Changes in tissue oxygenation in response to sudden intradialytic hypotension

Journal of Artificial Organs - A 76-year-old woman on hemodialysis (HD) for diabetic nephropathy was admitted to our hospital with occasional intradialytic hypotension (IDH). We continuously...     

Evidence for the involvement of ecto-5′-nucleotidase (CD73) in drug resistance

Increased ecto-5′-nucleotidase (ecto-5′NT) protein expression in several multidrug-resistant (MDR) cell lines, documented previously by our group, suggests that this enzyme is involved in drug resistance. Here, Northern blot analysis of selected cell lines and their MDR variants positively correlated ecto-5′NT protein with its mRNA expression. An inhibitor of ecto-5′NT enzymatic activity, α,β-methyleneadenosine 5′-diphosphate (AMP-CP), was used to determine if functionally active enzyme had a role in drug resistance. AMP-CP (0.3 mM) reversed the resistance of ecto-5′NT-positive MDR cells (MCF7/A6, L1210/A) to doxorubicin, whereas it did not affect the doxorubicin sensitivity of the ecto-5′NT-negative parental cell lines or that of 2 ecto-5′NT-negative MDR cell lines (HL60/VCR and A2780/DX5). Furthermore, AMP-CP increased rhodamine uptake and inhibited rhodamine efflux from ecto-5′NT-positive MDR cells without affecting ecto-5′NT-negative MDR cells. The presence of exogenous adenosine (0.5 μM) circumvented AMP-CP-induced inhibition of rhodamine efflux from EL4/ADM cells. AMP-CP inhibited the growth of the ecto-5′NT-positive L1210/A MDR cells but had no effect on the growth of the parental cell line. Determination of intracellular ATP levels indicated that MDR cells which had increased ecto-5′NT expression also had a lower intracellular ATP level than their parental cells. Our results suggest that, in certain MDR cell lines, ecto-5′NT serves as a required accessory molecule in resistance mediated by ATP-dependent mechanisms and that growth-sustaining nucleosides are provided by this salvage pathway. © 1996 Wiley-Liss, Inc.     

Infection with GB virus C in leprous patients in Japan

The detection of hepatitis C virus (HCV) in blood donors and patients with acute and chronic hepatitis has brought to the fore another virus or viruses which can be transmitted parenterally and induce liver disease. The RNA of a candidate virus designated GB virus C (GBV-C) was determined by the polymerase chain reaction with primers deduced from a helicase-like region in 229 leprous patients in Japan. GBV-C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%). Three patients were coinfected with GBV-C and HCV. The nine patients infected with GBV-C alone had aminotransferase levels lower than the three patients with the mixed infection or the 38 patients infected with HCV only (P < 0.001). Sequence comparison within 100 base pairs in the helicase-like region suggested that two, three and three patients, respectively, would have been infected with three distinct strains of GBV-C. These results indicate that patients with leprosy are at increased risk for infection not only with HCV, but also with GBV-C, and that the infection with GBV-C alone would not induce hepatic injuries as severe as HCV infection. © 1996 Wiley-Liss, Inc.     

Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection

An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection(ESD) for early gastric cancer(EGC).Two years after the initial ESD, a 0-Ⅱc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum.The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma.ESD was performed for this lesion and en bloc resection with negative margins was achieved.Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer(1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection.Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection.Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD.Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known.The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.     

Salmon growth hormone receptor: molecular cloning, ligand specificity, and response to fasting

To better understand the role of growth hormone in regulating fish growth, the cDNA of growth hormone receptor (GHR) was cloned from the liver of masu salmon (Oncorhynchus masou) and characterized. The masu salmon GHR (msGHR) sequence revealed common features of a GHR, including a (Y/F)GEFS motif in the extracellular domain, a single transmembrane region, and Box 1 and Box 2 in the intracellular domain. However, the amino acid sequence identity was low (49%) compared to GHRs of other vertebrates including seven teleosts, and the putative msGHR protein lacked one pair of cysteine residues in the extracellular domain. To verify the identity of the msGHR, the recombinant protein of the extracellular domain was expressed with a histidine tag protein (His-msGHR-ECD), refolded and purified for analysis of its ligand specificity. In competition experiments, the specific binding between His-msGHR-ECD and radioiodine-labeled salmon GH was displaced completely by only salmon GH, and not by salmon prolactin or somatolactin. A real-time RT-PCR assay was used to measure salmon GHR mRNA in the liver of fed and fasted coho salmon (Oncorhynchus kisutch). The levels of hepatic GHR mRNA were lower in fasted fish compared to fed fish after 3 weeks, suggesting that GHR gene expression is reduced following a long-term fast. These results confirm the identity of the salmon GHR based on ligand specificity and response to fasting.     

Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat

Recent reports have shown that thiazolidinediones have preventive effects on urinary albumin excretion in diabetes. However, the mechanism leading to these effects has not yet been elucidated. We studied here the effects of thiazolidinediones on albuminuria and hemodynamic and morphological changes in the kidneys of streptozotocin (STZ)-induced diabetic spontaneous hypertensive rats (SHRs). Diabetes was induced in SHRs by intravenous injection of STZ (50 mg/kg). The diabetic SHRs were divided into the following 3 groups: (1) STZ-SHRs given normal chow (STZ), (2) STZ-SHRs given chow mixed with 0.1% troglitazone (STZ + tro), and (3) STZ-SHRs given chow mixed with 0.001% pioglitazone (STZ + pio). Three groups of nondiabetic SHRs were also investigated: (4) SHR, (5) tro, and (6) pio. We evaluated the urinary albumin excretion rate (AER) every 4 weeks. After 12 weeks of treatment, the animals were killed and renal morphological examinations were performed. Thiazolidinediones did not affect blood pressure or blood glucose levels. Urinary AER were markedly increased in STZ-SHRs. After 12 weeks of treatment with thiazolidinediones, the urinary AER was significantly decreased while creatinine (Cr) clearance was left unchanged. Histologically, the loss of anionic sites of glomerular basement membranes (GBM) evaluated with polyetyleneimine was suppressed significantly in the diabetic SHRs treated with thiazolidinediones. In conclusion, administration of thiazolidinediones in diabetic SHRs decreased the urinary AER and suppressed the loss of anionic sites of GBM without affecting blood pressure, blood glucose levels, or Cr clearance. These results clarify the novel therapeutic action of thiazolidinediones on diabetic nephropathy.     

Case of Mycobacterium haemophilum misdiagnosed as Mycobacterium intracellulare due to one base insertion in the bacterial genome

Mycobacterium haemophilum is a slow‐growing, non‐tuberculous mycobacteria that causes cutaneous infection. We describe a case of cutaneous infection in a 68‐year‐old Japanese man with polymyositis. This was caused by M. haemophilum harboring one base insertion in gene sequence. At first, the causal microorganism was misidentified as M. intracellulare by COBAS^® TaqMan^® MAI test. However, poor growth on Ogawa media and growth enhancement on 7H11C agar around a hemin‐containing disk prompted us to reinvestigate the causal microorganisms, which were revealed to be M. haemophilum. Amplified polymerase chain reaction products were sequenced, and the 16S rRNA gene, rpoB, hsp65 and internal transcribed spacer region sequences showed a 100%, 100%, 99.66% and 99.7% match, respectively, with the corresponding regions of M. haemophilum, but it harbored a novel gene sequence in hsp65. The sequences determined by gene analysis of the M. haemophilum strain were deposited into the International Nucleotide Sequence Database. Although numerous cases of M. haemophilum infection have been reported in other countries, only six cases have been reported in Japan to date. It could be possible that this novel mutation lead to misdiagnosis. As M. haemophilum prefers a lower growth temperature (30–32°C) and it requires iron in the culture medium, M. haemophilum could be misidentified or overlooked. Accordingly, a M. haemophilum infection should be considered in cases of cutaneous infection of the body sites, of which surface temperature is low.     

Clinical features of asthmatic patients with increased urinary leukotriene E4 excretion (hyperleukotrienuria): Involvement of chronic hyperplastic rhinosinusitis with nasal polyposis

BACKGROUND: The urinary leukotriene E4 (U-LTE4) concentration is significantly increased in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic factors of asthma and the U-LTE4 concentration remains undetermined. OBJECTIVE: We sought to examine the clinical features of asthmatic patients with increased excretion levels of U-LTE4 (hyperleukotrienuria). METHODS: We measured the U-LTE4 concentrations in 137 asthmatic patients (including 64 patients with AIA) who were in clinically stable condition. A U-LTE4 concentration of 150 pg/mg creatinine or greater (mean U-LTE4 + 3 SDs of normal healthy control subjects) was indicative of hyperleukotrienuria. RESULTS: The basal concentration of U-LTE4 was significantly higher in the patients with AIA than in those with aspirin-tolerant asthma (ATA; median, 227.2 vs 90.3 pg/mg creatinine; P <.01). Compared with normal leukotrienuria in the patients with AIA, hyperleukotrienuria in the patients with AIA was associated with older age and decrease in pulmonary function. On the other hand, compared with normal leukotrienuria in the patients with ATA, hyperleukotrienuria in the patients with ATA was associated with severe asthma and chronic hyperplastic rhinosinusitis with nasal polyposis (CHRS/NP), which are well-known symptoms of the aspirin triad, as well as hypereosinophilia and anosmia. The patients with ATA with CHRS/NP excreted U-LTE4 at significantly high concentrations. There were significant decreases in the U-LTE4 concentrations before and after the sinus surgery in both the AIA and ATA groups (P <.05). CONCLUSION: Cysteinyl leukotrienes are not strictly associated with aspirin intolerance itself but rather with clinical features, such as CHRS/NP, that are similar to those seen in AIA. CHRS/NP might be involved in cysteinyl leukotriene overproduction in asthmatic patients.