Usefulness of carcinoembryonic antigen measurement in feces of patients with colorectal cancer

Anticarcinoembryonic antigen (CEA) antisera which showed no reactions with normal adult feces were prepared in guinea pigs. Using these, levels of CEA in feces from patients with colorectal carcinoma were measured by gel diffusion and rocket immunoelectrophoresis. Sixteen of 22 (73 percent) patients with carcinoma of the colon or rectum (Dukes' A4/6, B6/8, C6/7, D0/1) had detectable CEA in their feces, while none was detected in the feces of four patients with gastric ulcers or in those of 22 normal volunteers. Five of the 16 fecal CEA-positive patients showed no elevation of plasma CEA levels. Measurements using a commercial CEA kit (Abbott Laboratories) could not detect the differences between fecal CEA values of patients with colorectal carcinoma and benign diseases, or those of normal volunteers. These results suggest that measurement of fecal CEA by specific anti-CEA antisera will be valuable in screening and diagnosis of colorectal carcinoma.     

Liberal Policy in Living Donor Liver Transplantation for Hepatocellular Carcinoma: Lessons Learned

Background Living donor liver transplantation (LDLT) in cases of hepatocellular carcinoma (HCC) that do not fulfil accepted tumor criteria continues to be a matter of controversy. The aim of this study was to evaluate survival and prognostic factors associated with a liberal exclusionary policy. Material and Methods This is an analysis of data collected prospectively on 57 HCC patients who underwent LDLT at our institution between April 1998 and January 2007. Results Overall 3-year survival was 62%; this increased to 71% when 45-day mortality was excluded from the analysis. Age proved to be a predictor of survival irrespective of the 45-day mortality. In contrast, the Model for End stage Liver Disease (MELD) score predicted survival only when 45-day mortality was included in the analysis, while alpha fetoprotein (AFP) level predicted survival only when it was excluded. Significant cut-off values were patient age of over 60 years, MELD score above 22, and AFP level greater than 400 ng/ml. A scoring system was developed. Survival rate at 3 years—including 45-day mortality—was 72% for score =2 and 41% for score >2 (P = 0.0146). When 45-day mortality was excluded, the survival rate at 3 years was 90% for score =2 and 32% for score >2 (P = 0.00002). Conclusions Our results could further enhance current guidelines on age, MELD score, and AFP level for patients with HCC being evaluated to undergo LDLT.     

A case of a gastrobronchial fistula after esophageal reconstruction successfully closed with an intercostal muscle flap

A 63-year-old man with esophageal cancer underwent a subtotal esophagectomy via the thoracolaparotomy approach. Two years after the operation, a gastrobronchial fistula unexpectedly occurred in the right bronchus. After admission, medication including omeprazole and nutritional support administered through an enteral tube improved his general condition, and the gastrobronchial fistula was successfully closed with the seventh intercostal muscle flap. After the operation, sputa were aspirated with a bronchofiberscope through a tracheal incision rather than blindly with a catheter. He was in good condition 10 months after the operation.     

Peroxisome dependency of alkyl-containing GPI-anchor biosynthesis in the endoplasmic reticulum

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) play various roles in cell–cell and cell–environment interactions. GPI is synthesized in the endoplasmic reticulum (ER) from phosphatidylinositol (PI) through step-wise reactions including transfers of monosaccharides and preassembled GPI is transferred en bloc to proteins. Cellular PI contains mostly diacyl glycerol and unsaturated fatty acid in the sn-2 position, whereas mammalian GPI-APs have mainly 1-alkyl-2-acyl PI and almost exclusively stearic acid, a saturated chain, at the sn-2 position. The latter characteristic is the result of fatty acid remodeling occurring in the Golgi, generating GPI-anchors compatible with raft membrane. The former characteristic is the result of diacyl to alkyl-acyl change occurring in the third GPI intermediate, glucosaminyl-inositolacylated-PI (GlcN-acyl-PI). Here we investigated the origin of the sn-1 alkyl-chain in GPI-APs. Using cell lines defective in the peroxisomal alkyl-phospholipid biosynthetic pathway, we demonstrated that generation of alkyl-containing GPI is dependent upon the peroxisomal pathway. We further demonstrated that in cells defective in the peroxisome pathway, the chain composition of the diacyl glycerol moiety in GlcN-acyl-PI is different from those in the first intermediate N-acetylglucosaminyl-PI and cellular PI, indicating that not only diacyl to alkyl-acyl change but also diacyl to diacyl change occurs in GlcN-acyl-PI. We therefore propose a biosynthetic step within GlcN-acyl-PI in which the diacyl glycerol (or diacyl phosphatidic acid) part is replaced by diradyl glycerol (or diradyl phosphatidic acid). These results highlight cooperation of three organelles, the ER, the Golgi, and the peroxisome, in the generation of the lipid portion of GPI-APs.     

Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case–control study of 21 patients

Objective

To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.

Methods

Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case–control study to compare patients with and without PCP were performed.

Results

The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground‐glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.

Conclusion

PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.     

Graft size and donor age are independent factors for graft loss in adult-to-adult living-donor liver transplantation using the left liver

Background/purpose

Graft survival is affected by various factors, such as preoperative state and the ages of the recipient and donor, as well as graft size. The objective of this study was to analyze the risk factors for graft survival.

Methods

From September 1997 to July 2005, 24 patients who had undergone living-donor liver transplantation (LDLT) were retrospectively analyzed. Sixteen patients survived and the eight graft-loss cases were classified into two groups according to the cause of graft loss: graft dysfunction without major post-transplantation complications (graft dysfunction group; n = 3), and graft dysfunction with such complications (secondary graft dysfunction group; n = 5). Various factors were compared between these groups and the survival group.

Results

Mean donor age was 31.9 years in the survival group and 49.2 years in the secondary graft dysfunction group (P = 0.024). Graft weight/recipient standard liver volume ratios (G/SLVs) were 36.7% in the survival group, and 26.2% in the graft dysfunction group (P = 0.037). The postoperative mean PT% for 1 week was 48.6% in the survival group and 38.1% in the secondary graft dysfunction group (P = 0.05).

Conclusions

Our surgical results demonstrated that G/SLV and donor age were independent factors that affected graft survival rates.     

Intraductal Secretin Test Is as Useful as Duodenal Secretin Test in Assessing Exocrine Pancreatic Function

We assessed the clinical usefulness of theintraductal secretin test in order to ascertain whetherit can substitute for the conventional duodenal secretintest. Duodenal juice was obtained with a triple-lumen tube and pure pancreatic juice was obtained byretrograde cannulation of the main pancreatic duct usinga duodenofiberscope. Pancreatic secretion was stimulatedby a bolus intravenous injection of secretin (100 units). The two tests showed comparableinterindividual coefficients of variation, significantlygood correlations, and comparable diagnosticefficiencies. The intraductal secretin test showed noless reproducibility than that of the duodenalsecretin test as reported in the literature. In theintraductal secretin test, secretory volume, peak flowrate, bicarbonate output, and lipase output yielded the best diagnostic efficiency, followed by amylaseoutput and maximal bicarbonate concentration. In theintraductal secretin test, a 10-min collection providedas much information as a 20-min collection. We conclude, therefore, that the 10-minintraductal secretin test is as useful as theconventional duodenal secretin test in assessingexocrine pancreatic function and that the mostdiscriminatory parameters are secretory volume, bicarbonate output, andamylase (or lipase) output.     

Cleft palate and decreased brain γ-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase

In addition to its role as an inhibitory neurotransmitter, γ-aminobutyric acid (GABA) is presumed to be involved in the development and plasticity of the nervous system. GABA is synthesized by glutamic acid decarboxylase (GAD), but the respective roles of its two isoforms (GAD65 and 67) have not been determined. The selective elimination of each GAD isoform by gene targeting is expected to clarify these issues. Recently we have produced GAD65 −/− mice and demonstrated that lack of GAD65 does not change brain GABA contents or animal behavior, except for a slight increase in susceptibility to seizures. Here we report the production of GAD67 −/− mice. These mice were born at the expected frequency but died of severe cleft palate during the first morning after birth. GAD activities and GABA contents were reduced to 20% and 7%, respectively, in the cerebral cortex of the newborn GAD67 −/− mice. Their brain, however, did not show any discernible defects. Previous pharmacological and genetic investigations have suggested the involvement of GABA in palate formation, but this is the first demonstration of a role for GAD67-derived GABA in the development of nonneural tissue.     

Movements of truncated kinesin fragments with a short or an artificial flexible neck

To investigate the role of the neck domain of kinesin, we used optical trapping nanometry to perform high-resolution measurements of the movements and forces produced by recombinant kinesin fragments in which the neck domains were shortened or replaced by an artificial random coil. Truncated kinesin fragments (K351) that contain a motor domain consisting of ≈340 aa and a short neck domain consisting of ≈11 aa showed fast movement (800 nm/s) and 8-nm steps. Such behavior was similar to that of recombinant fragments containing the full-length neck domain (K411) and to that of native kinesin. Kinesin fragments lacking the short neck domain (K340), however, showed very slow movement (<50 nm/s), as previously reported. Joining an artificial 11-aa sequence that was expected to form a flexible random chain to the motor domain (K340–chain) produced normal fast (≈700 nm/s) and stepwise movement. The results suggest that the neck domain does not act as a rigid lever arm to magnify the structural change at the catalytic domain as has been believed for myosin, but it does act as a flexible joint to guarantee the mobility of the motor domain.