Biomedical subjects

T Nagasaka

Publications and source records attributed to T Nagasaka.

At least 37 records · Page 2Linked to original sources

PubMed2002

Clarithromycin increases the release of heat shock protein B from Helicobacter pylori.

BACKGROUND: Clarithromycin (CAM) may have certain indirect effects on Helicobacter pylori (H. pylori) other than its inhibitory activity on bacterial growth, as indicated in other infections with Gram-negative micro-organisms. In the present study, we examined the effects of lower concentrations of CAM on the release of heat shock protein B (HspB), one of the major antigenic proteins from H. pylori cells, as well as the changes in humoral immune response and histological degree of antral gastritis in patients who received eradication therapy with CAM. METHODS: The H. pylori strain 26695 and three CAM-resistant clinical isolates were cultured in broth with and without CAM (2-500 ng/mL). Expression of H. pylori proteins was examined by two-dimensional (2D)-electrophoresis followed by N-terminal amino acid sequencing. Changes in host immune response and histological degree of antral gastritis were monitored in patients with peptic ulcer disease who received H. pylori eradication therapy. RESULTS: 2D electrophoresis showed 26 spots in extracellularly released proteins with different profiles from those in cytoplasmic proteins. The release of HspB increased after incubation with CAM (30-500 ng/mL) in all three H. pylori clinical isolates tested. Patients with failed H. pylori eradication after triple therapy with CAM, but not those with failed eradication after dual therapy without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB along with a decrease in the degree of neutrophil and H. pylori colonization density in tissue sections. CONCLUSIONS: CAM may induce a humoral immune response against H. pylori and a decrease in gastric mucosal inflammation through up-regulation of the release of HspB from the bacteria in infected patients.

Amino Acid Sequence↗

PubMed2002

Polypoidal choroidal vasculopathy treated with macular translocation: clinical pathological correlation.

AIMS: To report the histopathology of two specimens of polypoidal choroidal vasculopathy (PCV) obtained from two eyes of Japanese patients. METHODS: Specimens were obtained under direct visualisation during macular translocation surgery with 360 degree retinotomy. The clinical findings were correlated with the light microscopic findings of the two specimens. RESULTS: One specimen from a 77 year old man was the central portion of the lesion that lay under the sensory retina on the retinal pigment epithelium (RPE). The specimen was made up mainly of fibrous tissue with small, thin walled vessels. Indocyanine green angiography after surgery revealed that active leaking polypoidal element remained under the RPE. Another specimen obtained from a 62 year old man was made up of a fibrovascular membrane situated within Bruch's membrane. The part of this specimen inferior to the foveal region included a collection of dilated, thin walled blood vessels without pericytes, surrounded by macrophages that stained positive for CD68. The dilated vessels appeared to be correlated with the orange coloured polyps observed by ophthalmoscopy, the polypoidal structure seen in indocyanine green angiograms, and the pyramidal elevation with intermediate reflectivity by optical coherence tomography. CONCLUSION: Polypoidal structures are located within Bruch's space. They are composed of clusters of dilated, thin walled blood vessels surrounded by macrophages and fibrin material. The positive immunohistochemical staining for vascular endothelial growth factor in the RPE and the vascular endothelial cells suggests that this fibrovascular complex is a subretinal choroidal neovascularisation.

Aged↗

PubMed2002

Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade.

AIMS: Abnormalities involving proliferation, apoptosis, and angiogenesis are important in tumorigenesis. The purpose of this study was to examine these three biological processes, and their relation with the clinical stage and cytological grade in multiple myeloma (MM). METHODS: Fifty four newly diagnosed patients with MM were studied by immunohistochemistry using bone marrow clot sections. Proliferation and apoptosis were evaluated for the proportion of MM cells (indicated by morphology and CD138 reactivity) positive for the Ki67 antigen and single stranded DNA (ssDNA), respectively. Angiogenesis was evaluated by measuring the intratumoral microvessel density (IMVD) and by assessing the immunoreactivity of vascular endothelial growth factor (VEGF). RESULTS: There were 30 men and 24 women (median age, 65 years; range, 37-84). At initial presentation, 15 (28%) were in Durie stage I, 15 (28%) in stage II, and 24 (44%) in stage III. Advanced clinical stage correlated with high cytological grade (p < 0.03). The medians for Ki67, ssDNA, and IMVD were 4.4% (range, 0-15%), 0.2% (range, 0-2.8%), and 15.5 (range, 0-63), respectively. Among these three continuous parameters, the only significant correlation was that between Ki67 and IMVD (p < 0.0001). Both Ki67 and IMVD also correlated with the clinical stage, cytological grade, and VEGF positivity (p <0.05). No correlation was found between ssDNA and all of the other parameters. CONCLUSIONS: These data suggest that proliferation is associated with angiogenesis in MM. Furthermore, proliferation and angiogenesis, but not apoptosis, may be important in disease progression. Lastly, increased production of VEGF may be one of the contributing factors to the increase in intratumoral vascularity seen in advanced MM.

Adult↗

PubMed2002

Fishing for bioactive substances from scorpionfish and some sea urchins.

Venom proteins from the dorsal spine of two scorpionfish, Hypodytes rubripinnis and Synanceia verrucosa were assayed for mitogenicity and cytotoxicity. The two venoms had both mitogenic and cytotoxic activity on murine splenocytes and murine P388 leukemic cells. In H. rubripinnis, the second gel chromatographic fraction showed cytotoxic activity on P388 leukemic cells. On native PAGE, the glycoprotein isolated by concavalin A sepharose chromatography appeared to have a molecular mass of 110 kDa. In addition, two D-galactose-binding lectins (SUL-I and SUL-II) and a heparin-binding lectin (TGL-I) were purified from the globiferous pedicellariae of the toxopneustid sea urchins, Toxopneustes pileolus and Tripneustes gratilla, respectively. SUL-I (Nakagawa et al., 1999a) had mitogenic activity and cytotoxic activity but SUL-II and TGL-I did not. SUL-I did not show sequence homology to SUL-II. A hemolytic lectin with a molecular mass of 29 kDa was isolated from the coelomic fluid of T. gratilla. The hemolytic activity of the lectin was dependent on Ca2+ concentration and inhibited by lactose. The present results suggest that some species of scorpionfish and sea urchins may be novel sources for biologically active substances such as anti-tumor compounds or new lectins.

Agglutination↗

PubMed2001

BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction.

Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell-associated C-type lectin 2. Anti-BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon alpha/beta production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon alpha/beta by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon alpha/beta in systemic lupus erythematosus patients.

Amino Acid Sequence↗

PubMed2001

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Aged↗

PubMed2001

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

Aged↗

PubMed2001

Adenocarcinoma of the nonpigmented ciliary epithelium: report of two cases with immunohistochemical findings.

BACKGROUND: Acquired neoplasms arising from the nonpigmented ciliary epithelium (NPCE) are much less common than uveal melanocytic proliferations. We report two cases of acquired neoplasms arising from the NPCE with immunohistochemical findings. METHODS: Case reports. RESULTS AND CONCLUSIONS: Patient 1 was a 39-year-old man who presented with a pigmented mass behind the iris and secondary exudative retinal detachment. The eye also developed neovascular glaucoma. Patient 2 was a 44-year-old woman with a ciliary body mass but without symptoms. Both of these tumors were classified histologically as low-grade adenocarcinomas of the NPCE from specimens successfully removed by iridocyclectomy. Immunohistochemical findings confirmed the origin of the tumor cells; however, some changes in the immunoreactivity to cytokeratin AE1 and epithelial membrane antigen were found.

Adenocarcinoma↗

PubMed2001

Tumor cell spillage to the vaginal cavity and vaginal stump during the surgery of endometrial carcinoma.

BACKGROUND: Our purpose was to investigate the spillage of the endometrial carcinoma cells to the vaginal cavity and vaginal stump during the surgery. METHODS: Cytologic examination of specimens obtained from the vaginal cavity and vaginal stump during surgery performed on 15 patients with endometrial carcinoma. And the risk factors of carcinoma cell spillage to the vaginal cavity were investigated. RESULTS: Carcinoma cells from the vaginal cavity were negative for nine patients and positive for six patients. Those from the vaginal stump were negative for l4 patients and positive for one patient. In one patient, both were positive. Total abdominal hysterectomy might be one risk of carcinoma cell spillage to the vaginal cavity compared with modified radical hysterectomy and radical hysterectomy. CONCLUSIONS: Endometrial carcinoma cells were spilled into the vaginal cavity in not a few cases and their spillage from there to the vaginal stump could follow during the surgery.

Adenocarcinoma↗

PubMed2001

Evaluation of pulse sequences used for magnetic resonance sialography.

OBJECTIVES: To determine the most appropriate sequences for the visualization of small parotid ducts in MR sialography. METHODS: MR images of a phantom consisting of distilled water in polyethylene tubes were obtained with turbo-spin echo (TSE), single-shot turbo-spin echo (SSTSE), half-fourier acquisition, single-shot turbo-spin echo (HASTE) and turbo gradient-spin echo (TGSE) pulse sequences and compared visually and quantitatively. MR sialograms obtained from healthy volunteers and patients with Sjögren's syndrome (SS) were obtained using the same four sequences. RESULTS: In the phantom, TSE images were best and the contrast-noise ratio (CNR) highest. In the volunteers, the main ducts were especially clearly visualized with TSE and in SSTSE; however, the majority of secondary and/or tertiary parotid ducts were not depicted by any of the sequences used. In SS patients, images of small main ducts and small pseudocysts were clearer using TSE. However, TSE could not depict the narrow main ducts or peripheral ducts or very small pseudocysts. CONCLUSIONS: TSE is considered the most suitable MR sequence for assessing small parotid gland ducts. However, further improvement is needed since it does not always visualize them sufficiently.

Adult↗

PubMed2001

Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides.

The placental leucine aminopeptidase (P-LAP)/oxytocinase whose serum level increases with gestation is thought to contribute to the maintenance of normal pregnancy. P-LAP mRNAs are expressed in various tissues other than the placenta. In this study, we identified P-LAP protein in the brain. In contrast with the placenta where a significant portion of P-LAP is released, the enzyme was localized in the membrane fraction in brain and PC12 cells and no soluble form of the enzyme was detected. When PC12 cells were differentiated into neuronal cells by nerve growth factor (NGF), a significant increase in the expression level of P-LAP in the cell was observed. As in the case of insulin treatment of 3T3-L1 adipocytes, treatment of PC12 cells with forskolin caused the translocation of the enzyme from intracellular vesicle to the cell surface plasma membrane. In addition, P-LAP was shown to degrade several bioactive neuropeptides such as Met-enkephalin and dynorphin A (1-8). These results suggest that P-LAP plays an important role in the regulation of neuronal cell function in the brain.

Amino Acid Sequence↗

PubMed2001

Localized amyloidosis and extramedullary plasmacytoma involving the larynx of a child.

Extramedullary plasmacytoma of the larynx and localized laryngeal amyloidosis are 2 uncommon disease entities that are exceedingly rare in children. We report a case of a 12-year-old girl presenting with progressive hoarseness who was subsequently found to have extramedullary plasmacytoma coexisting with localized amyloidosis involving the larynx. Results from the immunohistochemical and molecular studies showed that the tumor cells of the plasmacytoma were monoclonal (kappa-restricted), strongly supporting their neoplastic nature. The biochemical nature of the amyloid deposits was also shown to be of kappa immunoglobulin light chain, suggesting the pathogenetic relationship between the plasmacytoma and amyloid deposition in the larynx of this patient. There was no other evidence of malignancy or amyloidosis elsewhere. On a follow-up period of 4 years, this patient was well and asymptomatic. We believe that this represents the first case in the literature showing the coexistence of extramedullary plasmacytoma and localized amyloidosis of the larynx in children. This case also supports the concept that localized laryngeal amyloidosis may be a manifestation of low-grade B-cell neoplasms.

Amyloidosis↗

PubMed2001

Severe hepatitis caused by Epstein-Barr virus without infection of hepatocytes.

Although hepatitis is a common feature of primary Epstein-Barr virus (EBV) infection, severe liver injury is rare and its pathogenesis is unclear. A previously healthy girl developed severe hepatitis with prolonged jaundice. Serologic examination showed that she had primary infection with EBV. An extremely high Epstein-Barr viral load was observed in her peripheral blood. The viral load decreased in parallel with symptomatic improvement. Histologic examinations showed spotty necrosis of the liver parenchyma and infiltration by CD8(+) T cells. The CD8(+) T cells, not hepatocytes, were positive for EBV. Possible mechanisms of viral hepatitis without infection of hepatocytes are discussed.

Antigens, Viral↗

PubMed2001

Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells.

Neutral endopeptidase (NEP)/CD10, a cell-surface peptidase degrading various bioactive peptides, is mainly present in syncytiotrophoblasts in the human placenta. However, the change in NEP expression upon trophoblast differentiation remains to be clarified. In the present study, we examined the expression of NEP in the differentiating trophoblast using the BeWo choriocarcinoma cell line as a model system. Under the normal culture conditions, NEP was very weakly expressed on most proliferating cytotrophoblastic BeWo cells, while a minority of the cell population (less than 5 per cent ), consisting of giant, multinucleated cells, clearly expressed NEP at the cell membrane. Treatment of BeWo cells with forskolin (FSK) for 48-72 h resulted in an 11- to 44-fold increase in the level of hCG secretion and induced cell fusion leading to the formation of multinucleated syncytiotrophoblasts, indicating functional and morphological differentiation. Fluorescence-activated cell sorting (FACS) analysis revealed that treatment with FSK significantly increased the cell-surface protein expression of NEP on differentiating BeWo cells. Consistently, there was a significant increase in the NEP enzymatic activity after FSK treatment. The level of hCG secretion from the FSK-treated cells was further enhanced when the cells were treated in the presence of the NEP inhibitor phosphoramidon. Immunohistochemical analysis of normal chorionic villi and choriocarcinoma tissues revealed the localization of NEP in syncytiotrophoblastic cells, as opposed to weak or negative staining in cytotrophoblastic cells. These data demonstrate that induction of choriocarcinoma cell differentiation is associated with an increase of NEP/CD10 expression at the cell surface, suggesting a role of this enzyme in regulating differentiated trophoblast functions such as hCG secretion. NEP/CD10 may also be a new cellular differentiation marker of both the normal and neoplastic trophoblast.

Cell Differentiation↗

PubMed2001

Prognostic factors of patients with yolk sac tumors of the ovary.

OBJECTIVE: Our purpose was to evaluate the prognostic factors in yolk sac tumors of the ovary. STUDY DESIGN: We performed a retrospective review of 47 patients with yolk sac tumors of the ovary from 1979 to 1997. RESULTS: Twenty-two patients had pure yolk sac tumors and 25 had germ cell tumors with yolk sac tissue as a component of the disease. The 5-year survival rate in stages I, II, III, and IV was 95%, 75%, 30%, and 25%, respectively. Patients with stage I disease had a more favorable prognosis than those with stage III and IV disease (P <.001). All patients who did not respond to chemotherapy died of this disease within 36 months of the first treatment. Chemotherapy regimens that included cisplatin gave better results than those without cisplatin (P <.05). The difference in prognosis was significant in cases in which the size of residual tumor was <2 cm in diameter (P <.01) and in cases in which ascites was either absent or <100 mL in volume (P <.05). Coexistence of other components of ovarian germ cell tumors in histologic specimens, preoperative serum alpha-fetoprotein level, fertility-sparing surgery, dissection of intrapelvic nodes, and p53 status had no significant correlation with the prognosis in this study. CONCLUSIONS: Staging and tumor-reductive surgery strongly affected the prognosis of this disease. Tumor-reductive surgery is advisable when ascites is minimal. Cisplatin-based chemotherapy after surgery was superior to chemotherapy without cisplatin; however, p53 status seemed to have no impact on chemosensitivity in yolk sac tumors of the ovary.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumors of the pancreas (IPMT) spread along the main pancreatic duct (MPD) or branch duct, or both. It is important to intraoperatively determine the extent of IPMT lesions in the MPD to perform a successful operation. METHODS: This study included 27 consecutive patients with IPMT who were referred for operation and who had undergone endoscopic ultrasonography, endoscopic retrograde pancreatography, and computed tomography as a diagnostic examination. Intraoperative ultrasonography with a 7.5-MHz annular array transducer and a 7. 5-MHz conventional transducer was performed. All patients underwent operation, and the pathology was confirmed. Endoscopic ultrasonography, endoscopic retrograde pancreatography, intraoperative conventional ultrasonography, and intraoperative annular array ultrasonography results were correlated with those from a pathologic examination of the resected specimens. The diagnostic accuracy of these 4 modalities in the detection of IPMT lesions in the MPD and the branch duct was confirmed. RESULTS: The diagnostic criterion of IPMT lesions by intraoperative annular array ultrasonography was the presence of echogenic masses with irregular margins in the MPD or branch duct, or both. An IPMT lesion in the MPD was found in 22 of the 27 patients. Intraoperative annular array ultrasonography detected 5 cases of IPMT lesions in the MPD that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. In 3 of 5 patients, pancreatic resection was extended to remove IPMT lesions. Intraoperative annular array ultrasonography detected 3 multifocal lesions that could not be detected by preoperative examinations. For the diagnosis of IPMT lesions in the MPD, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 86%, 100%, and 89%; the respective values were 50%, 100%, and 59% for endoscopic retrograde pancreatography; 59%, 100%, and 67% for endoscopic ultrasonography, and 32%, 100%, and 44% for intraoperative conventional ultrasonography. For the diagnosis of IPMT lesions in the branch duct, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 95%, 100%, and 96%. CONCLUSIONS: Intraoperative annular array ultrasonography is suitable for longitudinal scanning of the MPD, useful for accurate diagnosis of the extent of IPMT in the pancreas, and valuable for planning surgical strategy and successful operations for IPMT.

Adenocarcinoma, Mucinous↗

PubMed2001

Histopathologic findings of cornea verticillata in a woman heterozygous for Fabry's disease.

PURPOSE: To report the histopathologic findings of the cornea verticillata observed in a woman who was heterozygous for Fabry's disease. METHOD: A 67-year-old woman was found to have a whorl-like corneal opacity on her visit to the Department of Ophthalmology. Aichi Saiseikai Hospital. Her visit was because of a sudden loss of vision in her right eye owing to a central retinal artery occlusion in association with an ophthalmic artery occlusion. The patient died suddenly of an acute heart failure; with family consent, an autopsy was performed and the right eye was removed for histopathologic examination by light and electron microscopy. RESULTS: Low levels of alpha-galactosidase in the leukocytes together with the corneal finding led to the diagnosis of heterozygous Fabry's disease. Light microscopy revealed a 0.3- to 0.5-microm thick layer between the epithelial and Bowman's layers. Oil red O positive deposits were accumulated in the subepithelial layer, and the density varied in different regions. Electron microscopy showed that subepithelial layer differed in thickness, and the basal lamina reduplicated regionally. We were not able to determine the structure that correlated with the "ridge" in the central part of the cornea. CONCLUSION: The oil red O positive deposits and their variation in density in the subepithelial area of the cornea may have caused the characteristic whorl-like corneal opacity in this woman who was heterozygous for Fabry's disease.

Aged↗

PubMed2001

Cardiac functional and structural alterations induced by endotoxin in rats: importance of platelet-activating factor.

OBJECTIVE: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: Research laboratory at a university. SUBJECTS: Male, Wistar rats (8-9 wks old; n = 83). INTERVENTIONS: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. MEASUREMENTS AND MAIN RESULTS: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 +/- 2 to 56 +/- 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 +/- 0.1 to 3.1 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 +/- 0.2 to 0.5 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 +/- 1% to 84 +/- 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. CONCLUSIONS: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV functional and structural alterations. The marked increase in LV wall thickness can be ascribed to the congestion of capillaries and edema in the LV myocardium. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

Animals↗