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Biomedical subjects

M I Kang

Publications and source records attributed to M I Kang.

16 recordsLinked to original sources

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation.

The relation between thyroid hormone changes and cytokines in bone marrow transplantation (BMT) patients has not been studied. This prospective study was designed to determine the relation between thyroid hormones and cytokine levels after BMT and their effects on the mortality. We studied 80 patients undergoing allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were measured before and serially during 6 months after BMT. Serum T(3) decreased to a nadir 3 weeks post-BMT and serum T(4) was lowest at 3 months post-BMT. Serum thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined thereafter. Serum tumor necrosis factor-alpha increased for 3 weeks after BMT and declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively correlated with serum T(3) and T(4) levels. A total of 29 patients died before 1 year post-BMT and 51 patients survived longer than 1 year. Those patients who died before 1 year post-BMT had significantly lower levels of T(4) at 3 weeks, 3 and 6 months than surviving patients. In conclusion, increased levels of serum IL-6 and TNF-alpha were negatively correlated with thyroid hormone concentrations in BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

Adult↗

The role of cytokines in the changes in bone turnover following bone marrow transplantation.

Osteoporosis is a common disease among patients undergoing transplantation and a loss of bone mass is usually detected after bone marrow transplantation (BMT), particularly during the immediate post-BMT period. Post-BMT bone loss is primarily related to gonadal dysfunction and immunosuppression. Cytokines, especially interleukin 6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study was to assess the relationship between bone turnover markers and cytokines, which are regularly sampled at peripheral blood and bone marrow before and after allogeneic BMT. This prospective study included two analyses. The first was a study of 46 BMT recipients (M/F 28/18), examining the relationship between bone turnover markers and serum cytokines that were measured before and at 1 week, 2 weeks, 3 weeks, 4 weeks and 3 months after BMT. Serum intact parathyroid hormone was measured before BMT and at 3 weeks after BMT and its relation to other cytokines and bone turnover markers was evaluated. The second analysis was a study of 14 (M/F 9/5) of 46 patients in whom bone marrow plasma cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)] were measured at 3 weeks after BMT. The relationship between bone marrow plasma cytokines and bone turnover markers was studied because bone marrow is the microenvironment where the real changes in bone turnover occur. Serum type I collagen carboxyterminal telopeptide (ICTP), a bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, a bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. Serum IL-6 increased until 2 weeks after BMT and declined thereafter. Serum TNF-alpha increased until 3 weeks after BMT and declined thereafter. There was a significant positive correlation between serum ICTP and bone marrow IL-6 levels at 3 weeks after BMT, when a marked change in bone metabolism occurs following BMT. However, a correlation between bone turnover markers and bone marrow TNF-alpha or peripheral blood cytokines was not found. At 3 months after BMT, there was a significant negative correlation between the mean daily steroid dose and the serum osteocalcin level (r = -0.43, p < 0.05). The correlation between the Mean daily steroid dose and serum ICTP was also significant (r = 0.41, p < 0.05). Our data suggest that the progressive increase in bone resorption during the immediate post-BMT period is related to both steroid dose and the increase in bone marrow IL-6, which is a potent stimulator of bone resorption in vivo.

Adult↗

Oncogenic osteomalacia associated with soft tissue chondromyxoid fibroma.

Oncogenic osteomalacia is a rarely described clinical entity characterized by hypophosphatemia, phosphaturia, and a low concentration of 1,25-dihydroxyvitamin D(3). It is most often associated with benign mesenchymal tumor and can be cured with surgical removal of the tumor. In this paper, we present a case of oncogenic osteomalacia caused by chondromyxoid fibroma in the soft tissue of the sole of the foot in a 56-year-old woman.

Bone Neoplasms↗

Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation.

Autoimmune diseases can be transmitted and eliminated by bone marrow transplantation (BMT). There have been several cases of autoimmune thyroid disease (AITD) occurring after BMT, but AITD remission has been rarely reported. We present four cases in which the remission or transfer of AITD occurred after an allogeneic BMT. Two patients with severe aplastic anemia (SAA) showed evidence of remission of Hashimoto's thyroiditis which they had before allogeneic BMT. One patient with SAA, which developed during treatment with propylthiouracil for Graves' disease, underwent allogeneic BMT and showed evidence of Graves' disease remission following BMT. In one patient, new AITD occurred after an allogeneic BMT from an HLA-matched sibling who already had AITD. These cases support the evidence that the immune system is newly reconstituted after BMT, and severe autoimmune disease can be an indication for BMT. To fully understand the real changes in autoimmune status after BMT, long-term prospective studies are necessary.

Adolescent↗

Hypodipsic hypernatremia with intact AVP response to non-osmotic stimuli induced by hypothalamic tumor: a case report.

Anatomical lesions of hypothalamic area associated with hypodipsic hypernatremia have been reported only rarely. We report here a case of hypodipsic hypernatremia induced by a hypothalamic lesion. A 25-yr-old man, who had been treated with radiation for hypothalamic tumor 5-yr before, was admitted for evaluation of hypernatremia and hypokalemia. He never felt thirst despite the elevated plasma osmolality and usually refused to drink intentionally. Plasma arginine vasopressin (AVP) level was normal despite the severe hypernatremic hyperosmolar state and urine was not properly concentrated, while AVP secretion was rapidly induced by water deprivation and urine osmolality also progressively increased to the near maximum concentration range. All of these findings were consistent with an isolated defect in osmoregulation of thirst, which was considered as the cause of chronic hypernatremia in the patient without an absolute deficiency in AVP secretion. Hypokalemia could be induced by activation of the renin-angiotensin-aldosterone system as a result of volume depletion. However, inappropriately low values of plasma aldosterone levels despite high plasma renin activity could not induce symptomatic hypokalemia and metabolic alkalosis. The relatively low serum aldosterone levels compared with high plasma renin activity might result from hypernatremia. Hypernatremia and hypokalemia were gradually corrected by intentional water intake only.

Adult↗

The effect of cilostazol on glucose tolerance and insulin resistance in a rat model of non-insulin dependent diabetes mellitus.

BACKGROUND: It has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined. METHODS: About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats. RESULTS: In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats. CONCLUSION: These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.

Animals↗

The short-term changes of bone mineral metabolism following bone marrow transplantation.

Organ transplantation is now the treatment of choice for many patients with life-threatening chronic diseases. A new set of side effects unique to these groups of patients has become recognized, and bone disease is one of these complications. However, little is known about the effects of myeloablative treatment followed by bone marrow transplantation (BMT) on bone mineral metabolism. We have prospectively investigated 31 patients undergoing BMT for hematologic diseases. Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones, and the biochemical markers of bone turnover were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 year after BMT. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry before BMT and 1 year after BMT. The serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively until 4 weeks after BMT. Thereafter, it began to decrease and reached basal values after 1 year. Serum osteocalcin decreased progressively until 3 weeks after BMT. After that, it increased and reached basal values after 3 months. No distinct differences were observed in the serum biochemical turnover markers between males and females, or between patients who received total body irradiation and those who did not. One year after BMT, lumbar spine BMD had decreased by 2.2%, and total proximal femoral BMD had decreased by 6.2%. Eighty-six percent of the women (12/14) went into a menopausal state immediately after BMT. This was caused by high gonadotropin levels and low estradiol levels. In contrast, gonadotropin levels and testosterone levels did not change significantly in the male patients after BMT. In conclusion, the rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in post-BMT bone loss.

Adolescent↗

Ganglion cysts in a juvenile dog.

Ganglion cysts were diagnosed in a 4-month-old male Afghan Hound. Grossly, the subcutaneous ovoid cysts around the caudal right elbow joint and left ischiatic tuberosity had abundant mucinous fluid and internal folding. The lesions recurred twice around the elbow joint after surgical removal. Neither cyst communicated with the joint cavity. Histologically, the cyst wall consisted of inner myxomatous and outer immature connective tissue. Some parts of the cyst wall had various stages of myxoid metaplasia of collagen tissue leading to new cyst formation. Ultrastructural study revealed that cells in the myxoid metaplastic lesion had well-developed cytoplasmic secretory elements, including abundant rough endoplasmic reticulum, Golgi apparatus, and many smooth-walled vesicles. These ganglion cysts apparently resulted from the metaplasia of fibroblasts to secreting cells.

Animals↗

New ADA criteria in the Korean population: fasting blood glucose is not enough for diagnosis of mild diabetes especially in the elderly.

BACKGROUND: To compare the 1997 American Diabetes Association (ADA) criteria with the 1985 World Health Organization (WHO) criteria in categorization of the diabetes diagnostic status of Koreans and to define clinical characteristics of subjects diagnosed differently by the two criteria. METHODS: In 810 Korean subjects, we analyzed blood glucose and insulin response during 75 g oral glucose tolerance test (OGTT). According to current WHO criteria, the cutoff values of FPG which distinguish normal and IGT from diabetes were determined. Then the subjects were categorized according to both WHO and ADA criteria. The clinical characteristics of the subjects with different diagnostic categories by the two criteria were defined. RESULTS: The FPG cut point distinguishing diabetes from IGT was 117 mg/dl, and from normal was 110 mg/dl. The overall agreement between the ADA criteria and the WHO criteria was moderate, as reflected in the kappa of 0.45. 141 of subjects categorized diabetes by WHO criteria were not diagnosed with ADA criteria. These discordant subjects were older in age and showed blunted early insulin response than concordant normal subjects. CONCLUSION: These results suggest that mild diabetes by the WHO criteria, especially in the elderly, would not be diagnosed as diabetes by the ADA FPG criteria only. Thus, in a group at high risk for developing diabetes or in a relatively older age group, we should continue using the OGTT.

Adolescent↗

Expression of multiple thyroid hormone receptor isoforms in rat femoral and vertebral bone and in bone marrow osteogenic cultures.

Thyroid hormones influence both bone formation and bone resorption. Clinical data and animal studies provide evidence of skeletal site heterogeneity (hip vs. spine) of bone responses to thyroid hormones. In vitro studies also demonstrate direct effects of thyroid hormones on cells of the osteoblast lineage. Transcriptional regulation by thyroid hormone is mediated by ligand-dependent transcription factors called thyroid hormone receptors (TRs). Two genes, c-ErbAalpha and c-ErbAbeta, generate at least four TR isoforms in the rat: TRalpha(1), c-erbAalpha(2), TRbeta(1), and TRbeta(2). Although functional TRs have been identified in cells of the osteoblast lineage, it is still not known if TR isoform expression in bone differs depending upon which skeletal site is examined. We have used ribonuclease protection assay and Northern blot analysis to simultaneously examine the expression of TR isoform mRNAs in adult rat femoral and vertebral bone. TRalpha(1), c-erbAalpha(2), and TRbeta(1) are expressed in both femur and vertebra whole bone. Bone marrow cells from both skeletal sites were also cultured under conditions whereby the osteoprogenitors differentiated into osteoblasts and formed a mineralized extracellular matrix. TRalpha(1), c-erbAalpha(2), and TRbeta(1) mRNAs are each expressed in both femoral and vertebral osteoblast cultures. The presence of TRalpha(1), c-erbAalpha(2), and beta(1) proteins was confirmed by Western analysis of nuclear protein extracts from femoral and vertebral cell cultures. These results indicate that the three predominant TR isoforms are highly expressed in bone and osteoblasts from femurs and vertebrae. Whether there are distinct mechanisms of thyroid hormone action mediated by TRalpha(1), c-erbAalpha(2), and TRbeta(1) at these separate skeletal sites remain to be shown.

Animals↗

Thyroid hormone excess increases insulin-like growth factor I transcripts in bone marrow cell cultures: divergent effects on vertebral and femoral cell cultures.

Thyroid hormones (T3 and T4) regulate bone development, growth, and turnover. Studies have suggested that different skeletal sites respond differently to thyroid hormones. Therefore, we examined the in vitro T3 responsiveness of cells committed to the osteoblast lineage as a function of skeletal location. Bone marrow cells derived from female rat femurs and vertebrae were cultured using conditions that induce osteogenic differentiation. Cells from both sites formed mineralized bone nodules in primary and secondary culture. In femoral cultures, collagen type I (coll I) and osteocalcin (OC) messenger RNA (mRNA) levels increased from the earliest time point examined (day 3) to a maximum on day 12 and thereafter declined to undetectable levels. T3 increased both OC and coll I mRNA, resulting in a continuous expression throughout the culture period. Insulin-like growth factor I (IGF-I) gene expression was detected at very low levels by Northern analysis of femoral total RNA, and T3 only marginally enhanced IGF-I mRNA levels. In vertebral cultures, OC and coll I mRNA levels also increased with time in culture, but remained expressed throughout the culture period. OC and coll I mRNA levels were not markedly altered in response to T3. In contrast to femoral cells, IGF-I gene expression was easily visualized in Northern blots from untreated vertebral cultures and was markedly increased by the addition of T3. The continuous presence of T3 (10(-7) M) in the medium for 18 days caused a marked decrease in the number of alkaline phosphatase-positive colonies formed in femoral secondary cultures, but only a slight decrease in the number in vertebral cultures. In addition, short term (6 days) exposure to T3 (10(-7) M) at the beginning of the culture period decreased alkaline phosphatase activity in femoral cultures, but not in vertebral cultures. These findings indicate that there are skeletal site-dependent differences in the in vitro responses of cells of the osteoblastic lineage to thyroid hormone.

Alkaline Phosphatase↗

Chronic mesenteric ischemia: use of in vivo MR imaging measurements of blood oxygen saturation in the superior mesenteric vein for diagnosis.

PURPOSE: To determine if dogs and humans with chronic mesenteric ischemia demonstrate a decrease in the percentage of oxygenated hemoglobin (%HbO2) in the superior mesenteric vein (SMV) after a meal. MATERIALS AND METHODS: In 10 dogs, ameroid rings were surgically implanted around the superior mesenteric arteries to create gradual stenosis. Pre- and postoperative angiograms and pre- and postprandial magnetic resonance (MR) oximetry measurements of the SMV %HbO2, with flow-independent T2 measurements of venous blood, were obtained at different times. In 10 patients with atherosclerotic disease and six patients with symptomatic chronic mesenteric ischemia, the same measurements were obtained after at least 6 hours of fasting and at 15, 35, and 45 minutes after ingestion of a liquid nutritional supplement. RESULTS: In seven dogs, the postprandial SMV %HbO2 increased an average of 2.5% +/- 0.8 before surgery and decreased an average of 6.3% +/- 2.1 when hemodynamically significant (>70%) stenosis of the superior mesenteric artery developed 7-14 days after surgery. In the 10 patients without ischemia, the SMV %HbO2 increased by 4.6% +/- 0.6, whereas in the symptomatic patients a postprandial decrease of 8.8% +/- 0.7 occurred (P < .0001). CONCLUSION: Measurement of the SMV %HbO2 with MR oximetry is a promising test for diagnosis of chronic mesenteric ischemia.

Adult↗

Site selectivity of osteoblast gene expression response to thyroid hormone localized by in situ hybridization.

We have previously reported that thyroid-stimulating hormone (TSH)-suppressive doses of L-thyroxine (L-T4) decrease femoral, but not vertebral, bone mineral density (BMD) in rats. L-T4-induced decreases in BMD were associated with increased expression of genes, reflecting osteoblast activity in mRNA extracted from whole femurs but not from vertebrae. To document that this skeletal selectivity reflected altered osteoblast activity, we studied gene expression by in situ hybridization in 8-wk-old rats treated with L-T4 (20 microg x 100 g body wt(-1) x day(-1)) for 4 wk. TSH-suppressive doses of L-T4 were associated with decreased femoral (0.299 +/- 0.005 vs. 0.273 +/- 0.005 g/cm2, P < 0.01), but not vertebral (0.222 +/- 0.004 vs. 0.218 +/- 0.003 g/cm2), BMD. In situ hybridization documented that L-T4 administration for 4 wk increased expression of osteocalcin and alkaline phosphatase mRNA in femoral, but not vertebral, osteoblasts. This study demonstrates a differential gene expression response of vertebral and femoral osteoblasts to L-T4. This altered degree of gene expression markers of osteoblast activity documented by in situ hybridization may in part explain the apparent clinical differences in the effect of L-T4 on femoral and vertebral BMD.

Alkaline Phosphatase↗

Relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women.

BACKGROUND: Recently, klotho has been proposed as a link between cardiovascular diseases and premature aging, but the relationship between KLOTHO genes and cardiovascular risk factors, especially glucose metabolism, in humans is unclear. OBJECTIVES: We investigate the relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women. MATERIAL AND METHODS: In 251 women (mean age 51.3+/-6.9 yr), body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, insulin and lipid profiles were measured. The genotyping of polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene was performed by allelic discrimination using a 5' nuclease polymerase chain reaction assay. RESULTS: Allele frequencies of G395A polymorphism was 0.829 for the G allele and 0.171 for the A allele and allele frequencies of C1818T polymorphism were 0.804 for the C allele and 0.196 for the T allele, both of which were in compliance with Hardy-Weinberg equilibrium and the two polymorphisms were in linkage disequilibrium (D'=0.43, p<0.01). Mean systolic blood pressure was significantly higher in A allele carriers of G395A polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Mean fasting plasma glucose was significantly higher in T allele carriers of C1818T polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Subjects without any minor allele from either single nucleotide polymorphisms (SNP) had significantly lower mean values for systolic, diastolic blood pressure and fasting plasma glucose levels compared with subjects with both minor allele from either SNP. CONCLUSIONS: We observed that KLOTHO G395A polymorphism was associated with blood pressure and KLOTHO C1818T polymorphism was associated with glucose metabolism in Korean women. Further studies are needed to clarify this relationship.

Adult↗

Outbreak of Fowl cholera in Baikal teals in Korea.

Fowl cholera (FC) caused by Pasteurella multocida was diagnosed in waterfowl, Baikal teals (Anas formosa), submitted to the National Veterinary Research and Quarantine in Korea. The total number of mortalities was 13,228 out of approximately 100,000 birds that wintered in Cheonsoo Bay, the most important habitat area of Baikal teals in the world. Clinical signs were detected in only a few birds because of sudden death. Grossly, the dead Baikal teals had lesions consistent with FC, including multifocal necrotic foci in the liver with enlargement, petechial or ecchymotic hemorrhages on the heart, and mucoid exudates in the duodenal mucosa. Microscopically, there were hepatocytic necrosis with bacterial colonization, hemorrhage and necrosis in the myocardium, and hemorrhagic enteritis. Pasteurella multocida was isolated from the liver and the heart of all birds examined, and the isolate (P-627) was the serotype 1 X 12 X 13 by the agar gel immunodiffusion test. In order to estimate the virulence of P-627, 5-wk-old commercial ducks were exposed intramuscularly or intratracheally to the bacterium. On the basis of mortality rate, the isolate, P-627, was found to be highly virulent. This is the first report of an outbreak of FC in Baikal teals in Korea.

Animals↗