Plasticity and Slip System of Plate-Shaped Crystals of L-Lysine Monohydrochloride Dihydrate

Purpose. To identify the slip system of L-lysine monohydrochloride dihydrate (LH) and to relate it to the deformation behavior under uniaxial compression. Methods. The indentation hardness of the {100} face and the indentation moduli of the {100} and {011} faces of plate-shaped single crystals of LH (LHP) were determined using Knoop and Berkovich indenters, respectively. The deformation behavior during uniaxial compression was studied by the punch-stress vs. punch-displacement profile and by electron microscopy of the deformed crystals within cracked compacts. Results. The different indentation (elastic) moduli of the {100} and {011} faces of the crystals are consistent with the molecular packing density along these planes and suggest anisotropy. The existence of the {001} <100> slip system is proposed based on the pattern of changing indentation hardness with varying orientation of the Knoop indenter. A jagged uniaxial compression profile suggests deformation by mechanical twinning and not simple slip. The hypothesis of deformation by mechanical twinning is supported by the appearance of twin bands along the crystal faces as observed by electron microscopy of the cracked compacts. Conclusions. During compression, most LHP crystals have their {100} faces oriented normal to, or inclined to, the compression axis, thereby facilitating plastic deformation along the {001} <100> slip system by mechanical twinning. Due to the low attachment energy between them, the {001} planes can also act as cleavage planes. This study demonstrates that knowledge of the crystal structure and slip systems can be used to model the tableting and compaction behavior of molecular crystals, such as LH.     

Functional map and domain structure of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor

Little is known about the large ectodomain of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor (HGF/SF). Here, we establish by deletion mutagenesis that the HGF/SF and heparin-binding sites of MET are contained within a large N-terminal domain spanning the alpha-chain (amino acids 25-307) and the first 212 amino acids of the beta-chain (amino acids 308-519). Neither the cystine-rich domain (amino acids 520-561) nor the C-terminal half of MET (amino acids 562-932) bind HGF/SF or heparin directly. The MET ectodomain, which behaves as a rod-shaped monomer with a large Stokes radius in solution, binds HGF/SF in the absence or presence of heparin, and forms a stable HGF/SF-heparin-MET complex with 1:1:1 stoichiometry. We also show that the ligand-binding domain adopts a beta-propeller fold, which is similar to the N-terminal domain of alphaV integrin, and that the C-terminal half contains four Ig domains (amino acids 563-654, 657-738, 742-836, and 839-924) of the unusual structural E set, which could be modeled on bacterial enzymes. Our studies provide 3D models and a functional map of the MET ectodomain. They have broad implications for structure-function of the MET receptor and the related semaphorin and plexin proteins.     

Pericholecystic fistula: a study of 64 cases

Spontaneous biliary fistulas are found quite often. Although previously considered as a contraindication to laparoscopic surgery, they are now being treated laparoscopically with all its advantages. Of 8015 patients undergoing laparoscopic cholecystectomy, 64 patients were diagnosed preoperatively; conversion to open surgery was required in 8 patients. The highest incidence of pericholecystic fistulas was found in the >60-year age group. The postoperative stay ranged from 3 to 8 days. All the patients were well at follow up. Laparoscopic management of pericholecystic fistulas is possible with low morbidity and no mortality.     

Antineoplastic activity of Solidago virgaurea on prostatic tumor cells in an SCID mouse model

Solidago virgaurea (goldenrod) has traditionally been used as an anti-inflammatory herbal medicine for the treatment of various symptoms, including prostatic diseases. The plant has also been reported to have antibacterial, spasmolytic, and carminative properties. During the course of our screening for antineoplastic activities in various herbal plants, we found that the extract of S. virgaurea exhibits strong cytotoxic activities on various tumor cell lines. The active component mostly resides in the leaves of the plant and is soluble in water. When the extract was fractionated by a Sephadex G-100 column, the active fraction corresponded to a molecular weight of approximately 40,000. This cytotoxic activity is effective on various tumor cell lines, including human prostate (PC3), breast (MDA435), melanoma (C8161), and small cell lung carcinoma (H520). To examine the effect of the cytotoxic activity on tumor cells in vivo, we used the rat prostate cell line (AT6.1) and an SCID mouse model. AT6.1 cells were injected into the flank of SCID mice, and then the G-100 fraction of S. virgaurea was administered intraperitoneally or subcutaneously every 3 days. The size of the tumor was measured for up to 25 days. The growth of the tumor was significantly suppressed by the G-100 fraction at 5 mg/kg without any apparent side effects. Therefore, S. virgaurea is considered to be promising as an antineoplastic medicine with minimal toxicities.     

Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft

We have demonstrated previously that ectopic expression of a soluble betaglycan, also known as transforming growth factor (TGF) beta type III receptor, can suppress the malignant properties of human carcinoma cells by antagonizing the tumor-promoting activity of TGF-beta (A. Bandyopadhyay et al., Cancer Res., 59: 5041-5046, 1999). In the current study, we investigated the potential therapeutic utility of a recombinant preparation of human and rat soluble betaglycan (sBG). Purified recombinant human sBG showed similar properties to its rat counterpart (M. M. Vilchis-Landeros et al., Biochem J., 355: 215-222, 2001). It bound TGF-beta with high affinity and isoform selectivity and neutralized the activity of TGF-beta(1) in two bioassays. Peritumoral (50 micro g/tumor, twice a week) or i.p. (100 micro g/animal, every alternate day) injection of sBG into human breast carcinoma MDA-MB-231 xenograft-bearing athymic nude mice significantly inhibited the tumor growth. The administration of sBG also reduced metastatic incidence and colonies in the lungs. The tumor-inhibitory activity of sBG was found to be associated with the inhibition of angiogenesis. Systemic sBG treatment significantly reduced tumor microvessel density detected with histological analyses and CD-31 immunostainings, as well as tumor blood volume measured with hemoglobin content. In an in vitro angiogenesis assay, treatment with the recombinant sBG significantly reduced the ability of human dermal microvascular endothelial cells to form a capillary tube-like structure on Matrigel. These findings support the conclusion that sBG treatment suppresses tumor growth and metastasis, at least in part by inhibiting angiogenesis. As such, it could be a useful therapeutic agent to antagonize the tumor-promoting activity of TGF-beta.     

Benign laryngeal lesions — a clinicopathological study of eleven years and a case report of pleomorphic lipoma

In a retrospective cohort study, conducted in Department of Oto-Rhinolaryngology, Head and Neck Surgery, M.LX Medical College, Allahabad from January 1989 to December 1999, 81 benign laryngeal lesions were evaluated. Majority (69, 85.2%) presented with hoarseness of voice and stridor was the presenting complaint in 12 ( 14.8%) cases. Vocal cord polyp (33, 40.7%) dominated the non-neoplastic group, while squamous papilloma (18, 22.4%) was the most common neoplastic lesion. Adult unset multiple papiUoma of unilateral vocal cord (4, 4.9%) was an unexpected finding in our series. A rare case of pleomorphic lipoma of larynx in a 68-year-old male patient along with its CT characteristics has been presented. Conservative microlaryngeal surgery offered the most satisfactory mode of treatment without any mortality and with minimal recurrence.     

Benign laryngeal lesions — a clinicopathological study of eleven years and a case report of pleomorphic lipoma

In a retrospective cohort study, conducted in Department of Oto-Rhinolaryngology, Head and Neck Surgery, M.LX Medical College, Allahabad from January 1989 to December 1999, 81 benign laryngeal lesions were evaluated. Majority (69, 85.2%) presented with hoarseness of voice and stridor was the presenting complaint in 12 ( 14.8%) cases. Vocal cord polyp (33, 40.7%) dominated the non-neoplastic group, while squamous papilloma (18, 22.4%) was the most common neoplastic lesion. Adult unset multiple papiUoma of unilateral vocal cord (4, 4.9%) was an unexpected finding in our series. A rare case of pleomorphic lipoma of larynx in a 68-year-old male patient along with its CT characteristics has been presented. Conservative microlaryngeal surgery offered the most satisfactory mode of treatment without any mortality and with minimal recurrence.     

The role of antioxidant activity of Phyllanthus emblica fruits on prevention from indomethacin induced gastric ulcer

Pretreatment with the butanol extract of the water fraction of Phyllanthus emblica fruits at the dose of 100 mg/kg body-weight, orally administered to rats for 10 consecutive days, was found to enhance secretion of gastric mucus and hexosamine (P<0.001) in the indomethacin induced ulceration of rats. The morphological observations also supported a protective effect of the stomach wall from lesion. The indomethacin treatment of the premedicated animals with the drug hardly affected either the malondialdehyde (MDA) or superoxide dismutase (SOD) level in gastric tissue while the ulcerative agent itself significantly enhanced both the levels. An antioxidant property appears to be predominantly responsible for this cytoprotective action of the drug.