The region Ser333-Arg356 of the alpha-chain of human C4b-binding protein is involved in the binding of complement C4b

Human C4b-binding protein (C4BP) functions as a cofactor to factor I in the degradation of C4b and accelerates the decay rate of the C4b2a complex. In this study we describe a monoclonal antibody directed against the alpha-chain of C4BP that inhibits the binding of C4b to C4BP. In order to identify the structural domain of the alpha-chain of C4BP that interacts with C4b, tryptic fragments of C4BP were generated. Amino acid sequence analysis of the fragments revealed that the residues Ser333-Arg356 of the alpha-chain of C4BP contain the epitope of this antibody, and as a consequence, that this part of the alpha-chain of C4BP is likely to be involved in the interaction with C4b.     

Late onset peripheral seronegative spondyloarthropathy: report of two additional cases

Two more cases of late onset peripheral seronegative spondyloarthropathy (SpA) are reported. Like the patients reported by Dubost and Sauvezie, they had extensive pitting edema of the lower limbs, constitutional symptoms, elevated erythrocyte sedimentation rate and minimal involvement of the axial skeleton with marked signs of diffuse idiopathic skeletal hyperstosis.     

DNA analysis in hepatoblastoma by flow and image cytometry

BACKGROUND: In several types of tumors, including hepatocellular carcinoma, prognosis could be correlated with DNA ploidy. Few studies have been performed on hepatoblastoma with contradictory results. METHODS: Twenty-nine cases of nonpretreated hepatoblastoma were studied with flow cytometry and image cytometry for DNA index and proliferation index using paraffin-embedded tissue. RESULTS: Twenty-three (79.9%) tumors were diploid, and 6 (20.7%) were aneuploid (hyperdiploid). Patients with diploid tumors were younger than those with aneuploid tumors. With regard to stage, diploid tumors were almost equally distributed among stages (tumor, lymph node metastases, distant metastases), whereas aneuploid tumors tended to occur in higher stages (tumor, lymph node metastases, distant metastases). Diploid tumors had clearly a better prognosis than aneuploid tumors, although the difference was not statistically significant (flow cytometry, P = 0.06; image cytometry, P = 0.16). A more favorable prognosis was also noted for hepatoblastomas with low-proliferation index (< or = 7%), but the difference from tumors with high-proliferation index (> 7%) again was not statistically significant (P = 0.16). CONCLUSIONS: Although no statistically significant differences in prognosis between hepatoblastomas with diploid and aneuploid DNA content, respectively, were found, there is a clear tendency that diploid hepatoblastomas behave more favorably. The same is true for hepatoblastomas with low-proliferation index.     

ON THE USE OF BUFFER INVENTORIES TO MINIMIZE COSTS WITH AN UNRELIABLE MACHINE

In this paper, we discuss the problem of quality control with an unreliable machine which produces defects at a rate of Λ₀, per unit when in-control and a rate of Lambda; ₁, when out-of-control (where Λ₁ Λ ₀). Every h time periods, we sample n units, count the number of defects, and (using a process based on a Shewart c-chart) test the hypothesis that the machine is in control by comparing the total number of defects to an upper control limit (UCL). More important, we introduce the concept that a buffer inventory which immediately follows the unreliable machine may reduce expected total costs. This buffer serves to delay the movement of items from the unreliable machine to the next stage of the production process. In this way, we can isolate and repair most defective items before they are embedded in a product downstream or sold to customers where repair is more costly. To search for the optimal control policy, we find bounds for n, h, and UCL; given values for these variables, we show how the optimal buffer size can be determined directly. Numerical results illustrate the magnitude of potential savings.     

Indirect field-oriented control of an induction motor in thefield-weakening region

A self-organized field-oriented induction machine controller that addresses problems encountered in the field-weakening region is presented. The field-oriented controller (FOC) is based on model reference adaptive principles but relies on samples of the state of the machine to determine control inputs. The proposed controller is compared with other approaches to field-weakening operation, and the advantages and limitations of each are discussed. Experimental results are presented for the classical and the self-organized approaches to field-weakening operation     

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.     

Structural allograft in two-stage revisions for failed septic hip arthroplasty

We report 11 patients having revision of total hip arthroplasty using massive structural allografts for failure due to sepsis and associated bone loss. All patients had a two-stage reconstruction and the mean follow-up was 47.8 months (24 to 72). Positive cultures were obtained at the first stage in nine of the 11 patients, with Staphylococcus epidermidis being the most common organism. The other two patients had draining sinuses with negative cultures. There was no recurrence of infection in any patient. The mean increase in the modified Harris hip score was 45 and all the grafts appeared to have united to host bone. Two patients required additional procedures, but only one was related to the allograft. Complications included an incomplete sciatic nerve palsy and one case of graft resorption. Our results support the use of massive allografts in failed septic hip arthroplasty in which there is associated bone loss.     

Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis

The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis. The results indicate that the binding of the peptide substrate or peptide inhibitor is entropically driven; i.e., it is characterized by an unfavorable enthalpy and a favorable entropy change, in agreement with a structure-based thermodynamic analysis based upon an empirical parameterization of the energetics. Dissection of the binding enthalpy indicates that the intrinsic interactions are favorable and that the unfavorable enthalpy originates from the energy cost of rearranging the flap region in the protease molecule. In addition, the binding is coupled to a negative heat capacity change. The dominant binding force is the increase in solvent entropy that accompanies the burial of a significant hydrophobic surface. Comparison of the binding energetics obtained for the substrate with that obtained for synthetic nonpeptide inhibitors indicates that the major difference is in the magnitude of the conformational entropy change. In solution, the peptide substrate has a higher flexibility than the synthetic inhibitors and therefore suffers a higher conformational entropy loss upon binding. This higher entropy loss accounts for the lower binding affinity of the substrate. On the other hand, due to its higher flexibility, the peptide substrate is more amenable to adapt to backbone rearrangements or subtle conformational changes induced by mutations in the protease. The synthetic inhibitors are less flexible, and their capacity to adapt is more restricted. The expected result is a more pronounced effect of mutations on the binding affinity of the synthetic inhibitors. On the basis of the thermodynamic differences in the mode of binding of substrate and synthetic inhibitors, it appears that a key factor to understanding resistance is given by the relative balance of the different forces that contribute to the binding free energy and, in particular, the balance between conformational and solvation entropy.