Biomedical subjects

M Kajiwara

Publications and source records attributed to M Kajiwara.

At least 37 records · Page 2Linked to original sources

PubMed1999

Immunohistochemical distribution of bombesin-positive pulmonary neuroendocrine cells in a congenital diaphragmatic hernia.

Morphometrical analyses of the immunohistochemical expression of bombesin, which is one of the peptides produced by pulmonary neuroendocrine (PNE) cells, were carried out on the bronchioles of human congenital diaphragmatic hernia (CDH) neonates, and the findings were then compared with those in a gestational and postnatal age-matched control group. As a result, no difference was found in the number of bombesin-positive cells between the lungs of the control group and the unaffected side lungs in the CDH group except for the ratio of the bombesin-positive cells per unit of the bronchiolar surface area (P < 0.05). However, compared with the lungs in the control group, the affected side of the lungs in the CDH group showed a significant increase in the expression of bombesin, namely, the ratio of the bombesin-positive cells per bronchiole (P < 0.05), the ratio of the bombesin-positive cells per unit perimeter of the bronchioles (P < 0.05), and the ratio of the bombesin-positive cells per unit of the bronchiolar surface area (P < 0.01). These results thus suggest that hyperplasia of the PNE-cell system in the lungs of the CDH cases, especially on the affected side, exists in human fetuses. We also further speculate that PNE cells may thus play a role in the problems associated with CDH during intrauterine life in human beings.

Biometry↗

PubMed1999

WASP is involved in proliferation and differentiation of human haemopoietic progenitors in vitro.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study we investigated the role of WASP in the differentiation of CD34-positive (CD34+) cells isolated from the bone marrow of patients with WAS (n = 5) or with XLT (n = 4). Megakaryocyte colony formation was significantly decreased in patients with WAS when compared with normal controls. The formation of granulocyte-macrophage colonies and erythroid bursts were also decreased in WAS patinets. In contrast, in XLT patients, formation of all these colonies was normal. However, in vitro proplatelet formation of megakaryocytes induced by thrombopoietin was markedly decreased in both XLT and WAS. Electron microscopic examination revealed that megakaryocytes obtained from WAS or XLT patients grown in vitro had abnormal morphologic features, which seemed to be caused by defective actin cytoskeletal organization, including labyrinth-like structures of the demarcation membrane system and deviated distribution of the alpha-granules and demarcation membrane system. These observations indicate that WASP is involved in the proliferation and differentiation of CD34+ haemopoietic progenitor cells probably by its participation in signal transduction and in the regulation of the cytoskeleton.

Blood Platelets↗

PubMed1999

Villous tumor of the colon and rectum with special reference to roles of p53 and bcl-2 in adenoma-carcinoma sequence.

Villous tumors are rare and their histological diagnosis from biopsy specimens is often difficult. To ascertain its tumor progression, including the genetic events, would be useful for clinical treatment. Clinicopathological features and the expression of p53 and bcl-2 proteins were investigated in 50 villous tumors from 49 patients. The patients' ages ranged widely from 32 to 84 years (average, 61 years). Females were more frequently affected than males (male:female ratio, 20:29). Thirty-six (72%) of the villous tumors were present within the sigmoid colon and rectum. Histologically, 17 (34%) of these contained carcinomas in villous adenomas (CIVA), while 24 (73%) of 33 villous adenomas (VA) contained high-grade dysplasia. Most of the CIVA revealed well-differentiated adenocarcinoma, often with focal or diffuse mucin pools. Three lesions of invasive carcinomas were composed of extremely well-differentiated components. The average size of the CIVA (79 mm) was significantly larger than that of the VA (51 mm). Overexpression of p53 protein was recognized in 12% of VA, in 24% of mucosal components of CIVA and in 18% of invasive components of CIVA. Overexpression of bcl-2 was recognized in 57% of VA, 33% of mucosal components of CIVA, and 7% of invasive components of CIVA. Several characteristic features were recognized in villous tumors, which comprised: (i) a high frequency of coexistence of carcinoma; (ii) multiple foci of carcinomas arising in adenomatous tumors; (iii) a lower histological grade of carcinomas, often with mucin pools; (iv) the existence of extremely well-differentiated adenocarcinomas; and (v) less frequent expression of p53 protein in the carcinomatous components. According to these findings, the pathway of tumor progression in the villous tumors is possibly different from that of sporadic colorectal carcinomas. Because of the peculiarity of villous tumors, careful clinical management is required.

Adenocarcinoma↗

PubMed1999

Primary intracranial squamous cell carcinoma--case report.

A 50-year-old female presented with primary intracranial squamous cell carcinoma (SCC) at the right cerebellopontine angle manifesting as right facial nerve paresis. She had undergone gross total removal of a right cerebellopontine angle epidermoid cyst 10 years before and had done well until recently. Magnetic resonance imaging showed a heterogeneous tumor with markedly enhanced irregular margin. Subtotal removal of the tumor was achieved. Histological examination showed moderately differentiated SCC. After surgery, she underwent chemotherapy and gamma radiosurgery. She is now well 5 years after the diagnosis of SCC.

Adult↗

PubMed1998

Expression of clara cell 10-kDa protein (CC10) in congenital diaphragmatic hernia.

Clara cell 10 kDa protein (CC10) has been thought to be fairly specific to Clara cells and a major secretory protein that is both synthesized and released from Clara cells. In the present study, morphometric analyses of the immunohistochemical expression of CC10 were carried out on the bronchioles of human neonates with congenital diaphragmatic hernia (CDH) and then compared with morphometric analyses from a gestationally and postnatally age-matched control group in order to clarify the immaturity of Clara cells in CDH lungs. No difference was found in CC10 expression between the affected side and the unaffected side of the lungs in the CDH group. However, compared with the lungs of the control group, the CDH group showed a significant decrease in CC10 expression, namely, the ratio of CC10-positive cells per bronchiole, per unit perimeter of bronchiole, and per unit bronchiolar surface area. These results suggest that in the lungs of CDH cases, a possible delay in either functional maturation or the development of CC10 synthesis by the bronchioles may exist, and this retardation of functional maturation of the airway is also considered to play a role in the postnatal respiratory insufficiency observed in CDH patients.

Bronchi↗

PubMed1998

Enhancement of tumor cell lysis by natural killer cells after blocking of HLA-monomorphic determinant using F(ab')2 fragment of W6/32.

It has been known that negative signal of natural killer (NK) cells is triggered by HLA-polymorphic determinant (PMD) of target cells. However, it is not clear whether or not the negative signal is triggered by HLA-monomorphic determinant (MMD). In this study, we determined the interaction of NK receptor and MMD by mean of a blocking test. For the blocking, W6/32, which is an antibody to the MMD, was used. As target cells, we used a tumor cell line H42 and several cell lines. The H42 was established from a bladder cancer patient after radiation therapy. This cell line was demonstrated to be PMD negative but MMD positive and showed NK sensitivity. We had established one more cell line, H41, from the same patient before the radiation therapy. However, the H41 possessed both the PMD and MMD and exhibited NK resistance. Thus, the NK sensitivity of the H42 may be due to depression of the PMD. We performed a blocking test against the MMD of these cell lines. When the H42 was pretreated with F(ab')2 fragment of the W6/32, the killing by NK cells increased. Other cell lines, EB33, KMT-1, and HMy2-C1R, which possessed low levels of PMD, were killed moderately after the pretreatment, although the H41 and other cell lines (KO, MT-2, OKM-3T), which possessed high levels of PMD, were killed only slightly. These findings suggest that the negative signal may be triggered not only by the PMD but also by the MMD.

Adult↗

PubMed1998

Timing of effective natural killer cell collection in cancer patients after high dose chemotherapy, compared to peripheral blood stem cell collection.

Natural killer (NK) and lymphokine-activated killer (LAK) activities in patients with seminoma were determined, and the timing of effective NK cell collection was evaluated, compared to autologous peripheral blood stem cell (PBSC) collection. After chemotherapy, patients were injected with granulocyte-colony stimulating factor (G-CSF). CD56 cells decreased in parallel with white blood cells and then were restored. After discontinuing the G-CSF, the CD56 cells increased and reached peak 3-5 days after PBSC collection. The peak showed higher levels than those at premedication. Recovery-peripheral blood lymphocytes (PBL) which were obtained 4 days after PBSC collection showed higher NK and LAK activities than the PBL obtained before chemotherapy (Before-PBL). They exhibited a high expression of CD2, CD18, CD29, and CD49d. Furthermore, the LAK cells generated from the Recovery-PBL could acquire 9.6 folds of killer unit compared with the Before-PBL-LAK. These results suggest that, in order to obtain large numbers of NK cells, Recovery-PBL collection may be more advantageous than PBL collection in no relation with the chemotherapy.

Antigens, CD↗

PubMed1998

Isolation of a major metabolite (i-OHAP) of aprindine and its identification as N-[3-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol.

i-OHAP, a major metabolite of aprindine (AP), was isolated by TLC from rat feces and identified as N-13-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol, based on 1H-NMR, the H-H correlation spectroscopy (COSY) spectrum, MS and LC-MS. Its structure was also confirmed by comparison with the synthesized compound. The hydroxy group of i-OHAP was located at the 5-position of the indan ring. AP is a prochiral compound, and the metabolism of AP to i-OHAP was stereoselective. The ratio of (+)/(-)-i-OHAP in rat feces and in human urine was about 5 and 15, respectively.

Adult↗

PubMed1998

Optimum conditions for the 13C-phenylalanine breath test.

We have conducted optimization studies to develop a superior 13C-phenylalanine breath test for the diagnosis of liver disease. First, we examined the optimum 13C-labeling position in phenylalanine for use in a breath test based on infrared spectroscopic detection of 13CO2 in exhaled air. L-[1-13C]Phenylalanine gave the best result. Next, a suitable dosage to give a short peak time (the time expressed in minutes at which 13CO2 excretion is maximal) after administration was determined. The 13CO2/12CO2 ratio in exhaled air after administration of 100 mg/body of L-[1-13C]phenylalanine peaked sharply at 15 min. We also examined the effect of food on the hepatic metabolism of L-[1-13C]phenylalanine. We found that a fasting period of over 7 h before the test resulted in a higher 13CO2 peak excretion. The peak appeared sooner than that in the 13C-phenacetin breath test and, therefore, the 13C-phenylalanine breath test appears preferable for the rapid evaluation of hepatic function.

Breath Tests↗

PubMed1998

Screening system for urease inhibitors using 13C-NMR.

Urease inhibitors are candidate drugs to treat infection with the human pathogen, Helicobacter pylori, which produces a potent urease [urea amidohydrolase; EC 3.5.1.5]. We developed a screening system based on 13C-NMR measurement of the time course of decrease in the signal of 13C-urea in the presence of urease. The effect on urease activity of known inhibitors, hydroxamic acids, L-ascorbic acid, 2,2'-dipyridyl disulfide and ninhydrin, was speedily and conveniently measured by this method.

Binding, Competitive↗

PubMed1998

Relation of natural killer cell line NK-92-mediated cytolysis (NK-92-lysis) with the surface markers of major histocompatibility complex class I antigens, adhesion molecules, and Fas of target cells.

Natural killer (NK) cell line NK-92 has recently been established by Klingemann et al. In this study, we compared the NK-92-mediated cytolysis (NK-92-lysis) with the killing of healthy volunteers' NK cells and lymphokine-activated killer (LAK) cells. The NK-92-lysis was partially different from the NK- and LAK-lysis. 1) The NK-92 could kill most of major histocompatibility complex (MHC) class I antigen-positive tumor cells. 2) The NK cells killed a myeloid leukemia cell line K562, but the NK-92 showed low killer activity against it. 3) The LAK cells could not kill a CD58-deficient cell line OKM-2T, whereas the NK-92 could kill it sufficiently. 4) The NK-92 could not kill CD54-, CD102-deficient cell lines T98G and U373MG; however, the LAK cells could kill them. Blocking tests using specific antibodies revealed the reason for these differences. The K562 expressed relatively low levels of CD54 and CD102. When the K562 was pretreated with anti-CD54 and anti-CD102, the NK-92 could not kill it at all, whereas the NK cells could still kill it, although the killing level decreased. The NK-92 could not kill the anti-CD54- and anti-CD102-treated OKM-2T. The LAK cells could not kill anti-CD58-treated U373MG and T98G. These findings suggest that NK-92-lysis may require the CD54 and CD102 but that NK-lysis does not require them as much, whereas the LAK-lysis may be rather in relation with the CD58. The NK-92 has high killer activity, and may be applicable for clinical use. However, it should be considered that the NK-92 cannnot kill CD54-, CD102-deficient tumor cells.

Antigens, CD19↗

PubMed1998

[Ethanol-induced injury and GI bleeding].

Ethanol-induced injury of digestive organs closely linked to the GI bleeding. The gastric or esophageal mucosal hemorrhage evoked by extra-amounts of alcohols is initiated by the microcirculatory damage of gastrointestinal mucosa. Many investigators focused on the ethanol-induced gastric ulcer formation as well as the ethanol-induced gastroesophageal reflux injury. Although the most important treatment for such a damage is of course to stop the drinking, it is also important to protect the gastrointestinal mucosa by potentiate the mucosal defense systems.

Alcoholic Beverages↗

PubMed1998

A lymphokine-activated killer (LAK)-resistant cell line, and low expression of adhesion molecules LFA-3 and VCAM-1 on its cell surface.

Tumor cell lines are generally killed by lymphokine-activated killer (LAK) cells. In this study, however, we report a LAK-resistant cell line, OKM-2T. The OKM-2T is an adult T-cell leukemia (ATL) cell line, and was compared to other ATL cell lines and non-ATL cell lines. The LAK cells were generated from healthy volunteers. Cell surface markers were determined by a flow cytometry test. The ATL and non-ATL cell lines were killed by the LAK cells, markedly or moderately. However, the OKM-2T was scarcely killed. The adhesion tendency of the OKM-2T to the LAK cells was preserved at the same level as that of the other cell lines, whereas the OKM-2T showed low levels of adhesion molecules CD58 (LFA-3), CD86, and CD106 (VCAM-1). We determined blocking tests using specific antibodies. Anti-CD58 blocked the LAK lysis. Anti-CD54 and anti-CD106 enhanced the blocking effect of the anti-CD58; anti-CD86 did not show such an effect. These results suggest that the low expression of CD58 in the OKM-2T may have an intimate relationship with LAK resistance, and that the low expression of CD106 may also be responsible for it, in part.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1997

Determination of unbound warfarin enantiomers in human plasma and 7-hydroxywarfarin in human urine by chiral stationary-phase liquid chromatography with ultraviolet or fluorescence and on-line circular dichroism detection.

Enantiomers of warfarin and 7-hydroxywarfarin in human plasma and urine, respectively, were determined by high-performance liquid chromatography using a cellulose-derivative column with UV or fluorescent detection, and their absolute configuration was determined simultaneously by a circular dichroism spectropolarimeter connected in series. Enantiomers of warfarin and its major metabolites [i.e., (R)-6-hydroxywarfarin, (S)-7-hydroxywarfarin and (RS)-warfarin alcohol] were well resolved. The method was precise and sensitive: within- and between-day coefficients of variation were <9.6% for warfarin enantiomers in plasma and <7.1% for 7-hydroxywarfarin enantiomers in urine, respectively, and the lower detection limits were 20 ng/ml for (R)-warfarin, 40 ng/ml for (S)-warfarin, 2.5 ng/ml for (R)-7-hydroxywarfarin and 4.5 ng/ml for (S)-7-hydroxywarfarin in 0.5 ml of both plasma and urine. The ultrafiltration technique was used for determining unbound concentrations of warfarin enantiomers in plasma using [14C]warfarin enantiomers resolved by the present HPLC system. Clinical applicability of the method was evaluated by determining unbound concentrations of warfarin enantiomers in five consecutive plasma samples obtained from a patient exhibiting an unstable anticoagulant response to warfarin (4 mg/day, p.o.). Results indicated that the present method would be useful in clarifying factors responsible for a large intra- and inter-patient variability in warfarin effects with regard to unbound plasma enantiomer pharmacokinetics.

Anticoagulants↗

PubMed1997

Generation of NK1.1+ T cell antigen receptor alpha/beta+ thymocytes associated with intact thymic structure.

The development of T cells within the thymus is largely dependent on intact cortical and medullary epithelial cells. However, it has been reported that positive selection of natural killer antigen 1.1+ (NK1.1+) T cell antigen receptor (TCR)-alpha/beta+ thymocytes recently identified among CD4+8- and CD4-8- subpopulations is attributable to major histocompatibility complex class Ib ligands expressed on bone marrow (BM)-derived components in the thymus. In the present study, we investigated generation of NK1.1+ TCR-alpha/beta+ cells in the thymus of the aly/aly mouse which lacks lymph nodes and Peyer's patches and shows abnormalities of thymic and splenic structure. We found that the proportion of the NK1.1+ TCR-alpha/beta+ thymocytes was extremely low in these mice as compared with aly/+ and normal C57BL/6 mice. Thymic reconstitution by BM cells from aly/+ mice that possess a normal population of NK1.1+ TCR-alpha/beta+ cell population did not restore the NK1.1+ TCR-alpha/beta+ cell population in the thymus of lethally irradiated aly/aly mouse. When deoxyguanosine-treated fetal thymi from (B6 x B10.G)F1 mice were transplanted to aly/aly mice that had been thymectomized and reconstituted with BM cells of aly/aly mice, normal proportions of the NK1.1+ TCR-alpha/beta+ thymocytes were present in the thymus grafts. These findings demonstrate that the development of NK1.1+ TCR-alpha/beta+ thymocytes is accomplished under the influence not only of BM-derived components, but also of irradiation-resistant or deoxyguanosine-resistant components and an intact microenvironment of the thymus.

Animals↗

PubMed1997

Comparison of natural killer (NK) sensitivities of two tumor cell lines established from a cancer patient before and after radiation therapy.

Major histocompatibility complex (MHC) class I positive tumor cells are generally resistant to natural killer (NK) cells. In this report, we compared the NK sensitivities of tumor cell lines H41 and H42, which were established from a cancer patient at surgery. H41 was established before radiation therapy and H42 was established after the radiation therapy in 1985. H41 was resistant to NK cells, whereas H42 was NK-sensitive. Both cell lines reacted with W6/32, which is an antibody to the HLA common epitope determinant. However, H42 did not react to anti-HLA-locus-specific antibodies, although H41 reacted to them. When these cell lines were treated with interferon-gamma, H41 showed an increase in HLA-locus-specific antigenicity, whereas H42 did not show such a tendency. This suggests that there may have been interference in the expression of the HLA-locus-specific determinants on H42. Therefore, it was assumed that the NK sensitivity of H42 may be due to depression of an HLA-locus-specific determinant, and this depression may be related to the radiation therapy. The patient recovered from the disease after the radiation therapy and the last surgery. He is now in a tumor-free state. We propose that his recovery may be related to the conversion of the tumor cells from NK-resistant to NK-sensitive.

Carcinoma, Transitional Cell↗

PubMed1997

Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia.

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and persistent pulmonary hypertension. Recent experimental studies suggest that surfactant deficiency may also contribute to CDH pathophysiology. In this report, the authors immunohistochemically and morphometrically examined whether or not the hypoplastic lungs of CDH are associated with the immaturity of the surfactant system, especially alveolar type II cell function. Nine autopsy cases with CDH were immunohistochemically examined for the expression of surfactant apoprotein, using anti-IgG against human surfactant apoprotein A (SP-A), and the findings were compared with those in a gestational and postnatal age-matched control group. The lung/body weight ratio in the CDH was less than that in the controls (0.010 +/- 0.005 versus 0.021 +/- 0.013, P < .01). The radial alveolar count (RAC) of the CDH cases were also significantly less than that of the control cases (2.10 +/- 0.52 versus 3.48 +/- 0.39, P < .01). In the CDH cases, the RAC of the lung on the affected side were also significantly less than that of the lung on the unaffected side (1.71 +/- 0.34 versus 2.50 +/- 0.26, P < .01). In the immunohistochemical distribution of SP-A, compared with the control cases, the number of SP-A-positive cells on the alveolar septa of the CDH cases decreased in number, and this immunohistochemical reaction was weak even in positive type II cells. In addition, the immunoreaction observed in the alveolar type II cells of the unaffected side lungs in the four CDH cases was stronger than that of the unaffected side lungs. These results suggest that in the lungs of the CDH cases, especially on the affected side, there is a possible delay in both the structural growth and functional maturation or development of SP-A synthesis by alveolar type II cells, and this retardation of the functional maturation in alveolar type II cells is also considered to play a role in postnatal respiratory insufficiency in CDH patients.

Apolipoproteins A↗

PubMed1997

A case of congenital intraspinal neuroblastoma.

A case of congenital intraspinal neuroblastoma with paraplegia in a newborn is described, and a review of previously reported cases is presented. Calcification within the spinal canal and abdominal mass was noted. At age 75 days, the patient underwent a resection of almost the entire retroperitonial tumor. A magnetic resonance scan showed hepatic metastasis, and chemotherapy was changed to a more intensive regimen. The liver metastasis disappeared; however, neurological signs persisted. A literature review of 38 cases showed 26 patients had a laminectomy and 12 patients did not. Treatment with or without laminectomy was associated with a poor prognosis for neurological recovery, suggesting cord compression must occur antenatally, and irreversible damage occurs before birth. Congenital intraspinal neuroblastoma has a relatively good prognosis (survival rate, 91.9%), although complete neurological recovery is highly unusual. Based on these findings, the authors conclude that a laminectomy is not indicated for those patients.

Calcinosis↗