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Biomedical subjects

Y Haga

Publications and source records attributed to Y Haga.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intracerebral Schwannoma--case report.

A 15-year-old girl presented with a rare intracerebral schwannoma manifesting as epileptic seizure. Computed tomography, magnetic resonance imaging, and cerebral angiography showed a right parietooccipital lobe tumor. The preoperative diagnosis was malignant glioma, but immunohistochemical and ultrastructural examinations showed the tumor was indistinguishable from peripheral schwannoma. Only 29 cases of schwannomas not related to the cranial nerve have been reported, mostly in children and young adults. The origin appears to be ectopic or perivascular elements in the brain. Such intracerebral schwannomas can be classified according to origins into intra-axial, periventricular, dural attachment, and other types.

Adolescent↗
PubMed1997

1 beta-Methyl-2-(5-substituted pyrrolidin-3-ylthio)carbapenems. 3. Synthesis and antibacterial activity of BO-2727 and its related compounds.

The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)- 5-substituted pyrrolidin-3-ylthio]- 6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid in which hydroxy-substituted aminoethyl, aminopropyl, and aminobutyl groups were introduced as substituents, are described. These derivatives showed potent antibacterial activity against Gram-positive and Gram-negative bacteria including P. aeruginosa. Among them, lenapenem (BO-2727, 7b), carrying an (R)-1-hydroxy-3-(N-methylamino)propyl group, was selected as a development candidate.

Anti-Bacterial Agents↗
PubMed1997

[Current medical therapies for Crohn's disease in Japan].

Current available therapies for Crohn's disease in Japan are reviewed in this report. Elemental diet is most effective for both inducing and maintaining remission in Japan. There appears to be no difference between elemental diet, oligopeptide diet and intact nutrients in effectiveness for active Crohn's disease. Although corticosteroid is also useful for treating active Crohn's disease, low dose of it is not effective for maintaining remission. Steroid has important role in combined therapy with elemental diet. New steroid, budesonide appears to be fascinate because of less adverse effects. Recently, instead of salazosulfapyridine, 5-aminosalicylic acid (5-ASA) proved to be more effective not only for active disease but also for maintenance of remission including small intestinal type of Crohn's disease with reduced adverse effects. Azathioprine, 6-mercaptopurine (6-MP), methotrexate and metronidazole are second choice treatment in patients whose disease relapse frequently. Although methotrexate appears to be effective for active Crohn's disease, the role of it has to be defined. Evidences support the use of 5-ASA and methotrexate for prophylaxis after surgery. It is important to chose and combine the therapies, thinking of the situation of each patient.

Aminosalicylic Acids↗
PubMed1997

Neutrophil elastase inhibitor (ONO-5046.Na) decreases production of proinflammatory cytokines by lipopolysaccharide-stimulated human monocytes.

This study investigates in vitro effects of specific neutrophil elastase inhibitor ONO-5046.Na on production of proinflammatory cytokines by human monocytes in a neutrophil-free system. Isolated human monocytes were cultured with lipopolysaccharide in the presence or absence of ONO-5046.Na. The production of proinflammatory cytokines was assessed by the measurement of cytokine level in the culture supernatant. ONO-5046.Na significantly inhibited the production of IL-1 beta and IL-6 at the doses between 10(-9) and 10(-7) M, and TNF-alpha at the doses between 10(-9) and 10(-4) M. These results suggest that ONO-5046.Na at clinically available concentrations can inhibit the cytokine production by monocytes. This drug could act as a dual inhibitor of neutrophils and monocytes in inflammatory tissue destruction.

Cells, Cultured↗
PubMed1996

Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human lymphocytes.

Septic complications have been major problems in the management of patients with obstructive jaundice and neonatal jaundice. This study investigates effects bilirubin on human T lymphocyte responses against allogeneic mixed lymphocyte reaction. In vitro exposure of human peripheral blood mononuclear cells (PBMNC) with unconjugated bilirubin at pathological levels (6 to 12 mg/dl) did not alter the subsets of CD3, CD4, CD8, CD14, CD19 and CD56 positive populations, or expression of costimulatory surface molecules CD2, CD3, CD4 and CD8. Further incubation of bilirubin-treated PBMNC with irradiated B lymphoid Raji cells after removal of the extracellular bilirubin resulted in a dose-dependent decrease of cytotoxic T lymphocyte (CTL) activity, DNA synthesis, and expression of Tac antigen (CD25) and transferrin receptor (CD71). However, no significant change of interleukin-2 (IL-2) production was observed after this incubation between bilirubin-treated and -untreated PBMNC. These results suggest that bilirubin inhibits the induction of CTL activity, and this defect may result from the impaired responsiveness against IL-2. These observations may help explain the increased infection observed in hyperbilirubinemic patients.

Antibodies↗
PubMed1996

Unconjugated bilirubin inhibits in vitro major histocompatibility complex-unrestricted cytotoxicity of human lymphocytes.

Septic complications have been major problems in the management of patients with obstructive jaundice and neonatal jaundice. This study investigates effects of unconjugated bilirubin on lymphocyte-mediated cytotoxicity against human tumor target cells. In vitro exposure of human peripheral blood lymphocytes (PBL) with bilirubin IX alpha in bovine albumin solution resulted in a dose-dependent decrease of both natural killer activity and antibody dependent cellular cytotoxicity (ADCC) activity. Inhibition of both activities correlated with the amounts of intracellular bilirubin. Expression of cell surface CD16, CD56 antigen, and IL-2 receptor beta chain was unchanged in bilirubin-treated PBL as compared to bilirubin-untreated PBL. When bilirubin-treated PBL were cultured with interleukin-2 (IL-2), a dose-dependent decrease of lymphokine-activated killing activity, ADCC activity, and DNA synthesis was observed. Expression of CD56 antigen and IL-2 receptor alpha chain was unchanged in bilirubin-treated PBL following IL-2 stimulation as compared to bilirubin free control. These results suggest that bilirubin inhibits major histocompatibility complex-unrestricted cytotoxicity in both unstimulated and IL-2 stimulated lymphocytes. These observations may help explain the increased susceptibility to infection observed in hyperbilirubinemic patients.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1996

Intracellular accumulation of unconjugated bilirubin inhibits phytohemagglutin-induced proliferation and interleukin-2 production of human lymphocytes.

Decreased immune responses have been documented in hyperbilirubinemic patients. This study investigates the effects of intracellular bilirubin accumulation on lymphoproliferative response to phytohemagglutin A (PHA). Human peripheral blood mononuclear cells (PBMNC) were preincubated with unconjugated bilirubin dissolved in bovine albumin solution at pathological levels seen in clinical hyperbilirubinemia (0-12 mg/dl), washed, and further cultured with PHA. DNA synthesis was measured by [3H]thymidine uptake. Interleukin-2 (IL-2) activity was determined by the CTLL proliferation assay. The amount of intracellular bilirubin and expression of cell surface antigens were analyzed by flow cytometry. In vitro exposure of normal PBMNC to bilirubin resulted in the accumulation of intracellular bilirubin and a decrease in DNA synthesis after PHA stimulation in a time- and dose-dependent manner. Addition of autologous untreated monocytes could not correct the decreased DNA synthesis of bilirubin-treated lymphocytes. IL-2 production by bilirubin-treated PBMNC after PHA stimulation was significantly decreased compared to bilirubin-untreated PBMNC. However, addition of exogenous IL-2 to pretreated PBMNC could not correct the decreased DNA synthesis. Expression of Tac antigen and transferrin receptor on bilirubin-treated lymphocytes after PHA stimulation was not significantly different from bilirubin-untreated cells. These results suggest that decreased PHA-induced T-lymphocyte proliferation following bilirubin-pretreatment may result from impairment of proliferation at a step beyond transferrin receptor expression. These observations may help explain the increased susceptibility to infection often observed in hyperbilirubinemic patients.

Antigens, CD↗
PubMed1996

Pericholangitis in a rabbit colitis model induced by injection of muramyl dipeptide emulsified with a long-chain fatty acid.

Rabbit colitis has been induced by injection of muramyl dipeptide emulsified with a long-chain fatty acid. The muramyl dipeptide emulsion was injected submucosally at six portions of the rectum and colon, 10 cm proximal to the anus, using a flexible endoscope. Six rabbits were injected six times every 2 weeks and subsequently killed 2 weeks after the last injection. The histological changes of the colon that occurred in all 6 rabbits were mononuclear cell and histiocyte infiltration with sporadic eosinophils, transmural infiltration, and well-maintained goblet cell populations. These changes were different in degree. In 4 of 6 rabbits histological examination of the liver showed pericholangitis and periductal fibrosis mimicking the pericholangitis frequently seen in patients with inflammatory bowel disease. Fibrosis bridging between the portal and portal veins occurred in 2 rabbits, and noncaseating granuloma was seen in 1 rabbit. These histological changes in our model have led to the suggestion that continuous stimulation with bacterial cell wall fragments may be involved in chronic intestinal inflammation and extraintestinal manifestations such as pericholangitis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Extraintestinal manifestations of granulomatous enterocolitis induced in rabbits by long-term submucosal administration of muramyl dipeptide emulsified with Freund's incomplete adjuvant.

We examined whether extraintestinal manifestations of granulomatous enterocolitis in rabbits might be produced by the long-term administration of muramyl dipeptide which represents the basic fragment of the bacterial cell wall, emulsified with Freund's incomplete adjuvant. Muramyl dipeptide emulsion was injected submucosally at six sites in the rectum and colon, 10 cm proximal to the anus, each time with a flexible endoscope. Seven rabbits were injected nine times or more every month, and all were sacrificed 1 month after the last injection. The histological changes in the colon in the seven rabbits were mononuclear cell infiltration, epithelioid granulomas, granulomatous lesion, and denuded and regenerative epithelia, although the changes differed in degree. In five of the seven rabbits, histological examination of the liver showed pericholangitis and periductal fibrosis, findings analogous to sclerosing cholangitis in patients with inflammatory bowel disease. In four of the seven rabbits, fibrosis bridging mainly between portal and portal veins, and, in places, between portal and central veins, was seen. Two of the seven rabbits developed polyarthritis. The histological changes in our model suggest that continuous stimulation with bacterial cell wall fragments may be involved in the extraintestinal manifestations of chronic intestinal inflammation such as that seen in inflammatory bowel disease.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

The effect of ventricular activation sequence on cardiac performance during pacing.

The aim of this study was to evaluate the importance of a normal ventricular activation pattern for cardiac performance. In nine mongrel dogs, atrial pacing was compared to AV synchronous pacing at three different AV delays (150, 100, and 60 ms). In six dogs, proximal septal AV synchronous pacing was compared to apical AV synchronous pacing at three different AV delays. AV synchronous pacing was performed after RF induced complete heart block. Hemodynamics were evaluated by assessment of positive and negative dP/dt, cardiac output, and left ventricular and pulmonary pressures. Atrial pacing was superior to AV synchronous pacing with respect to positive and negative dP/dt and cardiac output. This difference was present at all AV delays. Proximal septal pacing was associated with a higher positive and negative dP/dt compared to apical pacing at all AV delays. Left ventricular activation time was significantly shorter during proximal septal pacing than during apical pacing (88 +/- 4 vs 115 +/- 4 ms, P < 0.001). We conclude that atrial and proximal septal pacing improves cardiac function and shortens the ventricular activation time compared to apical AV synchronous pacing independent of the AV interval.

Animals↗
PubMed1996

Effects of calcium blockers on the cytosolic calcium, H2O2 production and elastase release in human neutrophils.

Activated neutrophils are assumed to be one plausible cause of tissue injury in the ischaemic and reperfused myocardium. We studied the inhibitory effects of the calcium antagonists felodipine, nimodipine and verapamil on human neutrophil activation in order to elucidate the mechanisms underlying their myocardioprotective effects and to determine whether calcium antagonists with different chemical structures vary in their effect on neutrophil activation. Neutrophils were stimulated with formyl-Met-Leu-Phe (0.1 microM) or by phorbol myristate acetate (0.16 microM), and the rise in cytosolic calcium and the H2O2 production were determined. For felodipine, the inhibitory effect on granulocyte elastase release was also studied. The calcium antagonists reduced formyl-Met-Leu-Phe and phorbol myristate acetate-induced neutrophil activation in a concentration-dependent manner, the order of potency being: felodipine > nimodipine > verapamil. For felodipine, the IC50 (concentration causing 50% reduction) values were 3 x 10(-6) and 2 x 10(-6) M for the formyl-Met-Leu-Phe-induced cytosolic calcium increase and H2O2 production, respectively. The IC50-value for the phorbol myristate acetate-induced cytosolic calcium increase was 6 x 10(-6) and for H2O2 production 4 x 10(-6) M. For formyl-Met-Leu-Phe-induced granulocyte elastase release, the IC50-value was 5 x 10(-6) M. The inhibitory effect of felodipine on the phorbol myristate acetate-induced granulocyte elastase release did not exceed 50%. Nimodipine was a less potent inhibitor than felodipine for both formyl-Met-Leu-Phe- and phorbol myristate acetate-induced cell activities. Verapamil was even less potent than the other two agents. The present study demonstrates that felodipine potentially suppresses neutrophil activation at micromolar concentrations. However, this observation should not be directly extrapolated to explain the tissue protection by the compounds without evidence of profound local accumulation.

Calcium↗
PubMed1996

Absence of measles viral genomic sequence in intestinal tissues from Crohn's disease by nested polymerase chain reaction.

The aetiology of Crohn's disease remains unknown, although evidence for a viral cause has long been sought. Recent studies have shown inflammation of the submucosal microvascular endothelium and granulomata, and endothelial cell cytoplasmic inclusions, consistent with paramyxovirus, were identified by electron microscopy suggesting a persistent measles virus infection in Crohn's disease. Measles, mumps, and rubella viruses were tested for Crohn's disease by polymerase chain reaction (PCR). RNA was extracted from resected intestinal specimens from 15 patients with Crohn's disease, 14 with ulcerative colitis, and 14 controls without inflammatory bowel disease. This was used to perform nested PCR after reverse transcription (RT) of the RNA to cDNA with primer pairs directed against two regions in the genome of the measles virus and one region in the mumps and rubella viral genomes. Despite enhanced sensitivity of nested RT-PCR, measles, mumps, and rubella viral genomic sequences were not found in any intestinal specimen.

Adolescent↗
PubMed1996

Immunohistological evaluation on respiratory lesions of pigs intranasally inoculated with Actinobacillus pleuropneumoniae serotype 1.

Nine-week-old pigs were inoculated intranasally with 6.10 X 10(3) (group 10(3)), 10(5) (group 10(5)) and 10(7) (group 10(7)) colony-forming unit of Actinobacillus pleuropneumoniae (App) serotype 1 designated HA-337 strain, respectively. One pig in group 10(5) and 2 pigs in group 10(7) died with dispnea and hemorrhagic pleuropneumonia within 20 to 48 hr post inoculation (PI). All pigs necropsied on 7 days in groups 10(5) and 10(7) had focal fibrous pleuropneumonia. Histologically, pulmonary lesions were classified into three stages; peracute, acute and subacute. Fatal cases in group 10(7) had peracute lesion composed of severe edema, hemorrhage and necrobiosis of alveoli, with mononuclear cells infiltration in the dilated interlobulus. The fatal case in group 10(5) had acute pulmonary lesion composed of focal or linear infiltration of round and fusiform cells that frequently showed swirling pattern in alveoli. The surviving cases in group 10(5) and 10(7) had subacute lesion composed of multifocal pulmonary necrosis surrounded by fibrous tissue. The swirling pattern was clearly seen in demarcation zone. Immunohistochemically, App antigens scattered as intact bacteria in alveoli, dilated interlobular septa and pleura, and lymph vessels in peracute and acute lesions. Areas of necrosis were also stained weakly. Although no antigen was detected in cytoplasm of macrophages and infiltrated cells in peracute lesions, App antigen was detected as positively stained mass in cytoplasm of some macrophages in acute lesions. In subacute lesions, App antigens were recognized as intact bacteria in necrotic areas and among the swirling pattern cells of demarcation zone. Macrophages had App antigens as a large mass of pigment in the cytoplasm in area of fibrosis.

Actinobacillus Infections↗
PubMed1996

[A case of alveolar soft-part sarcoma with cerebral metastases].

A case of alveolar soft-part sarcoma with multiple cerebral metastases in addition to multiple lung and bone metastases is reported. This is a rare tumor which thus far has only been recognized as a malignant soft tissue tumor with great uncertainty. A 24-year-old man with a chief complaint of left frontal headache was admitted to our unit on September 26, 1994. A tumor of the right forearm had been surgically removed 9 years previously, and surgery had been followed by two courses of chemotherapy with vincristine, cyclophosphamide and actinomycin-D and subsequent irradiation for bone metastasis. The chemotherapy, however, did not have any clear effect. Neurological examination at the time revealed only bilateral papilledema, but CT and MRI scan of the brain showed a round mass in the left occipital lobe with homogeneous enhancement and another small mass was detected in the right occipital lobe. A cerebral angiogram showed a vascular tumor. The preoperative diagnosis was multiple cerebral metastases of alveolar soft part sarcoma. Left occipital craniotomy was performed on October 12, 1994, and the tumor was completely removed by lobectomy. Specimens of the tumor showed typical histological features of alveolar soft-part sarcoma. Whole-brain radiotherapy was administered postoperatively, and the patient is well neurologically without right homonymous hemianopsia. The clinical features of alveolar soft-part sarcoma are discussed. Only a few cases have been reported in the literature, but the most frequent site of the primary lesion has been the lower extremities, and cerebral metastasis has not been rare. All efforts should be focused on discovering this tumor in the early stage because surgical removal can yield good results, and radiotherapy is thought to be effective in terms of patient "quality of life".

Adult↗
PubMed1995

Rabbit granulomatous enterocolitis induced by injection of muramyl dipeptide emulsified with Freund's incomplete adjuvant.

We induced granulomatous enterocolitis in rabbits by injecting them with muramyl dipeptide (MDP), a subunit of the peptidoglycan polymers that endow the bacterial cell wall with structural rigidity, emulsified with Freund's incomplete adjuvant (FIA). Injections of 0.1 ml of a water-in-oil emulsion of MDP and FIA were given submucosally at six sites in the rectum and colon, 10 cm proximal to the anus, using a flexible endoscope. Four rabbits each were sacrificed 1, 2, and 4 weeks after a single injection of the emulsion. Another 4 rabbits each were injected six times at 1- and 2-week intervals, and were sacrificed 1 and 2 weeks after the last injection of the emulsion, respectively. In all 20 rabbits, injected with the MDP emulsion, histological findings of the colon consisted of cellular infiltrations of plasma cells and lymphocytes, granulomatous lesions, and granulomas, although the findings differed in degree. Cellular infiltration in hyperplastic villi and denuded epithelia of the small intestine were seen in 2 of 8 rabbits repeated that received MDP emulsion injections. The histological changes in this animal model may be useful for studying the pathogenesis of inflammatory bowel disease in humans.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Do ictal, clinical, and electroencephalographic features predict outcome in West syndrome?

Ictal electroencephalographic/video recordings of 42 patients with West syndrome (WS) were reviewed to define the relation between ictal, clinical, and EEG features and etiology or prognosis. The duration and type of spasms, the number of spasms per cluster, and the interval between spasms did not correlate with the etiology or the short-term prognosis. However, eye deviation, asymmetric spasms, and partial seizures concomitant with spasms were observed only in symptomatic WS patients with poor outcome. In particular, all 8 patients with concurrent partial seizures had severe psychomotor retardation. The ictal EEG characteristics did not correlate with etiology and prognosis. There was no significant difference between the patients with persistence or reappearance of hypsarrhythmia and the patients without interspasm hypsarrhythmia.

Electroencephalography↗