Positive Rates of Preliminary Crossmatches Among Transplantation Candidates Waitlisted for Different Organs in the Korean Network for Organ Sharing.

OBJECTIVE: For deceased-donor organ transplantations, negative T cell crossmatches (XMs) are mandatory for kidney and pancreas allocation in the Korean Network for Organ Sharing (KONOS) organ allocation system. Submission and periodic renewal of serum to the KONOS is required for all transplantation candidates of kidney or pancreas and these sera are distributed to 23 laboratories for preliminary XMs. We have investigated how sensitization status varies among transplantation candidates waitlisted for different organs. METHODS: Positive rates of T cell XMs performed during recent 1-year period (from March 2014 to February 2015) in the Korea Organ Donation Agency laboratory have been analyzed according to different organs. For 163 cases of deceased donors, 3605 recipients (22.1 recipients per one donor) were crossmatched using both of National Institutes of Health and antihuman globulin complement-dependent cytotoxicity (CDC) methods and flow cytometry method. RESULTS: T cell XM positive rates varied among transplantation candidates for different organs. The positive rate was high for kidney (485/3,145, 15.4%), and low for pancreas or kidney/pancreas (7/200, 3.5%), lung (0/41, 0%), and heart (11/221, 5.0%). Among XM-positive individuals, nearly two-thirds of the kidney transplantation candidates showed strong sensitization status with CDC+/flow+ results (64.5%), whereas pancreas or kidney/pancreas transplantation candidates more commonly showed weaker sensitization status with CDC-/flow+ results (85.7%). CONCLUSION: Kidney transplantation candidates show a much higher positive rate and stronger sensitization status than candidates for other organs. The results of this study would be useful for determining the number of candidates to be crossmatched for different organs.

Identification of two novel HLA alleles: HLA-DRB1*12:03:03 and HLA-DRB1*13:143.

The novel alleles DRB1*12:03:03 and DRB1*13:143 differ from DRB1*12:03:02 and DRB1*13:02:01 by one nucleotide in exon 2, respectively.

HLA-B*40:179, a novel allele identified by sequence-based typing in cord blood from a Korean woman.

The novel allele B*40:179 showed one nucleotide difference with B*40:01:01 in exon 4.

HLA-A*02:328, a novel allele identified by sequence-based typing in cord blood from a Korean woman.

The novel allele A*02:328 showed one nucleotide difference with A*02:06:01 in exon 3 resulting in an amino acid change at codon 120 from Gly to Arg.

Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGF-beta signaling.

Diabetic nephropathy (DN) characterized as nephrotic syndrome and diffuse glomerulosclerosis can cause renal failure and end-stage kidney disease. Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of DN. This study investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose (HG). Human renal MC were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 d in the presence of water or ethanol extracts from raw licorice (LW, LE) or roasted licorice (RLW, RLE). Non-polar components including glycyrrhetic acid were elevated during licorice roasting, whereas polar components soluble in water extracts were diminished. Exposure of cells to HG caused significant increases in collagen IV secretion and connective tissue growth factor (CTGF) expression, which was appeased by RLW and RLE at transcriptional levels. The inhibitory potency was high in the order of RLE > or = RLW > or = LE > > LW. Non-polar glycyrrhetic acid but not glycyrrhizin retarded HG-stimulated mesangial matrix deposition through diminishing CTGF expression. In addition, RLW and RLE but not LW modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. However, HG-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination. These results demonstrate that extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetes nephropathy due to longstanding diabetes mellitus.

An outbreak of skin and soft tissue infection caused by Mycobacterium abscessus following acupuncture.

Although outbreaks of Mycobacterium abscessus infection have been reported, none of these reports has identified the potential sources of infection and modes of transmission. In April 2008, we identified and investigated an outbreak of M. abscessus skin and soft tissue infections following acupuncture among the patients who visited an oriental medical clinic. Active surveillance of patients who had visited the clinic was conducted to define the extent of the outbreak. Environmental cultures and a case-control study were performed to elucidate the source of infection and mode of transmission. From 1002 patients interviewed, 109 patients were identified as having suffered M. abscessus skin and soft tissue infections at acupuncture sites. A single strain of M. abscessus was isolated from the wounds of 31 patients and nine environmental samples, including a diluted glutaraldehyde solution. The case-control study revealed that a higher numbers of visits to the clinic for acupuncture (adjusted OR (aOR) 20.12; 95% CI 4.34-93.35) and the use of interferential current therapy or low-frequency therapy (aOR 36.12; 95% CI 5.54-235.44) were associated with the development of M. abscessus infection. The contaminated diluted glutaraldehyde solution that was used to disinfect the physical therapy devices may have been the source of the outbreak of M. abscessus infection in the 109 patients who underwent acupuncture.

Economic cost of tobacco use in India, 2004.

OBJECTIVE: To estimate the tobacco-attributable costs of diseases separately for smoked and smokeless tobacco use in India. METHODS: The prevalence-based attributable-risk approach was used to estimate the economic cost of tobacco using healthcare expenditure data from the National Sample Survey, a nationally representative household sample survey conducted in India in 2004. Four major categories of tobacco-related disease-tuberculosis, respiratory diseases, cardiovascular diseases and neoplasms-were considered. RESULTS: Direct medical costs of treating tobacco related diseases in India amounted to $907 million for smoked tobacco and $285 million for smokeless tobacco. The indirect morbidity costs of tobacco use, which includes the cost of caregivers and value of work loss due to illness, amounted to $398 million for smoked tobacco and $104 million for smokeless tobacco. The total economic cost of tobacco use amounted to $1.7 billion. Tuberculosis accounted for 18% of tobacco-related costs ($311 million) in India. Of the total cost of tobacco, 88% was attributed to men. CONCLUSIONS: The cost of tobacco use was many times more than the expenditures on tobacco control by the government of India and about 16% more than the total tax revenue from tobacco. The tobacco-attributable cost of tuberculosis was three times higher than the expenditure on tuberculosis control in India. The economic costs estimated here do not include the costs of premature mortality from tobacco use, which is known to comprise roughly 50% to 80% of the total economic cost of tobacco in many countries.

Ambivalent role of gallated catechins in glucose tolerance in humans: a novel insight into non-absorbable gallated catechin-derived inhibitors of glucose absorption.

Prolonged postprandial hyperglycemia is a detrimental factor for type 2 diabetes and obesity. The benefit of green tea extract (GTE) consumption still requires confirmation. We report the effects of circulating green tea catechins on blood glucose and insulin levels. Oral glucose loading 1 h after GTE ingestion in humans led to higher blood glucose and insulin levels than in control subjects. Gallated catechins were required for these effects, although within the intestinal lumen they have been known to decrease glucose and cholesterol absorption. Treatment with epigallocatechin-3-gallate hindered 2-deoxyglucose uptake into liver, fat, pancreatic beta-cell, and skeletal muscle cell lines. The glucose intolerance was ameliorated by gallated catechin-deficient GTE or GTE mixed with polyethylene glycol, which was used as an inhibitor of intestinal absorption of gallated catechins. These findings may suggest that the gallated catechin when it is in the circulation elevates blood glucose level by blocking normal glucose uptake into the tissues, resulting in secondary hyperinsulinemia, whereas it decreases glucose entry into the circulation when they are inside the intestinal lumen. These findings encourage the development of non-absorbable derivatives of gallated catechins for preventative treatment of type 2 diabetes and obesity, which would specifically induce only the positive luminal effect.

Successful endoscopic hemoclipping of an esophageal perforation.

We describe a case of esophageal perforation that resulted from a fishbone. A 71-year-old man had had a fishbone impacted in the lower esophagus for 2 days. At presentation, the bone was dislodged at endoscopy; one round opening in a deep ulceration was detected when the fishbone was removed. The perforation was closed by endoscopic hemoclipping, after the removal of the fishbone. A thoracic computed tomography revealed air around the esophagus, aorta and bronchus and the presence of a pleural effusion. These findings suggested mediastinal emphysema and mediastinitis due to the esophageal perforation after the removal of the fishbone. Esophagography revealed a focal esophageal defect and linear contrast leakage at the distal esophagus. The mediastinal emphysema and pleural effusion successfully resolved after the endoscopic hemoclip application and conservative management of the perforation.

Economic burden of smoking in China, 2000.

OBJECTIVE: To assess the health-related economic burden attributable to smoking in China for persons aged 35 and older. METHODS: A prevalence-based, disease-specific approach was used to estimate the smoking attributable direct costs, indirect morbidity costs, and costs of premature deaths caused by smoking-related diseases. The primary data source was the 1998 China National Health Services Survey, which contains the smoking status, medical utilisation, and expenditures for 216,101 individuals. RESULTS: The economic costs of smoking in 2000 amounted to $5.0 billion (measured in 2000, USD) in total and $25.43 per smoker (> or = age 35). The share of the economic costs was greater for men than women, and greater in rural areas than in urban areas. Of the $5.0 billion total costs, direct costs were $1.7 billion (34% of the total), indirect morbidity costs were $0.4 billion (8%), and indirect mortality costs were $2.9 billion (58%). The direct costs of smoking accounted for 3.1% of China's national health expenditures in 2000. CONCLUSION: The adverse health effects of smoking constitute a huge economic burden to the Chinese society. To reduce this burden in the future, effective tobacco control programmes and sustained efforts are needed to curb the tobacco epidemic and economic losses.

Regulation of expression and signalling modulator function of mammalian tribbles is cell-type specific.

The constant need to respond to changes in the environment is a common feature for all life forms. During evolution, a number of intracellular signal processing systems have evolved to fulfill this requirement. One of the most ancient such systems is the mitogen activated protein kinase (MAPK) signalling network, shared by all eukaryotes. Activation of MAPKs is key to regulation of mitosis and in cellular responses to stress or hormones, for instance. In addition, activity of this signalling system is essential during embryonic development. However, many aspects of MAPK mediated responses are strongly cell-type specific. A family of proteins, called tribbles have recently been described as novel regulators of MAPK function. Our group has previously shown that alterations in tribbles levels lead to profound changes in the activation of the various MAPKs. However, little is known about the cell-type specific aspects of regulation of tribbles expression. Here, we report that expression of all three members of the human tribbles family is dynamically controlled in response to inflammatory stimulation. This regulation, however, is strongly cell-type dependent. Our observations suggest regulation of tribbles expression may play an important role in the cell-type specific cellular responses, mediated by the MAPK network.

The economic burden of smoking in California.

OBJECTIVE: To develop estimates of the direct and indirect costs of smoking for California in 1999. METHODS: A prevalence based approach was used to estimate the annual costs of smoking. Econometric models were used to estimate the smoking attributable fraction (SAF) for direct costs (hospitalisations, ambulatory care, prescription drugs, home health care, and nursing home services) and indirect costs due to lost productivity from smoking related illness. The models controlled for socioeconomic factors and other risk behaviours. Epidemiological methods were used to estimate the SAF for indirect costs due to lost productivity from premature deaths. The SAFs were applied to total health care expenditures, days lost, and deaths to obtain smoking attributable total costs. RESULTS: In 1999, the total costs of smoking in California were 15.9 billion dollars, 475 dollars per resident, and 3331 dollars per smoker. Direct costs were 8.6 billion dollars (54% of the total), indirect costs due to lost productivity from illness were 1.5 billion dollars (10%), and indirect costs due to premature deaths were 5.7 billion dollars (36%). The cost of smoking was 9.4 billion dollars for men and 6.3 billion dollars for women. There were 43,137 deaths attributed to smoking, representing a total of 535,000 years of life lost. The value of life lost per death averaged 132,000 dollars, or 12.4 years. CONCLUSIONS: California smoking related costs are high. The cost methodology presented is useful for other states and nations interested in estimating their costs of smoking. Cost estimates can be used to evaluate the level of cigarette taxes and other policies related to smoking.

The behaviour of purchasing smuggled cigarettes in Taiwan.

OBJECTIVE: Since market liberalization in 1987, the Taiwan Tobacco and Wine Monopoly Bureau (TTWMB) annual statistics indicate that both the demand for imported cigarettes as well as the number of seized smuggled packs have increased with an average revenue loss of NT dollars 4942 million over the past 15 years. The NT dollars 10 average increase in cigarette prices after Taiwan entered the World Trade Organization (WTO) and the implementation of the Tobacco and Alcohol Tax Law in 2002 are forcing policy makers to examine smuggling even more closely. This study evaluates factors that affect an individual smoker's decision to purchase smuggled cigarettes, particularly when faced with higher prices. DESIGN: 437 male smokers of imported cigarettes were drawn from a national interview survey on cigarette consumption, which the Division of Health Policy Research at the National Health Research Institutes conducted during the year 2000. Multiple logistic regression models were used to analyse the behaviour of purchasing smuggled cigarettes with respect to demographic factors, economic factors, smoking behaviour, and other variables. RESULTS: Cigarette price was the driving factor most closely linked to the purchase of smuggled cigarettes--a 1% increase in cigarette price raised the likelihood of purchasing smuggled cigarettes at least 2.60 times (95% confidence interval (CI) 1.08 to 6.26). Smokers who spent more than NT 1000/month dollars on cigarettes were twice as likely to purchase smuggled cigarettes as those who spent less than NT 1000 dollars (odds ratio (OR) 2.34, 95% CI 1.48 to 3.70). Betel nut chewers were more likely to purchase smuggled cigarettes (OR 1.80, 95% CI 1.09 to 2.90). Smokers who opposed cigarette taxation policy were 1.69 times more likely to buy smuggled cigarettes. Personal income was not significantly associated with smuggled cigarettes purchases. CONCLUSIONS: This study evaluates what causes smokers to purchase smuggled cigarettes. We have determined that cigarette price is the most important factor and that betel nut vendors are the main suppliers. Our study provides policy makers with information that can help them develop effective strategies to curb cigarette smuggling after Taiwan's recent cigarette tax reform, which has increased cigarette prices.

The burden of osteoporosis in California, 1998.

This study estimates the cost of osteoporosis in California, including health care services and the value of lives lost prematurely to the disease. Costs are estimated for diagnoses of "osteoporosis" and for the proportion of spine, forearm, hip and other fractures that are caused by the disease. The additional costs resulting from a secondary diagnosis of osteoporosis are also included. Osteoporosis accounted for over $2.4 billion in direct health care costs in 1998, and over $4 million in lost productivity resulting from premature death. Most of the cost results from hip fractures and other fractures. In fact, only 15% of costs are for people with a diagnosis of "osteoporosis" per se, and, of this group, most of the costs are associated with a secondary, not a primary diagnosis. The disease is largely a diagnosis of older white women: three-quarters of the hospitalization costs are incurred by women, 80% of those hospitalized are white, and three-quarters are over age 65 years. As would be expected, Medicare pays for most of the hospital care -- almost three-fourths of the total. Nursing home care represents the largest cost for people with osteoporosis, accounting for 59% of the money spent treating the disease.

Advancing age and cervical cancer screening and prognosis.

OBJECTIVES: To determine associations between advancing age and screening behavior and prognosis in long-term members of a prepaid health plan diagnosed with invasive cervical cancer (ICC). DESIGN: Case series. SETTING: Prepaid health plan. PARTICIPANTS: All women diagnosed with ICC at Kaiser Permanente Medical Care Program-Northern California health plan from 1988 to 1994. MEASUREMENTS: From medical records, we recorded participants' age, stage at diagnosis, tumor histology, and results of and reasons for all previous cervical smears. We limited our analysis to women who had been members of the health plan for at least 30 of the 36 months preceding diagnosis (n = 455). RESULTS: Women in older age groups were less likely than younger women to have been screened within the 3 years before diagnosis (P = .005 for trend). Nonadherence to follow-up of abnormal cervical smears was uncommon (17/455, 3.7%) and not age related (P = .932 for trend). The proportions of ICC that were interval cancers, defined as ICC diagnosed within 3 years of a negative screening smear, were highest in women under age 30 (P = .004 for trend). In multivariate analyses controlling for stage at diagnosis, women age 60 and older were not more likely to die of ICC within 3 years of diagnosis than were women younger than age 60 (odds ratio 1.30, 95% confidence interval 0.75-2.28). CONCLUSION: The disproportionate burden of cervical cancer observed in older women appears to be largely attributable to lack of screening within the 3 years before diagnosis.

Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1.

A mutant of Bacillus subtilis IMR-NK1, which is used for the production of domestic "natto" in Taiwan, produced high fibrinolytic enzyme activity by solid-state fermentation using wheat bran as medium. In addition, a strong fibrinolytic enzyme was purified from the cultivation media. The purified enzyme was almost homogeneous, as examined by SDS-PAGE and capillary electrophoresis. The enzyme had an optimal pH of 7.8, an optimal temperature of 55 degrees C, and a K(m) of 0.15% for fibrin hydrolysis. The molecular mass estimated by gel filtration was 31.5 kDa, and the isoelectric point estimated by isoelectric focusing electrophoresis was 8.3. The enzyme also showed activity for hydrolysis of fibrinogen, casein, and several synthetic substrates. Among the synthetic substrates, the most sensitive substrate was N-succinyl-Ala-Ala-Pro-Phe-pNA. PMSF and NBS almost completely inhibited the activity of the enzyme. These results indicate that the enzyme is a subtilisin-like serine protease, similar to nattokinase from Bacillus natto.

Cigarette consumption and sales of nicotine replacement products.

BACKGROUND: The first nicotine replacement product, Nicorette Gum, was marketed in 1984 as an adjuvant to help smokers quit smoking. In 1992, sales of nicotine patches were begun. Before 1996, nicotine gums and nicotine patches were prescribed by physicians and supplemented with behavioural counselling. Since 1996, nicotine gums and patches became available over the counter. OBJECTIVES: To examine the effect of sales of nicotine replacement products on national cigarette consumption. DESIGN: National time series quarterly cigarette consumption, sales of nicotine gums and patches data between 1976 and 1998 are used to estimate a time series autoregressive moving average intervention model. PARTICIPANTS: National reported statistics. MAIN OUTCOME MEASURES: Per capita cigarette sales. RESULTS: A 10% increase in sales of nicotine replacement products will lead to a 0.04% reduction in cigarette sales. The model indicates that a 0.076% reduction in cigarette consumption is associated with the availability of nicotine patches after 1992. The over the counter dummy variable (after 1996) has a negative sign, but is not significant, perhaps due to only a few quarters of data in the study period. CONCLUSIONS: Nicotine replacement products (nicotine gums and nicotine patches) play a significant role in reducing cigarette consumption, in addition to the negative effect of increasing cigarette price and the overall trend of declining cigarette consumption (as reflected by the time trend variable). The findings of this study suggest that additional efforts for promoting sales of nicotine replacement products will be another effective alternative to discouraging cigarette consumption.

Papanicolaou smear history and diagnosis of invasive cervical carcinoma among members of a large prepaid health plan.

BACKGROUND: Despite the widespread use of Papanicolaou (Pap) smear screening, substantial morbidity and mortality from cervical carcinoma continue in the U.S. Although access to screening is a major barrier to use of the Pap smear, invasive cervical carcinoma (ICC) still is observed in health plan members who have comprehensive preventive care coverage. METHODS: For all women diagnosed with ICC between 1988 and 1994 in a large prepaid health plan, the authors retrospectively reviewed the medical records for prediagnosis Pap smear history to identify antecedents to ICC. RESULTS: Of 642 women diagnosed as having ICC, 455 (71%) had been plan members for > or = 30 of the 36 months before diagnosis. Of these 455 women, 240 (53%) had no Pap smear during the 6-36 months prior to diagnosis (i.e., were nonadherent to screening), 127 (28%) had only "normal" Pap smear results, 42 (9%) had at least 1 abnormal Pap smear and were adequately followed, 17 (4%) had at least 1 abnormal result without adequate follow-up, and 29 (6%) were classified as "other." Compared with adherent women, more nonadherent women presented with later stage disease, were symptomatic at the time of diagnosis, were older, and were of a race/ethnicity other than non-Hispanic white. CONCLUSIONS: Nonadherence to screening recommendations was found to be the most important modifiable antecedent to ICC in this population. The rate of incidence of ICC could be reduced by interventions to increase screening in women who do not have Pap smears regularly and by the use of newer screening technologies to reduce the false-negative rate of Pap smears.

Purification and properties of beta-N-Acetylhexosaminidase from cabbage.

beta-N-Acetylhexosaminidase was purified from the extract of cabbage by sequential steps of ammonium sulfate fractionation, chromatofocusing, DEAE-Sepharose CL-6B ion exchange chromatography and Sephacryl S-200 HR gel filtration. By these steps, the purity of the enzyme increased by 256 fold with a recovery of 8%. The purified enzyme was homogeneous as examined by native PAGE. It showed an optimal pH of 4, an optimal temperature of 60 degrees C and a Km of 0.94 mM for hydrolysis of pNp-beta-GlcNAc. The molecular mass of the enzyme determined from filtration through Sephacryl S-200 was 150 kDa. Three subunits with molecular mass of 64, 57 and 51 kDa were observed as determined by SDS-PAGE. NBS (0.025 mM), DEPC (3 mM) and WRK (30 mM) significantly inhibited the activity of the enzyme. The enzyme also showed activity toward pNp-beta-GalNAc, N,N'-diacetylchitobiose, N,N',N"-triacetylchitotriose and N,N',N",N"'-tetraacetyl chitotetraose but showed no activity toward pNp-alpha-GlcNAc, chitin and ethylene glycol chitin.

Missed opportunities for cervical cancer screening of HMO members developing invasive cervical cancer (ICC).

OBJECTIVE: To identify potential missed opportunities and to suggest interventions for cervical cancer screening in members of a prepaid health plan by examining the membership histories and medical records of women who had no Pap smear performed in the 3 years prior to the diagnosis of ICC. METHODS: Medical records of all 642 members of a prepaid health plan developing ICC during the period from 1988 to 1994 were reviewed and details of patient interaction with the health care system were abstracted. Assessment of screening history and history of clinic visits was limited to the period 36 months prior to diagnosis, but excluded the last 6 months prior to diagnosis, so as to avoid including smears or visits which were part of the evaluation that led to the recognition of ICC. RESULTS: Of women developing ICC, 384/642 (60%) had not had a smear in the period from 36 months to 6 months preceding the diagnosis. Of these 384 unscreened women, 241 (63%) had been insured by our HMO for at least 30 of the 36 months prior to diagnosis. Contact with the medical system in one of the primary care outpatient clinics was documented in 180/241 (75%) of these long-standing members during the specified period. Considering only Internal Medicine and Family Practice clinic visits, 169/241 (70%) had been seen at least once and 101/241 (42%) had been seen 3 or more times. CONCLUSION: Most long-standing HMO members developing ICC without benefit of recent Pap smear screening were seen in primary care outpatient clinics in the 3 years preceding their diagnosis.