Transglutaminase 2 is dispensable but required for the survival of mice in dextran sulfate sodium-induced colitis

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes crosslinking, polyamination or deamidation of glutamine residues in proteins. It has been reported that TG2 is involved in the pathogenesis of various inflammatory diseases including celiac disease, pulmonary fibrosis, cystic fibrosis, multiple sclerosis and sepsis. Recently, using a mouse model of bleomycin-induced lung fibrosis, we showed that TG2 is required to trigger inflammation via the induction of T helper type 17 (Th17) cell differentiation in response to tissue damage. However, the role of TG2 in inflammatory bowel disease (IBD), which is thought to be a Th17 cell-associated disease, has remained elusive. In this study, we investigated the role of TG2 in dextran sulfate sodium (DSS)-induced colitis, the most widely used mouse model for IBD. Age- and sex-matched wild-type and TG2(−/−) mice were fed 2% DSS for 7 days or 3.5% DSS for 5 days in drinking water. An in situ TG activity assay revealed that DSS treatment activates TG2 in various colon cell types, including columnar absorptive cells and goblet cells. DSS-treated TG2(−/−) mice showed lower interleukin (IL)-6, but higher IL-17A and RORγt (retinoic acid receptor-related orphan receptor-γt) expression levels in the colon tissues than that in the wild-type mice. Moreover, TG2(−/−) mice showed higher mortality than the wild-type mice because of DSS treatment. Nevertheless, we found no significant differences in changes of body weight, colon length, morphology, immune cell infiltration and in vivo intestinal permeability between DSS-treated wild-type and TG2(−/−) mice. These results indicate that TG2-mediated Th17 cell differentiation is not required for the pathogenesis of DSS-induced acute colitis.

Transglutaminase 2 inhibits apoptosis induced by calciumoverload through down-regulation of Bax

An abrupt increase of intracellular Ca2+ is observed in cells under hypoxic or oxidatively stressed conditions. The dysregulated increase of cytosolic Ca2+ triggers apoptotic cell death through mitochondrial swelling and activation of Ca2+-dependent enzymes. Transglutaminase 2 (TG2) is a Ca2+-dependent enzyme that catalyzes transamidation reaction producing cross-linked and polyaminated proteins. TG2 activity is known to be involved in the apoptotic process. However, the pro-apoptotic role of TG2 is still controversial. In this study, we investigate the role of TG2 in apoptosis induced by Ca2+-overload. Overexpression of TG2 inhibited the A23187-induced apoptosis through suppression of caspase-3 and -9 activities, cytochrome c release into cytosol, and mitochondria membrane depolarization. Conversely, down-regulation of TG2 caused the increases of cell death, caspase-3 activity and cytochrome c in cytosol in response to Ca2+-overload. Western blot analysis of Bcl-2 family proteins showed that TG2 reduced the expression level of Bax protein. Moreover, overexpression of Bax abrogated the anti-apoptotic effect of TG2, indicating that TG2-mediated suppression of Bax is responsible for inhibiting cell death under Ca2+-overloaded conditions. Our findings revealed a novel anti-apoptotic pathway involving TG2, and suggested the induction of TG2 as a novel strategy for promoting cell survival in diseases such as ischemia and neurodegeneration.

Characteristics and Treatment of Steinstrasse after ESWL / 대한비뇨기과학회지

To evaluate the predisposing factors and characteristics of the steinstrasse after ESWL and to suggest the proper management of it, we analyzed 1,144 urolithiasis patients who were managed by ESWL with the second generation lithotripter, Siemens Lithostar, at Seoul National University Hospital from March 1989 to October 1995. Steinstrasse developed in 72 patients with the incidence of 6.3% after ESWL. As the risk factor for developing steinstrasse after ESWL, stone size and volume significantly influenced the development of steinstrasse (p<0.01, by student t-test), and multiple stones induced steinstrasse more frequently than single stones (p<0.05, by chi-square test). Stones located at renal pelvis induced more steinstrasse after ESWL than calyceal stones or ureter stones t<0.05, by chi-square test). Clinically, 61.1% of the patients who developed steinstrasse didn't have any symptoms or upper tract changes. Nineteen steinstrasse (26.4%) were resolved spontaneously without any intervention, with the median duration of 12 days after detection of the steinstrasse. In 51 steinstrasse which was not resolved spontaneously or with severe symptoms, ESWL was performed resulting in successful resolution in 94.1% of the patients. These results suggest that expectancy could be the first line strategy of the management of steinstrasse, and repeated ESWL could be recommended for patients refractory to expectancy and patients with severe symptoms.

Ureteroscopic Manipulation for Ureteral Calculi: Comparison with ESWL / 대한비뇨기과학회지

Ureteroscopy has been used widely to remove ureteral calculi, especially distal ureter stones. Also extracorporeal shock wave lithotripsy (ESWL) has widened its applicability to ureter stones including distal ureter stones. In this study we tried to evaluate the exact role of ureteroscopic manipulation to get rid of ureter stones in the era of ESWL. Success rates and complications of 111 ureteroscopic stone removal procedures performed from December 1986 to May 1995 and those of another 369 patients managed with ESWL from May 1989 to May 1995 were analyzed. Success was defined as complete removal of the stones or residual stones less than 2 mm, immediate postoperatively in ureteroscopic manipulation and 2 weeks after ESWL. The success rate of the ureteroscopic manipulation was 38.9% (7/18), 46.2% (6/13) and 67.5% (54/80) in upper, middle and lower ureter stones, respectively. According to the size of the stone, success rate was 72.4% (21/29), 63.5% (40/63) and 14.3% (9/63) when it was less than 5 mm, 6 to 10 mm and larger than 10 mm. So the overall immediate postoperative success rate of ureteroscopic stone removal was 60.4%, and in another 8.9% of the patients the residual fragmented stones were expelled spontaneously in one month after the procedure. Complications were found in 9.9% of the procedures, including 5 mucosal avulsions and 2 ureteral strictures Success rate of the single session of ESWL was 64% without any differences regardless of the location of the stones in ureter, and it increased up to 88% when another 2 more sessions were tried. Success rate of the single session of ESWL according to the size of the stone was 91.7% (22/24), 67.9% (144/215) and 53.89S (70/130) in stones less than 5 mm, 6 to 10 mm and more than 10 mm, respectively. Complications were found in 3.4% of the patients, including 1.7% of steinstrasse and 1.4% of severe nausea and vomiting. From these observations we can conclude that it seems to be mandatory to renovate the indications of the ureteroscopic stone removal procedures in the era of ESWL.

The Efficacy of Terazosin in the Treatment of Benign Prostatic Hyperplasia: A Randomized, Placebo-controlled Double Blind Study / 대한비뇨기과학회지

Since it has shown that the smooth muscle is the dominant cellular constituent of the hyperplastic prostate and outlet obstruction in benign prostatic hyperplasia (BPH) is mediated by sympathetic nerve system via prostatic smooth muscle alpha 1 receptor, various kinds of alpha blocker have been tried in the treatment of BPH with moderate effectiveness. From May 1994 to December, 1994, a randomized placebo-controlled double blind study of long-acting selective alpha 1 blocker terazosin was undertaken to evaluate short-term effects of pharmacotherapy for BPK Of 80 patients with symptomatic BPH who were randomized to receive placebo or terazosin, 42 completed the study. At baseline, the irritative, obstructive and total symptom score (mean+/-SD) were 8.4+/-3.3, 11.8+/-4.9, 20.2+/-7.6 in placebo group and 8.3+/-4.3, 12.1 +4.6, 20.4 +7.3 in terazosin group and the peak and mean urinary flow rate (ml/ sec) were 10.7+/-2.6 and 5.5+/-2.0 in placebo group and 9.8+/-3.6 and 5.1+/-2.1 in terazosin group. After 28 days trial, the irritative, obstructive and total symptom score (mean+/-SD) were 7.4+/-3.8, 9.3+/-5.6, 16.8+/-9.2 in placebo group and 5.2+/-3.6, 6.2+/-4.0,11.4+/-6.6 in terazosin group(p<0.05, p<0.05 and p<0.01) and the peak and mean urinary flow rate (ml/sec) were 11.1+/-5.1 and 5.8+/-3.1 in placebo group and 14.7+/-6.4, 8.0+/-3.9 in terazosin group. (p<0.01 and p<0.01) At least 30% improvement in total symptom score and peak flow rate were observed in 67% (14/21) and 76% (16/21) of patients respectively in terazosin group. The common side effects were mild dizziness in 5(22%) in terazosin group and 1(5%) in placebo group but premature termination was observed in only 2(9%) patients in terazosin group and 1(5%) in placebo group. The mean change in baseline systolic pressure was 2mmHg for normotensive group and 19mmHg for hypertensive group. In conclusion, this study showed beneficial short term result for the safety and efficacy of long acting selective alpha 1 blocker terazosin in the management of symptoms of BPH However, the durability of the safety and efficacy of terazosin needs to be evaluated for longer periods.

An Experimental Study of the Effect of Ginkgo biloba Extract on the Human and Rabbit Corpus Cavernosum Tissue / 대한비뇨기과학회지

The Ginkgo bi1oba extract (GBE) is a complex enriched with many active ingredients prepared from the leaves of Ginkgo biloba, several components of which are known to have vasoregulatory activity of arteries, capillaries and veins resulting in increased blood flow. Among the fractions of GBE, nonginkgolide nonflavonoid fraction (NGF) has the most potent relaxing effect on vascular smooth muscle. We subfractionated NGF and speculated that some of subfractions might have very potent relaxing effect on corpus cavernosal smooth muscle in both human and animals. To investigate the effect of subfractions of NGF on the corpus cavernosal smooth muscle and the possibility whether they could be used for the treatment of impotence, we have studied on the human and rabbit corpus cavernosum using organ bath and electrical field stimulation experiments. The results suggested that subfractions of NGF, especially 304U-1, have relaxing effect on corpus cavernosum tissue. 304U-1 which showed the most potent relaxing effect can be possibly used as a drug for intracavernosal injection therapy. Considering the fact that the value of ED50 is too high, further fractionation and in vivo study are needed before clinical usage in an oral form.

Effect of Freezing Method, Thawing Temperature and Post-thaw Dilution/Washing on Motility and Morphology Characteristics of High-quality Human Sperm / 대한비뇨기과학회지

Ten semen samples of high initial quality donated by fertile men were processed to compare the effect of two freezing methods, two thawing temperatures and the effect of dilution and washing on sperm motility (CASA) and morphologic characteristics (stricter criteria). Semen samples were divided in two equal parts and frozen either by fast vapour freezing or by slow computer-controlled freezing. For each freezing method, half of the straws were thawed at room temperature (22 degrees C), the other half were thawed at 37 degrees C. From each freeze-thawing treatment, one straw was evaluated immediately post-thawing; another straw was washed to remove the cryoprotectant solution. In this way, each semen sample was subjected to eight freeze-thawing treatment. The freezing and thawing of each semen sample was uniformly associated with a decrease in a sperm quality. The most commonly observed adverse effect was severe impairment of sperm motility. No effect of the freezing method and thawing temperature was observed on motility characteristics evaluated by computer-assisted semen analysis, nor on morphology parameters evaluated by stricter criteria. Only in regard to normal morphology was computer-controlled freezing slightly superior to fast vapour freezing. Post-thaw dilution and washing exerted a detrimental effect on sperm motility by reducing percentage motility by 30% - 40% compared to unwashed thawed specimens. Post-thaw dilution and washing obviously impaired normal morphology of spermatozoa by increasing percentage of small heads while linearity was increased significantly. Freezing-thawing was most effective when fast vapour freezing was followed by 37 degrees C thawing , and when slower computer-controlled freezing was combined with 22 degrees C thawing, causing linearity increased significantly Otherwise significant interactions between the freezing method and the thawing temperature were not observed. From these data, we think that vapour freezing is similar to computer-controlled freezing for high-quality semen in terms of recovery of morphologically normal with adequate progressive motility. For cryopreservation flow quality spermatozoa from patients, the effect of each freeze-thawing treatment is eligible for testing in another study.

In Situ Extracorporeal Shock Wave Lithotripsy for Ureteral Calculi: Investigation of the Factors Influencing on Stone Fragmentation and the Appropriate Session for Changing Treatment Modality / 대한비뇨기과학회지

To determine the factors influencing on stone fragmentation and the appropriate session for changing treatment modality of ureteral calculi refractory to in situ ESWL, we analyzed 369 patients with ureteral calculi primarily treated by second-generation lithotripter, Siemens Lithostar from March,1989 to December, 1993. The results obtained were as follows: 1.Three hundred and forty two(92.7%) of the total 369 patients were ultimately free of stones by repetitive performance of in situ ESWL ranging from the first session to the tenth session. 2. The cumulative stone-free rates of the first, second and third session were 64%, 81% and 88%, respectively, and the increment of cumulative stone-free rate thereafter with further repeated in situ ESWL was minimal(p0.05). 4. According to the size of stone, the cumulative stone-free rate at third session was 100%, 90%, 87%, 70%, 67%, 50% in stones less than 5 mm, 6-10 mm, 11-15 mm, 16-20 mm, 21-25 mm and above 25 mm, respectively(p<0.001). 5. According to the radio-opacity of stone, the cumulative stone-free rate at third session was 96% in stones with minimal opacity, 94% with moderate opacity and 70% in highly opaque stones(p<0.001). 6. According to the degree of ureteral obstruction due to stone, the cumulative stone-free rate at third session was l00% without ureteral obstruction, 80% with mild, 57% with moderate, 67% with severe ureteral obstruction, and it was 50% in patients with non-visualization of the kidney(p<0.05). From these observations, it could be concluded that the factors influencing on stone fragmentation were the size of calculi, radio-opacity and the degree of ureteral obstruction, whereas the location of the ureteral calculi did not influence on the cumulative success rate of repetitive in situ ESWL. Also, it is preferable to restrict the repetitive sessions of in situ ESWL within third session in patients with the ureteral calculi refractory to in situ ESWL, and early change of surgery would be retreatment modality either to ureteroscopic manipulation or to open commended if there are risk factors listed above.

Hypospadias Repair: Current Experience Using Operating Microscope / 대한비뇨기과학회지

Currently improving results of hypospadias repair depend on careful application of surgical principles. Optical magnification. microsurgical instruments, fine suture materials, less reactive tubes and bio-occlusive dressings have been used to decrease postoperative complications requiring secondary surgery. We evaluated the effectiveness of microscopic surgery which was performed in 28 children with hypospadias from December, 1991 to June, 1994. Nine patients underwent hypospadias repair before 2 years-old whereas 19 patients after 2 years-old, whose success rate was 78% and 63% respectively. One-stage repair was performed in 19 patients and two-stage repairs in 9 patients, whose success rate was 69% and 67% each other. In chronological review, success rate was 50%, 29%, 77% and 100% in 1991, 1992, 1993 and 1994 respectively, which showed a rapidly increasing success rate. According to dressings and catheters, excellent results were obtained when we used Duodenum dressings and silastic Foley catheters, of which each complication rate was 7% and 0% respectively. In 9 patients(32 %), we experienced 20 surgical complications which included urethrocutaneous fistula (9), meatal stenosis(4) stricture(2) and others(5). The success rate of fistula repair was 61% in initial, 40% in secondary and 33% in tertiary repair. From these data, we think that the use of operating microscope with microsurgical principles and proper postoperative managements can improve success rate of hypospadias repair.

A study on the relationship between tooth size and arch dimension in dental crowding / 대한치과교정학회지

This study was undertaken to examine relationship between tooth size and arch dimension in dental crowding. Two groups of dental casts were selected on the basis of dental crowding. One group, consisting of 51 pairs of dental casts (24 male and 27 female), exhibited remarkable dental crowding. A second group, consisting of 60 pairs of dental casts (30 male and 30 female), exhibited little or no crowding. Mean and standard deviation of the following parameters were used to compare two groups: individual and collective mesiodistal tooth diameters, buccal and lingual arch widths and arch area. The following results were obtained. 1. The crowed group revealed larger tooth size than non crowd group. (p<0.01) 2. The crowded group smaller maxillary dental arch dimension than noncrowded group except lingual arch width at canine region. (p<0.01) 3. The crowded group revealed smaller mandibular dental arch dimension than noncrowded group except lingal arch width at second premolar region in the male and buccal arch width at canine, premolar region in the female. (p<0.01) 4. The crowded group revealed smaller arch area than noncrowded group in the female (p<0.01), but there was no significance in the male.