this study. As long as patients are carefully selected, this technique is though to be useful for both the reduction of late complications and dose escalation in postoperative radiotherapy.

Adolescent↗