Molecular mechanism of kNBC1–carbonic anhydrase II interaction in proximal tubule cells

We have recently shown that carbonic anhydrase II (CAII) binds in vitro to the C-terminus of the electrogenic sodium bicarbonate cotransporter kNBC1 (kNBC1-ct). In the present study we determined the molecular mechanisms for the interaction between the two proteins and whether kNBC1 and CAII form a transport metabolon in vivo wherein bicarbonate is transferred from CAII directly to the cotransporter. Various residues in the C-terminus of kNBC1 were mutated and the effect of these mutations on both the magnitude of CAII binding and the function of kNBC1 expressed in mPCT cells was determined. Two clusters of acidic amino acids, L⁹⁵⁸DDV and D⁹⁸⁶NDD in the wild-type kNBC1-ct involved in CAII binding were identified. In both acidic clusters, the first aspartate residue played a more important role in CAII binding than others. A significant correlation between the magnitude of CAII binding and kNBC1-mediated flux was shown. The results indicated that CAII activity enhances flux through the cotransporter when the enzyme is bound to kNBC1. These data are the first direct evidence that a complex of an electrogenic sodium bicarbonate cotransporter with CAII functions as a transport metabolon.     

Preparation, characterization, and performance of magnetic iron-carbon composite microparticles for chemotherapy

Magnetic microcarrier particles useful for delivering chemotherapeutic drug molecules are described. The particles are formed by joint deformation of iron and carbon in a ball mill. Physical, chemical, and functional characterization has been carried out on the particles. Physical characteristics include microscopy, particle size analysis (0.5-5 microm), surface area (250 m2/g), water vapor adsorption isotherm (hydrophobic surface), and analysis of the iron-carbon interface by M?ssbauer spectroscopy, X-ray diffraction, and differential thermal analysis. Chemical analysis was used to identify elements in the particles other than carbon and iron. Functional characteristics measured included the particles' ability to adsorb and desorb doxorubicin, cytotoxicity, and their magnetic susceptibility.     

Ca2+ clearance in visual motion-sensitive neurons of the fly studied in vivo by sensory stimulation and UV photolysis of caged Ca2+

In motion-sensitive visual neurons of the fly, excitatory visual stimulation elicits Ca(2+) accumulation in dendrites and presynaptic arborizations. Following the cessation of motion stimuli, decay time courses of the cytosolic Ca(2+) concentration signals measured with fluorescent dyes were faster in fine arborizations compared with the main branches. When indicators with low Ca(2+) affinity were used, the decay of the Ca(2+) signals appeared slightly faster than with high affinity dyes, but the dependence of decay kinetics on branch size was preserved. The most parsimonious explanation for faster Ca(2+) concentration decline in thin branches compared with thick ones is that the velocity of Ca(2+) clearance is limited by transport mechanisms located in the outer membrane and is thus dependent on the neurite's surface-to-volume ratio. This interpretation was corroborated by UV flash photolysis of caged Ca(2+) to systematically elicit spatially homogeneous step-like Ca(2+) concentration increases of varying amplitude. Clearance of Ca(2+) liberated by this method depended on branch size in the same way as Ca(2+) accumulated during visual stimulation. Furthermore, the decay time courses of Ca(2+) signals were only little affected by the amount of Ca(2+) released by photolysis. Thus Ca(2+) efflux via the outer membrane is likely to be the main reason for the spatial differences in Ca(2+) clearance in visual motion-sensitive neurons of the fly.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Comparative Carcinogenicity of 5,5-Diphenylhydantoin with or without Perinatal Exposure in Rats and Mice

Volume 21, Number 2 (1993), in the article "Comparative Carcinogenicityof 5,5-Diphenyihydantoin with or without Perinatal Exposurein Rats and Mice," by R. S. Chhabra, J. R. Bucher, J. K. Haseman,M. R. Elwell, P. J. Kurtz, and B. D. Canton, pages 174–186:Since the publication of the above article, the authors havefound that the feed and estimated DPH consumption data reportedin Tables 2 and 6 were incorrect. The following Tables 2 and6 contain revised feed and DPH consumption data:     

Laparoscopic assisted vaginal hysterectomy: one group's experience

Laparoscopic assisted vaginal hysterectomy (LAVH) has been reported worldwide. We report our experience with LAVH in 51 patients, 23 with the laparoscopic stapling device, 12 with a combination of stapler and bipolar coagulation, and 16 by bipolar coagulation exclusively. No operations were converted to laparotomy, and there were few minor complications. Average operating time was 1 h and 38 min. Hospital stay averaged 2.2 days. Average hospital costs were greater for the stapling devices ($7815.00) compared with bipolar coagulation ($7150.00). Postoperative patient satisfaction was high (96%), with high resolution of the symptoms (94%). We conclude that LAVH is a safe, effective operation in selected cases and may be a valid alternative to abdominal hysterectomy.