We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.
Among MGC patients (n=108), who received S-1 (40 mg m−2 b.i.d., days 1–14) and cisplatin (60 mg m−2, day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).
Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3% P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.
Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.
cisplatin; CYP2A6; ERCC1; gastric cancer; polymorphism; S-1
A uterus-like mass is a rare, benign extra-uterine tumour composed of smooth muscle and endometrium. The majority of uterus-like masses occur in the ovary. Rarely, uterus-like masses occur in the broad ligament, small bowel, small bowel mesentery or uterine cervix. Here, we report a case of a uterus-like mass in the sigmoid mesocolon. A well-defined, markedly enhanced soft-tissue mass with central cystic change and haemorrhage was observed on CT. The current report describes the CT characteristics of this sigmoid mesocolon uterus-like mass together with the differential diagnoses.
A case of Cushing's syndrome due to bilateral pigmented nodular adrenal disease in a 35-year-old male is presented. The adrenals showed multiple, black, variable sized nodules. Histologically the cells contained lipofuscin and either had a clear cytoplasm or an eosinophilic cytoplasm with a prominent nucleus. Lymphocytic infiltration and fatty metaplasia within the nodules are two of the prominent histological features. There is extreme internodular atrophy which suggests that primary pigmented nodular adrenocortical disease is a non-adrenocorticotropic hormone dependent condition. Since the disorder appears to involve primarily the cortex of both adrenals, the treatment of choice is bilateral adrenalectomy followed by steroid replacement. The characteristic clinicopathological manifestations that separate this diagnosis from other types of adrenal disease are also discussed. This is the first reported case in Korea to be documented with the pertinent clinicopathological findings.
We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m−2 b.i.d.) and docetaxel (25–40 mg m−2); MTD was 45 mg m−2 b.i.d. S-1/35 mg m−2 docetaxel and RD was 40 mg m−2 b.i.d. S-1/35 mg m−2 docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.
S-1; docetaxel; metastatic gastric carcinoma; phase I/II study
Little was known about work situation and work-related difficulties, including housework after stomach cancer diagnosis. We aimed to compare employment status and work-related difficulties between stomach cancer survivors and the general population. We enrolled 408 stomach cancer survivors from two hospitals 28 months after diagnosis and 994 representative volunteers from the general population from 15 geographic districts. Working was defined as being employed (including self-employed) and nonworking as being retired or a homemaker. Nonworking was significantly higher among stomach cancer survivors (46.6%) than in the general population (36.5%). Compared with the general population, the survivors had more fatigue in performing both housework (adjusted odds ratio (aOR)=2.08; 95% confidence interval (95% CI)=1.01–4.29) and gainful work (aOR=4.02; 2.55–6.33). More cancer survivors had reduced working hours (aOR=1.42; 95% CI=4.60–28.35) and reduced work-related ability (aOR=6.11; 95% CI=3.64–10.27) than did the general population. The association of nonworking with older age and being female was significantly more positive for survivors than for the general population. Among survivors, poorer Eastern Cooperation Oncology Group Performance Status and receiving total gastrectomy were positively associated with nonworking. Stomach cancer survivors experienced more difficulties in both housework and gainful employment than did the general population. Our findings on stomach cancer survivors' work-related difficulties and the predictors of nonworking will help physicians guide patients towards more realistic postsurgical employment plans.
employment status; work; stomach cancer survivor; general population
Peptide hydrolases, catalyzing the hydrolysis of 13 dipeptides and 5 tripeptides into their respective amino acids, were studied in small intestinal mucosa and other tissues, in man and in the rat.
Studies on the subcellular distribution of these enzymes showed enzyme activities in both the soluble and brush border fractions of the rat small intestinal mucosa, the former constituting 80-90% and the latter 10-15% of the total activity. Zymogram studies of peptide hydrolases, in both fractions, yielded multiple bands indicating multiple zones of enzyme activity. With most substrates a rather broad range of enzyme activities was observed in the soluble fraction differing only slightly from substrate to substrate, the exception being when L-leucyl-L-proline was used: this latter led to a zymogram pattern which was quite distinct. The synthetic substrates, L-leucyl-β-naphthylamide and L-leucinamide appeared to be hydrolyzed by two electrophoretically distinct enzymes, different from those hydrolyzing other leucyl-containing peptide substrates.
Zymogram patterns of the brush border membrane fraction were quite different from those of the soluble fraction of rat small intestine indicating that enzymes from the two sources may be different. No comparable human data were obtained.
Peptide hydrolases in the soluble fractions of various organs from the same species gave similar zymogram patterns, while those from the plasma membrane-bound fractions of different organs in the same species were peculiar to each organ. From these data, it is suggested that peptide hydrolases in the brush border and the soluble fractions of small intestine are distinct enzymes and may play different roles in cellular function.
Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125–6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.
The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m−2) and irinotecan (70 mg m−2) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1–18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3–60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8–5.2 months) and overall survival was 8.2 months (95% CI, 5.8–10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.
docetaxel; gastric cancer; irinotecan
smoking is the major causal factor in the development of chronic
obstructive pulmonary disease (COPD), only 10-20% of chronic heavy
cigarette smokers develop symptomatic COPD which suggests the presence
of genetic susceptibility. This genetic susceptibility to COPD might
depend on variations in enzyme activities that detoxify cigarette smoke
products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S
transferase (GST). As there is increasing evidence that several genes
influence the development of COPD, multiple gene polymorphisms should
be investigated to find out the genetic susceptibility to COPD.
of 83 patients with COPD and 76 healthy smoking control subjects were
determined by polymerase chain reaction (PCR) followed by restriction
fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and
multiplex PCR for GST M1 and GST T1 genes. The frequencies of
polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared
both individually and in combination in patients with COPD and healthy smokers.
were observed in the frequency of polymorphic genotypes in exons 3 and
4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and
healthy smokers. The frequencies of any combination of these genotypes
also showed no differences between the COPD group and the control group.
polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated
with the development of COPD in Koreans.
lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of
reproductive age and leading to progressive respiratory failure in
spite of treatment. In Korea the first case was reported in 1984 and by
1997 a total of 23 cases had been reported. The clinical findings of
these Korean cases are reviewed.
METHODS—The details of
10 cases of LAM on file at Seoul National University Hospital were
reviewed together with those of 13 cases previously reported from other
Korean institutes. Two, including the only one to be reported in a man,
were excluded after reviewing the clinical, radiological, and
pathological findings, leaving a total of 21 cases in the present study.
RESULTS—All 21 patients were women and in all cases the disease was proven
pathologically. The mean (SD) age at onset of symptoms was 32 (8.6)
years. The most common symptoms were dyspnoea and pneumothorax which
were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary
function tests showed decreased transfer factor (TLCO)
(100%) and airflow limitation (67%). All the cases had characteristic
cysts on high resolution computed tomographic (HRCT) scanning. The
overall severity score based on HRCT scans correlated with the
percentage predicted TLCO/VA (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with
medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable
change clinically or in lung function on medroxyprogesterone and/or
tamoxifen, but the remaining patients all deteriorated with two dying
of respiratory insufficiency and one of infection following lung transplantation.
other countries, in Korea LAM occurs exclusively in women and
progresses despite hormonal treatment.
The purpose of the present study was to determine whether chronic high-fat diet (HF) induces insulin resistance independently of obesity. We randomly divided 40 rats into two groups and fed them either with a HF or with a high-carbohydrate diet (HC) for 8 weeks. Whole body glucose disappearance rate (Rd) was measured using a euglycemic hyperinsulinemic clamp. Firstly, we defined whether insulin resistance by HF was associated with obesity. Plasma glucose and triglyceride concentrations were significantly increased in HF. Rd was decreased (10.6+/-0.2 vs. 9.1+/-0.2 mg/kg/min in HC and HF, respectively) and the hepatic glucose output rate (HGO) was increased in HF (2.2+/-0.3 vs. 4.5+/-0.2 mg/kg/min in HC and HF, respectively). Rd was significantly correlated with %VF (p<0.01). These results implicate that visceral obesity is associated with insulin resistance induced by HF. In addition, to define whether dietary fat induces insulin resistance regardless of visceral obesity, we compared Rd and HGO between groups 1) after matching %VF in both groups and 2) using an ANCOVA to adjust for %VF. After matching %VF, Rd in HF was significantly decreased by 14% (p<0.001) and HGO was significantly increased by 110% (p<0.001). Furthermore, statistical analyses using an ANCOVA also showed Rd for HF was significantly decreased even after adjusting %VF. In conclusion, we suggest that dietary fat per se could induce insulin resistance in rats fed with chronic HF independently of obesity.
We investigated the change in activity of the sympathetic nervous system (SNS) in high-sucrose diet (HSD)-induced obese rats compared with controls. Power spectral analyses of R-R interval variability were performed to obtain the low frequency (LF, 0.04-0.699 Hz) and high frequency (HF, 0.7-3.0 Hz) powers. The percents of fat mass to body weight (%F/BW) and fat to muscle ratios (F/M) were significantly increased in HSD-fed rats. Plasma glucose, leptin, and triglyceride concentrations in rats fed with HSD were significantly increased. LF in normalized units (LFn), which represents both sympathetic and parasympathetic activities, was significantly increased whereas HF in normalized unit (HFn), which represents parasympathetic activity, was significantly decreased in HSD-fed rats. LF/HF, which represents sympathetic activity, was significantly increased in HSD-fed rats and was correlated with leptin (r=0.549, p<0.023), %F/BW (r=0.513, p<0.035), F/M (r=0.536, p<0.038), and triglyceride (r=0.497, p<0.042). When adjusted for leptin concentrations, however, LF/HF of HSD-fed rats was significantly decreased. In conclusion, HSD-induced obese rats showed increased LF/HF, which was significantly decreased by adjustment for leptin concentrations. We suggest that stimulating effect of leptin on SNS is reduced, which might play a role in induction of obesity by HSD.
To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.
In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration.
Pulmonary alveolar proteinosis is such an extremely rare disease in Korea, that only a few cases have been reported. Meanwhile five cases were experienced at Seoul National University Hospital over ten years since 1987. We summarized the clinical characteristics and courses of them. Seven cases reported in the literature were included to add data about clinical characteristics and courses although only a few case reports mentioned patient's course. Middle aged male patients were mainly affected. No association with particular environmental or occupational exposure was identified. Dyspnea on exertion was the main symptom. Bilateral crackles were consistent, and bilateral parahilar hazy infiltrations on plain chest radiograph and ground glass opacity on high-resolution CT were characteristic. Superimposed infection was not identified in any patient at the time of diagnosis. Decreased diffusing capacity and hypoxia were present in almost every case. Whole lung lavage proved to be an effective therapeutic measure. The response to treatment was good. Long-term course of the disease, e.g. recurrence rate, is not yet known.
The case of a cyanotic infant with a rare combination of atypical pulmonary artery sling, imperforate anus, absence of the left kidney, interruption of the inferior vena cava, left side hemihypertrophy and diffuse-type pulmonary arteriovenous fistula is described. The clinical features were confusing, because of compounding abnormalities involving the respiratory tract and pulmonary circulation. The diagnostic approach to the etiology of cyanosis is discussed and the embryonic origin of pulmonary artery sling is reviewed.
A successful attempt at percutaneous transluminanl coronary angioplasty (PTCA) to relieve stenosis of the mid-portion of the left anterior descending artery was achieved in a 6-year 9-month old boy who had multiple coronary aneurysms and stenosis due to Kawasaki disease. Despite the progression of coronary stenosis he had been well except for the perfusion defect of the anterior wall of myocardium on 99mTc-MIBI SPECT with dipyridamole infusion until PTCA was carried out after 4-year 4-months of the onset of illness. The area of stenosis was 70% before PTCA and 20% after PTCA. No restenosis at the site of PTCA was observed on follow-up angiography at 26 months after PTCA. This successful attempt may indicate that this procedure should be considered early in subclinical stenosis to prevent ischemic cardiac damage.
Osteopontin (OP) and osteonectin (ON) are bone matrix proteins produced by mammary and other cancers. These proteins may play a role in tumor invasion and metastasis through integrin-mediated signal transduction. We evaluated expressions of OP and ON in 253 resected infiltrating ductal carcinoma of the breast, using immunohistochemical staining and follow-up data. OP and ON were detected 87.4% and 54.2% of 253 cases, respectively. The OP and ON positive staining were localized in the cytoplasm of carcinoma cells. OP and ON did not correlate with various clinicopathological parameters, such as age, lymph node involvement, tumor size, histologic grade, expression of p53 and estrogen receptor (ER). In the multivariate model, lymph node involvement and histologic grade were statistically significant prognostic factors. Assessed by a log rank test, the 5-year-survival rates of OP and ON positive groups and their negative groups were not statistically different. In conclusion, OP and ON immunopositivity of infiltrating ductal carcinomas of the breast provide no additional prognostic information in this study.
Sinus histiocytosis with massive lymphadenopathy is a non-neoplastic self-limiting disease of the bone marrow stem cell origin. It is characterized by painless, bilateral cervical lymphadenopathy accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. Extranodal involvement including bone is rare. The patient is a 45-year -old female with multiple punch out lesions on her skull. MRI findings included iso-signal intensity mass at the diploid space on T1 weighted image and on T2 weighted image, mild high signal intensity was obtained. Histologically, the lesion showed proliferation of histiocytes in the fibroblastic background with formation of reactive germinal centers and many plasma cells. The histiocytes show round nuclei and occasional nucleoli and abundant cytoplasms. In area, there is lymphocytophagocytosis. Immunohistochemically, the histiocytes were positive for S-100 protein and lysozyme.
CD44 is a member of cell surface glycoproteins which are involved in cell-matrix adhesion and tumor metastasis. Certain types of tumors express complex CD44 isoforms generated by alternative splicing of 2v-10v exons, and their expression appears to promote metastasis of tumor cells. Using a nested RT-PCR, we analyzed expression of CD44 variants in 26 stomach carcinoma, 21 matched normal tissues, and 2 carcinoma cell lines. We observed frequent and complex patterns of CD44 variant expression in tumor tissues. While exons 6v and 7v expression was detected in most normal and tumor tissues, exon 9v was most rarely detected. Exon 5v showed a significantly frequent expression in carcinoma, suggesting that its expression might contribute to the malignant progression. While exon 9v was frequently observed in diffuse-type tumors, the other 8 variant exons including 6v showed more frequent expression in intestinal-type tumors. Exons 9v and 10v were predominantly expressed in advanced tumor tissues and exon 8v was expressed more frequently in tumors of lymph node metastasis. We believe that series with a longer follow-up now need to be tested to clarify the association between CD44 splice variant expression and distant metastasis or long-term prognosis.
We report an unusual case of extralobar pulmonary sequestration (ELS) with an associated cyst of mixed bronchogenic and esophageal type. A 58-year-old woman was incidentally found to have a 6 x 6 x 5 cm sized mass in the right superior mediastinum. The mass consisted of sequestrated pulmonary tissue and an unilocular cyst with a direct communication. The cyst could not be easily classified because it was lined by squamous or respiratory epithelium with two distinct muscle layers and bronchial glands. Bronchial cartilage was present in close proximity to the ELS. This unusual combination of ELS with a foregut cyst might be a part of bronchopulmonary foregut malformation, attributed to a common embryologic pathogenesis.
We report a case of pancreatic endocrine tumor admixed with a diffuse microcystic adenoma in a 67-year-old woman with a six months history of melena. Whipple's operation and near-total pancreatectomy were performed under the impression of a pancreatic cancer with duodenal invasion. The pancreas was enlarged and was entirely replaced by sponge-like tiny cysts, which were lined by a single layer of periodic acid Schiff positive cuboidal cells. Also encountered was a gray white solid area at the head portion which extended to the duodenum with an intraluminal polyp formation. The compact area was composed of solid and acinar structures of tumor cells, which showed a positive reaction for chromogranin A and neuron specific enolase, separated by delicate highly vascularized stroma. To the best of our knowledge, this is the first case report published with immunohistochemical studies to deal with a pancreatic endocrine tumor admixed with a diffuse microcystic adenoma.
To know the effects of nicotinamide (NCT) treatment for 5 weeks at the early age on insulitis and development of diabetes in non-obese diabetic (NOD) mice, this experiment was performed. Ten ICR (Institute of Cancer Research) and 15 female NOD mice at 4 weeks of age were used. Mice were assigned to ICR and NOD groups, and NOD mice were randomly divided to control and NCT-treated groups. NCT was administered to mice orally as a solution and in a dose of 500 mg/kg body weight a day from the age of 4 to 8 weeks. Diabetes onset was 18 weeks of age in control group, and 22 weeks of age in NCT-treated group. Cumulative incidences of diabetes at 25 weeks of age in control and NCT-treated NOD mice were 63 and 29%, respectively. Insulitis occurred in all NOD mice. Incidence of insulitis in total islets was decreased by NCT treatment in diabetic NOD mice, but intensity of insulitis was not improved by NCT treatment. Blood glucose level was increased markedly, and plasma insulin level was decreased by diabetes development in NOD mice. Plasma triglycerides and total cholesterol levels were increased in diabetic mice than in non-diabetic mice. In conclusion, these results suggest that NCT treatment for 5 weeks at the early age in NOD mice inhibits development of diabetes and insulitis in diabetic NOD mice.
It has long been known that almost all isoniazid (INH) resistant mycobacteria lose the catalase and peroxidase activities along with reduced or no virulence for guinea pigs. Recently resistance to INH has become known to be associated with mutations of katG gene encoding the HPI (Hydroperoxidase I) type catalase and peroxidase. Among these mutations, the point mutation of codon 463 of katG gene is found frequently, and is suggested as being associated with INH resistance. Therefore we performed this study in order to confirm the correlation between the point mutation of codon 463 of the katG gene and INH resistance of M. tuberculosis in Korea. Fifty isolates, 32 of which were resistant to INH, and 18 of which were sensitive to INH, were selected for this study. We used PCR-SSCP and RFLP analysis to detect the point mutation of the codon 463 of katG gene and confirmed the CGG (arginine) to CTG (leucine) mutation by direct sequencing analysis. Among 32 resistant isolates, 7 isolates (22%) had the same restriction pattern compared with that of the reference strain (H37Rv), and 25 isolates (78%) showed a different restriction pattern. Among 18 sensitive isolates, 7 isolates (39%) had the same restriction pattern compared with that of H37Rv, and 11 isolates (61%) showed a different restriction pattern. These results suggest that the CGG to CTG change of codon 463 of katG gene of M. tuberculosis may be a polymorphism not related with INH resistance.
We have treated a total of 16 cases of advanced Kienböck's disease, stage III and IV by Lichtman's classification, with triscaphe fusion, tendon ball replacement arthroplasty after excision of lunate, proximal row carpectomy as a salvage procedure and limited wrist fusion, since 1985. All cases were followed for minimal 16 months after each operation. Tendon ball replacement arthroplasty after excision of lunate could not prevent further carpal collapse with persistent chronic wrist pain. The triscaphe fusion or radio-lunate fusion induced a marked limited wrist motion later, and the triscaphe fusion alone was not fit for the treatment of advanced one because of progressive proximal migration of capitate and continuous wrist pain due to ligamentous carpal instability in follow-up. So we tried to simultaneously combine tendon ball replacement arthroplasty after excision of lunate with triscaphe fusion in far advanced Kienböck's disease, and their end results was favorable. Proximal row carpectomy could be done in far advanced Kienböck's disease with reasonably painless wrist motions. The overall end results of proximal row carpectomy are much better than any form of carpal arthrodesis. Conclusively the proper way to treat advanced Kienböck's disease seems to depend on the patient's age, their job and sex, and the stage of disease. And the cause of wrist pain in advanced Kienböck's disease seems due to ligamentous carpal instability rather than osteoarthritis on radio-lunate joint.