Interleukin-1beta induces elevation of spermidine/spermine N1-acetyltransferase activity and an increase in the amount of putrescine in synovial adherent cells from patients with rheumatoid arthritis

OBJECTIVE: To investigate polyamine metabolism in rheumatoid synovial adherent cells stimulated by interleukin- 1beta (IL-1beta). METHODS: Synovial adherent cells obtained from patients with rheumatoid arthritis (RA) were cultured and incubated in the presence or absence of human recombinant IL-1beta at a concentration of 10 ng/ml for 24 h. The cellular contents of polyamines as well as the activities of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) were measured. RESULTS: Polyamines in synovial adherent cells decreased significantly after 24 h incubation in the absence of IL-1beta. However, in the presence of IL-Ibeta, putrescine and N'-acetylspermidine increased significantly. No significant difference was observed between the amount of spermidine in synovial adherent cells incubated with and without IL-1beta. Spermine and N8-acetylspermidine in synovial adherent cells incubated with IL-1beta decreased significantly more than in synovial adherent cells incubated without. SAT activity reached a peak 12 h after the addition of IL-1beta and then decreased, while the ODC activity did not increase. SAT activity was elevated by the addition of IL-1beta in a dose dependent manner. CONCLUSION: An increase in the putrescine level in rheumatoid synovial adherent cells as a result of the elevation of SAT activity induced by IL-1beta may play a role in RA.     

Polyamines in 1 alpha, 25-dihydroxycholecalciferol-induced differentiation of human promyelocytic leukemia cells, HL-60

The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.     

Is it necessary to adjust the replacement dose of thyroid hormone to the season in patients with hypothyroidism?

Hypothalamo-pituitary-thyroid activity varies with the temperature of the environment; we therefore measured variables involved with thyroid function in summer and winter in normal controls and in patients with primary hypothyroidism. All seven patients had impalpable thyroid glands and had received a set replacement dose of thyroxine for over a year. In the patients, serum T3 and FT4 levels were slightly but significantly lower in winter, and TSH levels and delta TSH at 30 minutes in the TRH tests were significantly higher. In the controls, there were no significant differences between summer and winter in these values. These findings suggest that the dose required for replacement of thyroid hormone in patients with hypothyroidism may be higher in winter than in summer.     

Combination of preoperative embolization of the right portal vein and hepatic artery prior to major hepatectomy in high-risk patients: a preliminary report

BACKGROUND/AIMS: Preoperative transhepatic portal vein embolization may not always be sufficient to achieve the desired changes in contralateral hepatic volume and function. The beneficial role of additional transcatheter arterial embolization performed after inadequate response to preoperative transhepatic portal vein embolization is described. METHODOLOGY: Four patients underwent both preoperative transhepatic portal vein embolization and transcatheter arterial embolization, and 6 control patients underwent preoperative transhepatic portal vein embolization only. Changes in right liver lobe volume fraction, residual left lobe volume fraction, and prediction score (low-risk, < 45; borderline, 45-55; high-risk > 55); were evaluated. RESULTS: 1) The change in right liver lobe volume after both preoperative transhepatic portal vein embolization and transcatheter arterial embolization (volume after/before) was 0.75 times that of the original level whereas after preoperative transhepatic portal vein embolization, they were only 0.81 times that of the original level. 2) The change in residual left liver volume after both preoperative transhepatic portal vein embolization and transcatheter arterial embolization (volume after/before) was 1.40 times that of the original level whereas after preoperative transhepatic portal vein embolization they were only 1.30 times than the original level. The changes in left liver volume after preoperative transhepatic portal vein embolization/transcatheter arterial embolization was more favorable than those after preoperative transhepatic portal vein embolization only. 3) The change in prediction score after both preoperative transhepatic portal vein embolization and transcatheter arterial embolization (after/before) was 0.81 times that of the original level. All prediction score in high-risk patients recovered to the borderline or safety zone. Change after preoperative transhepatic portal vein embolization only (before/after) was 0.87 times that of the original level. 4) All 4 patients who underwent both preoperative transhepatic portal vein embolization and transcatheter arterial embolization received right hepatic lobectomy successfully and returned to their normal life style. CONCLUSIONS: Preoperative occlusion of right hepatic inflow vessels increased the volume and function of the contralateral lobe where high-risk patients recovered to the borderline zone for major hepatic resection.     

Rare somatic inactivation of the multiple endocrine neoplasia type 1 gene in secondary hyperparathyroidism of uremia

The molecular pathway of autonomous growth of the parathyroid glands in uremic patients is poorly understood. Loss of heterozygosity at the recently identified multiple endocrine neoplasia type 1 (MEN1) gene locus on chromosome 11q13 has been found in a subset of parathyroid glands from patients with refractory hyperparathyroidism. To clarify the role of the MEN1 gene in parathyroid tumorigenesis, we analyzed 81 parathyroid glands from 22 Japanese uremic patients for allelic loss on chromosomal arm 11q13 DNA using 3 flanking markers (PYGM, D11S4946, and D11S449) and for mutations of the MEN1-coding exons by PCR-based single strand conformation polymorphism analysis and sequencing. Allelic loss on 11q13 was observed in 6 glands (7%), and 1 of 6 demonstrated a previously unrecognized somatic frameshift deletion (331delG) of the MEN1 gene. This mutation would probably result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and pathological characteristics of hyperparathyroidism were unrelated to the presence or absence of loss of heterozygosity on 11q13 and MEN1 gene mutations. These observations indicate that somatic inactivation of the MEN1 gene contributes to the pathogenesis of uremia-associated parathyroid tumors, but its role in this disease appears to be very limited.     

Hypervascular liver metastasis from hypovascular ductal cell carcinoma of the pancreas

In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.