Comparative study of FK 506, cyclosporine, and triple regimen immunosuppression with FK 506, cyclosporine, and mizoribine.
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Biomedical subjects
Publications and source records attributed to K Imai.
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Twenty cases of Japanese non-Hodgkin's lymphoma with B cell markers were studied with respect to their immunoglobulin heavy (IgH) chain gene loci on chromosome 14 and BCL2 loci on chromosome 18. All of the 20 cases showed IgH gene rearrangement on at least one of the alleles. Molecular analysis using two chromosome 18-specific DNA probes (pFL1 and pFL2) showed rearrangement of the BCL2 region in three of 20 cases. As these three samples showed the rearranged allele of the IgH gene comigrating with that of the BCL2 gene, polymerase chain reaction (PCR) was carried out to amplify the juncture between IgJH on chromosome 14 and BCL2 on chromosome 18. In all of these three cases, gene amplification between the two loci was found to occur, indicating that molecular mechanisms involved in this type of chromosomal translocation in Japan might be similar to cases in the United States (U.S.) in a limited number of cases. Furthermore, this amplification technique revealed minimal tumor cells circulating in peripheral blood, even though lymphoma cells could not be identified morphologically. Thus, the PCR technique is useful for both the detection of minimal tumor cells as well as for the determination of the molecular nature of chromosomal translocation in some of Japanese cases.
Prostatic cancer is one of the most common malignant tumors in the field of urology. The number of patients is increasing rapidly and its importance as a mortal disease is gathering attention. In 1985, we organized a registration system for prostatic cancer patients found in and around Gunma prefecture. In this study, we analyzed the clinical characteristics of the 730 patients registered from 1985 to 1989. The results were as follows. Mean age was 74.0 years old and the number of the patients was the greatest in the eighth decade. Voiding disturbance was the most common chief complaint, followed by pollakisuria, gross hematuria and miction pain. Stage and grade distribution were as follows. Stage A 16.2%, B 21.1%, C 17.0%, D 45.7%, well differentiated 27.4%, moderately differentiated 48.2% and poorly differentiated 24.5%, respectively. A statistically significant relationship between stage and grade was observed. Bone was the most common metastatic site. The highest incidence of bone metastasis was in lumbar vertebra, followed by ribs, ilium, thoracic vertebra and ischium. The value of PAP, ALP and ESR tended to be higher in high stage patients, and that of Hb was lower. Fifty two patients were detected by mass screening. Most of these patients were in an early stage. Most of the patients were treated by hormonal therapy. LH-RH agonists constituted 39.2% of the cases given hormonal therapy.
Eight patients with recurrent prostate cancer were treated with Etoposide and CDDP or Etoposide alone. Etoposide was administered at a dose of 20 approximately 50 mg/m2/day for 5 consecutive days and CDDP was administered at a dose of 30 approximately 50 mg/m2 on the first day. Treatment was repeated every 3 or 4 weeks. Patients who were treated with combination chemotherapy (Etoposide + CDDP) were those with no hematological abnormalities, no renal dysfunction and good performance status. Three patients were treated with Etoposide and CDDP and five were treated with Etoposide alone. Clinical evaluation was as follows: 3 patients (2 with Etoposide and CDDP, 1 with Etoposide alone) had PR (37.5%) and 5 patients had PD (62.5%). We obtained the impression that lesions of soft tissue metastasis responded well to this chemotherapy and that this combination chemotherapy was more effective than Etoposide alone. Major complications were myelosuppression, gastrointestinal upset and loss of hair. However, they were tolerable in patients with good performance status. This combination chemotherapy (Etoposide + CDDP) seems to be worth further clinical trials to patients who were tolerable.
It is well known that some adrenal androgens are converted into testosterone and dihydrotestosterone which are more powerful androgens than the adrenal androgens. However, most of the experiments to investigate the antiprostatic agents have been done on rats which secrete only a marginal amount of adrenal androgen. A study was performed to investigate the effects of antiprostatic agents on the action of the adrenals in rats. Non-sterodidal antiandrogens flutamide and 1-chloro-2-hydroxy-2-methyl-N-(3,4,5-trichlorophenyl)propanamide (AA560), steroidal anti-androgens, chlormadinone acetate (CMA) and 17 alpha-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione (TZP-4238) and 5 alpha-reductase inhibitor, sodium (-)-4[2-[2,3-dimethyl-4-[1-(4-isobutylphenyl)ethoxy]benzolamino ] phenoxy]butyrate (ONO-3805) and N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-l-ene-17 beta-carboxamide (MK-906) were tested in rats treated with dehydroepiandrosterone sulfate (DHEA-S) and androstenendione (A). In the noncastrated rats not treated with DHEA-S and A, all of these agents decreased the accessory organ weights in a dose dependent manner. In the rats treated with LHRH agonist and DHEA-S and A, all agents (3.3 mg/day) showed similar effects in intact rats. However nonsteroidal antiandrogens and TZP-4238 were stronger than the others. It was not clear whether this effect was mediated through the suppression of adrenal androgen action or the inhibition of physiological increase in testosterone caused by an LHRH agonist. The effects of Flu, ONO-3805, CMA and TZP-4238 on the accessory sex organs were investigated in castrated rats receiving DHEA-S and A.(ABSTRACT TRUNCATED AT 250 WORDS)
A biological activity database and a physicochemical property database are described. They are intended to complement the protein sequence database of PIR-International. The Biological Activity Database and the Physicochemical Property Database contain information regarding the biological activity and the physicochemical properties of proteins, respectively. In addition they also provide information about wild-type molecules with which information concerning variant molecules may be compared. Data on artificial variant molecules are stored in the Artificial Variant Database which is described separately.
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The most common toxicities of nonsteroidal anti-inflammatory drugs (NSAIDs) are gastropathy, renal dysfunction, and liver function abnormalities. We outline an approach to monitoring patients on long-term NSAID therapy, focusing on the early detection of complications. Gastropathy caused by NSAID use is more common in elderly patients or those with a history of dyspepsia, peptic ulcer disease, or alcohol abuse. Fecal occult blood testing and hemograms are less accurate in detecting gastropathy than direct visualization but are convenient and relatively inexpensive. We recommend the periodic use of these tests to detect NSAID-induced acute or chronic blood loss. Renal toxicity is seen in patients with preexisting renal disease or functional volume depletion and in the elderly. Complications include renal insufficiency, hyponatremia, hyperkalemia, and protein-uria. Renal function should be monitored during the first few weeks of NSAID therapy, especially in high-risk patients, with periodic testing thereafter. Hepatic toxicity is less common but warrants occasional determinations of alanine aminotransferase levels. Elderly patients and those with renal insufficiency or alcohol abuse have a higher risk of complications. Nonsteroidal anti-inflammatory drugs should be used cautiously in those patients at high risk for complications. Strategies can be used to limit toxicity. Patients taking these drugs long term should be monitored periodically for signs of blood loss, renal dysfunction, and hepatic dysfunction.
Most of human follicular lymphomas (approximately 90% in U.S.A. or approximately 30% in Japan) possess the t(14; 18) chromosome translocation that directly involves the IgH locus on chromosome 14 and the bcl-2 gene on chromosome 18. The t(14; 18) chromosome translocation occurs nearly exclusively at two hot spots, a major breakpoint clustering region (mbr) within the 2nd exon noncoding region and the minor breakpoint clustering region (mcr) within the 3' flanking region of the bcl-2 gene. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately 10%) of B-CLL. All of the rearranged bcl-2 genes were juxtaposed with Ig lambda or Ig kappa genes, implying that the bcl-2 gene is preferentially linked to the IgL genes in CLL.
To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose.
Between 1977 and 1989, we treated 114 new patients with prostatic cancer, and 99 of them responded to initial hormone-based treatment. Recurrence was seen in 28 of the 99 responders. The age at first admission ranged from 56 to 84 years, with a mean of 72.4 years. The mean interval between the start of follow-up and recurrence was 21.0 +/- 15.4 months (M +/- SE). The interval was 33.3 months for patients in stages B2 and C at initial treatment, 34.3 months for those in stage D1, and 15.6 months for those in stage D2. Stage D2 patients showed significantly earlier recurrence than the other patients (p less than 0.05). Patients with well, moderately, or poorly-differentiated adenocarcinoma at initial treatment developed recurrence after 62.5, 14.8, and 23.0 months, respectively, and there was no significant difference due to histological grade. As the mode of recurrence, the appearance of new lesions and the elevation of tumor marker levels were more frequently seen than local progression in patients with progressive disease at initial treatment. Pathological examination showed the tendency of recurrence for higher grade tumors. In comparison with those without recurrence, patients with recurrence had more advanced disease (p. 0.05). Only 11% of the patients showed partial response (PR) and 14.3% showed no change (NC) with multimodal therapy. The actual survival rates following initial treatment were 51.5% and 31.2% at 3 and 5 years, respectively, while those after recurrence were 49.3% and 12.5% at 1 and 3 years.
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The frequency of patients requiring non-cardiac surgery complicates ischemic heart disease (IHD) is increasing, however, there have been few reports of combined coronary revascularization and abdominal surgery. In this paper, we describe three patients with IHD and cholecystolithiasis in whom simultaneous coronary artery bypass grafting (CABG) and cholecystectomy was successfully performed. Initially, CABG was performed employing standard extracorporeal circulation through median sternotomy. After closure of chest, cholecystectomy was carried out through right pararectal laparotomy. Their postoperative course was uneventful. Relief of angina and freedom from epigastralgia were obtained in all patients. Combined CABG and cholecystectomy is beneficial for the selected patients.
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We have isolated from B16 mouse melanoma cells a complementary DNA (Mel-18), whose deduced amino acid sequence possesses a characteristic zinc finger structure. Immunostaining with antibodies raised against partial Mel-18 peptide sequences demonstrated nuclear localization of the gene product. We have also demonstrated that this protein has DNA-binding capacity, and the zinc finger is responsible for the DNA binding. At the transcriptional level the Mel-18 mRNA was detected in all tumor cells examined as well as melanoma cells (ontogenically of neural origin) but was scarcely present in normal tissues except neural organs. The transcript is developmentally regulated. These data suggest that Mel-18 may play a role in transcriptional regulation and also in control of cell proliferation and/or neural cell development.
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