Search PubMed⌕ Search

Biomedical subjects

Y Okuno

Publications and source records attributed to Y Okuno.

At least 127 records · Page 7Linked to original sources

Protection against the mouse-adapted A/FM/1/47 strain of influenza A virus in mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2 strains.

The monoclonal antibody designated C179 was found to neutralize all of the H1 and H2 strains of influenza A virus studied (Y. Okuno, Y. Isegawa, F. Sasao, and S. Ueda, J. Virol. 67:2552-2558, 1993). In the present study, the ability of C179 to protect mice from the lethal effect of the A/FM/1/47 (H1N1) strain was examined. When the mice were injected intraperitoneally with 100 micrograms of C179 per mouse a day before the virus challenge (2.0 x 10(3) focus-forming units per mouse), all of the mice survived. Moreover, significantly higher survival rates were observed in mice receiving 1,000 micrograms of C179 per mouse 2 days after the virus challenge than in those receiving phosphate-buffered saline alone. These results indicate that C179 is effective not only for prevention but also for treatment of mice infected with H1 and H2 strains. The possibility that C179 can be used for passive immunization in humans is discussed.

Amino Acid Sequence↗

Stomachic principles in ginger. III. An anti-ulcer principle, 6-gingesulfonic acid, and three monoacyldigalactosylglycerols, gingerglycolipids A, B, and C, from Zingiberis Rhizoma originating in Taiwan.

An anti-ulcer constituent, 6-gingesulfonic acid, and three monoacyldigalactosylglycerols, gingerglycolipids A, B, and C, were isolated from Zingiberis Rhizoma, the dried rhizome of Zingiber officinale Roscoe which was cultivated in Taiwan, together with (+)-angelicoidenol-2-O-beta-D-glucopyranoside. Based on chemical reactions and physicochemical evidence, the structures of 6-gingesulfonic acid, gingerglycolipids A, B, and C have been determined. In addition, the absolute stereostructure of (+)-angelicoidenol-2-O-beta-D-glucopyranoside was clarified on the basis of its synthesis from d-borneol. 6-Ginesulfonic acid showed weaker pungency and more potent anti-ulcer activity than 6-gingerol and 6-shogaol.

Animals↗

Synthesis of new immunosuppressive myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxomyriocin, and nor-deoxomyriocins: their structure-activity relationships.

Eight new myriocin analogs, 2-epi-myriocin, Z-14-deoxomyriocin, and nor-deoxomyriocins, and a known myriocin derivative, 14-deoxomyriocin, were synthesized from 2-deoxy-D-glucose via common intermediates in previous myriocin and Z-myriocin syntheses. The immunosuppressive activities of new myriocin analogs and Z-myriocin on mouse allogeneic mixed lymphocyte reaction were examined, and, by comparing with those of myriocin and 14-deoxomyriocin, some structure-activity relationships have been found.

Animals↗

Total synthesis of a novel immunosuppressant, myriocin (thermozymocidin, ISP-I), and Z-myriocin.

Myriocin (thermozymocidin, ISP-I), which was known to exhibit several interesting biological properties such as potent immunosuppressive and antifungal activities, and a new analog Z-myriocin were synthesized from 2-deoxy-D-glucose. This synthetic pathway comprises a stereoselective formation of the chiral alpha, alpha-disubstituted amino acid structure in myriocin and Z-myriocin from the isopropylidene six-membered ketone by using a modified Darzen reaction as its key step.

Fatty Acids, Monounsaturated↗

[A case of temporary severe disequilibrium hypercalcemia].

The patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. Laboratory data on admission revealed severe hypercalcemia of 14.9 mg/dl and renal dysfunction with serum creatinine of 2.9 mg/dl. As reflected by increased urinary excretions of pyridinoline and deoxypyridinoline and suppressed serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D, increased bone resorption seemed to be a main factor for the development of hypercalcemia. The development of hypercalcemia seemed to be acute because of (i) her severe symptoms caused by hypercalcemia and (ii) impaired renal function which improved after normalization of serum calcium. Following combination therapy of saline infusion and furosemide, there was a gradual decrease and later normalization of serum calcium together with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level has remained within the normal range. Measurement of serum factors which have hypercalcemia effects such as PTH, parathyroid hormone-related peptide and cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, hypercalcemia in this patient was regarded as a kind of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and has not recurred despite no treatment, her hypercalcemia developed due to imbalance in calcium regulation but not due to any organic disease.

Acute Disease↗

A case of temporary severe disequilibrium hypercalcemia.

We report a rare case of temporary and severe hypercalcemia: the patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. The laboratory data on admission revealed severe hypercalcemia (14.9 mg/dl) and renal dysfunction with increased serum creatinine level (2.9 mg/dl). The urinary excretion of pyridinoline and deoxypyridinoline was increased, and serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D were decreased. The data suggested that increased bone resorption was a probable main factor in the development of the hypercalcemia. The development of hypercalcemia seemed to be of acute onset because of (1) her severe symptoms caused by hypercalcemia and (2) impaired renal function which was improved after normalization of serum calcium level. Combination therapy with saline infusion and furosemide was administered, and there was a gradual decrease and subsequent normalization of serum calcium level along with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level remained within the normal range. The measured values of serum factors which are suspected to have a hypercalcemic effect, such as PTH, parathyroid hormone-related peptide and the cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, the hypercalcemia in this patient was regarded to be a type of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and did not recur even in the absence of treatment, the hypercalcemia was concluded to have developed due to an imbalance in calcium regulation rather than as a result of organic disease.

Aged↗

[Anatomical studies on the thumb muscles of the human hand].

The thenar muscles in 34 cases of 25 human adults were dissected using a stereoscopic microscope. The main supplying branch of the median nerve is often called the recurrent branch because of its characteristic recurrent course, and it enters the muscles between the abductor pollicis brevis and the superficial head of the flexor pollicis brevis. The other branch of the median nerve enters the latter muscle directly close to the tendon of the flexor pollicis longus laterally. This is called the direct branch, and was observed in 32 cases. Of these 32, it passed medial to the tendon in 7 cases. The deep terminal branch of the ulnar nerve supplies the transverse and the oblique heads of the adductor pollicis. One of the branches passes laterally piercing through the latter, and connects with the direct branch of the median nerve under the tendon of the flexor pollicis longus. The anastomosis between the two nerves was observed in 31 cases (91%). The obtained results concerning the nerve supply of the thenar muscles are summarized in Table 1. As seen in this table, the boundary of the supplying area between the median and ulnar nerves almost coincides with the position of the tendon of the flexor pollicis longus. In the other three cases in which a thick anastomosis, about 1 mm in thickness, existed between the median and ulnar nerves in the forearm (Martin-Gruber anastomosis), remarkable expansion of the supplying area of the ulnar nerve within the thenar muscles was observed, as seen in Table 2. According to the descriptions from clinical fields, the opponens pollicis and even the abductor pollicis brevis are sometimes supplied by the ulnar nerve. Such an extreme case may be explained by the existance of the anastomosis described above. The palmar interosseous muscle of the thumb has been described in textbooks. In this study, it is identified as the muscle fascicle of the adductor pollicis dorsal to the princeps pollicis artery, and was observed in 22 cases (65%). The macaca fuscata was also examined in 5 cases. In contrast to humans, all the thenar muscles can be identified without difficulty because no fusions are observed among them and because the nerve supply for each muscle is fairly constant.

Adult↗

[Sleeve S6 segmentectomy for early bronchial squamous cell carcinoma--a case report].

A 60-year-old male complaining cough was referred to our hospital. His chest roentgenogram showed left hilar abnormal shadow and his sputum cytology was reported to be class V. Bronchoscopy revealed a squamous cell carcinoma of the orifice of the left B6. It suggested early hilar carcinoma with obstructive pneumonia. We performed sleeve segmentectomy of the S6 with bronchoplastic procedure. Bronchial wall invasion of squamous cell carcinoma was observed histologically and it was confirmed as early hilar lung cancer. His postoperative course was uneventful and no evidence of recurrence is observed 12 months after operation. Patency of the basal bronchus is excellent and his vital capacity and forced expiratory volume in one second are almost equal to preoperative values. In such early hilar lung cancer that occupied the orifice of the B6, the margin of oral side bronchus resected by sleeve S6 segmentectomy is almost same as by lower lobectomy. We believed that this procedure can be minimum invasive standard operation in such cases.

Bronchi↗

Effect of iodinated contrast media on ionic calcium.

This study was conducted to characterize the alterations in serum ionized calcium induced by contrast media (CM) and to determine the cause of the change. Fresh human blood samples as well as an electrolyte solution (ES) containing 1.2 mM calcium ions were diluted with CM and alterations in ionized calcium were measured using an electrometer. The CM tested were diatrizoate, iopamidol, iohexol, ioxaglate, isotonic saline, Na2-Ca-EDTA and pure meglumine. When CM were mixed with blood, ionic CM produced a greater decrease in ionized calcium than nonionic CM or saline. When mixed with ES, a significant reduction of ionized calcium was induced by ioxaglate and diatrizoate in comparison with saline. Na2-Ca-EDTA and meglumine caused no reduction in ionized calcium. Ioxaglate and diatrizoate caused calcium binding due to anions; binding induced by the latter was more prominent than that by the former. These observations suggest that a nonionic CM is more desirable for coronary arteriography of high-risk patients.

Adult↗

Specific interaction between a novel enediyne chromophore and apoprotein in macromolecular antitumor antibiotic C-1027.

The DNA cleavage experiments show that C-1027 chromophore is selectively incorporated into C-1027 apoprotein and is strongly protected by the apoprotein from loss of its DNA cleaving activity. Fluorescence and circular dichroism spectra reveal (1) important participation of tertiary structure of C-1027 apoprotein for the chromophore binding, (2) specific 1:1 binding of C-1027 chromophore to the apoprotein, and (3) significant interaction of the benzoxazine group in the chromophore-apoprotein complex. On the other hand, C-1027 apoprotein does not contribute to sequence-specificity DNA cleavage by C-1027 antibiotics.

Aminoglycosides↗

70-kDa heat-shock cognate protein colocalizes with karyophilic proteins into the nucleus during their transport in vitro.

Recently, we showed that antibodies against 70-kDa heat-shock cognate 66otein (hsc70) inhibit nuclear transport of karyophilic proteins in vivo. In this study, we examined the involvement of hsc70 in nuclear transport using a digitonin-permeabilized cell-free transport system. Depletion of the cytosolic extract required for nuclear transport of hsc70 by incubation with anti-hsc70 antibodies reduced the nuclear transport activity significantly, and addition of purified hsc70 to the depleted extract restored the transport activity. We examined the localization of hsc70 during nuclear transport in vitro by indirect immunofluorescence studies. Hsc70 accumulated in the nucleus when bovine serum albumin (BSA) conjugated to SV40 large T-antigen nuclear localization signal (NLS) peptides (T-BSA) or nucleoplasmin was added exogenously to the cytosolic extract, but not when BSA conjugated to transport-incompetent point-mutated NLS peptide was added. This karyophilic protein-dependent accumulation of hsc70 was dependent on the cytosolic extract, temperature, and ATP and was sensitive to wheat germ agglutinin. Addition of excess unlabeled T-BSA to the cytosolic extract competitively inhibited the nuclear accumulation of fluorescently labeled T-BSA or nucleoplasmin, but did not affect accumulation of hsc70 into the nucleus. These results show that hsc70 is required for nuclear transport and that it is colocalized with karyophilic proteins during their active import into the nucleus in vitro.

Adenosine Triphosphate↗

DNA replication of parvovirus B 19 in a human erythroid leukemia cell line (JK-1) in vitro.

A major limitation of studies on the parvovirus B 19, a causative agent of transient aplastic crisis, has been the absence of appropriate cell lines permissive for the virus. In the present study, a human erythroid leukemia cell line (JK-1) was shown to support B 19 virus DNA replication in vitro. Forty-eight hours after virus inoculation of JK-1 liquid cell cultures, the average number of B 19 genome copies was estimated at 3,000 per cell by DNA dot blot analysis. The addition of erythropoietin increased B 19 copy number to 10,000 per cell. The presence of replicative forms of the B 19 virus genome was genome was demonstrated by Southern blot analysis. Although persistent infection of B 19 virus was not observed in JK-1 cells, this culture system will be of value in elucidating the molecular basis of the erythroid specificity of parvovirus B 19.

DNA Replication↗

Liver damage in patients with colony-stimulating factor-producing tumors.

PURPOSE: We have demonstrated that colony-stimulating factor (CSF)-producing tumor cell lines produce not only CSF but also interleukin-1 (IL-1) and interleukin-6 (IL-6). Clinically, we have observed that patients bearing such tumors present with liver dysfunction and fever in addition to marked leukocytosis. The purpose of this study was to determine whether or not the liver damage was specifically related to CSF-producing tumors. PATIENTS AND METHODS: Clinicopathologic examinations were performed in six autopsied patients with CSF-producing tumors. We also transplanted two tumor cell lines (KHC287 and CHU-2), which produce granulocyte (G)-CSF, IL-1, and IL-6, to nude mice. RESULTS: Of the six patients, five had G-CSF- and one had granulocyte/macrophage (GM)-CSF-producing tumors. IL-1 and IL-6 concentrations in plasma or culture supernatant were elevated in these patients. Biochemical examinations revealed high serum enzyme levels of the biliary system in contrast to normal or slight increases in transaminase levels in all patients studied. Serum direct bilirubin was elevated in five of the six patients. Three common pathologic changes of the liver were found: (1) focal necrosis associated with neutrophil infiltration in the centrilobular zones, (2) fibrous change and enlargement of the portal area associated with neutrophil infiltration, and (3) intrahepatic cholestasis. The same pathologic changes, except for cholestasis, were reproduced in the liver of mice transplanted with KHC287 or CHU-2. CONCLUSION: These results indicate that patients with CSF-producing tumors have characteristic liver damage, and suggest a new paraneoplastic syndrome of leukocytosis and liver damage.

Aged↗

In vivo and in vitro effects of glucocorticoids on glucose transport in human polymorphonuclear leukocytes.

In order to study whether or not exogenous and/or endogenous glucocorticoids affect the glucose transport rate in human cells, we examined the transport rate of a non-metabolizable hexose analogue, 3-O-methyl-D-glucose, in polymorphonuclear leukocytes from patients with hypercortisolism. The mean glucose transport rate was prominently decreased in 5 patients with Cushing's syndrome compared with 29 healthy controls (5.4 +/- 1.8 vs 10.4 +/- 2.5 fl/cell.sec, mean +/- SD, p < 0.001) and the transport rate returned to normal range after adenoma resection in 2 of them. In 10 patients with nephrotic syndrome treated with prednisolone, a significant negative correlation was found between transport rates and daily prednisolone doses. When prednisolone of 40 mg/day was administered to a diabetic patient and the dose was gradually reduced, glucose transport rate was transiently decreased during the initial period. In an in vitro study, a synthetic glucocorticoid, dexamethasone, directly inhibited glucose transport rate in those cells in time- and concentration-dependent manners by mainly reducing Vmax. These results suggest that either exogenous or endogenous hypercortisolism in humans is associated with a decrease in glucose transport rate in polymorphonuclear leukocytes, and that the direct effect of glucocorticoids accounts at least in part for the decreased glucose transport rates found in those cells.

3-O-Methylglucose↗

Evaluating bronchial drainage pathways in patients with lung disease using digital subtraction angiography.

RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate the venous drainage pathways of the bronchial circulation during bronchial embolotheraphy or infusion therapy. METHODS: The subjects consisted of 21 patients with lung disorders. All of them underwent bronchial arteriography for drug infusion or embolization. Bronchial arteriography was done using both cut-film and digital subtraction methods. RESULTS: The venous drainage pathways of arteriograms could be determined in 15 (71%) patients and classified into the four types: type 1, direct drainage into a pulmonary vein; type 2, drainage into a pulmonary artery with antegrade flow; type 3, drainage into a pulmonary artery with retrograde flow; and type 4, drainage into a bronchial vein. No drainage route could be identified in six (29%) patients. CONCLUSIONS: Digital subtraction angiography can depict the venous drainage pathways in most patients. Drainage occurs into a pulmonary vein in the majority of patients.

Angiography, Digital Subtraction↗

Diabetic gastropathy in patients with autonomic neuropathy.

Diabetic autonomic neuropathy causes abnormal gastric electrical activity which results in delayed gastric emptying or diabetic gastroparesis. Delayed gastric emptying causes unstable glucose control because of unpredictable emptying of food from the stomach. Prokinetics are effective in improvement of delayed gastric emptying, which leads to better glycemic control in diabetic patients. Through the mechanism of how prokinetics act on gastric electrical events, improvement of delayed gastric emptying in patients with autonomic neuropathy should be achieved not only for the relief of GI symptoms but also for stable glycemic control.

Autonomic Nervous System↗

A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains.

When mice were immunized with the A/Okuda/57 (H2N2) strain of influenza virus, a unique monoclonal antibody designated C179 was obtained. Although C179 was confirmed to recognize the hemagglutinin (HA) glycoprotein by immunoprecipitation assays, it did not show hemagglutination inhibition activity to any of the strains of the three subtypes of influenza A virus. However, it neutralized all of the H1 and H2 strains but not the H3 strains. Moreover, it inhibited polykaryon formation induced by the H1 and H2 strains but not by the H3 strains. Two antigenic variants against C179 were obtained, and nucleotide sequence analysis revealed that amino acid sequences, from 318 to 322 of HA1 and from 47 to 58 of HA2, conserved among H1 and H2 strains were responsible for the recognition of C179. Since the two sites were located close to each other at the middle of the stem region of the HA molecule, C179 seemed to recognize these sites conformationally. These data indicated that binding of C179 to the stem region of HA inhibits the fusion activity of HA and thus results in virus neutralization and inhibition of cell-cell fusion. This is the first report which describes the presence of conserved antigenic sites on HA not only in a specific subtype but also in two subtypes of influenza A virus.

Amino Acid Sequence↗