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Nature of hapten-modified determinants involved in induction of T cell tolerance and suppressor T cells to NDFB contact sensitivity.

Unresponsiveness to DNFB contact sensitivity induced by DNP-modified lymphoid cells (DNP-LC) is mediated by two separable pathways: a rapidly induced, long lasting inhibition of reactive T cell clones (donor tolerance), and a transient period of suppressor T cell (Ts) activity. The present report has examined the nature of the hapten-modified determinants responsible for the induction of these pathways by utilizing soluble DNP-LC cell lysate preparations as tolerogens. The results indicate that both DNP-modified MHC and non-MHC encoded determinants can mediate donor tolerance 7 days after tolerization. On the other hand, the induction of Ts requires DNP-modified MHC determinants, since DNP-LC lysates passed over lentil lectin or specific anti-H-2 immunoabsorbent columns lost their ability to induce Ts. Additional experiments showed that the injection of DNP-LC lysate compatible with the recipient strain at the H-2K and H-2D region of the MHC was sufficient for the induction of Ts. We propose that Ts induction involves the direct presentation of DNP-H-2 determinants to Ts precursors, whereas the induction of donor tolerance may involve host processing and presentation of DNP-modified membrane determinants in conjunction with host MHC structures.

Animals↗

[Molecular mechanisms of photoreception. V. Reconstitution of a sodium channel on an artificial lipid membrane modified by bovine rod outer segment components].

An attempt is made to reconstitute the Na+-conductivity elements of rod outer segment (ROS) plasma membrane on the artificial lipid membrane (ALM). ALM were modified by preparation with bovine ROS plasma membrane fragments. Discrete fluctuations of the ALM conductivity were observed at addition of this preparation to the ALM bathing solutions to a final concentration of 0.1--1.0 microgram/ml. The magnitude of these fluctuations was about 25 pS at 140 mM NaCl. The modified ALM possessed preferentially the Na+-conductivity, which was at least five times as great as that for K+ or Li+. The modified ALM showed practically no conductivity for Cl-. The Na+-channels were voltage-dependent. The Na+-channels were "sensitive to visible light" at some experimental conditions. The optimal conditions were obtained for reconstitution of Na+-channel on the ALM. The temporal and termal stabilities of the modified preparation were investigated. It was shown that the frequency of the modified ALM conductivity fluctuations are dependent on temperature and on lipids composition of ALM. The data obtained in our work are in a good agreement with the results of electrophysiological studies of photoreceptor cells. It may be indicated, that the investigated ALM contains the Na+-channel of the ROS plasma membranes. It is suggested that the reconstituted system will be useful for studying the principles of regulation of ROS plasma membrane sodium conductivity and the nature of a mediator in a photoreceptor transduction mechanism.

Animals↗

The action of thrombin on modified fibrinogen.

The modification of canine fibrinogen with citraconic anhydride modified the epsilon-amino groups of the fibrinogen and at the same time generated additional negative charges into the protein. The addition of thrombin to the modified fibrinogen did not induce polymerization; however, the fibrinopeptide was released at a faster rate than from the unmodified fibrinogen. The physical properties of the citraconylated fibrinogen were markedly altered by the modification of 50-60 lysine residues in one hour. A modified fibrinopeptide-A was released by thrombin from the modified fibrinogen and was electrophoretically more anionic than the unmodified fibrinopeptide-A. Edman analysis confirmed the modification of the lysine residue present in the peptide. The rate of removal of citraconylated fibrinopeptide-A from modified fibrinogen by thrombin was 30 to 40 percent greater than the cleavage of unmodified fibrinopeptide-A from unmodified fibrinogen. However, the modification of 60 or more lysine residues in the fibrinogen produced a decrease in the rate of cleavage of citraconylated fibrinopeptide-A. The results suggest that additional negative charge in the vicinity of the attachment of fibrinopeptide-A to canine fibrinogen aids in the removal of the peptide by thrombin.

Amino Acids↗

[An experimental study on temporal changes of post-operative anti-reflux effect by modified Mark IV operation for esophageal achalasia].

This study was intended to elucidate possible temporal changes of the valve and fundoplication which are formed by modified Mark IV operation as a surgical treatment of esophageal achalasia. Heller's procedure was also studied in terms of its comparison with the above operation. Adult mongrel dogs were operated on as follows and studied at the following postoperative points: Heller's procedure at the forth postoperative week, Modified Mark IV operation at the forth postoperative week, Modified Mark IV operation at the third postoperative month. Postoperative comparative studies were made on temporal changes of the anti-reflux effect by intraesophagogastric pressure and withdrawal pH examinations, measurements of intragastric pressure at reflux through simultaneous evaluation of intraesophageal pH and inner pressures at 3 points, i.e. the esophagus, the high pressure zone and the stomach, and histological and morphological examination. From the above the following conclusion was drawn: The valve formed by modified Mark IV operation showed temporally a shortening tendency, and a significant shortening of the length of valve was observed also in comparisons of values between the forth postoperative week and the third postoperative month. Also in terms of the measurement of inner pressures, a significant decrease was observed in the length and the force of high pressure zone. However, comparisons of the intragastric pressure values at reflux revealed no significant difference in values between the forth week and the third month after the modified Mark IV operation and almost similar anti-reflux effects between both in spite of a shortening of the valve. The above results suggested that more reliable and long-term sustaining of the anti-reflux effect needed more extensive formation of the fundoplication.

Animals↗

[Experimental carcinogenesis of the stomach and its modifiers].

Modifiers of gastric carcinogenesis are reviewed with evidence of experimental results using rats. 1) Physical modifiers: Route of administration, medium (vehicle) of carcinogens, detergents, dosage (concentration), period (frequency) of administration, exposure time, and condition of mucus. Effects of surfactants and presence of a foreign body in the stomach lumen are also samples of physical enhancing factors. 2) Biological modifiers: Species, genetics, sex, hormonal factors, nutrition, and age. Moreover, effect of preexisting ulceration is important. 3) Chemical modifiers: Chemical substances administered prior to, simultaneously with, or following exposure of experimental animals to chemical carcinogens, or promoters of carcinogenesis. Chemical modifiers are: co-initiators, tumor promoters and inhibitors. NaCl having both co-initiator and tumor promoter action on MNNG gastric carcinogenesis is clearly shown in our investigations.

Age Factors↗

Randomized comparison of the modified wire-guided and standard intra-aortic balloon catheters.

We have designed a modified intra-aortic balloon (IAB) catheter to facilitate balloon insertion and minimize the complications of vascular dissection, perforation, and thrombosis. The modified balloon catheter is fabricated of a new polyurethane, Avcomat-100; it has a central lumen which allows for pressure monitoring, contrast injection, and introduction of a guide-wire under fluoroscopic control. In a randomized study, we compared the modified balloon with the standard Avco balloon catheter. Eighteen patients were randomized, 10 to receive a standard balloon catheter (control group) and eight to receive a modified balloon catheter. In two of the 10 patients assigned to the control group, introduction of the standard catheter failed but a central-lumen balloon was successfully introduced using the guide wire. A guide wire was needed for introduction of the modified balloon in three of the eight patients assigned to the central-lumen catheter group. The Avcomat-100 catheter material was less thrombogenic, with a lower rate of femoral thrombosis--20% in the control group and 0% in the central-lumen group. Scanning electron miroscopy also showed a reduced area of catheter surface covered with fibrin and clot. This study demonstrates the safety, decreased thrombogenicity, and increased facility of insertion of this new balloon catheter.

Adult↗

Direct comparison of standard and insulin modified protocols for minimal model estimation of insulin sensitivity in normal subjects.

Estimates of in vivo insulin sensitivity (S1) can be derived from minimal model analysis of a frequently sampled intravenous glucose tolerance test (FSIVGTT). Modification of the FSIVGTT by administration of tolbutamide improves the correlation between S1 and more traditional glucose clamp measurements. Recently, a modified FSIVGTT using insulin infusion (instead of tolbutamide) has been described. This modification may be useful for studying subjects with poor insulin secretion. We directly compare the standard FSIVGTT with the insulin modified FSIVGTT in ten normal subjects (age 29 +/- 2 yr, BMI 22.5 +/- 1.2 kg/m2). Each subject received both tests. The order of the studies was randomized and the interval between paired studies was approximately one week. After an overnight fast, glucose (0.3 g/kg) was infused from time 0 to 2 min. For the modified FSIVGTT, insulin (4 mUkg-1.min-1) was infused from time 20 to 25 min. None of the subjects became hypoglycaemic after insulin infusion. Paired t-test analysis did not reveal significant differences between the two protocols for any of the minimal model parameters. The standard FSIVGTT gave estimates for S1 of 5.63 +/- 1.32 x 10(-4) min-1 per microU/ml while the insulin modified FSIVGTT gave estimates for S1 of 5.11 +/- 0.83 x 10(-4) min-1 per microU/ml. However, the fractional standard deviation for S1 was significantly smaller with the insulin modified protocol (3.6 +/- 1.0 vs. 22.2 +/- 9.0, p < 0.037). Thus, under our experimental conditions, insulin infusion during FSIVGTT appears to improve the precision of minimal model estimation of S1 in normal subjects.

Adult↗

A modified posterolateral approach to the thoracic spine.

We describe a modified technique for posterolateral approach to the thoracic spine and report the use of this procedure in 21 patients. The technique is safe and effective for selected indications. The evolution of the posterolateral or costotransversectomy approach to the thoracic spine has in large part focused on enlarging the exposure to the vertebral bodies and epidural space by resecting an increasing number of ribs and removing a wider portion of those ribs resected. In this modified approach to the thoracic spine, the costovertebral articulation is preserved, and no rib resection is necessary to gain adequate exposure to the thoracic vertebral body and epidural space. We did a retrospective review of 21 patients undergoing 22 modified posterolateral approaches to the thoracic spine. Sixteen patients had biopsies of thoracic vertebral lesions through this approach; 3 underwent decompression of the thoracic spinal cord; 2 approaches were done for the removal of a herniated thoracic disc; and in one, the pedicle was removed. This modified posterolateral approach allowed adequate exposure for selected indications. One complication, a wound infection, developed after biopsy for suspected osteomyelitis. This modified posterolateral approach is well suited to provide access for biopsy of thoracic spinal lesions; for decompression of a paraspinal abscess; and for decompression of the thoracic spinal cord by anterolateral compressive lesions such as herniated thoracic disc or epidural tumor when resection of the vertebral body is not necessary; or the approach may be used for patients who are debilitated or at poor risk to undergo thoracotomy.

Adult↗

Poxviral modifiers of cytokine responses to infection.

Poxviruses include some of the most virulent of all human pathogens. In part, the virulence of these viruses stems from their abilities to counter host defenses against infection. A family of cytokine-response modifiers encoded by the poxviruses contribute to these countermeasures. The poxviral cytokine-response modifiers appear to affect cytokine responses in at least four different ways: (a) by inhibiting the synthesis and release of cytokines from infected cells; (b) by interfering with the interaction between a cytokine and its receptor; (c) by inhibiting cytokine signal transmission; and (d) by synthesizing virus-encoded cytokines that antagonize the effects of host cytokines mediating antiviral processes. Known poxviral, cytokine-response modifiers include CrmA, an inhibitor of the interleukin-1 beta converting enzyme; several secreted soluble receptors for tumor necrosis factor, interleukin-1, and interferon-gamma; and poxvirus-encoded growth factors resembling epidermal growth factor. Collectively, these and other as yet unidentified cytokine-response modifiers contribute to the inhibition of a variety of nonspecific and virus-specific immune defenses against virus infection. Information gained on the mechanisms used by poxviruses to modify cytokine-mediated processes should assist the development of novel therapies for a variety of diseases.

Animals↗

Nutrient-specific effects of modified sham feeding on pancreatic polypeptide release.

OBJECTIVE: To study the effect of meal composition on pancreatic polypeptide release during modified sham feeding. DESIGN: In random order and on separate occasions, isocaloric, isothermic, isoosmotic, homogenized meals (1050 kJ; 250 kcal) either rich in fat (walnuts; 64 g fat, 7 g protein, 15 g starch per 100 g), protein (codfish, 1 g fat, 23 g protein per 100 g) or carbohydrates (bananas; 22 g starch, 1 g protein per 100 g) were sham-fed for 30 min by tasting and spitting out the meal. The plasma pancreatic polypeptide response was monitored by radioimmunoassay at 10 min intervals from 20 min before to 120 min after modified sham feeding. SETTING: Department of Gastroenterology and Hepatology of a University Hospital. SUBJECTS: Seven healthy volunteers: 3 male, 4 female; age 45 (range 30-77) years. RESULTS: Integrated plasma pancreatic polypeptide responses to modified sham feeding of codfish (1088 +/- 395 pM*120 min; P < 0.05) and walnuts (1200 +/- 542 pM*120 min) were distinctly higher (P < 0.05) than to modified sham feeding of bananas (-390 +/- 291 pM*120 min). CONCLUSIONS: These results demonstrate that the pancreatic polypeptide response to modified sham feeding is dependent on the composition of the meal.

Adult↗

[Modified CHOP and radiation therapy in an aged patient with angioendothelial lymphoma].

A 77-year-old man was admitted because of high fever and general malaise. Whole-body CT showed large bilateral adrenal masses and para-aortic lymphadenopathy. Needle biopsy of the adrenal mass revealed mononuclear tumor cells within the lumens of small vessels, indicating the features of angioendothelial lymphoma. Immunohistochemically, these tumor cells were B cell lineage (positive for LCA, Mx-pan B, MB-1, and negative for factor VIII-related antigen, UEA-1, QB/ENDO 10). We used a modified CHOP therapy (500 mg of cyclophosphamide, 40mg of 4'-o-tetrahydropyranyl doxorubicin, 2mg of vindesine, and 50 mg of prednisolone) due to the patient's advanced age and general condition. Following the first course of this modified CHOP, the adrenal masses and para-aortic lymph nodes decreased dramatically in size, and his subjective symptoms also improved remarkably. Following three courses of modified CHOP, the patient developed dementia and disturbance of consciousness. Brain MRI revealed enhanced multiple nodular lesions. A diagnosis of multiple brain metastasis was made and modified CHOP and radiation therapy were begun, which relieved his symptoms for some time. However, he later died of pneumonia with severe leukopenia. A postmortem examination was performed. Microscopic examination showed no residual tumor cells in the adrenal gland. brain lymph nodes, or other organs. These results suggest that modified CHOP and radiation therapy may have beneficial anti-tumor effects against angioendothelial lymphoma.

Adrenal Gland Neoplasms↗

Structural requirements for the binding of modified proteins to the scavenger receptor of macrophages.

Oxidized low density lipoprotein (LDL) and certain chemically modified LDL are recognized by the scavenger receptor of macrophages. All of these modifications involve charge-neutralizing derivatization of lysine amino groups. However, it remains controversial whether recognition of modified LDL by this receptor is due to the modification per se, or to other factors such as a conformational change of apoB. In this study, LDL and other proteins including bovine serum albumin, human high density lipoprotein, and murine IgG were derivatized with oxidation products generated from arachidonic acid by thermal autoxidation. Modified proteins had increased negative charge, and showed a more than 10-fold enhancement of degradation by mouse peritoneal macrophages via the scavenger receptor pathway. Modification was prevented by blocking lysine residues of the proteins by prior reductive methylation. Amino acid analysis revealed dose-dependent modification of lysine residues with no significant effects on any other amino acid. Fab fragments of monoclonal antibodies specific for adducts of oxidation products with lysine prevented the uptake of oxidation product-modified LDL and oxidized LDL by macrophages. Chromatography of oxidation product-modified LDL over Sepharose CL-4B showed that uptake by macrophages did not require LDL aggregation. These results suggest that a relatively simple domain consisting of a cluster of suitably derivatized lysine residues is sufficient for recognition by the scavenger receptor of macrophages.

Apolipoproteins B↗

A comparison of sputum examination for acid fast bacilli by modified Schaeffer & Fulton stain, Ziehl-Neelsen stain & cold stain.

A comparative study of Ziehl-Neelsen stain, cold stain and modified Schaeffer and Fulton stain was carried out to evaluate the efficiency of modified Schaeffer and Fulton method in sputum examination for acid fast bacilli (AFB). Of 187 sputum samples studied, 67 (35.82%) were reported positive by Ziehl-Neelsen stain and cold stain method while 66 (35.29%) were reported positive by modified Schaeffer and Fulton method. In comparison with Ziehl-Neelsen staining, 98.58 per cent positivity was reported by modified Schaeffer and Fulton method. Modified Schaeffer and Fulton method is found to be simple, reliable, less expensive and as efficient as Ziehl-Neelsen stain and cold stain for demonstration of acid fast bacilli in sputum.

Bacillus↗

Modified and improved anti-acetylcholine receptor (AchR) antibody assay: comparison of analytical and clinical performance with conventional anti-AChR antibody assay.

We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3-7.8%) CVs, greater linearity, lower cost, and shorter assay time than the conventional method. ROC curve analysis indicated almost identical specificity and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and conventional assays were also equivalent for blocking anti-AChR Ab assay. Moreover, the modified anti-AChR Ab assay, differently from the conventional assay, allowed us to reveal anti-AChR Ab concentration differences among different clinical grades of MG.

Adolescent↗

Modified intraparietal vagotomy in the treatment of perforated duodenal ulcer.

BACKGROUND/AIMS: The purpose of this study was to introduce modified intraparietal vagotomy as a safe procedure and a method of choice in the treatment of perforated duodenal ulcers. METHODOLOGY: Eighty-six patients with perforated duodenal ulcers underwent oversewing of the perforated ulcer and modified intraparietal selective vagotomy. The site of perforation was sewn over and an abdominal cavity lavage was performed. The posterior vagal nerve was resected, and a modified intraparietal anterior vagotomy was performed. During the postoperative period, after twenty days, six months and one year, respectively, we analyzed the following data: body weight, signs of gastroesophageal reflux, subjective discomfort, early postoperative complications, gastroduodenoscopic findings, basal acid output (BAO), and maximal acid output stimulated by pentagastrin (PAO). RESULTS: There was no mortality in our group, the post-operative morbidity was insignificant, and the duration of operation was shorter in comparison to other vagotomy methods. BAO and PAO values were similar to those in the literature when proximal selective vagotomy (PSV) was performed. There were no cases of duodenogastric or gastroesophageal reflux nor re-occurrence of ulcer disease, as confirmed by gastroduodenoscopy. According to the modified Visick's criteria, 94% of the patients followed-up were classified as group 1. CONCLUSION: We consider the modified intraparietal vagotomy to be the method of choice in the treatment of perforated duodenal ulcers because of the simple surgical technique involved, the shorter duration of surgery, and the avoidance of standard PSV complications. The surgery can be performed even by a less experienced surgeon, independently of the patient's age and condition. This modification is suitable for laparoscopic surgery.

Adult↗

The system of the modified transcochlear approach: a lateral avenue to the central skull base.

OBJECTIVE: This study aimed to update the authors' experience with the modified transcochlear approach for the management of lesions of the central skull base. The surgical technique, classification, indications, and results also are presented. STUDY DESIGN: A retrospective review of the charts of 66 consecutive patients treated in our centers by the modified transcochlear approach was conducted. SETTING: The study was performed in two tertiary referral centers. PATIENTS: All patients treated by the modified transcochlear approach were included. Thirty-five patients had extradural lesions, whereas 31 lesions were intradural. INTERVENTION: All patients were treated surgically using the modified transcochlear approach either in its basic form (type A) or with its extensions (types B, C, and D). MAIN OUTCOME MEASURES: The outcome of surgery is evaluated with particular emphasis on the incidence of morbidity, mortality, and the degree of total tumor removal. RESULTS: Total tumor removal was accomplished in 58 cases either in single or staged procedures. A second-stage procedure for total tumor removal is planned in five other patients. Subtotal tumor removal was performed in three patients. Mortality occurred in two cases. Ipsilateral hearing loss and immediate facial nerve palsy constituted the major drawbacks of this approach. However, 67.5% recovered to grade III facial function or better 1 year after surgery. CONCLUSIONS: The modified transcochlear approach provides a relatively safe, wide, and versatile access to large lesions of the central skull base.

Adolescent↗

Immunodetection of modified lipoproteins in plasma and arterial walls of patients with coronary heart disease.

Data from literature indicate that immune processes play an important role in atherogenesis. Modified lipoproteins might be immunogenic and generate autoantibodies in plasma. To determine whether the level of such circulating autoantibodies correlates with the extent of atherosclerosis expressed as cholesterol values in plasma (C), very low density (VLDL-C), low density (LDL-C), and high density lipoproteins (HDL-C), we compared the level of plasma autoantibodies of a group of coronary heart disease patients (CHD-P) with that of normal, age-matched donors, with no history of cardiac disease (N). All CHD-P (even normocholesterolemic) were characterized by an LDL-C/HDL-C ratio > 4, while all N (even hypercholesterolemic) had this ratio < 4. A double level of circulating autoantibodies against VLDL and LDL in CHD-P as compared to N group was detected. The anti-LDL antibodies level correlated well with LDL-C level and was negatively correlated with the age of patients. For tissue localization of native and modified LDL (as well as other possibly modified proteins) we used immunohistochemical techniques, employing antihuman LDL, antihydroxynonenal-lysine (HNE-Lys), and antiadvanced glycation end-products (AGE) proteins. Antibodies were applied on consecutive cryosections of the aortic arch, valves and coronary arteries of CHD-P. The immunodetected antigens were colocalized in focal deposits, in the cap and shoulders of the atheroma. Native LDL and modified proteins (AGE, HNE-Lys) were detected either diffuse-extracellularly or associated with macrophage-derived foam cells and smooth muscle cells of the intima. These data indicate the following: a) the existence of an elevated level of circulating autoantibodies against VLDL and LDL, which correlates negatively with the age of CHD patients; b) the presence of LDL (possibly glycated or oxidized) in detectable amounts in the intima of atherosclerosis-affected arteries; c) the modified lipoproteins are immunoactive components in the atherosclerotic process.

Aged↗

A comparison of clinical and photographic scoring using the TF and modified DDE indices.

OBJECTIVE: To compare the results of recording enamel opacities using the TF and modified DDE indices. DESIGN: Enamel opacities on the maxillary central incisors were recorded two weeks apart. On the first occasion scoring was according to the criteria of the TF index and on the second occasion the modified DDE index was used. An intraoral colour slide photograph was taken of the teeth of each subject and these were scored on two occasions in random order, first using the TF index and secondly using the modified DDE index. SUBJECTS: Three hundred and twenty-five 9-year-old children who were life time residents in an area where the domestic water was fluoridated at one part per million. RESULTS: Agreement between clinical and photograph scoring was good for both TF and modified DDE indices, Spearman's Rank Correlation Coefficients being 0.77 and 0.69 respectively. There was also good agreement between the distribution of scores for the two indices as indicated by Coefficients of 0.75 for clinical scores and 0.76 for photographic scores. CONCLUSIONS: There was good agreement between the TF and modified DDE indices when recording the distribution of milder types of enamel opacities in a population of 9-year-old children.

Child↗