Different patterns of G/T and A/C mismatch repair in simian cells correspond to the specificity of a mismatch binding protein isolated from simian and HeLa cells.

The two transition mispairs G/T and A/C are corrected with different efficiencies and specificities in CV-1 African green monkey kidney cells. G/T mispairs are corrected with 99% efficiency and almost always in favor of guanine, while A/C mispairs exhibit a 31% uncorrected sector and are otherwise randomly corrected. The higher correction efficiency and bias for the G/T mispair can be correlated with the substrate specificity of a protein, found in HeLa and CV-1 cell extracts, that binds selectively to oligonucleotide duplexes containing G/T mispairs. No binding can be detected to duplexes containing other mispairs, or to homoduplexes.

[Conversion laparatomies during cholecystectomies under laparoscopy. Apropos of 285 consecutive cholecystectomies]. / Les laparotomies de conversions au cours des cholécystectomies par laparoscopie. A propos de 285 cholécystectomies consécutives.

Retrospective analysis of a consecutive series of 285 cholecystectomies carried out by laparoscopy showed that 47 patients (17.5%) required conversion laparotomy. In 55% of these cases the conversion was due to difficulty in dissecting the gallbladder or cystic duct. Peri-operative cholangiography should be performed routinely, not only to verify the vacuity of the common bile duct (13% of the conversions) but, more particularly, to ensure the integrity of the principal biliary pathway during the dissection (8.5% of the conversions). Cholecystectomy under celioscopy is a proven and safe technique, on the condition that all stages of classical surgery can be carried out under good conditions.

[Results of laparoscopic cholecystectomy for acute cholecystitis in elderly patients]. / Résultats de la cholécystectomie coelioscopique pour cholécystite aiguë chez le sujet âgé.

OBJECTIVES: The aim of this retrospective study was to evaluate the feasibility and the morbidity of laparoscopic cholecystectomy for acute cholecystitis in elderly patients. METHODS: Among 891 consecutive patients who underwent cholecystectomy, 151 had acute cholecystitis. Fifty three patients of > or = 70 years of age (group 1) were compared to 98 younger patients (group 2). Analysis was made in "intention to treat" so directly open cholecystectomies during the same period were also included. RESULTS: Elderly patients had a lower success rate of laparoscopic treatment (52.8% versus 70.4%; p < 0.05). This difference was due to higher rate of directly open cholecystectomy in the elderly (17% versus 2%). There was no difference between both groups in conversion rate to laparotomy (30.2% versus 26.5%). Surgical morbidity was 7.5% in group 1 and 4% in group 2 (NS). General complications were more frequent in the elderly (p < 0.05). Five patients in group 1 (9.4%) died of general complications of which 3 were operated on directly by open cholecystectomy. There was no mortality in group 2. CONCLUSION: Acute cholecystitis in the elderly remains a severe disease in which laparoscopic treatment is only possible in about fifty percent.

In situ activation of human erythrocyte prolidase: potential for enzyme replacement therapy in prolidase deficiency.

Deficiency of prolidase is frequently associated with skin lesions and mental retardation. Biochemically, the condition is marked by iminodipeptiduria. We have investigated the feasibility of using donor erythrocytes to replace the deficient enzyme. Prolidase occurs in erythrocytes in an inactive form. If erythrocytes are incubated overnight at 37 degrees C in the presence of 1 mM MnCl2, the intracellular Mn++ concentration increases from 0.014 to 2.04 micrograms/ml. As a consequence, the activity of prolidase in hemolysates increases to 159 mumol glycyl-L-proline hydrolyzed/h/ml compared to 5 mumol/h/ml for hemolysates of cells incubated in the absence of Mn++. Hydrolysis of glycyl-L-proline by intact erythrocytes is reduced by the slow rate of iminodipeptide transport into the cell; however, intact cells hydrolyzed this substrate at a rate 10-20 times faster after preincubation with MnCl2. After exogenous MnCl2 is removed from the storage buffer, high levels of erythrocyte prolidase activity persist for at least 13 days. The kinetic parameters for intact activated erythrocyte-catalyzed hydrolysis of glycyl-L-proline have been estimated. These values predict that donor erythrocytes, activated with Mn++ before transfusion could play a significant role in the recovery of proline from dietary sources of iminodipeptides in patients with prolidase deficiency.

A human 200-kDa protein binds selectively to DNA fragments containing G.T mismatches.

G.T mispairs, the sole mismatch type that can arise in "resting" mammalian DNA (through spontaneous hydrolytic deamination of 5-methylcytosine), are corrected in vivo with high efficiency and mostly to a G.C. We identified a protein factor, present in HeLa cell extracts, that binds selectively to DNA substrates containing this mismatch. The partially purified protein was shown by gel-filtration chromatography and UV cross-linking experiments to have an apparent molecular mass of 200 kDa. Its binding to G.T mispairs was not influenced by sequences flanking the mismatch, but methylation of guanines either within the mismatch itself or in its immediate vicinity abolished the formation of the protein-DNA complex. The protein appears to lack both endo- and exonuclease activities and requires neither magnesium nor zinc nor ATP for binding. We discuss the possible role of this protein in a repair pathway, which helps mammalian cells counter the mutagenic effect of the hydrolytic deamination of 5-methylcytosine.