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Biomedical subjects

T S Kim

Publications and source records attributed to T S Kim.

At least 145 records · Page 8Linked to original sources

Prediction of facial nerve displacement in extra large vestibular schwannoma.

The primary objective in the surgery of extra large vestibular schwannoma is the total removal of the tumour mass while preserving the facial nerve. Preservation of the facial nerve in extra large tumours is reported as being notoriously difficult in the majority of cases. This study was undertaken to evaluate the accuracy in predicting displacement of the facial nerve by preoperative radiological imaging studies in 19 cases of extra large vestibular schwannoma. The direction of displacement of the facial nerve was predicted with preoperative axial and coronal MRI scans and verified intraoperatively. We achieved total removal of tumours in 84.2%, facial nerve displacement was predicted in 80% and we accomplished anatomical preservation in 80%. Prediction of displacement was difficult in tumours with little or no intracanalicular components or with severe bony destruction of the internal acoustic meatus. The preoperative prediction of facial nerve displacement in extra large tumours allows safe internal decompression of the tumour and careful dissection near the predicted area of the facial nerve during the operation. Consequently, a high rate of anatomical preservation of the facial nerve can be achieved.

Decompression, Surgical↗

Ventilatory dynamics of transient arousal in patients with obstructive sleep apnea.

The hyperpnea that accompanies arousal at the end of obstructive apnea is believed to be due to the progressive build-up in chemical drive during the apnea and a state-related decrease in upper airway resistance. We postulated the existence of a third component: a state-related transient increase in neural drive to the ventilatory pump muscles. To quantify this contribution, we measured the ventilatory response to arousal (VRA) in eight patients with obstructive sleep apnea (OSA) during continuous positive airway pressure (CPAP) therapy, applied at individually titrated levels. CPAP application reduced total pulmonary resistance (RL) to approximately normal levels, stabilizing ventilation and sleep state. Transient arousal from stage 2 sleep was induced using 5-sec tones (60-90 dB). Mean inspiratory flow increased above control on the second and third post-arousal breaths (P < 0.05), with a peak increase of 7.8 +/- 2.9 L/min while the accompanying changes in RL were significant. The time-course of VRA measured in three normal subjects under CPAP was similar to that observed in the OSA patients. However, elimination of CPAP prolonged the VRA time-course. Taken together, these findings demonstrate that: (1) during arousal, the increase in state-related neural respiratory drive is short-lived but not substantial; and (2) the resulting VRA time-course is shaped by the dynamics of the upper airway response to arousal.

Acoustic Stimulation↗

Validity of radiographic measurement of interproximal bone loss.

The aim of the present study was to compare radiographic assessment of interproximal bone loss using a loupe with a 0.1 mm calibrated grid and a computer-assisted analysis system (LMSRT). In 35 patients suffering from untreated advanced periodontal disease, 62 standardized radiographs were taken presurgically. The horizontal and vertical angulation difference of the central beam from the orthoradial projection was calculated for each radiograph. At the time of surgery, for 115 interproximal defects, the distances from the cementoenamel junction (CEJ) to alveolar crest (AC), and CEJ to bottom of the bony defect (BD) were measured. In all radiographs, the linear distances CEJ to AC, and CEJ to BD were assessed using a loupe and LMSRT. Comparison between radiographic and intrasurgical assessments was performed using paired t-tests. A stepwise multiple linear regression analysis was used to evaluate factors that influence the discrepancy between radiographic and intrasurgical measurements. Both analyzing techniques underestimated interproximal bone loss as compared with intrasurgical measurements (CEJ-AC: loupe: 0.86 +/- 1.84 mm [p < 0.001]; LMSRT: 0.58 +/- 1.86 mm [p < 0.005]; CEJ-BD: loupe: 1.22 +/- 2.33 mm [p < 0.001]; LMSRT: 0.80 +/- 2.09 mm [p < 0.001]). LMSRT underestimated interproximal bone loss significantly less than the loupe (p < 0.001). The difference between LMSRT and intrasurgical assessments was modulated by the factors of vertical and horizontal angulation difference and defect depth (p < 0.1). Orthoradial projection reduced underestimation of radiographic assessment of bone loss. LMSRT underestimated interproximal bone loss to a lesser extent than conventional evaluation by loupe.

Alveolar Bone Loss↗

Potentiation of antigen-specific, Th1 immune responses by multiple DNA vaccination with an ovalbumin/interferon-gamma hybrid construct.

The preferential differentiation of T helper (Th) cells to Th1 or Th2 subsets is important with respect to susceptibility or resistance to particular infections, or to autoimmune diseases and allergic diseases. To more effectively drive immune responses toward antigen-specific Th1 responses, we constructed a mammalian expression vector (pOVA/IFN-gamma) carrying a hybrid gene in which the ovalbumin (OVA) (a model antigen) cDNA was covalently linked to murine interferon-gamma (IFN-gamma) cDNA. Intramuscular injection of BALB/c mice with the pOVA/IFN-gamma DNA increased both the production of OVA-specific IFN-gamma by CD4+ T cells and the ratio of anti-OVA immunoglobulin G (IgG) 2a to IgG1 isotypes, while the injection with the pOVA alone, or with the mixture of the pOVA and pIFN-gamma, caused no or little increase. Furthermore, the OVA-specific, Th1 immune responses were dramatically augmented by multiple injections with the pOVA/IFN-gamma DNA. These studies indicate that the direct linkage of an OVA gene to an IFN-gamma gene in the expression plasmid is required for efficiently confining the Th1 effects of IFN-gamma to the OVA-specific cells, and the linkage effect of the OVA/IFN-gamma DNA can be potentiated by multiple vaccination.

Animals↗

An experimental study on thrombogenicity of various metallic microcoils with or without thrombogenic coatings.

RATIONALE AND OBJECTIVES: Various metallic microcoils have been used as effective embolic materials (stainless steel, tungsten, and platinum). It also has been reported in several articles that the thrombogenicity of coils increased after soaking in thrombin solutions. To compare the thrombogenicity, the authors performed in vitro study, measuring whole blood clotting time (WBCT) of the various microcoils with and without coating with thrombin, gelatin, or both gelatin and thrombin. METHODS: Stainless steel, tungsten, and platinum microcoils were used in the study. For thrombin coating, the microcoils were soaked in 4 U/mL thrombin solution for 5 minutes, dried for 30 minutes, then soaked and dried again. For gelatin coating, the microcoils were soaked in 10% gelatin solution for 15 minutes, dried for 30 minutes, then soaked and dried again. For dual coating with both gelatin and thrombin, they were soaked in 10% gelatin solution first for 15 minutes, dried for 45 minutes, and soaked in 4 U/mL thrombin solution for 5 minutes, and dried. The authors introduced 1 mL of fresh blood immediately into the test tube containing the microcoil, and measured the time taken for complete coagulation of the 1 mL blood (WBCT). RESULTS: Untreated stainless steel, tungsten, and platinum microcoils reduced WBCT from 15.76 minutes to 7.15, 5.64, and 7.27 minutes, respectively. Stainless steel microcoils after soaking in thrombin, gelatin, and both gelatin and thrombin solutions showed WBCT of 5.77, 5.82, and 4.44 minutes, respectively. Tungsten microcoils after soaking in thrombin, gelatin, and both gelatin, and thrombin solutions showed WBCT of 3.25, 4.95, and 3.67 minutes, respectively. Platinum microcoils after soaking in thrombin, gelatin, and both gelatin and thrombin solutions showed WBCT of 5.70, 10.01, and 6.27 minutes, respectively. CONCLUSIONS: Untreated tungsten microcoils showed superior clot promoting activity compared with untreated stainless steel and platinum microcoils. Clot promoting activity of microcoils was increased after coating with thrombin, or both gelatin and thrombin compared with untreated microcoils.

Embolization, Therapeutic↗

Regenerative periodontal surgery with non-resorbable and biodegradable barriers: results after 24 months.

The aim of the present study was to compare the effects of guided tissue regeneration (GTR) with non-resorbable (ePTFE) and biodegradable barriers (Polyglactin 910). 23 patients provided 29 pairs of similar contralateral periodontal defects (12 pairs of interproximal intrabony lesions, 11 pairs of degree II and 6 pairs of degree III furcation defects). Each defect was randomly assigned to treatment with either non-resorbable (control [c]) or biodegradable (test [t]) devices. At baseline, 6, 12, 18, and 24 months after surgery, clinical measurements (PlI, GI, PPD, PAL-V, PAL-H) were performed. Standardized radiographs were obtained at baseline 12 and 24 months postsurgically. On the radiographs, the linear distances from the cemento-enamel junction (CEJ) to the alveolar crest (AC) and from the CEJ to bottom of the bony defect (BD) were measured using a computer-assisted analysing method (LMSRT). Both treatments revealed a significant (p<0.05) PPD reduction [all defects: -2.97 +/- 1.90 mm (t), -2.21 +/- 1.73 mm (c); intrabony defects: -4.00 +/- 1.96 mm (t), -3.00 +/- 1.87 mm (c); degree II furcations: -2.67 +/- 0.97 mm (t), -2.08 +/- 1.54 mm (c)], PAL-V gain [all defects: 2.02 +/- 1.83 mm (t), 1.18 mm +/- 1.50 (c); intrabony defects: 3.45 +/- 1.48 mm (t), 1.95 +/- 1.64 mm (c); degree II furcations: 1.33 +/- 0.94 mm (t), 0.92 +/- 1.47 mm (c)], PAL-H gain [degree II furcations: 2.22 +/- 0.94 mm (t), 1.86 +/- 0.60 mm (c)], and radiographic changes [CEJ-AC: -0.56 +/- 1.98 mm (t), -0.06 +/- 1.19 mm (c); CEJ-BD: 2.10 +/- 1.92 mm (t), 1.24 +/- 2.04 mm (c)] after 24 months. For degree III furcations, neither statistically significant PPD reduction nor PAL-V gain was observed. Similar clinical and radiographic results were found 12 and 24 months after surgical treatment using either non-resorbable or biodegradable barriers. More favorable results concerning PAL-V gain in interproximal intrabony defects could be observed with biodegradable barriers after 24 months than using nonresorbable membranes. Whereas interproximal intrabony lesions and degree II furcation defects responded favorably to GTR therapy, through-and-through furcations must be looked upon as a contraindication for this regenerative technique. Based on the results of the present study, the use of biodegradable barriers in GTR may be recommended and, thereby, a surgical re-entry to remove nonresorbable barriers can be avoided.

Adult↗

Invasive pulmonary aspergillosis: prediction at thin-section CT in patients with neutropenia--a prospective study.

PURPOSE: To evaluate prospectively the usefulness of thin-section computed tomography (CT) in the prediction of biopsy-proved invasive pulmonary aspergillosis in patients with neutropenia. MATERIALS AND METHODS: In 11 consecutively seen neutropenic patients, 12 open-lung biopsies were performed prospectively for suspected angioinvasive (n = 10) or airway-invasive (n = 2) pulmonary aspergillosis. Thin-section CT findings in the patients with angioinvasive pulmonary aspergillosis were reviewed, and the findings were compared with those of other diseases. RESULTS: Five of 12 biopsy specimens were positive for angioinvasive pulmonary aspergillosis; none was positive for airway-invasive pulmonary aspergillosis. In five (50%) of 10 cases, suspicion of angioinvasive pulmonary aspergillosis proved to be correct. The most common CT findings were segmental areas of consolidation plus ground-glass attenuation (four of five cases [80%]) and at least one nodule surrounded by a halo (two of five cases [40%]). Segmental areas of consolidation plus ground-glass attenuation were seen as isolated findings in three and mixed findings with nodules that have a surrounding halo in one case. In two patients, at least one nodule with a halo was an isolated finding in one patient and a mixed finding in one patient. Mucormycosis, organizing pneumonia, and pulmonary hemorrhage produced similar findings. CONCLUSION: At thin-section CT, segmental areas of consolidation plus ground-glass attenuation or at least one nodule with the halo sign were seen in patients with invasive pulmonary aspergillosis. The findings were nonspecific, however, and can be seen in neutropenic patients with mucormycosis, organizing pneumonia, or pulmonary hemorrhage.

Adolescent↗

Cloning and expression of rat lung acidic Ca(2+)-independent PLA2 and its organ distribution.

A clone for a rat acidic Ca(2+)-independent phospholipase A2 (aiPLA2) was isolated from a cDNA library prepared from rat granular pneumocytes with a probe based on the human aiPLA2 sequence (T.S. Kim, C.S. Sundaresh, S. I. Feinstein, C. Dodia, W. R. Skach, M. K. Jain, T. Nagase, N. Seki, K. Ishikawa, N. Nomura, and A. B. Fisher. J. Biol. Chem. 272: 2542-2550, 1997). In addition, a consensus sequence for mouse aiPLA2 was constructed from several mouse cDNA clones in the GenBank and dbEST databases. Each sequence codes for a 224-amino acid protein with 88% identity of the amino acids among the three species and conservation of a putative lipase motif (GDSWG). Translation of mRNA produced from the rat clone in a wheat germ system resulted in expression of PLA2 activity with properties similar to those of the human enzyme, i.e., acidic pH optimum and Ca2+ independence. The localization of aiPLA2 in rat tissues was studied with the human cDNA probe, polyclonal and monoclonal antibodies, and aiPLA2 activity. aiPLA2 is present in the lung as evidenced by high levels of mRNA and protein expression and by enzymatic activity that is inhibited by anti-PLA2 antibody and by the transition state analog 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33). Immunocytochemistry showed the presence of aiPLA2 in alveolar type II cells, alveolar macrophages, and bronchiolar epithelium. In the brain, heart, liver, kidney, spleen, and intestine, aiPLA2 mRNA content was < 50% of that in the lung, immunoreactive protein was not detectable, and enzymatic activity was not inhibited by MJ33 or aiPLA2 antibody. These results show marked enrichment of aiPLA2 in the lung compared with the other organs and suggest translational control of aiPLA2 expression.

Amino Acid Sequence↗

Four years' experiences in the treatment of pituitary adenomas with gamma knife radiosurgery.

To determine the tumor control rates and endocrinological responses after stereotactic radiosurgery for pituitary adenomas, we reviewed our experience in 65 patients (40 men, 25 women) treated in the Gamma Knife during the last 4 years. The mean age was 41.6 years (range 19-69 years). 43 patients had endocrinologically active tumors (20 growth hormone-secreting, 19 prolactin-secreting and 4 ACTH-secreting adenomas). 22 had nonfunctioning adenomas. 39 patients had a macroadenoma and 26 patients had a microadenoma. 33 patients underwent Gamma Knife radiosurgery for recurrent or residual tumors after microsurgery. 50 patients have had follow-up neuroimaging studies and/or hormonal evaluation. The follow-up period was 25.5 months (range 3 to 54 months). The margin of the tumor was incorporated within the 50 to 90% isodose. The mean number of isocenters was 3.8 and the mean marginal dose was 25.4 Gy (range 15 to 36 Gy). 27 out of 40 patients (65.7%) showed decreased tumor volume to less than 50% of the initial volume. In 17 out of 38 patients (44.7%) with endocrinologically active tumors, the hormonal level fell to within the normal range. Two patients had delayed complications: in one case there was pituitary insufficiency and in the other a visual disturbance. Gamma Knife radiosurgery seems to be effective adjuvant therapy for pituitary adenoma in selected cases. More long-term follow-up is required to evaluate the efficacy and side effects further.

Acromegaly↗

Reproducibility and validity of the assessment of clinical furcation parameters as related to different probes.

The aim of this study was to investigate the reliability of the assessment of clinical furcation parameters (horizontal attachment levels [CAL-H], class of furcation invasion). Replicate measurements of CAL-H and furcation class were performed within 14 days in 420 molars of 105 patients with advanced periodontitis using a Nabers- (n=50), a TPS- (n=30) and a PCPUNC15-probe (n=25). Validity of clinical assessments was assessed by intrasurgical measurements. The standard deviation of single measurements (s) was calculated as a measure of the reproducibility of CAL-H measurements and weighted kappa-coefficients (Kw) to estimate the agreement of furcation class assessments. The s ranged from 0.55 to 1.13 mm (Nabers), 0.55 to 1.02 mm (TPS), and 0.58 to 1.11 mm (PCPUNC15). For all probes, a statistically significantly smaller measurement error was observed in buccal and lingual sites than in mesiolingual and distolingual furcations (P < 0.005). The Kw ranged from 0.59 to 0.89 (Nabers), 0.50 to 0.80 (TPS), and 0.53 to 0.72 (PCPUNC 15). Multiple linear regression analysis identified distolingual location, probing depth (PD) and CAL-H as factors influencing the variability of CAL-H measurements. Whereas there was no statistically significant difference between pre- and intrasurgical CAL-H measurements using the Nabers probe, the TPS and PCPUNC15 probe underestimated CAL-H for distolingual furcations (P < 0.025). Using the Nabers probe, no asymmetries between pre- and intrasurgically obtained class of furcation involvement were revealed, while the TPS and PCPUNC15 probe underestimated furcation degrees (P < 0.1). Multiple linear regression analysis identified distolingual location and height of furcation, as well as PD, vertical attachment level (CAL-V) and type of probe, as factors influencing the validity of CAL-H measurements. Clinical diagnosis of furcation lesions using the 3 mm incrementally marked Nabers probe provides reproducible and valid information about furcation invasion.

Adult↗

Computed radiography of the chest in patients with paraesophageal varices: diagnostic accuracy and characteristic findings.

OBJECTIVE: The purpose of our study was to determine the diagnostic accuracy of computed radiography of the chest in the detection of paraesophageal varices and to describe the characteristic radiographic findings. SUBJECTS AND METHODS: From June 1995 through May 1997, in 100 consecutive patients, portal hypertension was diagnosed through both clinical and radiologic evidence. Computed radiographs of the chest and hepatic helical CT scans of these 100 patients with portal hypertension and 20 control subjects were analyzed by two chest radiologists and one abdominal radiologist, who were not aware of the results of the other study. RESULTS: On CT, paraesophageal varices were seen in 38 (38%) of 100 patients with portal hypertension. Overall, the sensitivity, specificity, and accuracy of chest computed radiography in the detection of paraesophageal varices were 53% (20/38), 90% (74/82), and 78% (94/120), respectively. In the patients with paraesophageal varices, splenomegaly (29/38, 76%), lateral displacement or obliteration of the inferior portion of the azygoesophageal interface (18/38, 47%), obliteration or nodularity of the inferior portion of the descending thoracic aorta interface (9/38, 24%), lateral displacement of the right inferior paraspinal interface (6/38, 16%), lateral displacement of the left inferior paraspinal interface (4/38, 11%), and varices in the left inferior pulmonary ligament (1/38, 3%) were seen on chest computed radiographs. Paraesophageal varices smaller than the diameter of the descending thoracic aorta (usually <2.5 cm) were not detected. CONCLUSION: Although chest computed radiography is only moderately sensitive for paraesophageal varices, the findings are characteristic when well developed, with a limited differential diagnosis. Splenomegaly, whether detected clinically or radiographically, eliminates most other diagnostic possibilities.

Adult↗

Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings.

OBJECTIVE: The purpose of our study was to describe high-resolution CT findings of nonspecific interstitial pneumonia with fibrosis and to compare findings seen on CT with pathologic findings. MATERIALS AND METHODS: High-resolution CT findings of biopsy-proven non-specific interstitial pneumonia with fibrosis from 23 consecutive patients (one man and 22 women) were analyzed retrospectively by two chest radiologists. CT findings were compared with pathologic findings. RESULTS: The predominant high-resolution CT finding, seen in all patients, was bilateral patchy areas of ground-glass opacity with (35%) or without (65%) areas of consolidation. Irregular linear opacities (87%), thickening of bronchovascular bundles (65%), and bronchial dilatation (52%) were also frequently seen. Honeycombing was not seen in any patient. All parenchymal abnormalities showed subpleural predominance. Areas of ground-glass opacity with or without irregular linear opacity or bronchial dilatation on CT corresponded pathologically to areas of interstitial thickening caused by varying degrees of interstitial inflammation and fibrosis showing temporal uniformity. Areas of consolidation, seen at five biopsy sites, represented the areas of bronchiolitis obliterans organizing pneumonia, foamy cell collections in alveolar spaces, or microscopic honeycombing with mucin stasis. CONCLUSION: On high-resolution CT, nonspecific interstitial pneumonia with fibrosis is most commonly revealed as patchy subpleural areas of ground-glass opacity mixed with irregular linear opacity or bronchial dilatation. These areas represent interstitial thickening caused by varying degrees of interstitial inflammation, fibrosis, or both.

Adult↗

Telomerase activity and telomere lengths in various cell lines: changes of telomerase activity can be another method for chemosensitivity evaluation.

For the cancer cells which have overcome the second mitotic clock (M2), activated telomerase is essential and used as another marker of immortality. Many trials had been initiated to target telomerase, which is known to be specific to tumors. To determine the best in vitro cell system for testing the efficacy of telomerase inhibitors, we evaluated the telomerase activity of various cancer cell lines and measured their telomere lengths. We also treated some cancer cell lines with adriamycin and measured the changes of telomerase activity. Telomerase activity was evaluated in various cell lines with the TRAP (telomeric repeat amplification protocol) assay. Telomerase activity was calculated and translated into arbitrary units by computer-assisted densitometry with the control of telomerase activity in the 293 control cell line. Also, terminal restriction fragment lengths were measured using Southern blotting. We also measured telomerase activity and telomere lengths in 11 benign breast tumor tissues and 19 paired stomach cancer and normal tissues. Cancer cell lines treated with adriamycin we evaluated for changes of telomerase activity and the cell proliferation by MTT assay and dye exclusion test. Telomerase activity of cell lines was 95.3 24.1 unit with a range of 27.6-129.6 unit, while the telomere lengths of those cell lines were variable from 5.0 to 10.4 kbp with a median of 6 kbp. In 11 cancer cell lines which were not yet firmly established, we could not detect any telomerase activity. Low telomerase activity was detected in only 2 benign tumor tissues of breast with a median telomere length of 8.8 (7-10.5) kbp. Among paired 19 gastric cancer and normal tissues, only 7 cancer tissues showed weak telomerase activity. After adriamycin treatment, telomerase activity in YCC-S-1, YCC-S-3, MCF-7 and MCF-7/ADR was decreased in accordance with the changes of the cell numbers. Telomerase is specific to cancer tissues and is expressed differently from organ to organ. Telomerase activity by TRAP assay could be used as a chemosensitivity assay.

Breast Diseases↗

The Na/Ca-K exchanger of rod photoreceptor exists as dimer in the plasma membrane.

The oligomeric state of the Na/Ca-K exchanger in the plasma membrane of bovine photoreceptors was investigated using chemical cross-linking techniques. In the natural membrane, virtually all Na/Ca-K exchanger could be cross-linked mainly to a complex having an apparent molecular mass of 490 kDa by cupric phenanthroline catalyzed disulfide bonding as evidenced by Western blotting. Stable cross-links of the exchanger were also obtained with the thiol-specific reagent N,N'-p-phenylidenedimaleimide. Neuraminidase treatment reduced the apparent molecular mass of the highly glycosylated Na/Ca-K exchanger and of the 490 kDa cross-link product by 50 and 85 kDa, respectively. DL-1,4-Bismaleimido-2,3-butanediol (BMBD), a novel cleavable dimaleimide, was synthesized in order to produce cross-links that were stable to reductive conditions. Purification of the BMBD cross-linked exchanger followed by two-dimensional SDS polyacrylamide electrophoresis identified the cross-linked homodimers of the exchanger. There was no indication of higher oligomers, suggesting that the exchanger exists as a dimer in the plasma membrane. Hydrodynamic properties of the detergent-solubilized exchanger were determined by velocity sedimentation and gel filtration chromatography. The Triton X-100-solubilized exchanger ran as a single species having a Stokes radius of 10.0 nm, a sedimentation coefficient of 5.4 S, and a partial specific volume of 0.74 mL/g in Triton X-100. Similar results were obtained for the CHAPS-solubilized exchanger. A molecular mass of 236 and 205 kDa was calculated for the exchanger-detergent complex and the detergent-free protein, respectively. Neuraminidase treatment further reduced the molecular mass of the exchanger indicating that glycosylation contributes significantly to the mass of the exchanger. Cross-links of the exchanger were not detected if cross-linking was attempted after solubilization in 10 mM CHAPS. However, after reconstitution of the purified exchanger into soybean phosphatidylcholine vesicles, chemical cross-linking yielded again dimers. On the basis of these cross-linking and hydrodynamic studies, we conclude that the exchanger exists as a homodimer in the rod outer segment plasma membrane but dissociates into a monomer when solubilized in detergent.

Animals↗

An ovalbumin-IL-12 fusion protein is more effective than ovalbumin plus free recombinant IL-12 in inducing a T helper cell type 1-dominated immune response and inhibiting antigen-specific IgE production.

Optimal treatment of allergic diseases requires that the cytokine profile of allergen-specific T cells be redirected, with the conversion of Th2 profiles into Th1 cytokine profiles. This conversion, however, is difficult, since Th2 effector cells have relatively fixed cytokine profiles. To more effectively redirect the cytokine profiles of T cells, we constructed a cytokine fusion protein that contained the Ag OVA, fused to IL-12. Immunization with the OVA-IL-12 fusion protein induced anti-OVA IgG2a Ab and large quantities of OVA-specific IFN-gamma production. The Ag specificity of this response was dependent upon covalent linkage of Ag and IL-12, since immunization of mice with OVA alone induced little or no IFN-gamma, while immunization with OVA and free rIL-12 enhanced T cell production of IFN-gamma, but the IFN-gamma production was not OVA specific. To examine the effects of OVA-IL-12 in reversing ongoing Th2-dominated immune responses, BALB/c mice previously primed with OVA in alum to induce a Th2-dominated response, were vaccinated with the OVA-IL-12 protein. In such mice, OVA-IL-12 was much more effective than OVA plus free rIL-12 in significantly increasing Ag-specific IFN-gamma production and significantly decreasing Ag-specific IL-4 production. Moreover, OVA-IL-12 increased serum anti-OVA IgG2a and decreased anti-OVA IgE. These studies indicate that OVA-IL-12 can convert immune responses characterized by high IL-4 and high IgE synthesis into Th1-dominated responses in an Ag-specific manner.

Animals↗

Identification of a human cDNA clone for lysosomal type Ca2+-independent phospholipase A2 and properties of the expressed protein.

A Ca2+-independent phospholipase A2 (PLA2) maximally active at pH 4 and specifically inhibited by the transition-state analogue 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33) was isolated from rat lungs. The sequence for three internal peptides (35 amino acids) was used to identify a 1653-base pair cDNA clone (HA0683) from a human myeloblast cell line. The deduced protein sequence of 224 amino acids contained a putative motif (GXSXG) for the catalytic site of a serine hydrolase, but showed no significant homology to known phospholipases. Translation of mRNA produced from this clone in both a wheat germ system and Xenopus oocytes showed expression of PLA2 activity with properties similar to the rat lung enzyme. Apparent kinetic constants for PLA2 with dipalmitoylphosphatidylcholine as substrate were Km = 0.25 mM and Vmax = 1.89 nmol/h. Activity with alkyl ether phosphatidylcholine as substrate was decreased significantly compared with diacylphosphatidylcholine. Significant lysophospholipase, phospholipase A1, or 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase activity was not observed. Enzyme activity was insensitive to p-bromophenacyl bromide, bromoenol lactone, trifluoromethylarachidonoyl ketone, mercaptoethanol, and ATP, but was inhibited by MJ33 and diethyl p-nitrophenyl phosphate, a serine protease inhibitor. SDS-polyacrylamide gel electrophoresis with autoradiography of the translated [35S]methionine-labeled protein confirmed a molecular mass of 25.8 kDa, in good agreement with the enzyme isolated from rat lung. By Northern blot analysis, mRNA corresponding to this clone was present in both rat lung and isolated rat granular pneumocytes. These results represent the first molecular cloning of a cDNA for the lysosomal type Ca2+-independent phospholipase A2 group of enzymes.

Amino Acid Sequence↗

Guided tissue regeneration with non-resorbable and biodegradable barriers: 6 months results.

The aim of the present study was to compare the effects of guided tissue regeneration (GTR) with non-resorbable (ePTFE [G]) and biodegradable barriers (Polyglactin 910 (V)). In 20 patients, providing 25 pairs of symmetrical periodontal defects (7 pairs of interproximal intrabony lesions, 12 pairs of degree II and 6 pairs of degree III furcation involvement), each defect was randomly assigned to treatment with either non-resorbable (control) or biodegradable (test) devices. At baseline and 6 months after surgery, clinical measurements (GI, PPD, PAL-V, PAL-H, P1I) and standardized radiographs were obtained. On the radiographs, the linear distances from the cemento-enamel junction (CEJ) to the alveolar crest (AC), and from the CEJ to bottom of the bony defect (BD) were measured using a computer-assisted analysing method (LMSRT). Both treatments revealed a significant (p < 0.05) PPD reduction (-2.90 +/- 1.33 mm (V), -2.71 +/- 1.41 mm (G)), PAL-V gain (1.78 +/- 1.27 mm (V), 1.46 +/- 1.35 mm (G)), PAL-H gain (2.00 +/- 0.82 mm (V), 1.60 +/- 0.59 mm (G)), and radiographic changes (CEJ-AC: 0.48 +/- 0.75 mm (V), 0.73 +/- 0.92 mm (G); CEJ-BD: -0.76 +/- 0.79 mm (V), -0.41 +/- 0.72 mm (G)) after 6 months. The mean differences between the changes for test and control were not significant for most clinical and radiographic parameters. Similar clinical and radiographic results were found 6 months after surgical treatment using either non-resorbable or biodegradable barriers. More favorable results concerning PAL-H gain could be observed with biodegradable barriers after 6 months. Therefore, based on these results, the use of biodegradable barriers in GTR may be recommended and, thereby, a surgical re-entry to remove non-resorbable barriers can be avoided.

Adult↗