Congenital tumors of heterotopic central nervous system tissue in the oral cavity: report of two cases.
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Publications and source records attributed to M Harada.
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Changes in the brain lactate concentration in cerebral extracellular fluid (ECF) during intravenous infusion of glucose and local administration of glucose were investigated in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were infused intravenously with either 25% sucrose solution or 25% glucose solution at a rate of 16.6 microliters.min-1.100 g-1 for three hours. The blood glucose concentration reached 17.0 +/- 2.6 mM at the end of the glucose infusion, and brain ECF glucose showed a parallel change with the blood glucose concentration and increased to 2.37 +/- 0.30 mM. However, blood and brain ECF glucose concentrations did not change in animals infused with the sucrose solution. On the other hand, the blood lactate concentration in the glucose-infused group also increased from 0.93 +/- 0.18 mM to 2.85 +/- 0.39 mM at the end of the glucose infusion, which was significantly higher than that measured in the sucrose-infused group. The blood lactate level in the glucose-infused group returned to the basal level by the end of the experiment. Brain ECF lactate concentrations increased from 1.21 +/- 0.06 mM to 1.69 +/- 0.11 mM in glucose-infused animals, but did not change in the sucrose-infused animals. The brain ECF lactate concentration showed a positive correlation with the brain ECF glucose concentration in glucose-infused animals. Another group of rats was administered glucose locally for 90 min after substitution of artificial cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Sensitive and specific two-side enzyme immunoassays (two-site EIAs) for pituitary adenylate cyclase activating polypeptides, PACAP38, and PACAP27, have been established using six monoclonal antibodies against PACAP38, and a rabbit antibody against a C-terminal portion of PACAP27. In extracts of rat hypothalamus, these EIAs detected not only PACAP38 and PACAP27 but also an immunoreactive (ir-) PACAP lacking an epitope of a monoclonal antibody, PA-1C, which recognizes the C-terminal portion of PACAP38. By the use of these EIAs, it was found that one of the human neuroblastoma cell lines, IMR-32, produced ir-PACAP. In reverse-phase (RP-)HPLC, intracellular and extracellular ir-PACAPs were separated into two peaks, of which one was eluted at a position close to that of PACAP38 and the other in rather hydrophobic fractions. Those ir-PACAPs also lacked PA-1C epitope of PACAP38. SDS-PAGE and immunoblot analysis of the two peaks of the RP-HPLC indicated that they consisted of several components including those with apparent molecular weights of 6.5 k and 10 k for the first peak ir-PACAP, and 14 k and 20 k for the second peak ir-PACAP. These results indicate that IMR-32 produces a precursor of PACAP and related peptides generated in various processing steps. Although the significance of the modification in the C-terminus of PACAP38 is unknown, IMR-32 may be a cell line useful for studying the regulation of the biosynthesis of PACAP.
An inducible NADP(+)-dependent D-phenylserine dehydrogenase [EC 1.1.1.-], which catalyzes the oxidation of the hydroxyl group of D-threo-beta-phenylserine, was purified to homogeneity from a crude extract of Pseudomonas syringae NK-15 isolated from soil. The enzyme consisted of two subunits identical in molecular weight (about 31,000). In addition to D-threo-beta-phenylserine, it utilized D-threo-beta-thienylserine, D-threo-beta-hydroxynorvaline, and D-threonine as substrates but was inert towards other isomers of beta-phenylserine and threonine. It showed maximal activity at pH 10.4 for the oxidation of D-threo-beta-phenylserine, and it required NADP+ as a natural coenzyme. NAD+ showed a slight coenzyme activity. The enzyme was inhibited by p-chloromercuribenzoate, HgCl2, and monoiodoacetate but not by the organic acids such as tartronate. The Michaelis constants for D-threo-beta-phenylserine and NADP+ were 0.44 mM and 29 microM, respectively. The N-terminal 27 amino acids sequence was determined. It suggested that the NADP(+)-binding site was located in the N-terminal region of the enzyme.
1-Ethoxymethyl-5-fluorouracil (EM-FU) is a fluorinated pyrimidine derived from 5-FU, and 3-cyano-2,6-dihydroxypyridine (CNDP) is a chemical modulator which suppresses the catabolism of 5-FU by inhibiting dihydrouracil dehydrogenase in the liver. In this study, the metabolism of EM-FU and the suppression of 5-FU catabolism by CNDP were observed by in vivo 19F magnetic resonance spectroscopy in comparison with other similar drugs, because it is considered that the most effective mode of therapy using 5-FU is to suppress the catabolism of 5-FU in the liver and so to maintain for longer an effective blood level of 5-FU. The metabolism of EM-FU was very slow and the production of fluoro-beta-alanine was very low as compared to the case of tegafur. The catabolic suppression by CNDP was much stronger than that of uracil. Therefore co-administration of EM-FU and CNDP should suppress catabolism and maintain an effective blood level of 5-FU for a long period of time.
Kinetics of circulating haematopoietic progenitors was analysed during chemotherapy- or chemotherapy plus granulocyte colony-stimulating factor (G-CSF)-induced mobilization of peripheral blood stem cells. Circulating progenitors including colony-forming unit granulocyte/macrophage (CFU-GM), burst forming-unit erythroid (BFU-E) and multilineage colony forming unit (CFU-Mix) were studied serially on alternate days during a recovery phase from chemotherapy for consolidation of complete remission. In 18 patients with acute leukaemia, 27 courses of consolidation chemotherapy were performed with a combination of an intermediate-dose cytosine arabinoside with etoposide (Ara-C/Etop) or mitoxantron (Ara-C/Mit). G-CSF (5 micrograms/kg) was administered during the recovery phase in 6/14 courses with Ara-C/Etop and in 4/13 courses with Ara-C/Mit. G-CSF induced a significant and synchronized increase of circulating CFU-GM, BFU-E and CFU-Mix by more than 4-fold at their peaks. The peak of CFU-GM was significantly correlated with that of both BFU-E and CFU-Mix, irrespective of additional G-CSF mobilization. G-CSF also produced a significant increase of monocytes in a synchronized fashion with an increase of circulating CFU-GM. Interestingly, peripheral blood monocytes spontaneously produced high concentrations of IL-6; a significant correlation was observed between absolute monocyte counts and plasma levels of IL-6 or peak levels of CFU-GM. These observations indicate that the addition of G-CSF to chemotherapy-induced mobilization can facilitate further expansion of a blood progenitor pool during the haematopoietic recovery, probably through the stimulation of monocytes to proliferate and to induce their monokine production such as IL-6. The data also suggest that absolute monocyte counts may be a useful indicator to predict the peak of circulating progenitors for collecting autologous blood stem cells.
We studied the utility of G-CSF for harvesting circulating haematopoietic stem cells in patients with leukaemia or lymphoma based on a comparative study in a single patient. Two successive cycles of leukapheresis following cytotoxic chemotherapy were performed in 22 patients as follows: the first cycle was performed with cytotoxic mobilization in all patients while the second cycle was randomized into two groups: cytotoxic (n = 10) and cytotoxic plus G-CSF (cytotoxic/G-CSF) (n = 12) mobilization. Repetitive cytotoxic mobilization did not alter the yields of mononuclear cells (MNC), myeloid (CFU-GM), and erythroid (BFU-E) progenitors. In contrast, cytotoxic/G-CSF mobilization produced significantly higher yields of MNC (2.6-fold), CFU-GM (5.5-fold), and BFU-E (3.9-fold) than did cytotoxic mobilization alone (P < 0.01). The ratio of CFU-GM to BFU-E was not affected by G-CSF. Furthermore, G-CSF led to an earlier peak of CFU-GM following chemotherapy. G-CSF is thus effective in expanding the pool of circulating haematopoietic progenitors.
A major issue in autologous blood stem cell transplantation (ABSCT) for leukaemia is whether peripheral blood stem cell (PBSC) harvests are less contaminated with leukaemic cells than bone marrow mononuclear cells (BMMNC). We compared leukaemic contamination in PBSC harvests and BMMNC, obtained simultaneously, by using reverse transcriptase polymerase chain reaction (RT-PCR) of leukaemia-specific chimaeric messenger RNA (mRNA), in three patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukaemia (ALL), one with Ph-positive acute myelogenous leukaemia (AML), and two with acute promyelocytic leukaemia (APL). Our two-step PCR method employed 'nested primers' in the second step and can detect one leukaemic blast diluted into 10(6) HL-60 cells. In three of four patients with Ph-positive ALL and AML we detected leukaemic contamination in both PBSC harvests and BMMNC. In the remaining patient with ALL, both PBSC harvests and BMMNC were PCR-negative. Both PBSC harvests and BMMNC from one patient with APL were PCR-positive. In contrast, PBSC harvests from another patient with APL, whose BMMNC could not be obtained because of bone marrow necrosis, were PCR-positive after the first course of consolidation chemotherapy, but became PCR-negative after the second course. The present study does not support the hypothesis that PBSC harvests are less contaminated by leukaemic cells than BMMNC, but suggests that PBSC harvests are contaminated when BMMNC are contaminated.
We studied the production of cytokines by peripheral blood monocytes and T cells during the period of haematological recovery following intensive chemotherapy. Twelve adults with haematological malignancies received consolidation chemotherapy of complete remission. Monocytes and T cells were collected during the phase of recovery from intensive chemotherapy, and were incubated for 24 h in a culture medium with 10% FCS. Concentrations of cytokines in the culture supernatant were measured with an enzyme-linked immunosorbent assay. During the recovery phase, concentrations of IL-6, G-CSF and IL-1 beta in the culture supernatant of the collected monocytes significantly exceeded those of the monocytes obtained from normal healthy subjects. Similarly, the concentrations of GM-CSF and IFN-gamma in the supernatant of recovery phase T cells significantly exceeded those of normal T cells. Plasma levels of these cytokines were also elevated. These data suggest that the monocytes and T cells may be activated in vivo to produce haemopoietic cytokines during haematological recovery, and that, during haematological recovery, the monocytes and T cells may be actively involved in the induction of haematopoiesis following the myelosuppression induced by chemotherapy.
We studied the long-term in vivo effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on in vitro growth of granulocyte/macrophage colony forming cells (GM-CFC) in bone marrow and peripheral blood obtained from two patients with autoimmune neutropenia, who received rhG-CSF. Along with rhG-CSF treatment for more than 40 d, numbers of GM-CFC-derived colonies from both bone marrow and peripheral blood gradually decreased to a significant level though white blood cells in peripheral blood and nucleated cells in bone marrow were increased in number. This observation suggests that long-term administration of rhG-CSF may preferentially activate a differentiation pathway for granulopoiesis while proliferation of GM-CFC is not induced as expected in response to rhG-CSF.
Dynamic magnetic resonance (MR) imaging was performed on a 1.5-T superconducting unit for evaluation of 26 stage I endometrial carcinomas. To establish the appearance of the normal uterus, 27 normal uteri were also evaluated. After rapid injection of gadopentetate dimeglumine, dynamic images were obtained every 30 seconds with the spin-echo technique in the sagittal plane. On dynamic studies of endometrial carcinoma, the tumor-myometrial contrast was marked at 120 seconds after administration of gadopentetate dimeglumine (contrast-to-noise ratio [C/N], 26.0). The tumor-myometrial contrast on the dynamic study was more marked than that on postcontrast T1-weighted images (C/N, 10.0) and on T2-weighted images (C/N, 2.14). Dynamic and postcontrast MR images were superior in enabling differentiation of viable tumors from necrosis or residual secretion in the endometrial cavity. In the evaluation of presence of tumor and myometrial invasion, the accuracy of T2-weighted imaging and dynamic imaging was 67.9% and 84.9%, respectively.
We previously reported that liposomes composed of phosphatidylethanolamine (PE) and fatty acid exhibited pH-dependent leakage, aggregation and fusion (N. Hazemoto, M. Harada, N. Komatubara, M. Haga and Y. Kato, Chem. Pharm. Bull., 38, 748 (1990)). In this study, we have examined the effects of phosphatidylcholine (PC) and cholesterol (Chol) on the pH-sensitivity of liposomes. Contents-leakage from liposomes was always accompanied by a change in light-scattering, suggesting that aggregation or fusion of liposomes causes the leakage. The pH-sensitivity was observed only when liposomes contained less than 32 mol% of PC. The leakage vs. pH curves shifted to the more acidic regions as the PC content of the liposomes increased, but the maximum leakage (%) did not change. The effect of cholesterol on the pH-sensitivity depended on the PC/PE ratio of the liposomes. Addition of cholesterol to PC/PE/oleic acid (OA) liposomes system induced two effects, that is, aggregation of liposomes via the reduction in PC content and the stabilization of the liposomal membrane. It was shown that pH-sensitivity can be controlled by addition of the appropriate amount of PC and/or Chol to liposomal lipids.
A 25-year-old Japanese man was diagnosed as having primary pulmonary hypertension, on the basis of the findings of cardiac catheterization and ventilation-perfusion scintiscans. The plasma level of plasminogen in this patient was found to be reduced to 43% by a functional assay and 61 mg/l by an antigenic assay. Based on the family study, the patient was considered to have a heterozygous congenital plasminogen deficiency. Accordingly, it is suggested that the defective fibrinolysis in this patient may have played an important role in the development of primary pulmonary hypertension through microthrombosis.
OBJECTIVE: Our purpose was to identify the conventional spin-echo and contrast-enhanced dynamic MR imaging features of intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: Eight patients with pathologically proved intrahepatic cholangiocarcinoma were examined with conventional spin-echo and contrast-enhanced dynamic MR imaging with a 1.5-T superconductive unit. The results were analyzed to include the signal intensity of the mass relative to liver parenchyma on conventional spin-echo images and the pattern and degree of enhancement on dynamic MR images. RESULTS: The characteristic appearance of intrahepatic cholangiocarcinoma was a large mass with an irregular margin, satellite nodules, and a central scar. Tumors were hypointense relative to liver parenchyma on T1-weighted spin-echo images and hyperintense on T2-weighted spin-echo images. On dynamic MR studies, tumors characteristically had minimal or moderate rim enhancement with progressive and concentric filling with contrast material. CONCLUSION: Our study suggests that intrahepatic cholangiocarcinoma has a typical pattern on contrast-enhanced dynamic MR images.
Severe postpartum hemorrhage can result from laceration of the genital tract during delivery. Hematomas may occur, but they often extend deep into the underlying tissues, frequently in the pelvic extraperitoneal space. Because of the relatively small amount of external hemorrhage, hematomas may be overlooked until the patient shows signs of shock [1]. Therefore, prompt diagnosis and recognition of the spread of hematomas are essential. The purpose of this essay is to illustrate the imaging findings of postpartum hematomas located in the extraperitoneal space of the pelvis.
It has been shown that molecular cytogenetics in interphase nuclei is applicable to paraffin embedded sections from formarin-fixed materials utilizing in situ hybridization (ISH). This allows precise identification of numerical abnormalities of chromosome in tumor cells without disruption of tumor morphology. Thirteen cases of bladder cancer and twenty six cases of prostate adenocarcinoma were evaluated for numerical aberrations of chromosome 1, 7, 10, 11, 17, 18, X and Y utilizing biotinylated probes specific for the alpha satellite region. In two cases from total prostatectomy, one case from total cystectomy and two cases from TUR-P specimen, hybridized chromosomes could not be detected in individual tumor cells. With respect to the appearance of the ISH signal, optical concentration and time for the digestion enzyme has to be established essentially. This technique can now be applied on the detection of biological activity in various types of urological cancer.
Histopathological comparison of clinical prostatic adenocarcinoma between Japan and the United States (US) has been made with retrospective analyses on 1,037 and 987 cases, respectively. All cases were histologically evaluated by the same pathologist (M.H.) without previous knowledge of clinical information according to application of the Japanese General Rules for Prostatic Cancer (JGRPC) based on the predominant degree of histological differentiation, the nuclear grading by WHO classification and the Gleason grading systems. The age distribution of the patients was slightly different among both groups. However, this difference appeared not to be essential, because there existed difference of the date on diagnosis between two groups. Even though considering this time difference on registration, much more cases from Japan had stage D disease. The observed incidence of the histological differentiation classified by JGRPC among over-all cases did not show significant difference, however, the incidence among the cases with same stage between two groups differed with some statistical significance. Much more cases from the US fell in well differentiated adenocarcinoma and frequency of moderately differentiated adenocarcinoma was higher in the Japanese even in the cases diagnosed at advanced stages. The observed incidence of nuclear grade 3 was also higher in the Japanese. Gleason primary and secondary grade 5 and score 9-10 appeared more frequently in the cases from Japan.(ABSTRACT TRUNCATED AT 250 WORDS)
Histopathological characteristics of stage A prostatic adenocarcinoma from Japan (137 cases) and the United States (51 cases) were comparatively evaluated by retrospective analysis. All cases were examined by one referee pathologist (MH) using classification based on Japanese General Rules for Prostatic Cancer (JGRPC), nuclear grading by Mostofi-WHO system and Gleason grading. The incidences of the cases with well differentiated, low nuclear anaplasia and Gleason grade 1 or 2 on primary and secondary grades as well as histologic score 2-4 were much more higher in the cases from Japan as compared with those from the US. In the cases from the US proportion of the cases with moderately differentiated adenocarcinoma and grade 2 nuclear anaplasia exceeded those with well differentiated and grade 1 anaplasia. Adenocarcinomas with Gleason grade 3 in primary and secondary grade and 6-8 of histologic score were also more frequently observed in the cases from the US. No different distribution of each histologic grade could be obtained among the Japanese cases classified stage A2 and entire cases from the US. These results suggest that much more stage A adenocarcinoma in the US might fall into A2 if strict criteria was applied for subcalssification of stage A, which may reflected in the remarkable difference in the incidence of clinical prostatic carcinoma.