Search

To evaluate the association between trabecular bone score (TBS) and new bone formation in ankylosing spondylitis (AS) patients, and to investigate whether TBS is independently associated with new bone formation.Sixty-eight patients with AS underwent spinal magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry of the lumbar spine to measure TBS and bone mineral density at baseline. Lateral radiographs of the cervical and lumbar spine (baseline and 2 years) were assessed for new bone formation (syndesmophyte formation and/or growth combined), and spinal MRIs were assessed for the presence or absence of fat metaplasia (FM) at the first to fourth lumbar vertebrae. The factors associated with new bone formation were analysed at the patient level and the vertebral level.New bone formation had developed in 17 patients (25%) at 2 year follow-up. Patients with new bone formation had a higher prevalence of FM and lower TBS at baseline than patients without new bone formation (p = 0.013 and p = 0.041). At the patient level, FM on MRI and low TBS ( 1.23) were significantly associated with new bone formation. At the vertebral level, new bone formation had developed in 25 out of 231 vertebrae (11%) after 2 years. Vertebrae with both FM on MRI and low TBS tended to have more new bone formation (p 0.001). Syndesmophytes and low TBS ( 1.23) independently increased the risk of new bone formation at the level of individual vertebrae.At both patient and individual vertebral levels, low TBS was associated with new bone formation independently of FM on MRI.

BackgroundRadiographic axial spondyloarthritis (r-axSpA) has increased risk of cardiovascular disease. Other cardiac manifestations such as conduction disturbance and valvular diseases were also suggested as co-morbidities in r-axSpA patients, however, the risk of these cardiac manifestation in r-axSpA were seldomly evaluated in large cohort.ObjectivesTo compare the incidences of aortic regurgitation, atrial fibrillation (AF), and atrioventricular (AV) block II–III between r-axSpA patients and the general population (GP).MethodsNational Health Insurance Services data were used. R-axSpA patients (N = 8,877) and the age- and sex-matched GP (N = 26,631) were followed from August, 2006 to December, 2019. Incidence rates and standardized incidence ratios (SIR) of aortic regurgitation, AF, and AV block II–III were compared between these groups. Ten year incidence rates and hazard ratios (HRs) were calculated by the Kaplan–Meier method and Cox regression analysis.ResultsIncidence rates of aortic regurgitation, AV block II–III, and AF in the r-axSpA group were 0.42, 0.21, and 4.0 per 1000 person-years, respectively. In the r-axSpA group, the SIR for aortic regurgitation was highest among 40–49-year-old men (4.11). Incidence rates of aortic regurgitation and AF were higher in the r-axSpA group than in the GP group (both p < 0.001), whereas the difference was insignificant for AV block II–III. In multivariate analysis, HRs for aortic regurgitation and AF were higher in the r-axSpA group than in the GP group (HR (95% confidence interval) = 2.55 (1.49–4.37) and 1.20 (1.04–1.39), respectively), but the difference was insignificant for AV block II–III.ConclusionCompared with the GP, r-axSpA patients are at increased risk of aortic regurgitation and AF, but not AV block II–III. These patients should be carefully monitored for occurrence of aortic regurgitation and AF.References[1]Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis 2017; 76: 17-28.[2]Szabo SM, Levy AR, Rao SR, et al. Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study. Arthritis Rheum 2011; 63: 3294-3304.[3]Morovatdar N, Watts GF, Bondarsahebi Y, et al. Ankylosing Spondylitis and risk of Cardiac Arrhythmia and Conduction Disorders: A systematic review and meta analysis. Curr Cardiol Rev 2021.[4]Bengtsson K, Forsblad-d’Elia H, Lie E, et al. Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population: a register-based study from Sweden. Ann Rheum Dis 2018; 77: 541-548.[5]Dik VK, Peters MJ, Dijkmans PA, et al. The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis. Scand J Rheumatol 2010; 39: 38-41.Disclosure of InterestsNone declared

Background and Objectives The Korean Red Cross began nucleic acid amplification testing (NAT) for HIV and HCV in February 2005, and added HBV NAT beginning in June 2012. The current NAT system utilizes a multiplex assay for simultaneous detection of HBV DNA, HCV RNA and HIV-1 RNA. For samples that are reactive in the multiplex assay, we do specific tests for each virus. However, there have been cases of non-discriminated reactive (NDR) results which appear to be the result of non-specific reactions or cross-contamination, although some cases are considered to arise from the presence of low levels of HBV DNA due to occult hepatitis B infection. Materials and Methods We examined the incidence of NDR results in previous donations of some NAT-reactive donors. Additionally, for those donors with NDR results, we performed an HBV core antibody (anti-HBc) assay. Results From November 2015 to March 2016, there were 408 NAT-reactive donors. Of these, nineteen HBV NAT-reactive donors showed a history of NDR results in the past donations. Seven donors showed NDR results more than once. Of 771 NDR donors, 362 (47·0%) were anti-HBc reactive. Conclusion The NDR donors had a substantially higher rate of anti-HBc reactivity than other blood donors indicating that some with anti-HBc reactivity represent donors with occult HBV. Therefore, the incorporation of an anti-HBc testing for NDR donors could improve blood safety testing for the Korean Red Cross.

This multinational study was conducted to investigate the association between a mitochondrial DNA (mtDNA) T16189C polymorphism and type 2 diabetes in Asians. The mtDNA 16189C variant has been reported to be associated with insulin resistance and type 2 diabetes. However, a recent meta-analysis concluded that it is negatively associated with type 2 diabetes in Europids. Since the phenotype of an mtDNA mutant may be influenced by environmental factors and ethnic differences in the nuclear and mitochondrial genomes, we investigated the association between the 16189C variant and type 2 diabetes in Asians.The presence of the mtDNA 16189C variant was determined in 2,469 patients with type 2 diabetes and 1,205 non-diabetic individuals from Korea, Japan, Taiwan, Hong Kong and China. An additional meta-analysis including previously published Asian studies was performed. Since mtDNA nucleotide position 16189 is very close to the mtDNA origin of replication, we performed DNA-linked affinity chromatography and reverse-phase liquid chromatography/tandem mass spectrometry and chromatin immunoprecipitation to identify protein bound to the 16189 region.Analysis of participants from five Asian countries confirmed the association between the 16189C variant and type 2 diabetes [odds ratio (OR) 1.256, 95% CI 1.08-1.46, p=0.003]. Inclusion of data from three previously published Asian studies (type 2 diabetes n=3,283, controls n=2,176) in a meta-analysis showed similar results (OR 1.335, 95% CI 1.18-1.51, p=0.000003). Mitochondrial single-stranded DNA-binding protein (mtSSB) was identified as a candidate protein bound to the 16189 region. Chromatin immunoprecipitation in cybrid cells showed that mtSSB has a lower binding affinity for the 16189C variant than the wild-type sequence.The mtDNA 16189C variant is associated with an increased risk of type 2 diabetes in Asians.

Women with hyperprolactinemia have been reported to have hyperandrogenemia and/or insulin resistance. However, little is known about the association of hyperandrogenemia and insulin resistance in these women. To investigate whether hyperandrogenemia and/or insulin resistance occur in hyperprolactinemic women, and to assess the relationship between them, we measured basal androgen level and both glucose and insulin levels after oral glucose administration in 20 hyperprolactinemic women and 7 female control subjects. Free testosterone level was higher and estradiol level lower in hyperprolactinemic women than in control subjects (p0.05), whereas dehydroepiandrosterone sulfate (DHEAS) and total testosterone levels were similar (p0.05). Both fasting glucose and insulin levels didn't differ in the two groups (p0.05). However, both serum glucose and insulin levels, after a 75 g glucose load, were significantly increased in hyperprolactinemic women, (p = 0.001, p0.001, respectively). In simple linear regression analysis in hyperprolactinemic women, only free testosterone level had a positive correlation with the incremental area under the insulin curve (insulin-IAU) (r = 0.47, p0.05). In multiple stepwise regression analysis, free testosterone level, mean blood pressure and DHEAS level were associated significantly with insulin-IAU (beta = 0.98, p0.0001; beta = 0.58, p = 0.002; beta = -0.67, p0.003, respectively). These results suggest that insulin resistance is closely related to elevated free testosterone level in hyperprolactinemic women.

The quality of ultrasonic images is crucially affected by the applied ultrasonic probe; thus, it is necessary to evaluate the ultrasonic probe to achieve optimal performance. In this paper, the 3D acoustic field analysis method using a hydrophone, one of the probe evaluation methods, was performed, and the efficacy of this evaluation method for quantitative evaluation was evaluated. To acquire the acoustic field distribution of ultrasound at 7.5 MHz, a 128-multi-element medical ultrasonic array probe, that is considered to be inferior, was attached to a shaft. The shaft could be controlled in the x, y, and z directions. The hydrophone was attached in a water bath. The acoustic field distribution of each channel was displayed, and some parameters such as maximum acoustic pressure, the volume of -3dB field, and the symmetry of acoustic field were calculated. Using these parameters, the acoustic fields of normal, abnormal and simulated channels were compared. Comparing acoustic field characteristics of each channel proves that the proposed 3D acoustic field parameters are reliable and efficient to assess the performance of the ultrasonic probe.

To assess the changes in bone mineral density and osteoblastic activity in patients with hyperthyroidism and to investigate the relationship between those changes, we measured bone mineral density and serum osteocalcin in 109 patients with Graves' disease, comprising 75 untreated patients and 34 patients under treatment, and 200 normal controls. The degree of change in bone mineral density was quantified with Z transformation, in which we used means and SDs of bone mineral densities obtained in the process of age- and sex-matched 1:1 pairing developed by ourselves. Bone mineral density was low in female patients with hyperthyroidism in the spine, femur neck, trochanter, and Ward's triangle, but was not low in male patients. Serum osteocalcin was elevated in patients with untreated Graves' disease and correlated negatively with the Z values of bone mineral densities of the spine, femur neck, and trochanter. In conclusion, indices of osteoblastic activity were elevated in patients with hyperthyroidism, probably secondary to a thyroid hormone-induced increase in bone resorption which resulted in reduced bone mineral density. Quantification of the change in bone mineral density by using the parameters derived in the process of age- and sex-matched pairing seems to be an efficient method for statistical analyses.

The expansion of the industrial economy and the increase of population in Northeast Asian countries have caused much interest in climate monitoring related to global warming. However, new techniques and better platforms for the measurement of global warming and regional databases are still old-fashioned and are not being developed sufficiently. With respect to this agenda, since 1993, at the request of the World Meteorological Organization (WMO), to monitor functions of global warming, the Korea Meteorological Administration (KMA) has set up a Global Atmospheric Watch (GAW) Station on the western coast of Korea (Anmyun-do) and has been actively monitoring global warming over Northeast Asia. In addition, atmospheric carbon dioxide (CO2) has been measured for a similar KMA global warming program at Kosan, Cheju Island since 1990. Aerosol and radiation have also been measured at both sites as well as in Seoul. The observations have been analyzed using diagnostics of climate change in Northeast Asia and also have been internationally compared. Results indicate that greenhouse gases are in good statistic agreement with the NOAA/Climate Monitoring and Diagnostics Laboratory (CMDL) long-term trends of monthly mean concentrations and seasonal cycles. Atmospheric particulate matter has also been analyzed for particular Asian types in terms of optical depth, number concentration and size distribution.

The authors established the genotype frequencies of cytochrome P450 (CYP1A1/MspI, CYP2E1/PstI, and CYP2E1/DraI), glutathione-S-transferase (GSTM1 and GSTT1), and p53 (exon 4/AcclI and intron 3/16-base pair duplication) gene polymorphisms in cervical carcinoma patients and controls and evaluated the association between the specific genotype or genotype combinations of these polymorphisms and the risk of cervical carcinoma.In this case-control study, the genotypes of 181 human papillomavirus (HPV)-16 or HPV-18 positive cervical carcinoma patients and 1-to-1 age-matched controls were determined using a polymerase chain reaction-based technique.Among these polymorphisms, the individuals carrying arginine/proline genotypes of p53 showed a 9.5-fold increase of cervical carcinoma risk (95% confidence interval [CI], 4.9-18.6) compared with those individuals carrying arginine/arginine genotypes. The frequency of overall GSTT1 null genotypes also was significantly higher in cervical carcinoma patients compared with that of GSTT1 positive genotypes (P = 0.003; odds ratio [OR] = 1.9; 95% CI, 1.2-2.9). The genotype combination of p53 and GST played a more important role in describing the relative risk of cervical carcinoma. The individuals carrying both the arginine/proline genotype of p53 and the null genotype of GSTT1 showed a 3.5-fold increase of cervical carcinoma risk (95% CI, 1.8-7.1) compared with those individuals carrying both the arginine/arginine genotype of p53 and the GSTT1 positive genotype. In the patients who were stratified into the two age groups, the null genotypes of GSTT1 (69.1% vs. 45.5%; P = 0.016) and GSTM1 (61.8% vs. 40.0%; P = 0.028) in cervical carcinoma were significantly overrepresented in the younger age subgroup (age 40 years or younger) compared with those of controls. Especially in this age group, the individuals carrying both null genotypes of GSTT1 and GSTM1 showed a 17.8-fold increase of cervical carcinoma risk (95% CI, 2.2-141.0) compared with the individuals carrying both positive genotypes of GSTT1 and GSTM1.The results of the current study suggested that the arginine/proline genotype of p53, independently or in conjunction with the GSTT1 null genotype, could affect the genetic susceptibility for cervical carcinoma, and HPV positive women carrying both null genotypes of GSTT1 and GSTM1 have an increased risk of cervical carcinoma developing before age 40 years.

It is generally accepted that parasite-specific IgE plays a crucial role in host defense against helminthic parasites. However, the role of high levels of nonspecific IgE in helminthic infections is still controversial. To investigate the role of nonspecific IgE in primary infections with P. westermani, the effect of anti-IgE mAb treatment on serum IgE, Fc epsilon RII/CD23 expression and worm burden in Paragonimus-infected mice were examined. In mice treated with anti-IgE antibody, the total IgE levels were not detectable (1 microgram/ml) throughout the experiment compared with untreated infected mice. The mean percentages of Fc epsilon RII/CD23 positive splenic B cells in anti-IgE treated mice (range: 20.3 - 30.5) were also decreased throughout the experiment compared with untreated infected mice (range: 35.7 - 44.4). Reduction of the total IgE and expression of Fc epsilon RII/CD23 on splenic B cells resulted in decreased worm burden six weeks post infection. These results suggest that high levels of nonspecific IgE in mice with primary infections of P. westermani play a harmful, rather than beneficial, role for the host, perhaps by interfering with CD23-dependent cellular pathways.

The prevalence of diabetes mellitus in Korea has increased tremendously during the past several decades. In addition to the explosive increase of diabetes mellitus, the clinical characteristics of diabetes mellitus in Korea seems to be quite different from those of Western countries. Most patients with non-insulin-dependent diabetes mellitus (NIDDM) are non-obese and many of them lose weight significantly during the course of developing diabetes. The pathogenic mechanism(s) underlying this phenotype is still unclear. A subgroup of patients known as slow onset IDDM exists, but this could not explain the majority of non-obese NIDDM in Korea. In order to examine whether insulin resistance/hyperinsulinaemia is important in the development of NIDDM we conducted the following studies. Fasting plasma glucose and insulin concentration were measured in subjects with normal glucose tolerance, impaired glucose tolerance and diabetes mellitus. The peak plasma insulin level was much lower than that of Pima Indians or Caucasians. We also found that the insulin sensitivity index measured by euglycemic hyperinsulinaemic clamp in the first degree relatives of Korean NIDDM patients was not lower than that in a control group. This data suggests that insulin resistance, or hyperinsulinaemia, does not play a major role in the development of NIDDM in Korea. Taken together with the rarity of obese NIDDM in Korea, it maybe suggested that the insulin secretory capacity of Korean people being smaller than Western people they cannot compensate for the insulin resistance imposed by recent changes in life style.

Alterations of fatty acid composition have been observed in a number of tissues in both experimental and human diabetes. Suppression of Δ6 desaturase in the liver, a key enzyme of fatty acid desaturation, has been reported to be responsible for these phenomena. We measured the fatty acid composition of the liver and the erythrocytes, and examined Δ6 desaturase activities to compare the effect of short-term insulin therapy on the tissues with and without Δ6 desaturase, ie., the liver and the erythrocytes using streptozotocin (STZ)-induced diabetic rats. Linoleic (P < 0.05), palmitic (P < 0.01) and docosahexaenoic (DHA) acid (P < 0.01) were higher and arachidonic (P < 0.01) and oleic acid (P < 0.01) were lower in the liver microsomes of diabetic rats when compared to those in control rats. These alterations were partly reversed with insulin treatment. In the erythrocyte membrane, linoleic (P < 0.01) and stearic acid (P < 0.05) were higher, and palmitic (P < 0.05), palmitoleic (P < 0.01), and arachidonic acid (P < 0.01) were lower in diabetic rats. In contrast to the case of the liver microsomes, however, these alterations were persistently observed after 48 h of insulin treatment. The activities of Δ6 desaturase in diabetic rats were 68% of those of controls (P < 0.05), and increased to 119% of controls after insulin treatment. These results show that insulin restores the fatty acid composition earlier in the liver microsome than in the erythrocyte membrane in STZ-induced diabetic rats. The erythrocyte membrane would not be suitable for the investigation dealing with rapid changes of fatty acid composition.

The mechanisms by which phorbol 12-myristate 13-acetate (PMA) and cAMP attenuate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) induced by ligation of the T-cell antigen receptor complex (TCR) was studied in the human Jurkat T-cell line. It has previously been shown that stimulation of Jurkat cells with antibodies to CD3, components of the TCR, elicits a rapid and transient phosphorylation of phospholipase C (PLC)-gamma 1, the predominant PLC isozyme in Jurkat cells, at multiple tyrosine residues and that such tyrosine phosphorylation leads to activation of PLC-gamma 1. Prior incubation of Jurkat cells with PMA or forskolin, which increases intracellular cAMP concentrations, prevented tyrosine phosphorylation of PLC-gamma 1 as well as the hydrolysis of PtdIns 4,5-P2 induced by ligation of CD3. Dose-response curves of PMA and of forskolin for the inhibition of PLC-gamma 1 tyrosine phosphorylation and of PtdIns 4,5-P2 hydrolysis were similar. These results suggest that the inhibition of PtdIns 4,5-P2 hydrolysis by PMA and cAMP is attributable to reduced tyrosine phosphorylation of PLC-gamma 1. Treatment of Jurkat cells with PMA or forskolin stimulated the phosphorylation of PLC-gamma 1 at serine 1248. PMA treatment also elicited the phosphorylation of PLC-gamma 1 at an unidentified serine site. Phosphopeptide map analysis indicated that the sites of PLC-gamma 1 phosphorylated in Jurkat cells treated with PMA and forskolin are the same as those phosphorylated in vitro by protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), respectively. Stimulation of Jurkat cells with antibodies to CD3 also elicited phosphorylation of PLC-gamma 1 at serine 1248 and at the unidentified serine site phosphorylated in PLC-gamma 1 from PMA-treated cells. Thus, phosphorylation of PLC-gamma 1 by PKC or PKA at serine 1248 may modulate the interaction of PLC-gamma 1 with the protein tyrosine kinase or the protein tyrosine phosphatase; this altered interaction may, at least in part, be responsible for the decreased tyrosine phosphorylation of PLC-gamma 1 seen in PMA- and forskolin-treated Jurkat cells. Furthermore, in the absence of PMA, activation of PKC by diacylglycerol provides a negative feedback signal responsible for reducing the phosphotyrosine contents of PLC-gamma 1.

Stimulation of rat basophilic leukemia (RBL-2H3) cells with oligomeric IgE elicited a rapid and transient phosphorylation of phospholipase C (PLC)-gamma 1 on tyrosine residues. Prior incubation of RBL-2H3 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma 1 as well as the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by oligomeric IgE. However, 5'-(N-ethyl)carboxamidoadenosine, which is known to activate PLC through a G protein, did not elicit tyrosine phosphorylation of PLC-gamma 1. These results, together with previous findings showing that tyrosine phosphorylation of PLC-gamma 1 enhances its catalytic activity, indicate that phosphorylation of PLC-gamma 1 by a nonreceptor tyrosine kinase is the mechanism by which IgE receptor aggregation triggers PLC activation.

The effects of the agents that are related to intracellular events on interferon-gamma-induced class II major histocompatibility complex antigen expression were studied using the technique of immunocytochemistry. Rat class II major histocompatibility complex antigen (RT1.B) was expressed in 88.3 +/- 3.3% (n = 3) of the functioning rat thyroid cells (FRTL-5) cultured in a medium containing 100 U/ml recombinant rat interferon-gamma (IFN gamma). Deprivation of bovine TSH had no effect on the expression of RT1.B antigen by IFN gamma. A23187 (1 nM to 2 microM) and/or 10 nM to 10 microM phorbol 12-myristate 13-acetate did not induce the expression of RT1.B antigen. IFN gamma-induced RT1.B expression was not inhibited by either 10 nM to 100 microM 1-(5-isoquinolysulfonyl)-2-methylpiperazine or 200 nM to 200 microM 8-(N,N-dimethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride. It was also not inhibited by either 5-200 microM verapamil or 500 nM to 20 microM trifluoperazine. However, 0.01-10 micrograms/ml cycloheximide inhibited IFN gamma-induced RT1.B antigen expression in a dose-dependent manner. These results suggest that IFN gamma induces RT1.B antigen expression in FRTL-5 cells via de novo protein synthesis independent of the cAMP system, phosphatidylinositide system, and voltage-dependent calcium channel.

It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to observe basal and angiotensin II (All)-stimulated aldosterone secretion in vitro by isolated bovine adrenal glomerulosa cells in the presence of varying concentrations of Na ion, and also to investigate the dependency of aldosterone secretion on extracellular Cl ion. When Na in the incubation medium was replaced iso-osmotically by choline or N-methylglucamine, the absence of Na markedly inhibited basal and All-stimulated aldosterone secretion, and concentrations of Na below 50mM impaired the ability of adrenal glomerulosa cells to respond to All. Basal aldosterone secretion was significantly higher at Na concentrations of 50 and 93mM in the choline substitution experiment, as compared with the normal concentration of Na, and the increment in aldosterone above basal levels by All stimulation reached a maximum at a Na concentration of 93mM. The absence of Cl ion in the incubation medium didn’t alter aldosterone secretion as Cl− was replaced totally by NO3− From these results, we conclude that extracellular Na ion appears to play an important role in the aldosterone secretion by isolated bovine adrenal glomerulosa cells.

When larvae of C. sinensis reach the biliary system and mature, the flukes provoke pathological changes, both as a result of local trauma and of toxic irritation. The appearances vary with duration and severity of the infestation, but they are sufficiently distinctive and characteristic to allow a classification into four phases as follows; 1st phase, desquamation of epithelial cells, 2nd phase, hyperplasia and desquamation of epithelial cells, 3rd phase, hyperplasia and desquamation of epithelial cells, and adenomatous tissue formation, and 4th phase, marked proliferation of the periductal connective tissue with scattered abortive acini of epithelial cells and fibrosis of the wall of the bile duct. The onset of symptoms and signs is at times gradual, at times sudden. Chill and fever up to 40 degrees C occur during the acute stage, i.e. the period less than a month after parasite invasion. And a few weeks later, the chronic stage follows with the classical clinical features. In general, symptoms and signs can be classified as follows: mild, essentially symptomless, progressive, with irregular appetite, gastrointestinal disturbances, oedema, hepatomegaly, etc., and severe, with a syndrome associated with portal cirrhosis and hypertension. Pathogenic changes and complications are generally restricted to foci, but may eventually affect the whole liver. Calculi, acute suppurative cholangitis, recurrent pyogenic cholangitis, cholecystitis, hepatitis, and acute pancreatitis are important complications. Carcinoma of the liver is often found in association with clonorchiasis, too.

A 40-year-old male who developed Graves' hyperthyroidism following primary hypothyroidism is reported. He presented with clinical signs of hypothyroidism and concomitant myasthenia gravis. The thyroid was not palpable. He was treated with T4, pyridostigmine and prednisolone. One year later he developed hyperthyroidism and goitre. His initial serum IgG had no intrinsic thyroid stimulating activity, but showed almost complete inhibition of TSH-stimulated cAMP generation (99.4%, normal 3H]thymidine incorporation (99.5%, normal3H]thymidine incorporation (5.5-fold increase). No inhibitory activities were noted. These findings suggest that clinical states of autoimmune thyroid diseases can be changed in accordance with changes of functional properties of TSH receptor antibodies.

We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H] thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3,0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H] thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; PP