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Yasuhiro Kishi

Publications and source records attributed to Yasuhiro Kishi.

16 recordsLinked to original sources
PubMed2006

Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid.

Autotaxin (ATX) is a cancer-associated motogen that has multiple biological activities in vitro through the production of bioactive small lipids, lysophosphatidic acid (LPA). ATX and LPA are abundantly present in circulating blood. However, their roles in circulation remain to be solved. To uncover the physiological role of ATX we analyzed ATX knock-out mice. In ATX-null embryos, early blood vessels appeared to form properly, but they failed to develop into mature vessels. As a result ATX-null mice are lethal around embryonic day 10.5. The phenotype is much more severe than those of LPA receptor knock-out mice reported so far. In cultured allantois explants, neither ATX nor LPA was angiogenic. However, both of them helped to maintain preformed vessels by preventing disassembly of the vessels that was not antagonized by Ki16425, an LPA receptor antagonist. In serum from heterozygous mice both lysophospholipase D activity and LPA level were about half of those from wild-type mice, showing that ATX is responsible for the bulk of LPA production in serum. The present study revealed a previously unassigned role of ATX in stabilizing vessels through novel LPA signaling pathways.

Animals↗
PubMed2006

Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid.

Autotaxin (ATX) is a multifunctional phosphodiesterase originally isolated from melanoma cells as a potent cell motility-stimulating factor. ATX is identical to lysophospholipase D, which produces a bioactive phospholipid, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC). Although enhanced expression of ATX in various tumor tissues has been repeatedly demonstrated, and thus, ATX is implicated in progression of tumor, the precise role of ATX expressed by tumor cells was unclear. In this study, we found that ATX is highly expressed in glioblastoma multiforme (GBM), the most malignant glioma due to its high infiltration into the normal brain parenchyma, but not in tissues from other brain tumors. In addition, LPA1, an LPA receptor responsible for LPA-driven cell motility, is predominantly expressed in GBM. One of the glioblastomas that showed the highest ATX expression (SNB-78), as well as ATX-stable transfectants, showed LPA1-dependent cell migration in response to LPA in both Boyden chamber and wound healing assays. Interestingly these ATX-expressing cells also showed chemotactic response to LPC. In addition, knockdown of the ATX level using small interfering RNA technique in SNB-78 cells suppressed their migratory response to LPC. These results suggest that the autocrine production of LPA by cancer cell-derived ATX and exogenously supplied LPC contribute to the invasiveness of cancer cells and that LPA1, ATX, and LPC-producing enzymes are potential targets for cancer therapy, including GBM.

Blotting, Western↗
PubMed2006

What should non-US behavioral health systems learn from the USA?: US behavior health services trends in the 1980s and 1990s.

Several countries, such as the USA, inadvertently created a different behavioral health payment system from the rest of medicine through the introduction of diagnostic-related group exemptions for psychiatric care. This led to isolation in the administration and delivery of care for patients with mental health and substance abuse disorders from other medical services with significant, yet unintended, consequences. To insure an efficient and effective health-care system, it is necessary to recognize the problems introduced by segregating behavioral health from the rest of medical care. In this review, the authors assess trends in behavioral health services during the last two decades in the USA, a period in which independently managed behavioral health care has dominated administrative practices. During this time, behavioral health has been an easy target for aggressive cost cutting measures. There have been no clinically significant improvements in the number of adults receiving minimally adequate treatment or in the percentage of the population with behavior health problems receiving psychiatric care with the possible exception of depression. While decreased spending for behavioral health services has been well documented during this period, these savings are offset by costs shifted to greater medical service use with a net increase in the total cost of health care. Targeting behavioral health for reduction in health-care spending through independent management, starting with diagnostic procedure code or diagnostic-related group exemption may not be the wisest approach in addressing the increasing fiscal burden that medical care is placing on the national economy.

Behavior Therapy↗
PubMed2005

Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells.

A proportion of patients with Hodgkin lymphoma carry Epstein-Barr virus (EBV), an oncogenic herpesvirus, in their tumor cells. Although it is generally assumed that EBV contributes to the malignant phenotype of Hodgkin lymphoma cells, direct evidence in support of this is lacking. Here we show that EBV infection of Hodgkin lymphoma cells results in the induction of autotaxin, a secreted tumor-associated factor with lysophospholipase-D activity. Up-regulation of autotaxin increased the generation of lysophosphatidic acid (LPA) and led to the enhanced growth and survival of Hodgkin lymphoma cells, whereas specific down-regulation of autotaxin decreased LPA levels and reduced cell growth and viability. In lymphoma tissues, autotaxin expression was mainly restricted to CD30+ anaplastic large-cell lymphomas and Hodgkin lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV positivity (P = .006). Our results identify the induction of autotaxin and the subsequent generation of LPA as key molecular events that mediate the EBV-induced growth and survival of Hodgkin lymphoma cells and suggest that this pathway may provide opportunities for novel therapeutic intervention.

Cell Line, Tumor↗
PubMed2005

Are the patients with post-transplant psychiatric consultation different from other medical-surgical consultation inpatients?

The present study examines the characteristics of post-transplant patients compared with non-transplant patients seen by consultation psychiatrists. Medical records of 541 consecutive psychiatric consultation patients at a university teaching hospital in 2001 were reviewed. Of the 541 patients who were evaluated, 67 were post-transplant patients. Post-transplant psychiatric consultation is different in some aspects from other psychiatric consultation. Post-transplant patients suffer complicated medical, psychiatric, and social burdens.

Academic Medical Centers↗
PubMed2005

General medical and pharmacy claims expenditures in users of behavioral health services.

OBJECTIVE: To quantify the magnitude of general medical and/or pharmacy claims expenditures for individuals who use behavioral health services and to assess future claims when behavioral service use persists. DESIGN: Retrospective cost trends and 24-month cohort analyses. SETTING: A Midwest health plan. PARTICIPANTS: Over 250,000 health plan enrollees during 2000 and 2001. MEASUREMENTS: Claims expenditures for behavioral health services, general medical services, and prescription medications. MAIN RESULTS: Just over one tenth of enrollees (10.7%) in 2001 had at least 1 behavioral health claim and accounted for 21.4% of total general medical, behavioral health, and pharmacy claims expenditures. Costs for enrollees who used behavioral health services were double that for enrollees who did not use such services. Almost 80% of health care costs were for general medical services and medications, two thirds of which were not psychotropics. Total claims expenditures in enrollees with claims for both substance use and mental disorders in 2000 were 4 times that of those with general medical and/or pharmacy claims only. These expenditures returned to within 15% of nonbehavioral health service user levels in 2001 when clinical need for behavioral health services was no longer required but increased by another 37% between 2000 and 2001 when both chemical dependence and mental health service needs persisted. CONCLUSIONS: The majority of total claims expenditures in patients who utilize behavioral health services are for medical, not behavioral, health benefits. Continued service use is associated with persistently elevated total general medical and pharmacy care costs. These findings call for studies that better delineate: 1) the interaction of general medical, pharmacy, and behavioral health service use and 2) clinical and/or administrative approaches that reverse the high use of general medical resources in behavioral health patients.

Adolescent↗
PubMed2004

Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma.

Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological activities and is detected in various biological fluids, including human seminal plasma. Due to its cell proliferation stimulatory and anti-apoptotic activities, LPA has been implicated in the progression of some cancers such as ovarian cancer and prostate cancer. Here, we show that prostatic acid phosphatase, which is a non-specific phosphatase and which has been implicated in the progression of prostate cancer, inactivates LPA in human seminal plasma. Human seminal plasma contains both an LPA-synthetic enzyme, lysoPLD, which converts lysophospholipids to LPA and is responsible for LPA production in serum, and its major substrate, lysophosphatidylcholine. In serum, LPA accumulated during incubation at 37 degrees C. However, in seminal plasma, LPA did not accumulate. This discrepancy is explained by the presence of a strong LPA-degrading activity. Incubation of LPA with seminal plasma resulted in the disappearance of LPA and an accompanying accumulation of monoglyceride showing that LPA is degraded by phosphatase activity present in the seminal plasma. When seminal plasma was incubated in the presence of a phosphatase inhibitor, sodium orthovanadate, LPA accumulated, indicating that LPA is produced and degraded in the fluid. Biochemical characterization of the LPA-phosphatase activity identified two phosphatase activities in human seminal plasma. By Western blotting analysis in combination with several column chromatographies, the major activity was revealed to be identical to prostatic acid phosphatase. The present study demonstrates active LPA metabolism in seminal plasma and indicates the possible role of LPA signaling in male sexual organs including prostate cancer.

Acid Phosphatase↗
PubMed2004

Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1.

Autotaxin (ATX) is a tumor cell motility-stimulating factor originally isolated from melanoma cell supernatant that has been implicated in regulation of invasive and metastatic properties of cancer cells. Recently, we showed that ATX is identical to lysophospholipase D, which converts lysophosphatidylcholine to a potent bioactive phospholipid mediator, lysophosphatidic acid (LPA), raising the possibility that autocrine or paracrine production of LPA by ATX contributes to tumor cell motility. Here we demonstrate that LPA and ATX mediate cell motility-stimulating activity through the LPA receptor, LPA(1). In fibroblasts isolated from lpa(1)(-/-) mice, but not from wild-type or lpa(2)(-/-), cell motility stimulated with LPA and ATX was completely absent. In the lpa(1)(-/-) cells, LPA-stimulated lamellipodia formation was markedly diminished with a concomitant decrease in Rac1 activation. LPA stimulated the motility of multiple human cancer cell lines expressing LPA(1), and the motility was attenuated by an LPA(1)-selective antagonist, Ki16425. The present study suggests that ATX and LPA(1) represent potential targets for cancer therapy.

Animals↗
PubMed2004

Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer.

Lysophosphatidic acid (LPA) is a simple bioactive phospholipid with diverse effects on various cells, that interacts with three G protein-coupled transmembrane receptors, LPA1, LPA2, and LPA3. The expression pattern and functions of these LPA receptors in various tumors have not been fully examined, except in ovarian cancer. To evaluate the LPA receptor expression profile in human colorectal cancer and in normal mucosa, we used real-time reverse transcription-polymerase chain reaction (RT-PCR) and measured the expression levels of LPA1, LPA2, and LPA3 messenger RNA (mRNA) in 26 colorectal cancers and 16 corresponding normal tissue samples. Normal epithelium expressed both LPA1 and LPA2 mRNA at similar levels. In comparison, colorectal cancers expressed LPA1 mRNA at a significantly lower level (0.3-fold; P<0.05), and LPA2 mRNA at a significantly higher level (three-fold; P<0.05), as compared with normal tissues. Thus, the ratio of LPA2/LPA1 increased markedly during malignant transformation (18-fold increase). LPA3 mRNA was expressed at only a low level in both normal and cancer tissues. We also assessed LPA2 expression immunohistochemically using a rat anti-LPA2 monoclonal antibody, and confirmed high expression of LPA2 in colorectal cancer at the protein level. As for LPA1, we examined Western blot analysis for 16 matched normal and cancer tissues. It revealed a significant decrease in the expression of LPA1 protein in cancer tissues compared to normal mucosa in nine of 16 cases, and in the remaining seven cases the expression levels was much the same. These results suggested that alteration of LPA receptor expression might be an important event in the development of colorectal cancer, and therefore, LPA and its receptors could be a chemopreventive target against colorectal cancer.

Adenocarcinoma↗
PubMed2004

Schizophrenia and narcolepsy: a review with a case report.

Several reports emphasize the importance of differentiating between psychosis in schizophrenia and the psychotic form of narcolepsy. The failure to identify narcolepsy leads to the labeling of patients as refractory to standard treatments for schizophrenia and retards consideration of intervention for narcolepsy in which psychosis can improve with psychostimulant treatment. Psychosis in patients with narcolepsy can occur in three ways: (i) as the psychotic form of narcolepsy with hypnagogic and hypnopompic hallucinations; (ii) as a result of psychostimulant use in a patient with narcolepsy; and (iii) as the concurrent psychosis of schizophrenia in a patient with narcolepsy. The present case report describes a difficult-to-treat patient who likely had concurrent schizophrenia and narcolepsy. It then summarizes the literature related to the treatment of the three types of patients with psychosis associated with narcolepsy.

Adult↗
PubMed2003

Current status of general hospital psychiatry in Japan.

The current status of general hospital psychiatry was overviewed to clarify the progress and the stagnation. To facilitate well-organized community psychiatric care, general hospital psychiatry should play a central role in psychiatry. The policy makers of the Japanese mental health system should place a special emphasis on general hospital psychiatric beds to further process of shifting from a hospital based to a community based psychiatry system. It is also necessary that general hospital psychiatry should become more aggressively involved in community psychiatry, e.g. emergency psychiatry. Consultation-liaison (C-L) psychiatry has been quickly developed and become one of the main psychiatric fields. For further development, a multidisciplinary team approach with co-medical staffs is necessary to supply efficient and effective care to medically ill patients. A proactive model of C-L care rather than a doctors' needs model should also be considered. Well designed research evaluating the efficiency and effectiveness of C-L activities in medical settings needs to be done to increase funding to general hospital psychiatry. This research evidence would also lead to a more fully integrated general hospital psychiatry into the practice of medicine and catch up with the ongoing medical reform in Japan.

Community Mental Health Services↗
PubMed2002

Serum lysophosphatidic acid is produced through diverse phospholipase pathways.

Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological activities that accounts for many biological properties of serum. LPA is thought to be produced during serum formation based on the fact that the LPA level is much higher in serum than in plasma. In this study, to better understand the pathways of LPA synthesis in serum, we evaluated the roles of platelets, plasma, and phospholipases by measuring LPA using a novel enzyme-linked fluorometric assay. First, examination of platelet-depleted rats showed that half of the LPA in serum is produced via a platelet-dependent pathway. However, the amount of LPA released from isolated platelets after they are activated by thrombin or calcium ionophore accounted for only a small part of serum LPA. Most of the platelet-derived LPA was produced in a two-step process: lysophospholipids such as lysophosphatidylcholine (LPC), lysophosphatidylethanolamine, and lysophosphatidylserine, were released from activated rat platelets by the actions of two phospholipases, group IIA secretory phospholipase A(2) (sPLA(2)-IIA) and phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)), which were abundantly expressed in the cells. Then these lysophospholipids were converted to LPA by the action of plasma lysophospholipase D (lysoPLD). Second, accumulation of LPA in incubated plasma was strongly accelerated by the addition of recombinant lysoPLD with a concomitant decrease in LPC accumulation, indicating that the enzyme produces LPA by hydrolyzing LPC produced during the incubation. In addition, incubation of plasma isolated from human subjects who were deficient in lecithin-cholesterol acyltransferase (LCAT) did not result in increases of either LPC or LPA. The present study demonstrates multiple pathways for LPA production in serum and the involvement of several phospholipases, including PS-PLA(1), sPLA(2)-IIA, LCAT, and lysoPLD.

Animals↗
PubMed2002

Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production.

Autotaxin (ATX) is a tumor cell motility-stimulating factor, originally isolated from melanoma cell supernatants. ATX had been proposed to mediate its effects through 5'-nucleotide pyrophosphatase and phosphodiesterase activities. However, the ATX substrate mediating the increase in cellular motility remains to be identified. Here, we demonstrated that lysophospholipase D (lysoPLD) purified from fetal bovine serum, which catalyzes the production of the bioactive phospholipid mediator, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC), is identical to ATX. The Km value of ATX for LPC was 25-fold lower than that for the synthetic nucleoside substrate, p-nitrophenyl-tri-monophosphate. LPA mediates multiple biological functions including cytoskeletal reorganization, chemotaxis, and cell growth through activation of specific G protein-coupled receptors. Recombinant ATX, particularly in the presence of LPC, dramatically increased chemotaxis and proliferation of multiple different cell lines. Moreover, we demonstrate that several cancer cell lines release significant amounts of LPC, a substrate for ATX, into the culture medium. The demonstration that ATX and lysoPLD are identical suggests that autocrine or paracrine production of LPA contributes to tumor cell motility, survival, and proliferation. It also provides potential novel targets for therapy of pathophysiological states including cancer.

Animals↗
PubMed2002

Assessment of Patients Who Attempt Suicide.

Suicidal behavior is influenced in varying degrees by biological, personal, and social factors. Identifying 4 common reasons for suicidal acts (psychosis, major depression, philosophical reasons, and poor impulse control) can be very helpful in evaluating suicidal patients quickly and making decisions about how patients should be treated. Educating the general public and primary care physicians about these reasons while addressing biological, personal, and social factors that contribute to them can improve understanding of suicidal behavior and patient involvement in and adherence to the treatment process.

Journal Article↗
PubMedDate not supplied

Factors affecting the relationship between the timing of psychiatric consultation and general hospital length of stay.

The purpose of this study was to examine the factors affecting the timing of psychiatric consultations and length of stay in the current managed care era. It also assessed the relationships between the timing of consultations and demographic/clinical characteristics. Medical records of 541 consecutive psychiatric consultation patients at a university teaching hospital in 2001 were reviewed for demographic characteristics, lengths of stay, number of days from admission to consultation, specialty services requesting consultations, reasons for the referral given by the referring physicians, and all five axes of DSM-IV. Earlier consultations independently predicted shorter lengths of stay. Delayed consultations were seen more often in women; surgical patients; those seen with a request to assess depression; and those seen with a diagnosis of adjustment disorder, delirium, or no psychiatric disorder. Delay in psychiatric consultations continues to be associated with longer lengths of stay in the current managed care environment. It is now possible that early detection strategies for high-risk patients with behavioral health problems in the medical setting, such as use of the INTERMED, may lead to reduction in delayed psychiatric consultations and thus shorter lengths of stay.

Demography↗