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Background: Asbestos is a well-known hazardous substance that causes occupational and environmental diseases including asbestosis (lung fibrosis). Silica exposure which causes silicosis (another type of lung fibrosis) has long been linked to the development of autoimmune diseases; however, there are few studies on the relationship between asbestos exposure and autoimmune diseases., Methods: A total of 54 individuals who had worked in a former asbestos textile factory underwent autoantibody-related blood tests, chest X-ray imaging, and pulmonary function tests. Based on the job exposure matrix (JEM), the estimated asbestos exposure concentrations were determined, and the presence of asbestosis was determined by chest radiography., Results: Scleroderma (Scl-70) and ribonucleoprotein (RNP) antibodies were significantly lowered in the pleural plaque present group than in the absent group. Additionally, Scl-70, RNP, and Sjögren's syndrome type B (SS-B) antibodies were significantly lowered in the asbestosis present group. When stratifying variables with or without asbestosis, Scl-70, Smith, SS-B, and RNP antibodies decreased in female, crocidolite handling group, and higher estimated asbestos exposure level group., Conclusions: Contrary to our expectations that autoantibody titers would be higher in groups with high asbestos exposure or in the asbestosis group, those with asbestosis showed lower titers. But as our research has some methodological limitations, the lowered titer of autoimmune antibody in our asbestos exposed subjects could not be simply interpreted as a lowered risk of autoimmune diseases. So careful interpreting should be taken when examine autoantibodies to screening or diagnose autoimmune diseases in people with asbestos exposure. In addition, it is necessary to establish relevance of asbestosis and autoantibodies through further studies of larger scale and higher confidence levels., Competing Interests: Competing interests: The authors declare that they have no competing interest., (Copyright © 2020 Korean Society of Occupational & Environmental Medicine.)

Background: This study aimed to determine the effect of specific working postures on the development of varicose veins (VV). By using Korea's National Health Insurance (NHI) and National Employment Insurance (NEI) data, we analyzed the general characteristic and difference in proportions of VV cases according to occupational working posture., Methods: From the NEI and NHI data, participant demographics, such as gender, age, body mass index, and number of workers in specific occupations or industries were obtained. We classified the 240 occupations into blue-collar (BC) and white-collar (WC) occupations and subdivided them into standing, sitting, and walking groups according to the dominant working posture., Results: The number of VV patients per 100,000 individuals increased with age, with a higher number of women than men and a higher number of patients in the BC than WC groups. For the BC group, the proportion of VV cases was the highest in the standing group, followed by the walking and sitting groups, but there was no significant difference between standing and walking groups in man. For the WC group, the standing group had a higher proportion of VV cases than the sitting group, but there was no significant difference between the standing and sitting group in man. In the BC group, the proportion of VV cases was the highest among medical and welfare-related elementary workers, bakers and cookie makers, automobile assemblers, cleaning and guarding-related elemental workers, and nurses and dental hygienists. In the WC group, the proportion of VV cases was the highest among food/lodging/tourism/entertainment/sports-related managers, environment/cleaning/protective services-related managers, finance and insurance clerks, accounting book-keeping clerks, and social welfare and counseling professionals., Conclusions: This study was performed to determine the characteristics of VV with different working posture among Korean workers. It is expected to be the basis of further studies on occupational musculoskeletal diseases., Competing Interests: Competing interests: The authors declare that they have no competing interest., (Copyright © 2020 Korean Society of Occupational & Environmental Medicine.)

Background: Lecitin cholesterol acyltransferase (LCAT) deficiency comprises a group of rare disorders related to HDL metabolism. These disorders are characterized by ophthalmologic, hematologic, and renal findings. Case diagnosis/treatment: A 15-year-old female who presented with nephrotic syndrome and hypertension was diagnosed with LCAT deficiency by renal biopsy and LCAT enzyme activity. Her edema and hypertension improved with diuretic and antihypertensive therapies. Continued care of her LCAT deficiency is ongoing., Conclusion: Although rare, LCAT deficiency should be in the differential diagnosis of nephrotic syndrome in the setting of abnormally low HDL cholesterol levels.

Clinical studies suggest metabolic memory to hyperglycemia. We tested whether diabetes leads to persistent systematic in vitro gene expression alterations in patients with type 1 diabetes (T1D) compared with their monozygotic, nondiabetic twins. Microarray gene expression was determined in skin fibroblasts (SFs) of five twin pairs cultured in high glucose (HG) for ∼6 weeks. The Exploratory Visual Analysis System tested group differences in gene expression levels within KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. An overabundance of differentially expressed genes was found in eight pathways: arachidonic acid metabolism (P = 0.003849), transforming growth factor-β signaling (P = 0.009167), glutathione metabolism (P = 0.01281), glycosylphosphatidylinositol anchor (P = 0.01949), adherens junction (P = 0.03134), dorsal-ventral axis formation (P = 0.03695), proteasome (P = 0.04327), and complement and coagulation cascade (P = 0.04666). Several genes involved in epigenetic mechanisms were also differentially expressed. All differentially expressed pathways and all the epigenetically relevant differentially expressed genes have previously been related to HG in vitro or to diabetes and its complications in animal and human studies. However, this is the first in vitro study demonstrating diabetes-relevant gene expression differences between T1D-discordant identical twins. These SF gene expression differences, persistent despite the HG in vitro conditions, likely reflect "metabolic memory", and discordant identical twins thus represent an excellent model for studying diabetic epigenetic processes in humans.

Desensitization therapies have been used with modest success in kidney transplantation. Some candidates, however, have such great breadth and depth of anti-HLA antibodies that they remain incompatible with potential donors. Bortezomib has been used without much success in desensitization regimens, but we hypothesized that its use during induction may be helpful in targeting antibody production by long-lived plasma cells. This report describes a high-risk positive crossmatch son-to-mother transplant that was performed after desensitization. The induction immunosuppression was supplemented with bortezomib. Pre- and post-transplant immunosuppression, antibody monitoring, biopsy data, and the clinical course are described in detail. Following transplant, the patient had excellent early graft function. Serial biopsies did not reveal acute antibody mediated rejection. Despite excellent graft function, the patient underwent withdrawal of care and died due to complications of calciphylaxis and deconditioning. This case details the first report of bortezomib used as part of induction therapy in solid organ transplant. Donor specific antibody production remained stable after transplant, with near complete abrogation of class I specificities. There were no bortezomib-related complications.

This experience demonstrates that a bortezomib-based regimen provided effective therapy for late, refractory AMR in an adult heart transplant recipient and was well tolerated. This remarkably positive experience despite the refractory nature of the AMR episode argues strongly for continued evaluation of bortezomib use in this patient population.

Nephropathic cystinosis is a lysosomal storage disorder, which, if untreated, results in renal failure by age 10 years. Oral cysteamine has been shown to preserve renal function in these patients. In this study, a 2-year-old girl with nephropathic cystinosis and severe gastrointestinal dysmotility was treated with intravenous (i.v.) administration of cysteamine hydrochloride (HCl). This is only the second report of long-term i.v. cysteamine therapy for nephropathic cystinosis. Unlike the treatment in the previous case, however, treatment in our patient was limited by liver toxicity.

Atubular glomeruli (AG) have been described in several renal disorders. However, little attention has been paid to AG in diabetic nephropathy (DN). Preliminary studies suggested that tip lesions were frequently present in type 1 diabetic (D) patients with proteinuria. The aim of this study was to determine the frequency of AG and their possible relationship with tip lesions in DN. Renal biopsies from eight proteinuric type 1 D patients with normal to moderately reduced GFR (76 +/- 26 ml/min per 1.73 m(2)) and eight normal subjects were studied by light (LM) and electron microscopy (EM). Glomerular volume, volume of the glomerular corpuscle, which is tuft, and the fractional volumes of proximal, distal, and atrophic tubules per cortex were estimated using appropriate stereologic methods. Glomerulotubular junctions were examined on serial sections and classified into glomeruli attached to: normal tubules (NT); short atrophic tubules (SAT); long atrophic tubules (LAT); atrophic tubules with no observable glomerular opening (ATNO); and atubular glomeruli (AG). EM studies showed typical diabetic changes in biopsies, including increased GBM width (P < 0.00001) and mesangial fractional volume (P < 0.0001) and decreased filtration surface density (P < 0.01) compared with normal subjects. Seventeen percent of glomeruli in the D patients were atubular, and 51% were attached to atrophic tubules. Tip lesions were present in all SAT, 64% of LAT, 82% of ATNO, and only 9% of NT and were never observed in normal subjects. The relative volume of AG was smaller than glomeruli in other categories (P < 0.05). Fractional volume of proximal (P < 0.01) and distal (P <0.01) tubules per cortex were decreased, while fractional volume of cortical interstitium (P <0.00001) and atrophic tubules (P <0.01) were increased in D patients. Fractional volume of atrophic tubules, %AG, and percent of glomeruli with tip lesion explained 94% of the GFR variability in diabetic patients (P <0.05). Thus, AG and glomerulotubular junction abnormalities may be important in the development and progression of DN.

Complete ureteral obstruction in rats rapidly leads to renal interstitial expansion and fibrosis and this process is ameliorated by concomitant angiotensin converting enzyme inhibition (ACEI). However, models of intervention initiated after unilateral ureteral obstruction (UUO) release may be more analogous to human obstructive renal disease where treatment could more reasonably follow the discovery of obstructive uropathy as compared to models where treatment is initiated at the time of experimentally induced obstruction. We studied interstitial changes in rats before and after release of UUO and examined the effect of ACEI with 200mg/L of enalapril (E) in the drinking water on these changes. Rats were sacrificed after 10 (n=10) and 20 (n=10) days (D) of UUO or 10D after release of 10D of UUO (n=18). Eleven rats received E for 10D after UUO release. Cortical interstitial volume fraction [Vv(I/C)] measured by point counting was increased at 10D (0.32 +/- 0.05) and 20D (0.41 +/- 0.05) of UUO compared to contralateral and sham-operated kidneys (both 0.05 +/- 0.01, ANOVA, p <0.001). Vv(I/C) 10D after release from 10D of UUO (0.26 +/- 0.04) was lower than that of 10D of UUO (p<0.05) and much lower than those with 20D of UUO (p<0.001). However, rats treated with E from the time of UUO release had lower Vv(I/C) (0.21 +/- 0.07) than UUO released E untreated rats (p<0.05). Release of UUO initiates regression of interstitial expansion in rats. ACEI with enalapril significantly accelerates reversal of interstitial expansion after UUO release. This could have important implications for treatment of obstructive nephropathy in humans.

Background: The remnant kidney model, usually involving sudden removal or ablation of 1- 1 / (2) to 1-5 / (6) of renal mass, results in compensatory hypertrophy followed by hypertension, proteinuria and declining glomerular filtration rate (GFR) associated with focal (FSG) and then global glomerulosclerosis (GS) and tubulointerstitial injury (TI). Since most renal diseases involve much more gradual injury, we asked whether slow ablation (SA) produced a different natural history than fast ablation (FA)., Methods: Male Münich-Wistar rats underwent heminephrectomy, 3 weeks later a second, and 3 weeks later a third heminephrectomy (SA). They were compared to littermates undergoing simultaneous removal of 1- 1 / (2) kidneys (FA) and sham operated controls (C)., Results: Three weeks after the second heminephrectomy, the SA rats had no FSG and glomerular volume (GV) was similar to that of FA rat renal tissue removed at that time. Eight weeks following the final surgical procedure (FSP), the SA and FA groups had similar blood pressures (BP) but higher than C. Albumin excretion rates (AER) were higher in SA and FA vs. C at 1 month after the FSP and, throughout most of the subsequent 5 months, greater in the SA vs. FA groups. At 24 weeks, cortical interstitial fractional volume was double C values in both the SA and FA groups. Percentage of glomeruli with FSG and size (score) of FSG lesions was much higher in SA and FA than C. Moreover, the percentage of FSG in SA (61.2+/-16%) and FSG score (1.7+/-0.7) was greater than in FA animals (35.6+/-11.9% and 0.9+/-0.4, p<0.01 for each comparison). Mean GV, increased at 24 weeks in both groups over C (1.4+/-0.2 X 10(6) micro m(3)) was greater in SA (3.4+/-0.7 X 10(6) micro m(3)) than FA rats (2.1+/-0.4 X 10(6) micro m(3); p<0.005)., Conclusions: The gradual uninephrectomy in the SA group, insufficient per se to produce significant renal damage, preconditioned the residual kidney, upon further removal of another 1 / (2) kidney, to more albuminuria and FSG lesions than occurred following sudden 1- 1 / (2) nephrectomy, despite similarly elevated BP. Perhaps more time for glomerular enlargement in the SA group preconditioned the remnant kidney to accelerated injury.

Mucoid otitis media (MOM), one of the leading causes of acquired hearing loss in children, is characterized by mucous cell hyperplasia in the middle ear cleft associated with mucin accumulation in the middle ear cavity. The factors that stimulate mucous cell metaplasia-hyperplasia and mucin hyperproduction are poorly understood. Recent studies demonstrated that tumor necrosis factor alpha (TNF-alpha), present in human middle ear effusion, stimulated mucin production in vitro and up-regulated mucin gene expression in vivo. These findings suggest that TNF-alpha is important in the development of mucous cell metaplasia-hyperplasia. This study demonstrated that inoculation of TNF-alpha into the middle ear cavity followed by eustachian tube obstruction stimulated mucous cell metaplasia-hyperplasia in the middle ear cleft, accompanied by abundant mucin or mucin-like glycoproteins in the middle ear effusion--a phenotype of MOM in humans. This finding suggests that TNF-alpha plays a key role in the pathogenesis of MOM through induction of mucous cell metaplasia-hyperplasia and mucin production.

Kidneys from mice, dogs, and humans with X-linked and autosomal-recessive forms of Alport syndrome were examined by immunofluorescence for expression of laminin alpha, beta, and gamma chains using monospecific antibodies. Laminin alpha2 chain was absent from glomerular basement membranes (GBM) in normal human, murine, and canine kidneys but was abnormally deposited in Alport GBM, regardless of species or inheritance pattern. In murine and canine Alport kidneys, laminin alpha2 seems to be deposited as part of both laminin-2 (alpha2beta1gamma1) and laminin-4 (alpha2beta2gamma1) but as part of only laminin-4 in human Alport kidneys. GBM laminin alpha2 chain deposition was not observed in a variety of non-Alport human glomerulopathies. This finding adds to the list of proteins that are aberrantly deposited in Alport GBM as a consequence of the absence of the alpha3, alpha4, and alpha5 chains of type IV collagen: (1) type IV collagen alpha1 and alpha2 chains, (2) type V collagen, (3) type VI collagen, and most recently (4) the laminin alpha2 chain and (5) the laminin alpha1 and beta1 chains in mice and dogs. These findings emphasize further the critical role played by the alpha3, alpha4, and alpha5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.