Biomedical subjects

Y Okamoto

Publications and source records attributed to Y Okamoto.

At least 217 records · Page 12Linked to original sources

PubMed1998

Role of nonselective cation channels as Ca2+ entry pathway in endothelin-1-induced contraction and their suppression by nitric oxide.

The present study was carried out to clarify the role of nonselective cation channels as a Ca2+ entry pathway in the contraction and the increase in [Ca2+]i induced by endothelin- in endothelium-denuded rat thoracic aorta rings, and their suppression by nitric oxide (NO). In Ca2+-free medium, the endothelin-1-induced contraction was suppressed to about 20% of control values, although the increase in [Ca2+]i became negligible. The contraction and the increase in [Ca2+]i monitored by fura 2 fluorescence were unaffected by a blocker of L-type voltage-operated Ca2+ channels nifedipine. A blocker of nonselective cation channels 1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl]-1H-imida zole . HCl(SK&F 96365) suppressed the endothelin-1-induced contraction and increase in [Ca2+]i to the level similar to that after removal of extracellular Ca2+. SK&F 96365 had no further effect on the endothelin-1-induced contraction in the absence of extracellular Ca2+. The endothelin-1-induced contraction and increase in [Ca2+]i were abolished by a donor of NO sodium nitroprusside. The effects of another NO donor 3-morpholinosydnonimine (SIN-1) were also tested and yielded essentially similar results to those for sodium nitroprusside on the endothelin-1-induced contraction. Furthermore, the inhibitory effects of sodium nitroprusside could be blocked with a guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) at 30 microM. These findings suggest that Ca2+ entry through nonselective cation channels but not voltage-operated Ca2+ channels plays a critical role in the endothelin-1-induced increase in [Ca2+]i and the resulting contraction and that inhibition by NO of the endothelin-1-induced contraction is mainly the result of blockade of Ca2+ entry through these channels.

Animals↗

PubMed1998

Synthesis and NK1 receptor antagonistic activity of (+/-)-1-acyl-3-(3,4- dichlorophenyl)-3-[2-(spiro-substituted piperidin-1'-yl)ethyl]piperidines.

(+/-)-1-Acyl-3-(3,4-dichlorophenyl)-3-[2-(spiro-substituted piperidin-1'-yl)ethyl]piperidines and their quaternary ammonium salts were prepared and evaluated for their NK1 receptor antagonistic activity. Some of these inhibited SP-induced contraction in guinea pig ileum with IC50 values at a level of 10(-9) M and showed potent inhibitory activity against selective NK1 receptor agonist-induced bronchoconstriction in guinea pigs.

Animals↗

PubMed1998

CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells.

To investigate the molecular mechanisms of stimuli-induced transcriptional activation in neuronal cells, we have investigated the light-induced gene expression in the neural retina of rats. The immunoreactivity for phosphorylated cAMP responsive element binding protein (PCREB-IR) was expressed in the outer half of the inner nuclear layer (INL) and the ganglion cell layer (GCL) after 5 min exposure to steady light also in mice. In addition to these cells, PCREB-IR was also detected in the inner border of the INL after 5 min exposure to flashing light. Both steady and flashing lights induced c-fos mRNA in the same types of cells as the PCREB-IR-positive cells. Majority of PCREB immunoreactive nuclei in the outer half of the INL were also immunopositive for anti-protein kinase C alpha (PKC alpha), a marker of rod bipolar cells, while CaM kinase IV immunoreactivity was not detected in these cells. PCREB-IR and c-fos gene expression in the PKC alpha positive rod bipolar cells were lost in mice lacking metabotropic glutamate receptor 6 (mGluR6). Thus, we propose that the transcriptional response of CREB to light stimulation in rod bipolar cells is regulated via mGluR6.

Animals↗

PubMed1998

Apoptosis and tumor angiogenesis in cervical cancer after preoperative chemotherapy.

The correlation between apoptosis and tumor angiogenesis in uterine cervical cancer treated by preoperative intraarterial infusion chemotherapy (IAC) was investigated. Cervical cancer samples surgically obtained from 12 patients (stages Ib-IIIb) receiving IAC and from 10 patients (stages Ib-IIb) receiving no chemotherapy and biopsy specimens from the 12 patients before IAC were examined. The apoptotic index (AI) was determined with an in situ end-labeling assay. Intratumoral microvessel density (IMVD) and thymidine phosphorylase (dThdPase) expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies. AIs were higher in the 8 patients with complete or partial response to IAC than they were in the 4 nonchemoresponsive patients and in the 10 patients who received no chemotherapy (P < 0.01) and were inversely related to IMVDs (r = 0.724; P < 0.01). AIs and IMVDs after IAC were higher and lower than those before IAC (P < 0.01), respectively. The expression of dThdPase, which has angiogenic activity, was markedly decreased after IAC. These results suggest that the antitumor effects of IAC are closely associated with apoptotic cell death, which may be influenced in part by the extent of tumor angiogenesis inhibition.

Adult↗

PubMed1998

Purification of a novel endothelin-converting enzyme specific for big endothelin-3.

Endothelin-3 (ET-3), a potent vasoactive peptide, is considered to be produced from big ET-3 by endothelin-converting enzyme (ECE) like the other members of the endothelin family (ET-1 and ET-2). We purified a novel ECE from bovine iris microsomes. The purified enzyme, a 140 kDa protein by SDS-PAGE analysis, converted big ET-3 to ET-3 but not big ET-1, with a Km value of 0.14 microM for big ET-3. The conversion to ET-3 was confirmed with sandwich EIA by monoclonal antibodies, the elution profile of HPLC, and intracellular calcium mobilization in CHO-K1 cells expressing recombinant human ET(B) receptors. The conversion activity was inhibited by an inhibitor of neutral endopeptidase 24.11 (NEP) phosphoramidon. These results show that ECE-3 purified from bovine iris is a novel metalloprotease totally different from ECE-1 or ECE-2, in that the enzyme is highly specific for big ET-3.

Animals↗

PubMed1998

Calibration of space-resolving VUV and soft X-ray spectrographs for plasma diagnostics.

Vacuum ultraviolet (VUV) and soft X-ray measurements are important means of diagnosing impurities in magnetically confined plasmas used in fusion research. Recently, space- and time-resolving flat-field VUV (150-1050 A) and soft X-ray (20-350 A) spectrographs have been constructed by using aberration-corrected concave gratings with varied-spacing grooves which give a wide simultaneous spectral coverage on a microchannel-plate intensified detector. Calibration experiments have been performed at beamlines 11A and 11C at the Photon Factory of the High Energy Accelerator Research Organization. The relative efficiency of the VUV spectrograph has been measured for P-polarization geometry in the spectrograph. In the soft X-ray spectrograph, efficiencies have been obtained for several different points of irradiation on the grating along the groove direction and for two (S and P) polarization geometries.

Journal Article↗

PubMed1998

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma.

PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.

Aged↗

PubMed1998

In SCID-hu mice, passive transfer of a humanized antibody prevents infection and atrophic change of medulla in human thymic implant due to intravenous inoculation of primary HIV-1 isolate.

Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif in the principal neutralizing determinant (PND) of HIV(MN), as well as the original mouse mAb mu5.5, neutralized HIV(MN) with high activity. Seven primary field isolates from Japanese hemophiliacs seropositive for HIV-1 clade B were compared for their reactivities to Rmu5.5. Rmu5.5 was effective, particularly against the viruses that matched amino acid sequences of the PND region of HIV-1, and it completely neutralized primary isolates. Moreover, the passive transfer of the Ab elicited protection against challenge by the primary isolates in SCID-hu or hu-PBL-SCID mice after i.v. inoculation with the virus by both quantitative PCR and PBMC-based virus isolation in vitro. Further, inoculation with the Ab also prevented the atrophic change in the medulla of the thymic transplant that was induced by i.v. inoculation of the virus. Thus, the humanized neutralizing Ab Rmu5.5 appears to protect SCID-hu mice from infection by primary field isolates.

Adult↗

PubMed1998

Thermal analysis of bones from ovariectomized rats.

Thermal analyses [thermogravimetry (TG) and differential thermal analysis (DTA)], X-ray diffraction, and infrared absorption analysis of bones from ovariectomized rats were carried out. The rats were divided into five groups: sham operated (Sham); ovariectomized (OVX); OVX given traditional Chinese (Kampo) medicine, Unkei-to; OVX given 17 beta-estradiol; and OVX given the estradiol vehicle, respectively. The activation energy (delta E), a kinetic parameter from TG data of OVX rats, increased by 57% from that in Sham rats. The administration of Unkei-to and 17 beta-estradiol to OVX rats clearly restored the delta E to the levels of Sham rats, while the vehicle for 17 beta-estradiol had no effect. DTA data from thermal analyses of rats from the Sham, OVX, and OVX given various compounds were almost the same except for OVX rats given 17 beta-estradiol. The X-ray diffraction pattern and infrared absorption spectrum of bone powders from Sham rats were not different from those of OVX rats or others. These results strongly suggest that kinetic parameter, delta E calculated from TG data, may be a useful method for assessing both experimentally induced osteoporosis and drug effects on it.

Animals↗

PubMed1998

Inhibitory actions of synthetic actin peptides and 2,3-butanedion monoxime on actomyosin system.

Interaction of myosin and actin has been studied in the presence of inhibitors in order to identify and characterize sites essential for the motor function. Acidic amino acid cluster of actin at the amino terminal region is known to interact with basic residue around 50K-20K connecting loop of the myosin heavy chain. In this study, an amino terminal peptide region of actin without the initial four acidic residue cluster is also shown to have important role in the interaction with myosin in the presence of ATP. A set of peptides corresponding to actin sequences from Leu8 to Arg28 or to Gly36 were synthesized. In the absence of actin, neither activation nor inhibition of MgATPase activity of S1 alone has been observed with both types of peptide. In the presence of actin, however, the longer peptide (L8G36) at 50 microM shows about 50% inactivation of the control value of actoS1 Mg2+ATPase activity. The shorter one (L8R28) has been a non competitive and weaker inhibitor. The inhibition could be interpreted as a results of impairing of one of the interactions necessary for normal progression of actomyosin ATPase reaction. Moreover, these results indicate a contribution of amino terminal sequence of actin without initial four acidic residues for the acto myosin interaction. Examination of the inhibitory mechanism of BDM has shown that the effect may not be due to lowering the binding affinity between actin and myosin.

Actins↗

PubMed1998

ER-34122, a novel dual 5-lipoxygenase/cyclooxygenase inhibitor with potent anti-inflammatory activity in an arachidonic acid-induced ear inflammation model.

OBJECTIVE AND DESIGN: To investigate the effect of ER-34122, a novel pyrazole derivative, on 5-lipoxygenase (LOX) and cyclooxygenase (COX) metabolite production in vitro, ex vivo and in vivo. MATERIAL: In vitro, lysate of rat basophilic leukemia cells, the microsome fraction of sheep seminal vesicles, human polymorphonuclear leukocytes, human synovial cells, and human monocytes. Ex vivo and in vivo, male Balb/c mice or SD rats. TREATMENT: In ex vivo study, ER-34122 (0.03-1 mg/kg) was orally administered 1 h before withdrawal of blood samples. In carrageenin-induced paw edema, ER-34122 (3-100 mg/kg) and indomethacin (1-10mg/kg) were orally administered 1 h before carrageenin injection. In arachidonic acid-induced ear inflammation, ER-34122 (0.3-10mg/kg), zileuton (10-100mg/kg) and indomethacin (0.3-3mg/kg) were orally administered 1 h before arachidonic acid application. METHODS: 5-Hydroxyeicosatetraenoic acid and other eicosanoids were determined by using an HPLC method and enzyme immunoassay, respectively. Rat hind paw edema and mouse ear edema were assessed by measuring paw volume and ear thickness, respectively. Myeloperoxidase (MPO) activity and eicosanoid content of the ear tissue were also determined. RESULTS: ER-34122 inhibited both LOX and COX product generation in vitro, and ex vivo. ER-34122 and indomethacin inhibited carrageenin-induced paw edema formation. In the arachidonic acid-induced ear inflammation, ER-34122 inhibited inflammatory responses (edema formation and MPO accumulation) as well as eicosanoids (LTB4, LTC4 and PGE2) generation. A representative LOX inhibitor, zileuton, also inhibited these inflammatory responses, while a COX inhibitor, indomethacin, did not suppress them though it completely inhibited PGE2 generation. CONCLUSIONS: The anti-inflammatory characteristics of ER-34122 are considered to be superior to those of COX inhibitors such as indomethacin, because in addition to its inhibitory activity on the COX pathway, ER-34122 inhibits LOX products generation, as revealed by the inhibition of edema formation or polymorphonuclear leukocyte infiltration in the arachidonic acid-induced ear inflammation model.

Animals↗

PubMed1998

Reliability of the anteroposterior axis and the posterior condylar axis for determining rotational alignment of the femoral component in total knee arthroplasty.

We examined the reliability of the anteroposterior and posterior condylar axes for determining rotational alignment of the femoral component in total knee arthroplasty (TKA). A computed tomography scan was taken at the level of the femoral epicondyle in 84 knees (27 varus knees with medial femorotibial arthritis (FT-OA) in 26 patients, 17 knees with patellofemoral arthritis in 14 patients, and 40 normal knees in 40 volunteers). On the image, an anteroposterior axis, a line perpendicular to the anteroposterior axis, an epicondylar axis and a posterior condylar axis were drawn, and the relationship between the three axes was assessed. The mean values for the 84 knees were evaluated, and the posterior condylar axis was 6.0 degrees +/- 2.4 degrees internally rotated relative to the epicondylar axis, while the line perpendicular to the anteroposterior axis was 1.4 degrees +/- 3.3 degrees internally rotated relative to the epicondylar axis. The internal rotation angle of the posterior condylar axis relative to the epicondylar axis was 6.2 degrees +/- 1.9 degrees in the knees with medial femorotibial arthritis, 6.4 degrees +/- 2.4 degrees in the knees with patellofemoral arthritis, and 5.8 degrees +/- 2.7 degrees in the normal knees, showing consistent values in normal and osteoarthritic knees. The internal rotation angle of the line perpendicular to the anteroposterior axis relative to the epicondylar axis was 0.1 degrees +/- 3.3 degrees, 1.3 degrees +/- 3. 3 degrees, and 2.3 degrees +/- 3.1 degrees in the three groups, respectively (i.e., there were significant differences between the medial FT-OA knees and the normal knees). The results demonstrated that the anteroposterior axis was rotated externally to a significant degree in medial FT-OA knees and was less reliable than the posterior condylar axis for use in alignment for TKA on medial FT-OA knees.

Aged↗

PubMed1998

Development of a dual color enzyme-linked immunospot assay for simultaneous detection of murine T helper type 1- and T helper type 2-cells.

The enzyme-linked immunospot (ELISPOT) assay is an efficient technique for the enumeration of single cells secreting antibodies and cytokines. For simultaneous differentiation of individual cells producing interleukin-2 (IL-2) and/or interleukin-4 (IL-4) at a single cell level, a dual color ELISPOT assay has been developed. In the present system, the red spots corresponding to IL-2-secreting cells (T helper type 1, Th1 cells) were developed with a horseradish peroxidase and the amino ethyl carbazole (AEC)/H2O2. The light blue spots corresponding to IL-4-secreting cells (T helper type 2, Th2 cells) were developed with an alkaline phosphatase and the Vector blue. The mixed colored (indigo) spots corresponding to both kinds of cytokine-secreting cells (T helper type 0, Th0 cells) were developed with both substrates. With this system, we could detect the IL-2- and/or IL-4-secreting cells simultaneously in crude spleen cell preparation or purified CD4 fraction. This procedure provides a useful tool for quantitatively analyzing micro-levels of dynamic immune responses.

Animals↗

PubMed1998

Posttranslational modifications of endothelin receptor type B.

Endothelin receptor type B (ETb) is one of the two ET receptor subtypes, both of which belong to the G protein-coupled receptor (GPCR) superfamily. The primary amino acid sequence of ETb, published in 1990, predicted potential posttranslational modifications of the receptor protein, and in the last couple of years, we and others presented direct experimental evidence for palmitoylation and phosphorylation of ETb. Functional evaluation of both substitution and deletion mutants indicated a negative role on the part of these modifications in the ligand binding capacities and cellular sequestrations of the receptors. At least one of them, palmitoylation, however, appears to be critically involved in the coupling with G proteins.

Journal Article↗

PubMed1998

New consecutive high-dose chemotherapy modality with fractionated blood stem cell support in the treatment of high-risk pediatric solid tumors: a feasibility study.

For the treatment of childhood solid tumors, we performed a pilot feasibility study of consecutive high-dose therapies, in which each course was followed by transplantation with granulocyte colony-stimulating factor-mobilized peripheral blood cells which had been separated into CD34-positive and -negative fractions by an Isolex system (Baxter). Positive selection of CD34+ cells has been associated with inevitable cell loss. To overcome this loss, CD34+ cells that had migrated into the negative fraction were saved and used for the first transplant, which was followed by a second transplant after a 3- to 5-month interval. In this phase I feasibility study, the results in six children were evaluated for safety and engraftment. Multi-drug cytoreductive regimens using ranimustine (MCNU), melphalan, thiotepa, carboplatin, cyclophosphamide or VP-16 were comparable between the two transplant procedures in terms of their intensity. The number of CD34+ cells in the 'CD34(+) fraction' was 3.31 x 10(6)/kg (0.63-4.3 x 10(6)/kg), while this number in the 'CD34(-) fraction' could not be evaluated correctly due their scarcity (<0.1%). The median numbers of infused MNC and CFU-GM were, respectively, 4.2 x 10(6)/kg and 1.75 x 10(5)/kg in the CD34(+) fraction, and 4.8 x 10(8)/kg and 3.35 x 10(5)/kg in the CD34(-) fraction. The number of days required to achieve an ANC >0.5 x 10(9)/l and a platelet count >20 x 10(9)/l and >50 x 10(9)/l were, respectively, 14.5, 15.0 and 19.5 in the first transplant with CD34- cells, and 13.5, 18.0 and 25.0 in the second transplant with CD34+ cells, with no essential difference between the two treatments. Although the small number of patients, the variation in clinical status and treatment, and the short follow-up invalidate any evaluation of the therapeutic benefit of this strategy, the encouraging results support the feasibility of this strategy, which enables an escalation of dose intensity with an improved cost/benefit ratio.

Adolescent↗

PubMed1998

Clinically applicable bulk isolation of blood CD34+ cells for autografting in children.

CD34+ cells were purified in bulk from apheresis-collected cells of children with cancer using monoclonal antibody (MoAb) and magnetic beads (Baxter ISOLEX system). To improve the purity of the final product for possibly better tumor cell purging and to make the manufacturer's original procedure more cost-effective, we incubated the cells for 30 min with l-phenylalanine methylester hydrochloride (PME) to reduce the cell number by removing contaminating granulocytes and monocytes in the initial step before incubation with MoAb. Our modification prevented nonspecific interactions between MoAb and magnetic beads, and thereby saved expensive materials for purification. A total of 40 purifications were performed with samples containing a mean of 3.1 x 10(9) blood cells mobilized from 15 children by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). The entire purification procedure, from the end of apheresis to storage, was completed within 5h. After incubation with PME and double-layered (40/60%) Percoll separation, the number of CD34+ cells was reduced to 48+/-29%, which suggests the possibility that half of the CD34+ cells in the inoculum were nonclonogenic in the hematopoietic progenitor assay. PME/Percoll-treated cells were then subjected to a final isolation procedure with MoAb according to the manufacturer's suggestions, and 52+/-42% and 32+/-22%, respectively, of the CFU-GM and CD34+ cells present in the initial bag inoculums were recovered. The recovery rates were, respectively, 54% and 67%, when the calculation was limited to the isolation procedure with MNoAb. The purity of isolated CD34+ cells and the plating efficiency in methylcellulose culture were, respectively, 77+/-24% and 33+/-13%. Fourteen children were subsequently autografted with purified CD34+ cells after marrow ablative chemotherapy. The median number of days to achieve an ANC of 0.5 x 10(9)/l was 12 and that to achieve a platelet count of 50 x 10(9)/l was 22.5, which were comparable to those in our historical group of 55 patients who underwent transplant with unmanipulated blood cells (13 and 16 days). These results suggest that our modified purification procedure with PME is useful for the initial reduction of cell numbers to save costly materials, and that cells isolated by this procedure can be directly used in clinical transplantation procedures.

Adolescent↗

PubMed1998

Cytokine regulation on the synthesis of nitric oxide in vivo by chronically infected human polymorphonuclear leucocytes.

To determine if nitric oxide (NO) is produced by chronically infected human polymorphonuclear leucocytes (PMNs) in vivo, inflamed exudates (periapical exudates: PE) collected from periapical periodontitis patients were examined. Cell-free supernatants and cells were separated by centrifugation. Significant levels of nitrite concentrations were observed in the supernatants. The production of inducible NO synthase (iNOS) in highly purified PMNs derived from PEs was then immunocytochemically determined using rabbit anti-human iNOS antiserum. In vitro, human peripheral blood PMNs (PB-PMNs) isolated from patients were cultured with a combination of Esherichia coli-lipopolysaccharide (LPS), recombinant human interferon-gamma (rhIFN-gamma) and/or interleukin-1 beta (rhIL-1 beta). The stimulated PB-PMNs showed steady-state levels of nitrite. The stimulation of LPS, rhIFN-gamma and rhIL-1 beta showed more NO induction than that of LPS with either IFN-gamma or IL-1 beta, suggesting the synergistic effects of cytokines. Cryostat sections of surgically removed periapical tissues were also immunohistochemically examined for iNOS, IFN-gamma and IL-1 beta. Two-colour immunohistochemistry revealed the interaction of iNOS-producing PMNs and IFN-gamma- or IL-1 beta-producing mononuclear cells. On the basis of these data, we concluded that with the stimulation of inflammatory cytokines derived from mononuclear cells, PMNs can spontaneously produce NO at the site of chronic infection. The present studies are consistent with a hypothesis suggesting that PMNs could be regulated and delicately balanced to produce NO by mononuclear cell-derived cytokines in vivo. NO-producing cells may play a pivotal role in chronic inflammation.

Adult↗

PubMed1998

Positive influence of a liaison program on the rate of psychiatric consultation referrals for cancer patients.

To improve access to psychiatric consultation for cancer patients as well as non-cancer patients with psychiatric disorders, a psychiatric liaison programme to communicate closely with physicians and ward staff regarding anticipated psychiatric morbidity in patients, was introduced in each ward of a general hospital. The rate of psychiatric consultation referrals for cancer patients was significantly higher after the psychiatric liaison programme was established. The programme had a greater impact on the rate of psychiatric consultation in a unit with cancer patients who were informed of their diagnoses. The greater consultation rates in cancer patients after the liaison programme might be, in part, associated with the physicians' attitude toward the more open disclosure of the cancer diagnosis.

Aged↗