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Biomedical subjects

R Okamoto

Publications and source records attributed to R Okamoto.

At least 109 records · Page 6Linked to original sources

[A case study of immunohistochemical findings of rheumatic pseudocystic lesions in the femoral lateral condyle and tibial plateau--the comparison with synovial lesions].

Rheumatoid pseudocysts of which pathogenesis are not well known, are commonly observed in the major joints of the body, especially knees in rheumatoid patients. This report investigated the pseudocysts in the knee of a rheumatoid patient radiologically and immunohistochemically. A sixty-three-year-old woman with rheumatoid arthritis who had pseudocysts in the femoral lateral condyle and tibial plateau was hospitalized to have the lesions surgically removed. The MRI findings showed a connection between the pseudocysts and the joint cavity. A window of 1 x 1 cm2 was made at the tibial anterior cortex and the contents of the pseudocyst were resected and hydroxyapatite granules were inserted into the lesion after the removal of the pseudocyst tissue. In the histological findings, the specimen from the tibial pseudocyst revealed fibrous connective tissue with a few inflammatory cells, while the synovial specimen revealed the fibrous tissue with intense inflammatory cells infiltration forming lymphoid follicules. In immunohistochemical findings, both specimens showed positive with anti-HLA class I, anti-HLA DR, anti-CD44 and anti-HSP70 antibodies. The pathological findings of the pseudocystic lesion were similar to those of synovia, and it was considered that the synovia had invaded into the bone and formed the pseudocystic lesion. The MRI findings also support this hypothesis. The pseudocystic lesion was surrounded by bone and it was isolated from cytokain-rich joint effusion. This isolation from rheumatic joint effusion may explain the weaker inflammation of the pseudocystic lesion than that of synovia.

Arthritis, Rheumatoid↗

Predicting relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation by bcr-abl mRNA and DNA fingerprinting.

Fourteen patients treated by allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr-abl-specific transcripts. Nine patients were transplanted in the first chronic phase, three in the second chronic phase, and two in the accelerated phase. All patients achieved a complete cytogenetic and hematologic remission after bone marrow transplantation. Twelve patients are alive (median, 18 months; range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA was detectable. bcr-abl mRNA was never detectable posttransplant in three patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients 8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but was negative at 50 months. Three of six patients who initially had bcr-abl mRNA detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the time of development of chronic graft-versus-host disease (GVHD). These results suggest that the detection of subclinical Ph1 positive cells by PCR is not associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus-leukemia (GVL) activity may contribute to the treatment of minimal residual disease in CML after allogeneic bone marrow transplantation.

Adolescent↗

Case report: inhalation therapy of paromomycin is effective for respiratory infection and hypoxia by cryptosporidium with AIDS.

A 24-year-old man with AIDS and hemophilia A had intractable diarrhea and fever. Upon examination of stool and of a sigmoidal biopsy specimen, cryptosporidium was revealed. Approximately 2 months after admission, respiratory infection with hypoxia due to cryptosporidium developed. Paromomycin inhalation was effective therapy. To the authors' knowledge, this is the first case of respiratory cryptosporidiosis treated successfully by paromomycin inhalation.

AIDS-Related Opportunistic Infections↗

Activated liver macrophages in human liver diseases.

Immunohistochemical analysis using monoclonal antibodies specific for cells of monocyte/macrophage lineage reveals that resident liver macrophages have a phenotype distinct from that of monocytes or activated liver macrophages. Liver macrophages consist of heterogeneous cell populations in maturation (matured 25F9-positive and immature 25F9-negative) but the ratio of two populations is constant in normal and diseased livers. The expression of CD14 is down-regulated in resident liver macrophages as compared to that in monocytes, while the expression of 25F9 is up-regulated. On the other hand, the expressions of CD14 and Fc gamma RI are up-regulated in activated liver macrophages in viral and autoimmune hepatitis. In vitro culture of monocytes in medium without cytokines induces the phenotype similar to that of resident liver macrophages. Addition of macrophage-colony stimulating factor or interferon-gamma into the culture medium induces the expression of Fc gamma RI, the phenotype of which resembles that of activated liver macrophages. These results suggest that liver macrophages consist of heterogeneous cell populations and that both phenotype and function are affected by the local milieu of cytokines.

Animals↗

Nucleotide sequence analysis of the carbomycin biosynthetic genes including the 3-O-acyltransferase gene from Streptomyces thermotolerans.

A 3.2-kb DNA fragment of the carbomycin biosynthetic region including the 3-O-acyltransferase gene (acyA) from Streptomyces thermotolerans was sequenced, and four ORFs were found in the fragment. The second ORF, designated ORF-A, was transcribed in the opposite direction to the other three ORFs. The first ORF was identified as carA, a gene for carbomycin resistance. The amino acid sequence of ORF-A was homologous to proteins of the cytochrome P-450 family. Streptomyces lividans transformed with pCB20, in which ORF-A was subcloned, epoxidized carbomycin B at its C-12, 13 positions, thus producing carbomycin A. The third ORF, the amino acid sequence of which showed a homology to macrolide antibiotics O-acyltransferases was identified as acyA. The last ORF (ORF-B), which starts just 3 bp downstream from the TGA termination codon of acyA, was thought to be a carbomycin 4-O-methyltransferase gene, because the amino acid sequence deduced from ORF-B showed high homology to a putative midecamycin 4-O-methyltransferase encoded on mdmC.

Acetyltransferases↗

Plasma levels of retinol, retinol-binding protein, all-trans beta-carotene and cryptoxanthin in low birth weight infants.

In neonatal medicine, it is thought that retinol is useful for preventing CLD and for fetal development. However, beta-carotene had other vitamin A precursors have not been studied in neonates with CLD or others disorders. Cord blood of neonates including ELBW and VLBW infants was assayed for plasma levels of retinol, RBP, beta-carotene and cryptoxanthin. Plasma beta-carotene levels in ELBW and VLBW were lower than that in term infants, but plasma cryptoxanthin levels in ELBW and VLBW were about the same as in term infants. Plasma retinol and RBP levels showed almost same levels during 23-41 gestational weeks. Maternal smoking reduced plasma beta-carotene but not cryptoxanthin, retinol, or RBP levels. IUGR was associated with increased cryptoxanthin levels in cord blood. Serious neonatal diseases, including CLD and ROP manifested no significant effects on the cord blood vitamin levels. Thus, the occurrence of these diseases at birth could not be predicted by examination of vitamin levels in cord blood.

Cryptoxanthins↗

New anthracycline antibiotics 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin.

Two new anthracycline antibiotics, 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin, were photochemically obtained from anthracycline metabolites D788-1 (10-carboxy-13-deoxocarminomy-cin) and D788-3 (10-carboxy-11-deoxy-13-deoxocarminomycin) and were examined for their growth inhibitory activities on cultured L1210 leukemic cells. Effects of the S configuration of C-10 and a hydroxyl group at C-11 on the bioactivity are discussed in comparison with oxaunomycin and 11-deoxyoxaunomycin.

Animals↗

Low-dose granulocyte colony-stimulating factor enables the efficient collection of peripheral blood stem cells after disease-oriented, conventional-dose chemotherapy for breast cancer, malignant lymphoma and germ cell tumor.

Peripheral blood stem cells (PBSCs) were collected from 29 adult patients (median age 42 years, range 14-59 years) with breast cancer, germ cell tumor and malignant lymphoma after disease-oriented, conventional-dose chemotherapy combined with daily subcutaneous injections of low-dose (50 micrograms/m2 or 2 micrograms/kg) granulocyte colony-stimulating factor (G-CSF). The median number of colony-forming units-granulocyte macrophage (CFU-GM) collected in an apheresis was 2.37 (range 0-60.6) x 10(4)/kg body weight. Taking into consideration the minimum number of CFU-GM for hematopoietic reconstitution (at least 1 x 10(5) CFU-GM/kg), it was suggested that sufficient PBSCs could be collected by a few leukaphereses, although the cell yields of PBSCs tended to differ among the chemotherapeutic regimens. Twelve patients subsequently received high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT), including four receiving PBSCT alone and eight both PBSCT and autologous bone marrow transplantation (BMT). When compared with the 20 patients who received high-dose chemotherapy followed by autologous BMT alone, the median day of recovery of a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x 10(9)/l was significantly shortened in those who received PBSCT (9 vs 12 days; P < 0.01 and 14 vs 30.5 days; P < 0.001), resulting in a lower platelet transfusion requirement (4.5 vs 9; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Autologous hematopoietic stem cell transplantation for the treatment of breast cancer].

To obtain higher anti-tumor efficacy for breast cancer (BC), high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) is believed to be one of most effective strategies. PBSCT shows earlier hematological recovery comparing with ABMT, therefore HDC could be performed more safety to introduce PBSCT in the treatment of BC. Several investigators have reported that higher complete response (CR) rate and continuously CR rate were obtained to employ HDC in the earlier course of treatment for patient with advanced or recurrent BC responding to standard-dose chemotherapy. The efficacy of HDC has been also observed in adjuvant setting for patient with high-risk (> or = 10 axillary lymph nodes) after mastectomy. Phase III studies will clarify the efficacy of HDC with ABMT, PBSCT for the treatment of BC in near future.

Antineoplastic Combined Chemotherapy Protocols↗

Tumor-associated Fever in Recurrent Breast Cancer with Liver Metastases.

Of 67 patients with recurrent breast cancer accompanied by liver metastases admitted to our facility between January 1990 and August 1993, 8(12%) were found to have tumor-associated fever. We examined the characteristics of these patents. These patients had fever (over 38 degrees C) for more than one week. Their leukocyte counts did not exceed 10000/mm(3), and C-reactive protein (CRP) was below 5 mg/dl in 6 patients. ALL 8 patients had extensive liver metastases. Six patients had massive metastatic lesions, while the remaining 2 had diffuse metastases. Following systemic chemotherapy, 3 patients showed a reduction in tumor size and remission of fever; they remain alive at 14, 16 and 19 months after treatment. Of the remaining 5 patients who did not respond to systemic chemotherapy, 4 died within 6 months. The results of this study suggest that unexplained fever in patients with recurrent breast cancer is closely related to liver metastases.

Journal Article↗

[Long-term observation of serum hormone fluctuations in aging model of gonadectomized rat].

Serum LH increased rapidly in both sexes after gonadectomy, showing a peak at the 8th week. Afterwards, LH decreased gradually until the 75th week. In general, LH values in males were lower than those in females. FSH, as well as LH, increased rapidly after gonadectomy. In male serum FSH reached a peak at the 8th week and then decreased showing two peaks at the 34th and 92nd weeks. Serum FSH level decreased remarkably after the 96th week in males. In females FSH increased gradually with a subsequent rapid increase from the 28th week and reached a peak at the 42nd week. Afterwards, this FSH level was maintained to the 128th week. Serum progesterone (P4) decreased after gonadectomy in females, whereas it increased to 4 fold in males. In males this high level was maintained to the 66th week. Serum estradiol (E2) decreased in both sexes until the 3rd week after gonadectomy. However, in males the serum E2 level increased at the 4th and 5th weeks and reached the level of the 1st week after gonadectomy. Afterwards, the E2 level decreased to 10pg/ml at the 40th week which was maintained to the 128th week. In females, E2 increased from the 5th to 22nd week and decreased again from the 33rd week, and then the E2 level decreased rapidly to about 10pg/ml which was maintained to the 128th week. The present experiment indicated two results in male rats. 1. Serum FSH decreased remarkably after the 96th week of gonadectomy. 2. Serum P4 increased in spite of gonadectomy.

Aging↗

Differential gene expression of fibroblast growth factor receptor isoforms in rat ovary.

The gene expression of four fibroblast growth factor receptors (flg, bek, FGFR-3, and FGFR-4) in rat ovary cells was studied. Northern blot hybridization revealed that flg and bek mRNAs were detectable during all stages except a diestrus stage, whereas FGFR-3 and FGFR-4 mRNAs were almost undetectable throughout the cycles. In situ hybridization also demonstrated that only flg and bek gene expression was detectable. A modest flg mRNA signal was detected in developing antral follicles and it was more prominent in the theca-interstitial cells than in the granulosa cells. A modest to weak flg mRNA signal was seen in the hypertrophied theca-interstitial cells of atretic follicles and a very weak flg mRNA signal was observed in the corpora lutea. On the other hand, a weak bek mRNA signal was seen in granulosa and theca-interstitial cells in developing follicles and also hypertrophied theca-interstitial cells of atretic follicles, but not in the corpora lutea. Intense signals for both flg and bek mRNAs were unexpectedly found in the epithelium of paroophoron at the hilus. These results demonstrate that the bFGF receptor isoforms are expressed differentially in the rat ovary cells.

Animals↗

Red blood cell sorbitol in diabetic children.

When red blood cells (RBC) were incubated with various concentrations of glucose, the RBC sorbitol level increased in a concentration-dependent manner. The elevated RBC sorbitol level was not reduced by further incubation in a glucose-free medium. In both diabetic and non-diabetic children, an increase of RBC sorbitol levels occurred in the oral glucose tolerance test and the return to baseline was delayed in diabetics compared with non-diabetics. In the majority of diabetics (87%), RBC sorbitol levels exceeded the upper limit of the normal range, which was arbitrarily determined as the mean + 2 s.d., in healthy non-diabetic children and adults. A good correlation was observed between RBC sorbitol levels and plasma glucose levels (r = 0.644). In both diabetics and non-diabetics, no correlation was observed between RBC sorbitol levels and age, and in diabetics the RBC sorbitol level was not related to the duration of disease. A good correlation was observed between RBC sorbitol levels, and hemoglobin Alc (HbAlc) or fructosamine levels in diabetic children.

Adolescent↗

Cloning of the macrolide antibiotic biosynthesis gene acyA, which encodes 3-O-acyltransferase, from Streptomyces thermotolerans and its use for direct fermentative production of a hybrid macrolide antibiotic.

A gene encoding the macrolide modification enzyme 3-O-acyltransferase (acyA) was cloned by chromosome walking onto the carbomycin biosynthetic region in Streptomyces thermotolerans TH475, with the 3' region of the gene encoding the macrolide modification enzyme 4"-O-acyltransferase (acyB1) as a probe. A shortened fragment (1.8 kb) containing acyA was subcloned with pIJ350. A high-level tylosin producer, Streptomyces fradiae MBBF, transformed with the plasmid could produce a hybrid macrolide, 3-O-acetyltylosin, most efficiently.

Acyltransferases↗

Synthesis of doxorubicin-cyclodextrin conjugates.

Doxorubicin-gamma-cyclodextrin conjugates have been synthesized by the coupling of 14-bromodaunomycin with mono half-ester compounds linked to a 6-hydroxyl group of gamma-cyclodextrin. Release of drug from the conjugates in saline phosphate buffer solution and in vitro antitumor activity against L1210 leukemia cells were also investigated.

Animals↗