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Biomedical subjects

M Okamura

Publications and source records attributed to M Okamura.

At least 109 records · Page 6Linked to original sources

Structure of an allergenic pentasaccharitol, Gp-1 beta-b6, isolated from a sea squirt antigen, Gi-rep, as a minimum structural unit responsible for its allergenicity.

An allergenic pentasaccharitol, Gp-1 beta-b6, was isolated as a minimum structural unit responsible for the allergic reaction in skin of patients with sea squirt allergy from a saccharitol fraction, Gp-1 beta-b, that had been liberated by beta-elimination from a glycopeptide in a Pronase digest of a sea squirt antigen, Gi-rep. Methylation/GC-MS and FAB-MS analyses indicated the sugar sequence of Gp-1 beta-b6 to be GalNAcl----2Fucl----(GalNAc1----) 3,4GlcNAc1----3GalNAc-ol. To analyze the structure in more detail, Gp-1 beta-b6 was labeled with p-aminobenzoic acid ethyl ester (ABEE), i.e., the reducing terminal 3-O-substituted GalNAc-ol of the saccharitol was oxidized to 2-O-substituted L-ThrNAc with equimolar periodate, and the resultant aldehyde was labeled with ABEE by reductive amination. The ABEE-labeled Gp-1 beta-b6 was subjected to sequential exoglycosidase digestion with beta-N-acetylhexosaminidase, alpha-N-acetylgalactosaminidase, and alpha-fucosidase, and the digests were chromatographed on an HPLC column of TSK gel Amide 80. From the results of the HPLC, methylation/GC-MS, and FAB-MS analyses of the digests of the labeled substrate, the structure of Gp-1 beta-b6 was determined to be GalNAc alpha 1----2Fuc alpha 1----3(GalNAc beta 1----4)GlcNAc beta 1----3GalNAc-ol. Enzymatic elimination of either the non-reducing terminal beta-GalNAc or the non-reducing terminal alpha-GalNAc led to inactivation of the allergenic pentasaccharitol. Accordingly, it is possible that the allergenic saccharitol contains two disaccharide units as the allergy-specific epitopes, one GalNAc alpha 1----2Fuc alpha 1---- and the other GlcNAc beta 1----4GLcNAc beta 1----.

Allergens↗

Corticosteroid- and furosemide-induced increase in proteinuria in nephrosis.

A corticosteroid- and furosemide-induced excessive increase in proteinuria developed in a 34-year-old nephrotic patient with focal glomerulosclerosis. The concentration of urinary protein increased almost in parallel with that of urinary glucose. This finding indicates that corticosteroids and/or furosemide can promote the disturbance of the tubular reabsorption mechanism together with increases in glomerular permeability and glomerular filtration rate.

Adult↗

Release characteristics of cisplatin chitosan microspheres and effect of containing chitin.

To increase cisplatin (CDDP) content, to suppress burst effect during the initial phase of drug release, and to improve the capacity of the system for sustained release, we prepared various types of CDDP chitosan microspheres incorporating chitin and investigated the content of CDDP and its in vitro release kinetics from these microspheres. The results of this study showed that the CDDP content increased with increasing chitosan concentration and that the incorporation of chitin in the carrier matrix produced a more pronounced increase in drug content. The addition of chitin also led to inhibition of the initial burst effect. The rate of CDDP release reduced with increasing concentration of chitosan: that is, the 50% CDDP release time was about 0.5 h with the microspheres prepared with 1.0% of chitosan and about 4.5 h with those prepared with 5.0% of chitosan, indicating about nine-fold prolongation. The addition of chitin further resulted in retardation of the rate of CDDP release. Meanwhile, our chitosan microspheres were shown to undergo enzymatic degradation by lysozymes.

Chitin↗

[Characterization of immunoreactive hCG beta-subunit in cultured fluids of the cell lines derived from gynecologic malignant tumors].

We characterize the hCG beta-like materials in cultured fluids from 12 different cell lines derived from gynecologic malignant tumors (SKG-1, -2, -3a and -3b cervical squamous carcinoma, SNG-M and -2 endometrial adenocarcinoma, SKN uterine sarcoma, RTSG ovarian undifferentiated adenocarcinoma, RMUG ovarian mucinous adenocarcinoma, RKN ovarian sarcoma, RMG ovarian clear cell carcinoma and NJG gestational choriocarcinoma) by three kinds of enzyme immunoassay (EIA) which were specific for whole hCG, free hCG beta and beta-core fragment, respectively. Of eleven nontrophoblastic cell lines, nine secreted hCG beta-like immunoreactive substance. The above-mentioned three EIAs for each fractionated specimens with gel chromatography on Sephadex G-100 revealed that the immunoreactivity in the SKG-2 and RTSG cultured fluids were totally attributable to free hCG beta but neither to whole hCG nor beta-core fragment. On the other hand, the NJG choriocarcinoma cell line secreted both whole hCG and free hCG beta, no beta-core fragment could be detected in the cultured fluid. The present results suggested that ectopically produced hCG beta-like material may represent the free hCG beta molecule, and that the beta-core fragment may not be a cellular secretory product.

Chorionic Gonadotropin↗

A case of congenital adrenal hyperplasia with concomitant abnormalities of steroid 21- and 11 beta-hydroxylase activities.

Abnormalities in the steroid 21-hydroxylase and 11 beta-hydroxylase activities were suspected in a 25-year-old female with congenital adrenal hyperplasia (CAH). The patient showed signs of masculinization such as hirsutism, amenorrhea, and enlarged clitoris, but the blood pressure was normal. Adrenocorticotropic was increased to 200 pg/ml. Plasma levels of deoxycorticosterone and 11-deoxycortisol as well as progesterone and 17-hydroxyprogesterone were elevated. Plasma cortisol level was normal at 5.8 micrograms/dl. CT scan revealed enlargement of the bilateral adrenal glands. This case suggests that enzyme abnormalities in CAH are more diverse than have been generally considered.

Adrenal Hyperplasia, Congenital↗

Role of specific lysine residues in binding cytochrome c2 to the Rhodobacter sphaeroides reaction center in optimal orientation for rapid electron transfer.

The role of specific lysine residues in facilitating electron transfer from Rhodobacter sphaeroides cytochrome c2 to the Rb. sphaeroides reaction center was studied by using six cytochrome c2 derivatives each labeled at a single lysine residue with a carboxydinitrophenyl group. The reaction of native cytochrome c2 at low ionic strength has a fast phase with a half-time of 0.6 microseconds that has been assigned to the reaction of bound cytochrome c2 [Overfield, R.E., Wraight, C.A., & DeVault, D. (1979) FEBS Lett. 105, 137]. Modification of lysine-55 did not affect the half-time of this phase but decreased the apparent binding constant by a factor of 2. The derivatives modified at lysines-10, -88, -95, -97, -99, -105, and -106 surrounding the heme crevice did not show any detectable fast phase but only slow second-order phases due to the reaction of solution cytochrome c2. These lysines thus appear to be involved in binding cytochrome c2 to the reaction center in an optimal orientation for electron transfer. The involvement of lysines-95 and -97 is especially significant, since they are located in an extra loop comprising residues 89-98 that is not present in eukaryotic cytochrome c. The reactions of horse cytochrome c derivatives modified at single lysine amino groups with trifluoroacetyl or [(trifluoromethyl)phenyl]carbamoyl were also studied. The derivatives modified at lysines-22, -55, -88, and -99 far removed from the heme crevice had nearly the same half-times for the fast phase as native cytochrome c, 6 microseconds.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The clinical significance of iC3b neoantigen expression in plasma from patients with systemic lupus erythematosus.

We studied the expression of an iC3b neoantigen (iC3b-NEO) in plasma from patients with systemic lupus erythematosus (SLE), by using a monoclonal antibody specific for iC3b/C3dg/C3d, to investigate the activation of the third component of complement in SLE. The plasma iC3b-NEO level in 40 untreated patients with active SLE was significantly higher than that in 36 normal subjects (mean +/- SD 31.5 +/- 13.9 micrograms/ml versus 12.3 +/- 3.3 micrograms/ml; P less than 0.001). The plasma iC3b-NEO level was highly correlated with clinical disease activity (tau = 0.62, P less than 0.0001), and it was the parameter most closely correlated with renal histologic activity in lupus nephritis (tau = 0.52, P less than 0.0001). Also, patients with diffuse proliferative lupus nephritis had the highest levels of plasma iC3b-NEO among all World Health Organization classes of lupus nephritis (P less than 0.01). We conclude that the plasma iC3b-NEO level is strongly associated with clinical disease activity and renal histologic activity in patients with SLE, and that plasma iC3b-NEO may be a sensitive and useful measure of complement activation in SLE.

Antibodies, Monoclonal↗

Plasminogen activation in plasma of patients with systemic lupus erythematosus.

We measured alpha 2-plasmin inhibitor-plasmin complexes (PI-PC) in plasma of patients with systemic lupus erythematosus (SLE) to examine the plasminogen activation in SLE. The plasma PI-PC level in 23 patients with SLE was significantly higher than that in 18 normal subjects (P less than 0.001) and the SLE patients with nephrotic syndrome had higher plasma PI-PC levels than those without nephrotic syndrome (P less than 0.01). In addition, the plasma PI-PC level was significantly correlated with the level of plasma C3 breakdown products (iC3b/C3dg) in the patients with SLE (r = 0.53, P less than 0.01). These results suggest that plasminogen is activated in plasma of patients with SLE and that the plasminogen activation may be associated with the activation of complement in SLE.

Adult↗

Possible involvement of interferon alfa in the pathogenesis of fever in systemic lupus erythematosus.

Serum concentrations of interferon alfa, interleukin 1, and tumour necrosis factor alpha were measured in 25 untreated patients with systemic lupus erythematosus (SLE). A close correlation was found between serum concentrations of interferon alfa and the degree of fever, while no significant correlations were found between fever and interleukin 1 or tumour necrosis factor alpha. These results suggest the possible involvement of interferon alfa in the pathogenesis of fever in SLE.

Fever↗

Preparation and evaluation of albumin microspheres and microcapsules containing cisplatin.

Albumin microspheres and microcapsules containing cisplatin (CDDP) were prepared and tested as chemotherapeutic agents for the treatment of hepatocellular carcinoma. CDDP albumin microspheres were prepared by hardening with glutaric aldehyde in accordance with the method to prepare W/O emulsion. On the other hand, microcapsules were prepared by formation of a coacervate by the phase isolation method. CDDP albumin microspheres and microcapsules thus prepared were sieved and sterilized by dry heat at 135 degrees C for 4h prior to use. The content and release of CDDP were determined. The CDDP contents for albumin microspheres and microcapsules were found to be 9.2% and 33.3%, respectively. Release of CDDP in vitro was found to be significantly different between the two formulations. CDDP release in vivo was also investigated by injecting albumin microspheres and microcapsules into the hepatic artery of adult dogs. The blood CDDP concentrations after injection of both formulations were lower than those noted after injection of CDDP injectable solution, indicating that CDDP might be accumulated in the liver at a higher concentration and that use of the two formulations might result in alleviation of CDDP side effects.

Albumins↗

Preparation and release characteristics of cisplatin albumin microspheres containing chitin and treated with chitosan.

Cisplatin (CDDP) containing albumin microspheres and microcapsules incorporating biodegradable macromolecules, chitin and chitosan, were prepared, and their CDDP content and releasing ability and susceptibility to various enzymes were examined. Chitin was incorporated during preparation of the microspheres, while chitosan was used to treat preformed microspheres. CDDP content was remarkably increased by chitin; when chitin was incorporated at a concentration of 1.5%, the CDDP content of the microspheres was found to be 16.2% (1.8 times that with no addition of chitin). CDDP release was suppressed by chitin and chitosan. The 50% CDDP release time was about 1.5 h when no chitin was added, but about 16 h was required when chitin was incorporated into the microspheres at a concentration of 1.5%. Chitin and chitosan suppressed the decomposition by protease. The microspheres treated with 70% deacetylated chitosan showed the greatest susceptibility to lysozyme. In conclusion, CDDP release can be controlled by the use of chitin or chitosan, and the microspheres should show no immunogenicity in vivo because of their susceptibility to lysozyme.

Albumins↗

Elevated activity of myeloid growth factor in bone marrow adjacent to joints affected by rheumatoid arthritis.

Myeloid growth activity of rheumatoid arthritis (RA) and normal serum was measured with a newly developed simple method. Abnormally high titers of this activity were found in the bone marrow blood serum adjacent to joints with RA where abnormal myelopoiesis had been found. Maximal activity for myeloid growth was found at a molecular weight of 70 kDa in gel filtration of serum, different from the size of any known factors involved with myelopoiesis.

Adult↗

[Surgical treatment of acute aortic dissection].

Sixty-seven patients subjected to this study composed of 32 patients treated surgically, 15 patients treated medically and 20 patients examined by autopsy for the past 8 years. Out of 32 surgical cases, 16 were operated on in an acute stage, within 2 weeks after onset and 9 out of these 16 acute cases belonged to DeBakey type I or II and 11 out of 15 autopsy cases belonged to type I or II either. Contrarily most of the medical cases were type III. Both causes of death in the acute autopsy group and operative indications in the acute surgical group were cardiac tamponade, heart failure due to aortic insufficiency, myocardial infarction and aortic rupture. Operative mortality rate was 12.5% in the acute cases and 19% in the chronic cases, late mortality rate was 19% in the acute cases and 0% in the chronic cases. Two cases of operative death had massive bleeding due to aortic rupture and massive myocardial infarction. These were the most dangerous complications of acute aortic dissections. We conclude that all patients with type I or II dissections should be operated on before fatal complications occur.

Acute Disease↗

Clinical significance of antibodies to histones in systemic lupus erythematosus.

IgG antibodies to whole histones and to individual histones H1, H2A+H4, H2B and H3 were measured by enzyme linked immunosorbent assay in serum samples from 46 untreated patients with systemic lupus erythematosus (SLE) who had undergone renal biopsy. Patients with the WHO Class IV lupus nephritis had significantly higher levels of antibodies to histones (except H1) than those with milder forms of nephritis. Among antibodies to individual histones, the levels of antibodies to H2B histones best correlated with the renal histologic and the clinical activity of disease (rs = 0.759, rs = 0.577, p less than 0.001, respectively).

Antibodies, Antinuclear↗

[Bone scintigraphy of metastatic calcifications].

The bone scintigrams of 4 cases with metastatic calcification in the lung, stomach and myocardium were presented. These four cases were malignancy with hypercalcemia. Metastatic calcifications were not able to be detected by radiographs and CT. Therefore, bone scan seems to be the most useful method for detection of metastatic calcification.

Aged↗

Mechanisms affecting the development of renal cystic disease induced by diphenylthiazole.

To provide information on the possible influence that hypertension or its treatment might have on the development of cysts in autosomal dominant polycystic kidney disease, we studied the effects of the sodium content of the diet, DOCA-salt hypertension, renovascular hypertension, and the administration of enalapril or furosemide on the development of 2-amino-4-5-diphenylthiazole (DPT)-induced renal cystic disease. DOCA-salt hypertension caused vascular and glomerular lesions and proteinuria, but it did not enhance the development of cysts. Cytogenesis was enhanced in experimental conditions where the renin-angiotensin system is known to be activated. On the other hand, interventions known to suppress the renin-angiotensin system lessened the development of cysts. We hypothesize that this effect might be mediated by intrarenal angiotensin II and its capacity to promote cell growth and to control the postglomerular vascular resistances and the compliance of the renal interstitium.

Animals↗

Idiopathic membranous nephropathy: the natural history of untreated patients.

We reviewed the diagnostic features and clinical course of 140 patients with idiopathic membranous nephropathy who had their index renal biopsies performed at the Mayo Clinic between 1972 and 1984. There were 93 males and 47 females (average age, 50.8 +/- 17 years); 116 patients (83%) had the nephrotic syndrome and 42 (30%) were hypertensive at diagnosis. Eighty-nine patients were not treated with corticosteroid or immunosuppressive drugs and 51 patients were treated mainly with short-term courses of prednisone alone; a minority of patients also received meclofenamate, cyclophosphamide, azathioprine, or chlorambucil. Five-year survival, including patients who received dialysis or a renal transplant, was 85%, 75% at 10 years, and no different from expected survival; there was no difference between untreated and treated groups. Also, there were no differences in the outcomes of renal function and protein excretion between untreated and treated patients. Among 28 patients (20%) who developed end-stage renal disease, 17 showed rapid progression within 2.5 years after diagnosis. Fifteen of the 17 patients were males; all were severely nephrotic and had impaired renal function at diagnosis. Only 1 of 24 patients with nonnephrotic proteinuria at index renal biopsy progressed to end-stage renal disease. Overall, a level of baseline proteinuria of 10 g or more per 24 hours and variable blood pressure control in hypertensive patients were associated with renal progression.

Adolescent↗