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At least 199 records · Page 11Linked to original sources
PubMed1991

A modified procedure for simultaneous extraction and subsequent assay of calcium-dependent and lysosomal protease systems from a skeletal muscle biopsy.

An extraction and assay system was developed for quantifying endogenous muscle proteases from a single 5-g sample. A single extraction buffer was developed for simultaneous extraction of both calcium-dependent proteases (CDP) and cathepsins. Protease activity determined by the modified procedure was compared to standard procedures currently used in our laboratory. The successful use of the modified procedure on muscle biopsies was verified. Activities per gram of ovine longissimus muscle of CDP system components for 50-g standard and 5-g modified procedures were not different (P greater than .05) for CDP-I (1.16 vs 1.08), CDP-II (.89 vs 1.03), or CDP inhibitor (2.34 vs 2.32), respectively. Activities of cathepsins per gram of muscle for standard and modified procedures were higher (P less than .05) for the modified procedure (cathepsins B + L, 202.0 vs 309.8), but not different (P greater than .05) for cathepsin B (76.6 vs 98.8). Cystatin-like activity was not different (P greater than .05; 3.4 vs 3.2). To test the effect of location within the longissimus muscle on protease activities, 5 g of longissimus muscle was removed immediately postmortem from each of six locations from each side of three steer carcasses. Location within the longissimus muscle had no effect (P greater than .05) on the protease activities measured. Protease activities determined on bovine longissimus muscle biopsies with the modified procedure were similar to immediate postmortem activities. These data verify that the modified procedure was as able to quantify endogenous muscle proteases as the standard procedures and could be used on muscle biopsies. This procedure should be useful in studying the role of endogenous muscle proteases in muscle growth and postmortem proteolysis.

Animals↗
PubMedDate not supplied

Control release of prostaglandin E2 from polylactic acid microcapsules, microparticles and modified microparticles.

Low molecular weight polylactic acid (PLA) microparticles containing prostaglandin E2 were prepared. An average particle size of 30 micron was obtained by grinding at low temperature. These particles were further treated by heating to modify the shape and the release pattern. Microscopic studies showed that the modified particles had a smoother surface than the non-modified particles. The drug was also incorporated into PLA microcapsules using the solvent evaporation process, but the incorporation efficiency was lower. We studied the release profiles of modified particles prepared using different molecular weight PLA. The release rate depended on the molecular weight with lower molecular weights having a greater release rate. In addition, the release studies showed different matrix forms made from the same molecular weight PLA had different release patterns. For example, the microcapsules released the drug very slowly whereas the modified particles exhibited a moderate release rate. It was also noted that the matrix release model could describe the release patterns of microcapsules and modified particles very well. However, the release patterns of non-modified microparticles did not follow this model.

Capsules↗
PubMed1993

The role of biological response modifiers in disease control.

Immune responses to infectious agents involve a complex set of interactions between cells and the factors they produce that culminate with disease resolution or death. Therefore, the manipulation of the immune system may have a great impact on the preservation and restoration of animal health. Biological response modifiers are agents that modify the host's response to pathogens with resultant beneficial prophylactic or therapeutic effects. The best known example of biological response modifiers are vaccines, by which administration of a nonpathogenic form of a microorganism prepares the immune system to produce a more effective response upon subsequent infection with the pathogenic form. Nevertheless, the use of biological response modifiers other than vaccines that enhance the immune response is now the focus of many investigations. In this review, a brief overview of the immune system is presented, and special emphasis is placed on possible areas of intervention with biological response modifiers and a description of the prophylactic and therapeutic potential of biological response modifiers. Specific examples are presented to demonstrate examples of disease modification by biological response modifiers through stimulation of nonspecific and antigen specific immunities.

Animals↗
PubMed1975

Treatment of carcinoma of the breast by modified radical mastectomy.

To evaluate the results of treatment of Stage I and Stage II-T1 and T2, NO and N1-carcinoma of the breast by modified radical mastectomy with preservation of the pectoralis major muscle, the survival rates of all such patients treated by the senior author from 1965 through 1968 were compared with the survival rates of a simultaneous group of patients with similar stage disease treated by conventional radical mastectomy by the same surgeon. There were a total of 134 patients, of whom 51 had modified radical mastectomy and 83 conventional radical mastectomy. The five year survival rate for those treated by standard radical mastectomy was 81 per cent, and for those treated by modified radical mastectomy, it was 84 per cent. In patients with histologically negative axillary lymph nodes, the rates were 86 per cent following both radical mastectomy and modified radical mastectomy. Four per cent of the surviving patients after modified radical mastectomy and 7 per cent of the five year survivors after radical mastectomy had evidence of metastases at five years. Locally recurrent disease was noted in 5 per cent of those who had modified radical mastectomy and 7 per cent of those who underwent standard radical mastectomy. This analysis demonstrates that there is no significant difference in the survival and recurrence rates after conventional radical mastectomy and ,odified radical mastectomy of the Patey type. There is a high incidence of recurrence-free survival after both of these operations. Since modified radical mastectomy is less traumatic, involving less damage to muscular tissues, and is followed by significantly decreased deformity, it is advised as the treatment of choice for patients with carcinoma of the breast having no or minimal evidence of axillary node involvement. More extensive tumors adherent to the pectoral fascia or associated with multiple or large palpable axillary nodes should still be treated by conventional radical mastectomy.

Adult↗
PubMed1975

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10-A recombinant mouse strains.

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to "modified self" are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.

Animals↗
PubMed1991

Respiratory tract gene transfer. Transplantation of genetically modified T-lymphocytes directly to the respiratory epithelial surface.

To evaluate the strategy for potentially treating respiratory disorders with genetically modified T-lymphocytes, the interleukin-2 (IL-2)-dependent murine T-cell line, CTLL2, was genetically altered with the Escherichia coli beta-galactosidase (beta-gal) gene (lacZ) in vitro with a retroviral vector and the modified T-cells were transplanted directly to the respiratory epithelial surface of syngeneic C57Bl/6 mice. Southern and Northern analyses confirmed that the neomycin-selected modified T-cells contained and expressed the lacZ gene. The fate of the modified T-cells (CTLL2/lacZ) was followed by flow cytometry with T-cell surface marker Thy1.2 and fluorescent beta-gal analysis. One day after transplantation (7.5 x 10(5) CTLL2/lacZ T-cells/g of body weight), 95 +/- 3% of the Thy1.2+ T-cells recovered from respiratory epithelial lining fluid (ELF) were beta-gal+. Importantly, the modified T-cells remained in the lung for some time; at 3 days, Thy1.2+ beta-gal+ T-cells represented 63 +/- 12% of ELF Thy1.2+ T-cells and 59 +/- 6% of Thy1.2+ T-cells recovered from the whole lung. At 7 days, 33 +/- 8% of the Thy 1.2+ cells in ELF and 75 +/- 6% of the Thy1.2+ cells in whole lung were Thy1.2+ beta-gal+. In contrast, the proportion of the Thy1.2+ beta-gal+ T-cells in the spleen, the major extrapulmonary lymphatic organ, never rose above 3 +/- 1% of the total Thy1.2+ cells. The number of Thy1.2+ beta-gal+ T-cells in the lung could be modified by the systemic administration of IL-2, with whole lung Thy1.2+ beta-gal+ T-cells increasing 4.6-fold 3 days after transplantation, compared with non-IL-2-treated animals. These studies suggest that direct transplantation of genetically modified T-cells into the lung is feasible and represents a viable strategy for lung-specific gene transfer.

Animals↗
PubMed1987

A double-monoclonal immunoenzymometric assay for alpha 1-fetoprotein modified for increased analytical precision.

We modified a one-step, two-site, double monoclonal immunoenzymometric assay (Abbott Laboratories) for serum alpha1-fetoprotein (AFP) to increase its sensitivity and improve test precision at the low end. We increased sample size, incubation interval, and reaction time and temperature, and decreased the final reaction volume. Interassay CVs for the modified method ranged from 6.2 to 8.0% for mean concentrations of AFP in serum of 5.2 to 34.2 micrograms/L--substantially better than those for the unmodified monoclonal method--and agreed well with those of the comparison method (modified Abbott polyclonal immunoenzymometric assay). AFP values by the modified monoclonal procedure (y) correlated well with results by the polyclonal method (x): y = 0.983x + 1.84 micrograms/L (r = 0.927, n = 59). The detection limit of the modified monoclonal test was 0.2 microgram/L, as compared with 1.0 and 1.4 micrograms/L, respectively, for the modified polyclonal and the unmodified monoclonal procedures. We recommend using the modified monoclonal method for monitoring cancer patients with low tumor burden.

Antibodies, Monoclonal↗
PubMed1983

T cell responses induced by the parenteral injection of antigen-modified syngeneic cells. I. Induction, characterization, and regulation of antigen-specific T helper cells involved in delayed-type hypersensitivity responses.

This report presents evidence for the role of antigen-specific helper T cells in augmenting the in vivo development of delayed-type hypersensitivity (DTH) responses to both hapten and protein antigens. The role of these helper T cells in the in vivo induction and regulation of DTH responses was investigated. Mice were primed subcutaneously with optimal numbers (3 X 10(7)) of either protein antigen- or TNP-modified syngeneic spleen cells. Primed spleen or lymph node cells, but not thymocytes or unprimed cells, were found to significantly augment the DTH response of syngeneic recipients injected subcutaneously with suboptimal numbers (1 to 2 X 10(6)) of antigen-modified syngeneic cells. Primed spleen or lymph node cells augmented both in vivo ear swelling reactions and in vitro antigen-induced T cell proliferative responses in recipient animals. The helper effect was found to be mediated by a population of radioresistant, Thy-1+, Lyt-1+2-, I-A+ cells, a phenotype identical to that of antigen-specific Tprlf cells found in primed lymph nodes. In contrast, effector TDH cells were found to be Thy-1+, Lyt-1+2-, I-A- cells. Splenic T cells from TNP-primed mice augmented TNP-specific DTH responses, but not DTH to irrelevant protein antigens, and vice versa. Helper T cell induction correlated with the presence of H-2 I-region determinants on the inducer cells, because antigen-modified spleen cells were the most efficient inducers, modified thymocytes were less efficient, and modified erythrocytes were ineffective. Mapping studies also indicated that I-region identity between the antigen-modified spleen cell immunogen and the Th donors was both necessary and sufficient for DTH Th cell induction. In addition, functional helper T cell activity could be both specifically tolerized and suppressed by the transfer or suppressor T cells raised by the i.v. injection of antigen-modified syngeneic cells.

Animals↗
PubMed1981

[Effect of tyrosine-74-modified cytochrome C on electron transfer in Keilin-Hartree submitochondrial particles].

The tyrosine-74 modified cytochrome c is obtained by the interaction of cytochrome c with N-(2, 2, 5, 5-tetramethyl-3-carboxy-piroline-oxyl) Imidazol. The absorbtion spectrum of the modified derivative at the visible region does not differ substantially from the native protein. The band of absorbtion at 695 nm, which shows that the performed modification is soft and the conformation of the modified cytochrome c is close to that of the native protein. Redox potential of the modified cytochrome c, determined by spectrophotometric titration, does not differ from that of the native protein. Submitochondrial particles, deficient of cytochrome c, are reconstructed with modified protein. In both substrates of biologic oxidation succinate and ascorbate the electron transport is restored by the modified protein in considerably higher concentrations than those of the native cytochrome c. Inspite of small conformation differences and unchanged redox potential of the modified cytochrome c substantial differences are observed in its electron-carrying properties as well as its interaction with the membrane cytochrome c reductase and oxydase.

Animals↗
PubMed1980

Hemodynamic and clinical comparison of the Hancock modified orifice and standard orifice bioprostheses in the aortic position.

Bioprosthetic aortic valve replacement in patients with a small aortic root has been associated with postoperative transvalvular gradients. A modified orifice Hancock xenograft bioprosthesis has been developed and is purported to increase significantly the effective orifice area (as evaluated by in vitro testing) compared to the standard orifice Hancock bioprosthesis. To assess the in vivo differences, we compared 481 patients with standard orifice prostheses with 156 patients with modified orifice prostheses. Postoperative catheterization was performed in 24 patients with modified orifice (valve diameters 19 to 25 mm) with 14 with standard orifice valves (valve diameters 21 to 25 mm). Actuarial rates of survival, valve failure, endocarditis, and thromboembolism did not differ significantly between the two subgroups. Peak aortic valve gradients on the whole were less in the modified orifice subgroup than in the standard origice subgroup (12 +/- 1 torr versus 20 +/- 6 torr [mean +/- SEM]), but the difference was not statistically significant (p greather than 0.05). The calculated in vivo aortic valve areas were slightly, but insignificantly, greater in the modified orifice subgroup than in the standard orifice subgroup (p greater than 0.05). These in vivo data partially corroborate the in vitro findings of increased effective orifice area and internal-to-external diameter ratio for the modified orifice bioprosthesis. The hemodynamic differences between the two valve types are small, however, and the putative clinical advantages inherent in the use of the modified orifice bioprosthesis remain to be completely defined.

Aortic Valve↗
PubMed1995

A prospective trial comparing the efficacy and complications of the modified Dornier HM3 and MFL 5000 lithotriptors for solitary renal calculi.

A prospective randomized study of 198 patients was conducted to compare the efficacy of the modified Dornier HM3 lithotriptor to the MFL 5000 lithotriptor. Entrance criteria included solitary stones at any location within the upper collecting system that had not previously been treated with lithotripsy. Following lithotripsy the patients were evaluated by a blinded radiologist with a plain abdominal film, tomograms and renal ultrasound at 1, 4 and 12 weeks. Patients were classified at 12 weeks after lithotripsy as failing treatment if any stone fragments were imaged. Of the patients 170 were available for complete 3-month followup. No statistical or clinical difference in stone-free rates was apparent for calculi in the ureter or renal pelvis in either group. Of patients with lower caliceal stones 80% had no residual fragments visualized at 12 weeks when treated with the modified HM3 device versus 56% with the MFL 5000 lithotriptor (p = 0.05). Treatment time on the MFL 5000 unit was significantly prolonged compared with the modified HM3 device (0.7 hours versus 0.4 hours, respectively) resulting in fewer patients being treated in a given day (p < 0.001). No statistical difference in complication rates could be found between the 2 machines. Steinstrasse were noted in 10% of the patients treated with the modified HM3 device and 6% of the MFL 5000 group. Subcapsular hematomas were noted in 4% of the MFL 5000 treatment arm compared to 1% in the modified HM3 group. Overall, the MFL 5000 lithotriptor was believed to offer no significant clinical advantage over the modified HM3 device in terms of lithotripsy efficacy, although the multifunctional table did offer more versatility for stone treatment. For a busy lithotripsy center, the modified HM3 lithotriptor is still the most efficacious.

Adult↗
PubMed1993

Structural determinants of quaternary ammonium blockers for batrachotoxin-modified Na+ channels.

Amphipathic quaternary ammonium (QA) compounds are potent blockers of batrachotoxin (BTX)-modified Na+ channels incorporated into planar lipid bilayers. To examine the topology of the QA binding site, we selected two series of QA compounds as structural probes. One series contains two separate hydrophobic moieties but with a common hydrophilic dimethyl QA ion. Most of the QAs within this group bind to BTX-modified Na+ channels with relatively high affinities. For example, benzyldimethyldodecyl ammonium ions, when applied internally, block single, muscle, BTX-modified Na+ channels in bilayers with a one-to-one relationship and display an equilibrium dissociation constant (Kd) of 0.2 microM at +50 mV. Furthermore, the QA dwell times appear to correlate with QA hydrophobic interactions with the channel. These results indicate that there are two large hydrophobic binding domains within the QA binding site. The QAs in the second series contain a hydrophilic head group (trialkylammonium) of variable size but with a common dodecyl hydrophobic tail. Tripropyldodecyl QAs block BTX-modified Na+ channels more effectively (Kd = 0.4 microM at +50 mV) than do trimethyl- and triethyldodecyl QAs, suggesting that the internal Na+ permeation pathway is at least 9 A wide. However, tributyl- and tripentyldodecyl QAs show much lower affinities for BTX-modified Na+ channels at comparable concentrations. These drugs are cut off from binding, probably as a result of the size of their hydrophilic heads (> 10 A), which may be too large to fit in the QA binding site and too bulky to travel freely within the internal permeation pathway. Under whole-cell voltage-clamp conditions, we have further found that BTX-modified Na+ currents in clonal GH3 cells can be blocked by these two series of QA ions, albeit only when the activation gate is open. Closed channels at rest do not bind appreciably with these QA ions. Binding of QA ions is reduced by external Na+ ions in GH3 cells in a manner indicating that external Na+ ions can clear the bound QA ions from the Na+ pore. These results from GH3 cells mirror those obtained with QA blockers in K+ channels of squid axons and suggest that the QA binding domains in BTX-modified Na+ channels and K+ channels may be structurally conserved.

Animals↗
PubMed1995

[Clinical experience with modified method of tubal ligation].

OBJECTIVE: To evaluate the clinical results with modified tubal ligation method. METHODS: From 1983 to 1992, 700 cases of modified tubal ligation operation with tubes cut and overlapped were performed in our hospital, and this was compared with 602 cases of Pomeroy's and 502 cases of modified Uchida's method. Patients were followed at 6 months, 2 and 5 years. Pregnancy rates, menstruation disturbances, lower abdominal or back pain, and leucorrhea were observed. RESULTS: Patients with modified tubal ligation method had a pregnancy rate of 0.43%, which was significantly lower than that of Pomeroy's 1.50% (P < 0.05). The modified method group also had few complications. The occurence rate of menorrhage and prolonged bleeding were apparently lower than that of Pomeroy's too (P < 0.01). CONCLUSION: This modified tubal ligation method is more effective and practicable than Pomeroy's and modified Uchida's method.

Adult↗
PubMed1996

Effects of immediate modified feeding on infantile gastroenteritis.

BACKGROUND: Standard treatment of infants who are dehydrated as a result of acute gastroenteritis is to administer oral rehydration therapy (ORT). Traditionally, food has been withdrawn for 24-48 h, but there is no conclusive evidence that this is of any real benefit to the patient. Immediate modified feeding, in which an infant on ORT is not starved but administered a limited diet, may have benefits in the treatment of gastroenteritis, especially in children who are nutritionally compromised before they develop the illness. AIM: A pilot study was carried out to investigate the effects of giving infants suffering from acute gastroenteritis a limited modified diet in conjunction with ORT. METHOD: Infants recruited into the study by their general practitioner or by a research doctor in the hospital casualty unit of Bristol Children's Hospital were randomly allocated to receive ORT with or without immediate modified feeding. The duration of diarrhoea, weight change, and incidence of vomiting and lactose intolerance were measured in both treatment groups, and the results were compared. RESULTS: Of the infants studied, 27 received ORT and immediate modified feeding, and 32 ORT alone. The duration of diarrhoea, and incidence of vomiting or lactose intolerance were no greater in the group receiving immediate modified feeding. Patients who received ORT and immediate modified feeding appeared to gain more weight than the infants who were starved for 24-48 h, but this difference was not statistically significant. CONCLUSION: Immediate modified feeding is safe and effective, and may have nutritional advantages over traditional ORT with starvation. A similar but multicentre study using unmodified diet, i.e. child's normal diet, is being carried out by a working group of The European Society of Paediatrics, Gastroenterology and Nutrition (ESPGAN).

Child, Preschool↗
PubMed1996

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation.

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.

Animals↗
PubMed1994

Studies on the usefulness of acetaldehyde-modified proteins and associated antibodies as markers of alcohol abuse.

Acetaldehyde, an intermediate in ethanol metabolism, has been shown to react with proteins to produce both stable and unstable adducts. These modified proteins are immunogenic, leading to the production of anti-adduct antibodies. In this report we describe studies carried out to determine whether anti-adduct antibodies could be used as a marker of alcohol abuse. We have used ELISAs to measure plasma immunoreactivity with unmodified and acetaldehyde-modified bovine serum albumin in groups of female and male social drinkers, heavy drinkers and alcoholics. When total immunoreactivity with the unmodified and acetaldehyde-modified proteins was measured it was found that each of the groups exhibited elevated reactivity with the modified protein as compared to the unmodified. Similar results were obtained when IgM immunoreactivity was measured. However, when IgA immunoreactivity was measured the reactivity with the modified protein was more greatly elevated in the heavy drinking and alcoholic groups than in the social drinking groups. There was no evidence of IgG reactivity with modified protein in any of the groups. These data suggest that elevated IgA reactivity with acetaldehyde-modified proteins may be a marker for high alcohol intake.

Acetaldehyde↗
PubMed1997

Immunological evidence for hypochlorite-modified proteins in human kidney.

Oxygen radicals and oxidatively modified proteins seem to participate in degenerative vascular and inflammatory diseases. Factors that contribute to the development of atherosclerosis, eg, oxidation of low-density lipoproteins (LDLs), may also contribute to glomerulosclerosis. Although the nature of the in vivo oxidants remains unknown, recent findings indicated that the myeloperoxidase (MPO)-H2O2-halide system could play an important role in modification of (lipo)proteins in human tissues. MPO, the enzyme responsible for hypochlorite (HOCl/OCl-) formation, is present in human atherosclerotic lesions and in inflammatory conditions. In the present study, MPO was identified by Western blot analysis and immunohistochemical technique in diseased human kidney either with primarily sclerotic or inflammatory lesions. Furthermore, the presence of HOCl-modified proteins was demonstrated in diseased renal tissues using a specific monoclonal antibody (clone 2D10G9), raised against HOCl-modified LDL, that does not cross-react with native LDL or Cu(2+)-, 4-hydroxynonenal-, or malondialdehyde-modified LDL. The antibody recognized HOCl-modified proteins in glomerular and tubulointerstitial inflammatory and fibrotic lesions and pronounced immunostaining was demonstrated in mononuclear cells. LDL or human serum albumin oxidized by HOCl in vitro, but not native LDL or human serum albumin, effectively competed with epitopes in diseased kidney for antibody binding. Western blot analysis in diseased kidney protein samples revealed at least two major proteins recognized by the anti-HOCl-modified protein monoclonal antibody. Densitometric evaluation of immunoreactive bands obtained under these conditions demonstrated that expression of HOCl-modified proteins is tightly coupled to expression of immunoreactive MPO in the same tissue samples. From our studies it is proposed that oxidation of proteins by HOCl might be a leading event in glomerular and tubulointerstitial injury. By this mechanism, mononuclear cells, a permanent source for MPO, may play a key role in the development of nephrosclerosis, glomerulo-clerosis, and tubulointerstitial fibrosis, respectively.

Adult↗
PubMed1976

[A new modified wick catheter for measurement of the brain tissue pressure-an evaluation of static and dynamic properties of the catheter (author's transl)].

The interstitial pressure of the brain was measured with wick catheter by Lassen in 1972. But original wick catheter inserted into the brain tissue does not always measure the real interstitial pressure as indicated by experimental results of Brodersen, because, the interstitial pressure is always affected by solid pressure such as cells in the brain tissue, in the condition of which surrounded by positive CSF pressure in the semiclosed skull box. It is not yet clarified what kinds of the pressure are measured by wick catheter method in the brain tissue. The size of wick catheter is 300-500 times as large as the width of interspace of the brain tissue and the catheter is easily obstructed by brain tissue. Therefore, a new, modified wick catheter is made for improvement of these problems which is observed by using original wick catheter. The new, modified catheter has 0.4 mm inside diameter and 10 cm length. The tip of catheter is closed and 6 small side holes(0.1 mm0)are made. Inside the catheter, several pieces of 0.04 mm diameter nylon threads are inserted as shown in figure 1, and the catheter is filled up with the cerebrospinal fluid. In this paper, the structure of the new, modified catheter is demonstrated, and the brain tissue pressure is measured, comparing with the results of the original wick catheter to test the function of the new, modified catheter. The results of measurement of the brain tissue fluid pressure with the new, modified catheter are as follows; 1) The brain tissue fluid pressure is relatively constant and shows a positive pressure of 5.2 mmHg. 2) As there are few blocking effects in the catheter, the new, modified catheter is useful for the measurement of the brain tissue fluid pressure for a long time. 3) The brain tissue fluid pressure is not altered by the number's of nylon threads in the catheter at static condition, but movement of brain tissue fluid pressure with respiration is a little dumped by the increased conductancy with the numbers of nylon threads in the catheter. 4) The tissue fluid pressure affected by the viscosity and osmolarity of the fluid in the catheter, CSF should be used for correct measurement. According to these results, it might be concluded that the new, modified wick catheter is better than the original wick catheter regarding prevention of obstruction of the catheter by brain tissue fragments, artifacts which causet by movement of wick fibers, measurement of brain tissue fluid pressure for a long time and clarify the resistance of catheter to pressure conductancy.

Animals↗