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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 163 records · Page 9Linked to original sources

Pharmacokinetics, tolerability, and preliminary efficacy of human anti-Pseudomonas aeruginosa monoclonal antibodies in pneumonia and burn infection patients.

Human monoclonal antibody (hMAb) cocktail SM-17220 (also known as BT-570), a heterofunctional antibody mixture of 3 human IgM MAbs (HI-223, MH-4H7, and IN-2A8; ratio of 1:10:10) directed against Pseudomonas aeruginosa, were administered to patients with pneumonia or burn wounds (or both) to assess the pharmacokinetics, safety, antigenicity, and preliminary efficacy. Twenty mg of SM-17220 was IV infused over 60 min once daily on 3 consecutive days. Twenty patients (8 pneumonia, 4 burns, and 8 both) completed the study. SM-17220 was safe and well tolerated, and no subjects developed antibodies to SM-17220 and mouse J-chain during the follow-up of 8 weeks. Each MAb of SM-17220 had a half-life ranging from 49 to 91 h, similar to native human IgM. Both MH-4H7 and IN-2A8 administration resulted in a high serum level for about 4 days over an effective concentration, whereas HI-223 showed a lower serum level than expected. Some indications of a potential efficacy were observed and are discussed here.

Adolescent↗

Evaluating the effect of superficial temporal artery to middle cerebral artery bypass on pure motor function using motor activation single photon emission computed tomography.

OBJECTIVE: We evaluated and analyzed the effect of superficial temporal artery to middle cerebral artery bypass for internal carotid artery occlusion on pure motor function using motor activation single photon emission computed tomography. METHODS: Motor activation single photon emission computed tomographic (SPECT) images were obtained for nine patients who had undergone superficial temporal artery to middle cerebral artery anastomosis for symptomatic internal carotid artery occlusion. All motor activation SPECT images using the finger opposition task on the affected side were obtained before bypass surgery and at 1 week, 1 month, and 3 months after bypass surgery. The results of motor activation single photon emission computed tomography were expressed as negative or positive. RESULTS: Before bypass surgery, the resting SPECT images revealed reduction of cerebral blood flow (CBF) on the affected side in all nine patients. The results of motor activation single photon emission computed tomography in three patients were positive. One week after bypass surgery, the results of the resting and motor activation CBF studies did not demonstrate any marked changes. One month after bypass surgery, the resting CBF increased in four patients. The results obtained for two of the patients revealed preoperative positive motor activation. The results of motor activation single photon emission computed tomography obtained for five patients were positive. Three months after bypass surgery, eight patients experienced improvement in the resting CBF, and the results of motor activation single photon emission computed tomography obtained for seven patients were positive. Among these, the results of preoperative motor activation single photon emission tomography obtained for four patients were negative. CONCLUSION: Superficial temporal artery to middle cerebral artery bypass is useful not only for resting CBF but also for pure motor function based on motor activation SPECT images. From the preoperative motor activation study, it was concluded that patients with preoperative positive motor activation could attain the effect of bypass earlier than patients with preoperative negative motor activation.

Aged↗

Effect of weight changes on serum transaminase activities in obese children.

To examine the effect of weight changes on serum transaminase activities, glutamic oxaloacetic and pyruvic transaminases (GOT/GPT), a 3-month observation of 110 obese outpatients treated by a mild regimen for obesity was carried out. Patients were divided into two major groups, group I (n = 73) and group II (n = 37), with or without persistent elevation of serum GOT/GPT (> 30 IU/L), and retrospectively classified into four subgroups according to weight changes: group A, weight loss > 5%; group B, weight loss of < 5%; group C, an increase of < 5%; group D, an increase > 5%. In group IA, the incidence of cases with normalization of serum GOT/GPT was 70% and was significantly greater than those of the other three subgroups, respectively (P < 0.01). The incidences of decreased serum GOT/GPT activities were observed corresponding to the degree of weight changes not only in group I (100-27%) but also in group II (100-33%). These facts indicate that a mild regimen for obese outpatients for 3 months, significantly improves serum transaminase activities in patients not only with weight reduction but also weight gain, and that fatty liver may be present even in obese children with normal serum transaminase levels. The normalization of serum GPT activity in patients with weight gain suggests the presence of another factor contributing hypertransaminasemia in pediatric obese patients.

Adolescent↗

Serum alanine aminotransferase activity in obese children.

To confirm the significance of the serum alanine aminotransferase (ALT) test for the diagnosis of fatty liver and to clarify the relationship between serum ALT activity and the duration of obesity, we analysed 310 obese young school children (195M, 115F), who were classified into three duration groups (1-3 y, 4-6 y, 7 + y), three age groups (6-7 y, 8-9 y, 10-11 y), and four obesity groups (weight excess: mild, 20-29%; moderate, 30-39%; severe, 40-49%; very severe, 50%). Seventy-seven patients with abnormal ALT test, > 30 IU/l, and 27 patients with normal ALT test were examined by ultrasound study to identify the fatty-fibrotic pattern of the liver. Abnormal results of the serum ALT test were found in 24% of all patients. The fatty-fibrotic pattern was identified in 64/77 (83%) patients with abnormal ALT test and in 5/27 (18%) patients with normal ALT test. The serum ALT test has a sensitivity of 0.92 for detecting the fatty-fibrotic pattern proven by ultrasound study. Frequencies of cases with abnormal serum ALT levels increased with the duration of obesity. In the shortest duration group, however, the frequencies of abnormal results in serum ALT test did not increase with advanced ages or the grades of obesity. In conclusion, the present study confirmed the usefulness of the serum ALT test for screening fatty liver, and showed that a longer duration of obesity is generally associated with the occurrence of fatty liver in a paediatric obese population. In young patients with mild obesity or a short duration of obesity, however, fatty liver or fatty fibrosis may develop. Early intervention should be made in the case of obese children.

Alanine Transaminase↗

Three cases of renal angiomyolipoma.

We report three non-typical cases of renal angiomyolipoma including clinical features, imaging examinations (with ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography) and histological findings. Microaneurysms observed by angiography were common to the three cases and were considered to be an important finding in the diagnosis of renal angiomyolipoma. Moreover, the short tau inversion recovery (STIR) method of MRI, which suppresses photon signals of fat, was considered to be useful for the diagnosis. Case 1 was accompanied by spontaneous rupture, Case 2 was difficult to diagnose because of little fat tissue and Case 3 revealed a very small tumor.

Adolescent↗

Hypothalamic hamartoma associated with dural arteriovenous fistula of the transverse-sigmoid sinus--case report.

A 32-year-old female presented with a hypothalamic hamartoma associated with a dural arteriovenous fistula (DAVF) of the left transverse-sigmoid sinus. She complained of pulsatile tinnitus in the left retroauricular region and infertility. Endocrinological examination revealed that the luteinizing hormone reaction to luteinizing hormone-releasing hormone was exceedingly high. Magnetic resonance imaging demonstrated a distinct mass occupying the suprasellar cistern and protruding into the third ventricle. Left carotid angiography demonstrated a DAVF of the left transverse-sigmoid sinus, which was treated by embolization. Histological examination of a biopsy specimen of the tumor revealed a hamartoma. She was free from pulsatile tinnitus after treatment for the DAVF.

Adult↗

Orbital varix diagnosed by color Doppler flow imaging--case report.

A 66-year-old male presented with an angiographically occult orbital varix. Angiography and phlebography failed to demonstrate the lesion. Computed tomography angiography showed the varix, but not the vascular flow. Color Doppler flow imaging clearly demonstrated the well-defined varix with slow flow velocity, as well as the precise anatomical location. We recommend color Doppler flow imaging as one of the differential diagnostic tools for intraorbital vascular lesions.

Aged↗

[Application of chimeric and humanized antibodies to autoimmune diseases therapy].

Monoclonal antibodies (MAbs) have been extensively developed for treating autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and intestinal bowl diseases. Recombinant DNA technology made it possible to manufacture chimeric and humanized MAbs, resulting in lower antigenicity, longer half-life in serum and higher biological activities compared to the original murine MAbs. Here, chimeric and humanized MAbs under clinical investigations in the field of autoimmune diseases are reviewed. At this time, non-deleting type of anti-CD4 MAb and anti-TNF alpha MAb have an attractive attention because of their excellent efficacy in the clinical trials. Although deleting type of anti-CD4 MAb failed to show the efficacy in double-blind phase III trials reproducibly, it should be re-evaluated on the administration dosage and duration. In the near future, MAbs to adhesion molecules and co-stimulatory molecules will be studied in clinics.

Animals↗

Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1).

Midkine (MK) is a heparin-binding growth factor which is strongly expressed during the midgestation period of mouse embryogenesis. Wilms' tumor is an embryonal kidney malignancy in infants, and WT1 has been identified as its tumor suppressor gene. The high expression level of MK in all Wilms' tumor specimens so far examined and the presence of two WT1 elements (5'-GCGGGGGCG-3') in the human MK promoter region led us to examine the possible role of the WT1 gene product in the regulation of MK gene expression. A gel shift assay verified the complex formation between the WT1 gene product and WT1 consensus sequence of MK gene. DNase1 footprint analysis also demonstrated that the downstream WT1 element was protected from DNase1 cleavage by the addition of the WT1 protein. The human MK promoter fused with the chloramphenicol acetyltransferase gene (phMK2.3kCAT) was co-transfected with an effector plasmid containing the WT1 gene into several cell lines. Transient transfection assays showed suppression of the MK promoter by WT1 co-transfection in recipient cells; deletion of the WT1 binding site abolished the suppression. The evidence reported in this study indicates that MK gene is a newly identified WT1 target gene.

3T3 Cells↗

Giant mediastinal lymphangioma in a neonate: report of a case.

We report herein the case of a male neonate with a giant cystic lymphangioma confined to the bilateral anterior mediastinum. He developed very severe respiratory distress on the 8th day of life due to the mediastinal mass, and almost total excision of the bilateral mass was performed on the 12th day of life through a right axillar thoracotomy. The pathological diagnosis was cystic lymphangioma. Postoperatively, right phrenic nerve dysfunction was evident, for which diaphragmatic plication could only be performed 5 weeks after the initial surgery due to the prolonged respiratory support. In the 4 years since undergoing surgery the child has shown no sign of recurrence and has not experienced any further respiratory problems.

Humans↗

Activating mechanism of CNTF and related cytokines.

Ciliary neurotrophic factor (CNTF) shares structural and functional properties with members of the hematopoietic cytokine family. It is composed of a four-helix bundle structure and shares the transmembrane signal transducing proteins, glycoprotein-130 (gp130) and leukemia inhibitory factor receptor (LIF-R). Structure-function analysis showed that the gp130-interactive proteins bind in a similar manner to that of growth hormone (site I and II). In addition, gp130-interactive proteins and granulocyte colony-stimulating factor (G-CSF) utilize another binding site (site III) at the boundary between CD loop and helix D. CNTF triggers the association of receptor components, resulting in activation of a signal transduction cascade mediated by specific intracellular protein tyrosine kinases. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways have been characterized in terms of gp130-interactive protein, and there should be other pathways and some crosstalk between them to enhance, prolong, or specify the signals.

Amino Acid Sequence↗

A polyreactive human anti-lipid A monoclonal antibody having cross reactivity to polysaccharide portions of Pseudomonas aeruginosa lipopolysaccharides.

A hybridoma cell line producing a human anti-lipid A monoclonal antibody (mAb), FKF-IF3 (IgM (k)) was obtained by cell fusion of Epstein-Barr virus-transformed cells and mouse myeloma. The mAb bound to not only Gram-negative bacterial lipid A, but also to polysaccharide portions of Pseudomonas aeruginosa lipopolysaccharides (LPS). The mAb seemed to recognize two distinct regions of P. aeruginosa LPS other than lipid A, namely the outer core regions of some serotype strains and the O-polysaccharide region of serotype A strains. The mAb cross-reacted with N-acetyl-beta-glucosamine-conjugated bovine serum albumin, N-acetyl-beta-galactosamine-conjugated bovine serum albumin, myosin and actin, but not with other autoantigens such as ss- and ds-DNA, cardiolipin and glycosaminoglycans. The mAb conferred protective activity against a mouse pseudomonal infection model. The evidence suggested that the mAb was a naturally occurring polyspecific antibody that participated in defense against pseudomonal infections.

Acetylgalactosamine↗