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PubMed1995

Modifications of transnasal and transoral stereotactic procedures--technical notes.

Stereotactic transnasal and transoral procedures have been reported by different authors in the past. In this paper, several modifications of these methods are described. The modifications are: transnasal approach to the frontal skull base and suprasellar regions; and transoral approaches to the clivus, the petroclival junction, medial part of the cerebellopontine angle and the lateral mass of C-1. Eleven patients were operated on using these modifications. The procedures were for biopsy and brachytherapy. No complications resulted from the procedures.

Adolescent↗
PubMed1994

Modification of monoclonal antibody carbohydrates by oxidation, conjugation, or deoxymannojirimycin does not interfere with antibody effector functions.

Site-specific attachment of metal chelators or cytotoxic agents to the carbohydrate region of monoclonal antibodies results in clinically useful immunoconjugates [Doerr et al. (1991) Ann Surg 214: 118, Wynant et al. (1991) Prostate 18: 229]. Since the capacity of monoclonal antibodies (mAb) to mediate tumor cell lysis via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) may accentuate the therapeutic effectiveness of immunoconjugates, we determined whether site-specific modification of mAb carbohydrates interfered with these functions. The chemical modifications examined consisted of periodate oxidation and subsequent conjugation to either a peptide linker/chelator (GYK-DTPA) or a cytotoxic drug (doxorubicin adipic dihydrazide). mAb-associated carbohydrates were also modified metabolically by incubating hybridoma cells in the presence of a glucosidase inhibitor deoxymannojirimycin to produce high-mannose antibody. All four forms (unaltered, oxidized, conjugated and high-mannose) of murine mAb OVB-3 mediated tumor cell lysis via CDC. Similarly, equivalent ADCC was observed with native and conjugated forms of mAb OVB-3 and EGFR.1. ADCC was achieved with different murine effector cells such as naive (NS), poly (I*C)- and lipopolysaccharide-stimulated (SS) spleen cells, or Corynebacterium-parvum-elicited peritoneal cells (PEC). All murine effector cell types mediated tumor cell lysis but differed in potency such that PEC > SS > NS. Excellent ADCC activity was also demonstrable by human peripheral blood mononuclear cells with OVB-3-GYK-DTPA and high-mannose OVB-3 mAb. ADCC activity was detectable in vivo: both native and conjugated OVB-3 inhibited growth of OVCAR-3 xenografts in nude mice primed with C. parvum. In conclusion, modification of mAb carbohydrates did not compromise their in vivo or in vitro biological functions. Therefore, combination therapy using immunomodulators to enhance the effector functions of site-specific immunoconjugates could be seriously contemplated.

1-Deoxynojirimycin↗
PubMed1977

Integration of a behavior modification program into a traditionally oriented residential treatment center for children.

The historical background and early contributions of the Emma Pendleton Bradley Hospital, the first psychiatric hospital for children in the United States, are described. The focus of this report is on the incorporation of the treatment modality of behavior modification into this traditional psychoanalytically oriented program. Beginning with exploratory studies in the mid-1960s, in recent years within the residential center there has been a separate Autistic Unit, in which the major treatment strategy is consistent application of behavior modification principles and programs. Changes that have occurred in the course of developing the behavior modification program are discussed to show some of the positive and negative aspects of introducing such a radical change into a traditional setting. Case studies are included to reveal both the failures and the successes that have been encountered in treating psychotic children with either psychotherapy or behavior therapy. Description of the current status of the program shows that treatment is comprehensive, including psychodynamic and behavioral approaches, medication when warranted, and special education. The role of parents in the program is now very different from that ascribed to them in traditional psychoanalytically guided treatment.

Activities of Daily Living↗
PubMed1995

Prevention of biofilm formation by polymer modification.

Bacterial biofilm formation on synthetic polymers plays an important role in industry and in modern medicine, leading, for example, to difficult-to-treat infections caused by colonized foreign bodies. Prevention of biofilm formation is a necessary step in the successful prophylaxis of such infections. One approach is to inhibit bacterial adherence by polymer surface modification. We have investigated polymer modification by glow discharge treatment in order to study the influence of the modified surface on bacterial adherence. Surface roughness, surface charge density and contact angles of the modified polymers were determined and related to the adherence of Staphylococcus epidermidis KH6. Although no influence of surface roughness and charge density on bacterial adherence was noticed, a correlation between the free enthalpy of adhesion (estimated from contact angle measurements) and adherence was observed. There seems to exist a certain minimum bacterial adherence, independent of the nature of the polymer surface. Modified polymers with negative surface charge allow for bacterial adherence close to the adherence minimum. These polymers could be improved further by the ionic bonding of silver ions to the surface. Such antimicrobial polymers are able to prevent bacterial colonization, which is a prerequisite for biofilm formation. It is suggested that modification of polymers and subsequent surface coupling of antimicrobials might be an effective approach for the prevention of bacterial biofilm formation.

Anti-Infective Agents, Local↗
PubMed1989

SH-1 modification of rabbit myosin interferes with calcium regulation.

The reactive thiol of the myosin head, SH-1, can be selectively labelled in glycerinated rabbit muscle fibres. This residue has been used as an attachment site for either fluorescent or spectroscopic probes which report on head movements and orientations in various functional states of muscle. We have specifically modified SH-1 in vitro, using purified rabbit myosin and conditions similar to those employed in the labelling of muscle fibres (low ionic strength [40 mM NaCl] at 4 degrees C), with stoichiometric amounts of either [14C]-iodoacetamide, 5-(2[iodoacetyl)amino)ethyl) aminonaphthalene-1- sulphonic acid (IAEDANS), or 4-(2-iodoacetamido-2,2,6,6-tetramethyl piperidinooxyl (IASL). The specificity of modification was determined by measuring the well-defined alterations in the high salt ATPase activities of myosin and by localizing both IAAm and IAEDANS to the 20-kDa C-terminal subfragment 1 (S1) which contains SH-1. The low ionic strength actin-activated Mg2+-ATPase of SH-1-modified rabbit myosin was measured in the presence of the thin filament regulatory, complex, troponin-tropomyosin. A significant increase in this activity in the absence of calcium, concomitant with a decrease in activity in the presence of calcium, was observed as the extent of SH-1 modification was incrementally increased from zero to one mole of label bound per mole of SH-1. The elevated myosin Mg2+-ATPase, which results from SH-1 modification, does not account for the increased actin-activated Mg2+-ATPase in resting conditions (i.e. in the absence of calcium).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Chemical modification of Staphylococcus aureus alpha-toxin by diethylpyrocarbonate: role of histidines in its membrane-damaging properties.

Staphylococcus aureus alpha-toxin causes cell damage by forming an amphiphilic hexamer that inserts into the cell membrane and generates a hydrophilic pore. To investigate the role of the three histidine residues of this toxin we modified them with diethylpyrocarbonate, obtaining N-carbethoxy-histidine whose appearance may be followed spectrophotometrically. Despite the statistical nature of random chemical modification, it was possible to establish that modification of any one of the three histidines was enough to impair alpha-toxin activity on red blood cells and platelets. Two out of three histidines were essential for the interaction of the toxin with model membranes such as lipid vesicles and planar bilayers. Loss of lytic activity in both natural and model membranes was due both to defective binding and to defective oligomerization. When alpha-toxin hexamers inserted into lipid vesicles were assayed for chemical modifiability two histidines per monomer were found to be protected from diethylpyrocarbonate modification, whereas only one was protected after delipidation of the oligomer with a detergent. A possible model for the role of each histidine in the monomer is presented.

Animals↗
PubMed1984

Effects of chemical modification of carboxyl groups on the voltage-clamped nerve fiber of the frog.

Voltage-clamped single nerve fibers of the frog Rana esculenta were treated with the carboxyl group activating reagent N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in the presence of different primary amines and without added amine. Carboxyl groups form stable amide bonds with primary amines in the presence of EEDQ. EEDQ treatment reduced the sodium current considerably and irreversibly, regardless of the presence of a primary amine in the Ringer's solution. The potassium current was also reduced. After modification the reduced sodium currents inactivated slowly and incompletely. The descending branch of the sodium current-voltage relation, INa(E), was shifted along the voltage axis in the depolarizing direction. The size of the shift was strongly dependent on the amine present during modification with EEDQ. The voltage-dependence of sodium inactivation, h infinity (E), was shifted to more positive values of membrane potential by EEDQ in the presence of ethylenediamine (11 mV) and glucosamine (3 mV). In contrast, a small shift to more negative potentials occurred in the presence of taurine (-3 mV) or without the addition of an amine (-2 mV). A tenfold increase of the calcium concentration still shifted the INa(E) and h infinity (E) curves of the chemically modified fibers. However, these shifts were smaller than those observed on untreated fibers. The currents remaining after the modification were completely blocked by tetrodotoxin; no change of the reversal potential occurred.

Animals↗
PubMed1996

Chemical modification of cationic residues in toxin a from king cobra (Ophiophagus hannah) venom.

The cationic groups of arginine and lysine residues in alpha-neurotoxin, Toxin a, isolated from king cobra (Ophiophagus hannah) venom were subjected to modification with trinitrobenzene sulfonate (TNBS) and p-hydroxyphenylglyoxal (HPG), respectively. The trinitrophenylated (TNP) derivatives of Toxin a at Lys-10, 56, or 71 showed approximately 25% residual lethality, and modifications on Lys-10 and 56 or Lys-10 and 50 resulted in a decrease of lethality by 84% and 86%, respectively. Modifications on Arg-34, 37, and 70 and Arg-34, 37, and 72 in Toxin a caused a decrease in lethality by 92% and 93%, respectively, and it almost completely lost its lethality and binding activity to nicotinic acetylcholine receptor (nAChR) when all four arginine residues were modified. These results indicate that in addition to the cationic residues on loop II (Arg-34, 37), loop III (Lys-50, 56), and the C-terminal tail (Arg-70, 72; Lys-71), Lys-10 on loop I is also related to the neurotoxicity of Toxin a.

Amino Acid Sequence↗
PubMed1996

Chemical modification of notexin from Notechis scutatus scutatus (Australian tiger snake) venom with pyridoxal-5'-phosphate.

Notexin from Notechis scutatus scutatus snake venom was subjected to Lys modification with pyridoxal 5'-phosphate (PLP), and one major modified derivative was purified on a cation-exchanger SP-8HR column. The results of amino acid analysis and sequence determination revealed that only 2 Lys residues at positions 82 and 115 out of 11 Lys residues in notexin were modified. The incorporation of PLP into the protein was accompanied by the loss of 53% lethal toxicity, but the modified notexin showed an about 1.2-fold increase in enzymatic activity. However, the secondary structure of the toxin molecule did not significantly change after modification with PLP as revealed by the CD spectra, and the antigenicity of PLP derivative remained unchanged. The modified derivative retained its affinity for Ca2+, indicating that the modified Lys residues did not participate in Ca2+ binding. These results indicate that modification of Lys residues causes a differential effect on the enzymatic activity and lethal toxicity of notexin, and suggest that notexin might possess two functional sites, one responsible for the catalytic activity and the other associated with its lethal effect.

Amino Acid Sequence↗
PubMed1996

Modifications of diazepam binding inhibitor and peripheral benzodiazepine receptors in the lymphocytes of epileptic patients.

Recent experimental evidence has suggested that peripheral benzodiazepine receptors (PBR) may play a role in epilepsy and antiepileptic drug action. Since PBR are also present in circulating lymphocytes, and may interact with anticonvulsant drugs, this study was designed to look for possible modifications of these receptors and their endogenous ligand diazepam binding inhibitor (DBI) in the lymphocytes of epileptic patients treated with various drugs. PBR levels were 50% to 80% higher in patients treated with carbamazepine, phenobarbital and valproic acid than in controls and untreated epileptics. DBI levels were significantly increased in the lymphocytes of untreated patients, and showed only a slight further increase after anticonvulsant therapy. The possibility that PBR and DBI modifications in the lymphocytes of epileptic patients may be linked to the immunological alterations reported in these patients and/or may represent possible markers of neurochemical modifications in the central nervous system is discussed.

Adolescent↗
PubMed1987

Dynamic modifications of the popliteal arterial axis in the sagittal plane during flexion of the knee.

The authors have studied, on the basis of purely radiologic data, the modifications of the popliteal arterial axis during flexion of the knee. They note the appearance in the sagittal plane of very marked flexures of the upper part of the artery, while the lower part describes a harmonious curve. These modifications take place between two fixed points: a cranial fixed point, represented by the origin of the descending artery of the knee, and a caudal fixed point represented by the origin of the anterior tibial artery. The pathologic importance of these modifications of the course of the artery should not be underestimated when obtaining revascularization by means of an arterial prosthesis.

Humans↗
PubMed1997

Eukaryotic ribosomal RNA: the recent excitement in the nucleotide modification problem.

Eukaryotic ribosomal RNA (rRNA) contains numerous modified nucleotides: about 115 methyl groups and some 95 pseudouridines in vertebrates; about 65 methyl groups and some 45 pseudouridines in Saccharomyces cerevisiae. All but about ten of the methyl groups are ribose methylations. The remaining ten are on heterocyclic bases. The ribose methylations occur very rapidly upon the primary rRNA transcript in the nucleolus, probably on nascent chains, and they appear to play an important role in ribosome maturation, at least in vertebrates. All of the methyl groups occur in the conserved core of rRNA. However, there is no consensus feature of sequence or secondary structure for the methylation sites; thus the nature of the signal(s) for site-specific methylations had until recently remained a mystery. The situation changed dramatically with the discovery that many of the ribose methylation sites are in regions that are precisely complementary to small nucleolar RNA (snoRNA) species. Experimental evidence indicates that structural motifs within the snoRNA species do indeed pinpoint the precise nucleotides to be methylated by the putative 2'-O-methyl transferase(s). Regarding base methylations, the gene DIM1, responsible for modification of the conserved dimethyladenosines near the 3' end of 18S rRNA, has been shown to be essential for viability in S. cerevisiae and is suggested to play a role in the nucleocytoplasmic transport of the small ribosomal subunit. Recently nearly all of the pseudouridines have also been mapped in the rRNA of several eukaryotic species. As is the case for ribose methylations, most pseudouridine modifications occur rapidly upon precursor rRNA, within core sequences, and in a variety of local primary and secondary structure environments. In contrast to ribose methylation, no potentially unifying process has yet been identified for the enzymic recognition of the many pseudouridine modification sites. However, the new data afford the basis for a search for any potential involvement of snoRNAs in the recognition process.

Adenosine↗
PubMed1978

Fatty acid metabolism in L1210 murine leukemia cells: differences in modification of fatty acids incorporated into various lipids.

L1210 leukemia cells can utilize all of the main fatty acids that normally are present in the ascites fluid in which they grow. This finding is consistent with the view that L1210 cells derive most of their fatty acids from the ascites fluid. From 80--90% of each fatty acid was incorporated into cell lipids without structural modification, suggesting that the lipid composition of these cells can be altered by changing the type of fatty acids to which they are exposed. Most importantly, the palmitate that was subsequently incorporated into total cell phospholipids was elongated and desaturated somewhat more than that incorporated into triglycerides. This difference was due primarily to more extensive modification of the palmitate incorporated into the ethanolamine phosphoglycerides fraction. Although there was no difference between total phospholipids and triglycerides with linoleate, more of the linoleate incorporated into ethanolamine phosphoglycerides was elongated and further desaturated than that incorporated into choline phosphoglycerides and triglycerides. These findings indicate fatty acids incorporated into various cell lipid fractions are not structurally modified to the same extent. There appears to be greater modification of fatty acid used for ethanolamine phosphoglyceride synthesis as compared with triglyceride and choline phosphoglyceride synthesis.

Animals↗
PubMed1990

Modification of phospholipid polar head group with monomethylethanolamine and dimethylethanolamine decreases cholesteryl ester and triacylglycerol synthesis in cultured human fibroblasts.

Modification of the phospholipid polar head group was achieved by supplementation of the growth medium of cultured human fibroblasts with the choline analogues monomethylethanolamine (ME) or dimethylethanolamine (DE) at a concentration of 80-200 micrograms/mL for 48 hr. The maximum concentration of phosphatidylmonomethylethanolamine (PME) or phosphatidyldimethylethanolamine (PDE) reached without affecting the phospholipid/protein ratio was about 45% of total phospholipids. Incorporation of oleic acid into cholesteryl esters and triacylglycerols was markedly inhibited after supplementation with ME or DE, and accounted for 60% and 40% of controls, respectively, at 200 micrograms/mL, whereas incorporation into phospholipids was not affected. AcylCoA:cholesterol acyltransferase (ACAT) and diacylglycerol acyltransferase (DGAT) activities measured on cell-free extracts appeared to be decreased also by phospholipid polar head group modification, whereas the overall phospholipid acyltransferase activity remained unchanged. The intracellular content of cholesteryl esters and triacylglycerols, determined by the isotopic equilibrium method with radioactive cholesterol and glycerol, was found to be diminished to 50-60% and 40-50% of controls, respectively, after supplementation with the choline analogues. The study showed that modification of the phospholipid polar head group affects the activity of membrane-bound enzymes involved in the metabolism of neutral lipids.

Acyltransferases↗
PubMed1981

Zero-cost modification of bright field microscopes for imaging phase gradient on cells: Schlieren optics.

A simple, zero-cost, reversible modification of a bright field microscope permits visualization of phase gradients in cells by transmitted illumination, yielding a Nomarski-like effect. This modification, based on schlieren optics, is simultaneously compatible with high-aperture epi-illumination fluorescence excitation. For many objectives that are intended for use in fluorescence work, but are unavailable in phase contrast versions, the modification provides a simple means for locating cells in culture with good image contrast and resolution.

Animals↗
PubMed1994

Overproduction of the Hsd subunits leads to the loss of temperature-sensitive restriction and modification phenotype.

The genes hsdM and hsdS for M. EcoKI modification methyltransferase and the complete set of hsdR, hsdM and hsdS genes coding for R. EcoKI restriction endonuclease, both with and without a temperature-sensitive (ts) mutation in hsdS gene, were cloned in pBR322 plasmid and introduced into E. coli C (a strain without a natural restriction-modification (R-M) system). The strains producing only the methyltransferase, or together with the endonuclease, were thus obtained. The hsdSts-1 mutation, mapped previously in the distal variable region of the hsdS gene with C1 245-T transition has no effect on the R-M phenotype expressed from cloned genes in bacteria grown at 42 degrees C. In clones transformed with the whole hsd region an alleviation of R-M functions was observed immediately after the transformation, but after subculture the transformants expressed the wild-type R-M phenotype irrespective of whether the wild-type or the mutant hsdS allele was present in the hybrid plasmid. Simultaneous overproduction of HsdS and HsdM subunits impairs the ts effect of the hsdSts-1 mutation on restriction and modification.

DNA Restriction Enzymes↗
PubMed2006

Modification of alternative splicing of Bcl-x pre-mRNA in bladder cancer cells.

To modify the splicing pattern of Bcl-x and compare the effect of this approach with that of the antisense gene therapy in BIU-87 cell line of bladder cancer, by using 5'-Bcl-x AS to target downstream alternative 5'-Bcl-x splice site to shift splicing from Bcl-xL to Bcl-xS and 3'-Bcl-x AS antisense to the 3'-splice site of exon III in Bcl-x pre-mRNA to down regulation of Bcl-xL expression, the inhibitory effects on cancer cells by modification of alternative splicing and antisense gene therapy were observed and compared by microscopy, MTT Assay, RT-PCR, FACS, Western bloting and clone formation. The growth of cells BIU-87 was inhibited in a dose- and time-dependent manner. Its inhibitory effect began 12 h after the exposure, reaching a maximum value after 72h. The number of cells decreased in S phase and the number increased in G1 phase. The ability to form foci was reduced and the antisense gene therapy was approximately half as efficient as modification of alternative splicing in inducing apoptosis. It is concluded that modification of splicing pattern of Bcl-x pre-mRNA in bladder cancer cell BIU-87 is better than antisense gene therapy in terms of tumor inhibition.

Alternative Splicing↗
PubMed1989

Correlations between age and rat dermis modifications. Ultrastructural-morphometric evaluations and lysyl oxidase activity.

The extracellular matrix is a complex, integrated macromolecular system which plays a crucial role in the economy of each organ. In this study we focused our attention on the correlations between age and rat skin dermis. The latter was chosen as a model of the connective tissue, and was analyzed by means of electron microscopy and by measurement of the activity of lysyl oxidase, the enzyme involved in collagen and elastin crosslink formation. Ultrastructural and morphometric evaluations associated to body weight growth, showed a progressive increase in the amounts of extracellular components and a progressive reduction in the cell density. Skin from adult animals appeared characterized by a well organized matrix; by contrast, in old rats, we observed several degenerative features such as the disorganization of collagen bundles, the vacuolization of elastic fibers, and the atrophy of the mesenchimal cells. Morphometric evaluations in old animals showed a slight but significant reduction in the percentage of the total collagen measured, a fair stability in the area occupied by the elastin fibers, and an increase of the apparently non-structured matrix. The fact that lysyl oxidase activity was diminished in old rats does not corroborate the observation by several authors that increased collagen insolubility is a consequence of higher intra- and intermolecular crosslinking. This would suggest that other chemical modifications, such as crosslink oxidation or non enzymatic glycosylation, might be involved during the aging of connective tissue. The qualitative and quantitative modifications observed at all ages illustrate the correlation between connective tissue modifications and structural and/or functional properties of the skin.

Age Factors↗