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H K Choi

Publications and source records attributed to H K Choi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study.

OBJECTIVE: Immune-mediated cochleovestibular disorders (IMCVDs) continue to present a management challenge to the otolaryngologist. Antirheumatic agents, commonly used for IMCVDs, are associated with variable efficacy and sometimes with serious side effects. The authors describe the preliminary result of their experience in patients with IMCVDs who have been treated with etanercept, a tumor necrosis factor alpha receptor blocker, recently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care hospital. PATIENTS: Twelve patients suspected of having IMCVD who did not respond to conventional therapies or experienced side effects of the conventional therapies. INTERVENTION: Etanercept 25 mg by subcutaneous injection twice per week. MAIN OUTCOME MEASURES: The main outcome measurement was assessment of hearing change by air conduction pure tone audiograms and/or word discrimination. When present, vertigo, tinnitus, and aural fullness were assessed as well. RESULTS: Follow-up of more than 5 months was available for all patients (range, 5-12 months). Eleven (92%) of 12 patients had improvement or stabilization of hearing and tinnitus, seven (88%) of eight patients who had vertigo and eight (89%) of nine patients who had aural fullness had resolution or significant improvement of their symptoms. The benefit persisted until the last visit (5-12 months after etanercept was begun). The condition of one patient improved dramatically at first but deteriorated after 5 months. The patient's hearing was rescued and stabilized with the addition of leflunomide to etanercept. Similarly, three other patients required a second antirheumatic agent to stabilize their hearing. There were no significant side effects from the etanercept therapy. CONCLUSIONS: Our limited data suggest that etanercept therapy is safe and may be efficacious in carefully selected patients with IMCVDs, at least on a short-term basis. These preliminary efficacy and safety results appear encouraging enough to warrant further follow-up and studies for better determination of the potential clinical utility of etanercept for IMCVDs.

Adult↗
PubMed2001

Temporal relationship between the sexually dimorphic spontaneous GH secretory profiles and hepatic STAT5 activity.

STAT5 transduces transcriptional responses to GH in liver and other tissues and is proposed to mediate the sexually dimorphic effects of plasma GH secretory profiles on rodent liver gene expression. Previous studies have suggested that STAT5 undergoes repeated activation in direct response to successive GH pulses in adult male rats, with STAT5 activation being desensitized in females by their more persistent pattern of GH exposure. These findings, however, were based on in vitro studies or single blood samples analyzed for GH in vivo. In view of the highly pulsatile nature of rat GH secretion, we presently examined these hypotheses by concurrent monitoring of spontaneous GH secretory profiles and hepatic STAT5 activity in conscious, free-moving adult male and female rats. Rats were killed at times associated with spontaneous peaks or troughs of the GH rhythm; livers were removed and analyzed for STAT5 DNA-binding activity. In males, liver STAT5 activity was highest during the initial phase (15-60 min) of a GH secretory episode (mean +/- SE relative STAT5 activity = 86.5 +/- 11.4; plasma GH = 146.7 +/- 22.4 ng/ml) and was significantly lower (P < 0.01) during the downswing of a pulse, 45-75 min after the GH peak (STAT5 = 26.1 +/- 1.7; GH = 33.3 +/- 13.1 ng/ml), consistent with a time-dependent down-regulation of GH signaling to STAT5. The lowest STAT5 activity was observed during the subsequent GH trough period (STAT5 = 3.6 +/- 1.1; GH = 2.6 +/- 0.1 ng/ml). In females, liver STAT5 activity was significantly lower (P < 0.05) than peak male levels during the initial phase of a GH secretory burst (STAT5 = 35.1 +/- 15.9; GH = 68.1 +/- 31.6 ng/ml) although similar to that of males during a plasma GH nadir (STAT5 = 11.0 +/- 2.6; GH = 8.4 +/- 2.2 ng/ml). We conclude that: 1) liver STAT5 is repeatedly activated by successive, spontaneous GH secretory episodes in intact adult male rats at approximately 3- to 3.5-h intervals; 2) time-dependent down-regulation of GH signaling to hepatic STAT5 in vivo begins by 45 min after GH peak stimulation; and 3) the lower level of liver STAT5 activation seen in adult female rats, compared with males, is a consequence of the sex-dependent differences in GH secretory patterns that characterize these animals (i.e. lower-amplitude GH pulses and lack of prolonged interpulse nadir of GH in the feminine, compared with masculine profile).

Animals↗
PubMed2001

Conjugation of Arg-Gly-Asp (RGD) sequence in copolymer bearing sugar moiety for insulinoma cell line (MIN6) culture.

Copolymers composed of an Arg-Gly-Asp (RGD) sequence for the adhesion molecule and sugar moieties were synthesized for an insulinoma cell (MIN6) culture. MIN6 cells attached on the poly(N-p-vinylbenzyl-D-maltonamide-co-6-(p-vinylbenzamido)-hexanoic acid-g-GRGDS) (p(VMA-co-VBGRGDS))-coated dishes were in a more aggregated form than other polymer-coated surfaces. P(VMA-co-VBGRGDS) also shows faster proliferation of MIN6 cells (about 18% higher) than with p(VLA-co-VBGRGDS). By interaction between cell and matrix, about 80% greater insulin secretion from MIN6 cells was produced with the p(VMA-co-VBGRGDS), and about 50% greater insulin secretion was produced with the poly(N-p-vinylbenzyl-D-lactonamide-co-6-(p-vinylbenzamido)-hexanoic acid-g-GRGDS) (p(VLA-co-VBGRGDS) as compared with unstimulated cells. Moreover, attachment of MIN6 cells treated with RGD monomer was suppressed approximately 50% for the p(VMA-co-VBGRGDS) surface. This result supported the idea that conjugation of adhesion molecules of RGD peptide in p(VMA-co-VBGRGDS) copolymer specifically interact with integrin families on MIN6 cell membrane.

Carbohydrate Sequence↗
PubMed2001

Incorporation of sulfonylurea into N-isopropylacrylamide as an extracellular matrix for an artificial pancreas.

High-molecular-weight N-isopropylacrylamide copolymers with small amounts of sulfonylurea (SU, typically 2-4 mol% in the feed) were synthesized by free radical polymerization in benzene. SU-incorporated polymer solutions (5, 6, 8, and 10% w/v) in a culture medium (pH 7.4, 0.15 M ionic strength) with islet cells were mixed and poured into Millicells which supported gel formation. In order to increase the gelation temperature, the SU-incorporated copolymer gel, p(NiPAAm-co-SU), was blended with the p(NiPAAm-co-AAc) polymer at a ratio of 4 to 96. Interaction between the islet cells and the synthetic matrix of SU-incorporated copolymer gel resulted in effective cell viability and such cell functions as insulin secretion. To verify the specific interaction between the SU (K+ channel closer)-incorporated copolymer and islet cells, the cells were pretreated with diazoxide, an agonist of the ATP-sensitive K+ channel (K+ channel opener), before interaction between the polymer and islet cells. This treatment suppressed the action of SU on the islet cells. The results from this study provide evidence that the SU-incorporated copolymer stimulated insulin secretion by specific interaction between SU moieties in the polymer and the islet cells.

Acrylamides↗
PubMed2001

Effect of iron on the virulence of Trichomonas vaginalis.

The role of iron was evaluated with respect to the virulence of Trichomonas vaginalis in mice. Iron-supplemented and iron-depleted Diamond's trypticase-yeast extract-maltose (TYM) media were prepared by adding 360 microM of ferrous sulfate and 100 microM of 2,2'-dipyridyl. Trophozoites cultivated from normal TYM and iron-supplemented TYM media produced subcutaneous abscesses; however, trichomonads grown in an iron-deficient TYM medium failed to produce any pathology. In addition to the increased virulence of trophozoites in mice, iron affects the level of adherence and the cytotoxicity of trichomonads to HeLa cells, which are significantly reduced in trophozoites grown in iron-deficient medium. In conclusion, it is suggested that under iron-depleted conditions such as that induced by 2,2'-dipyridyl the virulence of T. vaginalis is reduced.

Animals↗
PubMed2001

Therapeutic embolization of the dural arteriovenous malformation involving the jugular bulb.

Pulsatile tinnitus is a rarely occurring symptom of vascular origin. Most frequently, the symptoms are due to an arteriovenous malformation, to a tumor of the jugular glomus or to a local arterial stenosis. A 39-yr-old Korean male suffering from pulsatile tinnitus of the left ear was diagnosed to have dural arteriovenous malformation of the jugular bulb. Magnetic resonance imaging and angiography revealed a high-velocity vascular lesion encroaching the internal jugular vein and sigmoid sinuses. Digital subtraction angiography demonstrated a dural arteriovenous malformation involving the jugular bulb. The arterial supply was from the neuromeningeal branch of the left ascending pharyngeal artery and inferior tympanic artery. Stenosis of the left jugular vein caused retrograde venous drainage through the contralateral transverse sinus. Superselective embolization of these feeding arteries was successfully performed using 25% mixture of N-butylcyanoacrylate and lipiodol. In postembolization period, his complaints of pulsatile tinnitus and buzzing noise behind his left ear disappeared.

Adult↗
PubMed2001

Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies.

OBJECTIVE: The diagnostic value of tests for antimyeloperoxidase antibodies (anti-MPO) for systemic vasculitis is less established than that for cytoplasmic antineutrophil cytoplasmic antibody (cANCA)/antiproteinase 3 antibodies (anti-PR3). Controversy exists regarding the optimal utilization of indirect immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To summarize the pertinent data, we conducted a metaanalysis examining the diagnostic value of ANCA testing systems that include assays for anti-MPO. METHODS: We performed a structured Medline search and reference list review. Target articles in the search strategy were those reporting the diagnostic value of immunoassays for anti-MPO for the spectrum of systemic necrotizing vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria required specification of a consecutive or random patient selection method and the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA test results. Weighted pooled summary estimates of sensitivity and specificity were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti-MPO/pANCA + anti-PR3/cANCA. RESULTS: Of 457 articles reviewed, only 7 met the selection criteria. Summary estimates of sensitivity and specificity (against disease controls only) of assays for anti-MPO for the diagnosis of systemic necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and 96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was combined with anti-MPO testing, the specificity improved to 99.4%, with a lower sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti-MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%. CONCLUSION: These results suggest that while anti-MPO is relatively specific for the diagnosis of systemic vasculitis, the combination system of immunoassays for anti-MPO and IIF for pANCA is highly specific and both tests should be used together given the high diagnostic precision required for these conditions. Because patients with ANCA associated vasculitis have either anti-MPO with pANCA or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic performance of ANCA testing.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Effect of gramicidin on percutaneous permeation of a model drug.

This study investigated the enhancement effect of gramicidin, a cationic ionophore, on percutaneous absorption of a model drug, benzoic acid (BA), through rat abdominal skin. The mechanisms by which gramicidin increased skin permeability to BA were also investigated. Degree of hydration measured by the Karl Fisher method, the concentration gradient measured by cryostat analysis, and lipid concentration measured by the Fiske-Subbarow method were evaluated and compared. The results showed that BA permeation profiles through rat abdominal skin followed dose- and volume-dependent patterns. The pretreatment of gramicidin increased the permeation rate of BA through rat abdominal skin compared with the untreated control (18.89 vs. 10.86 microg/cm2/hour). Change in skin permeation rate of BA after gramicidin pretreatment was closely correlated with the remaining skin water content. There were no significant differences in the amounts of phospholipid phosphorous between gramicidin pretreated and untreated skin. The enhancing effect of gramicidin on percutaneous absorption of a model drug is mainly attributed to increasing the diffusivity in the hydration domain of the skin and rearranging the lipid bilayer in the stratum corneum.

Abdomen↗
PubMed2000

Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies.

OBJECTIVE: To report a potentially important limitation of antineutrophil cytoplasmic antibody (ANCA) testing: positive results in patients with subacute bacterial endocarditis (SBE). METHODS: We describe 3 patients with SBE who presented with features mimicking ANCA-associated vasculitis (AAV) and positive findings on tests for cytoplasmic ANCA (cANCA) by indirect immunofluorescence and for anti-proteinase 3 (anti-PR3)antibodies by antigen-specific enzyme-linked immunosorbent assay (ELISA). We also reviewed the published literature describing infectious diseases with (misinterpreted) positive ANCA results through a Medline search of English-language articles published between 1966 and January 1999. These previously reported cases were reinterpreted using an ANCA scoring system that combines the findings of immunofluorescence and antigen-specific ELISA testing. RESULTS: We are now aware of a total of 7 cases of SBE with positive cANCA and anti-PR3 antibodies. We are not aware of any cases of SBE associated with antimyeloperoxidase/perinuclear ANCA. Clinical manifestations mimicking AAV included glomerulonephritis, purpura, epistaxis, or sinus symptoms in 6 of the patients. Streptococcal species were identified in 5 patients, and cardiac valvular abnormalities were demonstrated in 6. All patients except 1, who died of a complication of SBE, recovered with antibiotic therapy. CONCLUSION: Findings of tests for anti-PR3/ cANCA antibodies may be positive in patients with SBE. When encountering ANCA positivity in patients suspected of having systemic vasculitis, physicians should take appropriate steps to rule out infectious diseases, including SBE, before committing the patient to long-term, aggressive immunosuppressive therapy.

Aged↗
PubMed2000

Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.

OBJECTIVE: The triggers that induce antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (APV) are largely unknown. However, there have been reports suggesting that hydralazine, propylthiouracil, and several other drugs may cause some cases of APV, and the majority of these cases have been associated with antimyeloperoxidase (anti-MPO) ANCA. Our experience led us to hypothesize that cases of high titers of anti-MPO antibodies are often drug-associated. METHODS: In this study, we determined the prevalence of exposure to hydralazine, propylthiouracil, and other drugs previously implicated in APV among 30 patients with vasculitis and the highest titers of anti-MPO antibodies newly detected in our laboratory between 1994 and 1998. The clinical, histologic, and other serologic features of these 30 patients were also examined. RESULTS: The 30 study patients accounted for 12% of the 250 new patients with APV and anti-MPO who were tested during the study period. All 30 study subjects had anti-MPO titers that were more than 12 times the median titer of the 250 patients. Ten (33%) of the 30 patients had been exposed to hydralazine and 3 (10%) had been exposed to propylthiouracil. An additional 5 patients (17%) had been exposed to 1 of the other previously reported candidate drugs: 2 to penicillamine, 2 to allopurinol, and 1 to sulfasalazine. One of the patients exposed to hydralazine had also been exposed to allopurinol. In all cases, the clinical and histologic findings were typical of APV. There was a strong association between the presence of antielastase and/ or antilactoferrin antibodies and exposure to candidate drugs. CONCLUSION: These data suggest that a sizable proportion of cases of APV with high titers of anti-MPO antibodies are drug-associated, especially following exposure to hydralazine or propylthiouracil. We recommend that the use of these drugs should be sought in cases of anti-MPO-positive vasculitis, particularly among patients with high titers of these antibodies.

Adolescent↗
PubMed2000

A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis.

OBJECTIVE: Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings. METHODS: We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes. RESULTS: In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results. CONCLUSION: Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable.

Arthritis, Rheumatoid↗
PubMed2000

Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.

OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Clinical study of SS-cream in patients with lifelong premature ejaculation.

OBJECTIVES: To investigate the clinical efficacy of SS-cream, the topical agent made from the extracts of nine natural products for the treatment of premature ejaculation, we performed a double-blind, randomized, placebo-controlled Phase III clinical study of patients with lifelong premature ejaculation in three medical centers. METHODS: One hundred six patients (mean age 38.7 +/- 0.61 years) completed this study. The ejaculatory latency measured by stopwatch and sexual satisfaction ratio of both partner and patient were investigated twice in the screening period and once after each treatment (1 placebo 0.20 g and 5 SS-cream 0.20 g for a total of six treatments). Patients were instructed to apply the cream on the glans penis 1 hour before sexual intercourse in a double-blind randomized fashion. Clinical efficacy was compared with the prolongation of ejaculatory latency and improvement of the sexual satisfaction ratio before and after each treatment. RESULTS: In the screening period, the mean ejaculatory latency was assessed at 1.37 +/- 0.12 minutes, and neither the patients nor their partners were satisfied with their sexual lives. After treatment, the mean ejaculatory latency was prolonged to 2.45 +/- 0.29 minutes in the placebo group and 10.92 +/- 0.95 minutes in the SS-cream group. The clinical efficacy of placebo and SS-cream as judged by an ejaculatory latency time prolonged more than 2 minutes was 15.09% and 79.81%, respectively. The improvement of sexual satisfaction to a grade higher than effective was 19.81% and 82.19%, respectively, for placebo and SS-cream. Of 530 trials of SS-cream, 98 (18.49%) resulted in a sense of mild local burning and mild pain. No adverse effect on sexual function or partner and no systemic side effects were observed. CONCLUSIONS: According to these results, SS-cream is effective and safe in the treatment of premature ejaculation, with mild local side effects.

Administration, Topical↗
PubMed2000

Total pelvic exenteration for locally advanced rectal cancer.

BACKGROUND: Since its first description in 1948, total pelvic exenteration has been a surgical option for the treatment of locally advanced rectal cancer in selected patients. During these 50 years, it has remained a formidable procedure with high mortality and substantial morbidity. This report describes the results of total pelvic exenteration for rectal cancer in terms of post-operative mortality, morbidity, and longterm survival in patients with locally advanced primary and recurrent rectal cancer. STUDY DESIGN: A study of the patient records revealed that 24 patients underwent total pelvic exenteration as the treatment for locally advanced primary or recurrent cancer of the rectum from 1983 to 1998. The charts of the patients were reviewed, and morbidity and mortality were documented. The survival of the patients was also analyzed. RESULTS: Fifteen patients had primary tumor and 9 had locally recurrent cancer. The mean age was 62 years old. There were no postoperative deaths, and the complication rate was 54%. In the treatment of primary tumor, bowel continuity was possible in 60% of the patients. Previous radiation or operation for recurrent disease was not associated with increased morbidity. The overall 5-year survival was 44%. The 5-year survival of patients with primary cancer was 64% and was significantly better than the rate for those with recurrent disease. Only one patient with recurrent disease survived more than 24 months. CONCLUSIONS: Total pelvic exenteration now can be performed with low mortality rates, but the morbidity remains high. In the treatment of primary rectal cancer, good survival (64%) can be achieved, but results are dismal for the treatment of recurrent disease. We suggest better selection of patients for this procedure, especially as a treatment for recurrent rectal cancer.

Adenocarcinoma↗
PubMed2000

Pulsatility of growth hormone (GH) signalling in liver cells: role of the JAK-STAT5b pathway in GH action.

The intracellular signalling molecule and transcriptional activator STAT5b is a key mediator of the effects of intermittent plasma growth hormone (GH) pulses on the male-specific pattern of liver gene expression and pubertal body growth rates in rodents. Experiments with Stat5b gene-knockout mice have revealed that these GH-regulated, male-specific phenotypes are a direct consequence of GH pulse-dependent STAT5b activation and that loss of function of STAT5b cannot be compensated for by the closely related signalling molecule STAT5a. Physiological plasma GH pulses are required to obtain the high levels of activated STAT5b seen in the livers of males, and down-regulation of the GH receptor (GHR)-JAK-STAT5b pathway in hepatocytes exposed to GH in a near-continuous fashion underlies the low level of liver STAT5b activity that is characteristic of adult female rats. Termination of nuclear STAT5b signalling occurs at the conclusion of a plasma GH pulse, with STAT5b deactivation catalysed by a tyrosine phosphatase. In males, termination of the intracellular signalling stimulated by a plasma GH pulse is proposed to be additionally facilitated by GH-STAT5b-inducible SOCS-CIS proteins, which block the further activation of STAT5b by binding to and inhibiting the action of the GHR-JAK2 complex via multiple mechanisms. In this manner, the liver cell is rendered temporarily unresponsive to further GH-signalling events. SOCS-CIS proteins synthesized in liver cells stimulated continuously with GH may also contribute to the apparent down-regulation of STAT5b signalling that is observed in the female rat liver.

Animals↗
PubMed2000

Multicenter study of the treatment of erectile dysfunction with transurethral alprostadil (MUSE) in Korea.

A Korean multicenter study was conducted to assess the effectiveness of transurethral alprostadil with MUSE in 334 subjects with chronic erectile dysfunction (ED) who were enrolled in 21 clinical centers. Patients with psychogenic impotence comprised about 30% of subjects. Intraurethral alprostadil was titrated in a stepwise fashion in the clinics from 250 to 500 or 1000 mcg based on erectile response and tolerability. The erectile responses were evaluated using an erection assessment scale (score of 1-5). The dose that produced a maximal penile response of score 5 (full rigid erection) or 4 (full tumescence, partial rigidity) was selected for home treatment. Patients who showed partial erection (score of 3) with 1000 mcg were also included in the home-treatment group. In-clinic phase: 198 men (59.3%) had maximal penile responses of score 4 or 5. The rate of maximal responses was not related to patient age, etiology or duration of the ED. A total of 228 (68.3%) men progressed to home treatment. The overall level of comfort of the transurethral alprostadil was rated as uncomfortable or very uncomfortable in 12%. Home phase: During the two-month period of home treatment, 178 (78.1%) men had successful sexual intercourse at least once, and 78.2% of administrations (1976) resulted in successful intercourse. The main causes of drop-out were insufficient erectile response in 27 men (11.8%), adverse reactions (mostly penile or urethral pain) in 7 (3.1%) or both in 7 (3.1%). In conclusion, transurethral alprostadil could be a suitable treatment option for patients with ED regardless of age and etiology of ED. Efficacy in an Asian population (Korea) is comparable to that reported previously in Caucasians.

Adult↗
PubMed2000

A comparative study of mammalian tracheal mucous glands.

We have compared the distribution, numbers and volume of mucous glands in the tracheas of 11 mammalian species. No glands were present in the rabbit. The mouse only contained glands at the border between the trachea and larynx. In the rat, glands were commonest in the cephalad third of the trachea, but on average were much scarcer than in the larger species. Between species, there was a significant correlation between airway diameter and gland volume per unit surface area, suggesting that the rate of deposition of inhaled particles may increase in large airways. In the ventral portion of the trachea of about half the species, the glands were concentrated between the cartilaginous rings; in others they were evenly distributed over and between the rings. In most species in which the trachealis muscle attached to the internal surface of the cartilaginous rings, the glands were external to the muscle. In all species in which the muscle attached to the external surface of the cartilaginous rings, the glands were internal to the muscle. In the ox, goat, dog and sheep, the volume of glands per unit tracheal surface area was markedly greater in the ventral than the dorsal aspect of the trachea. The reverse was true of the pig. In humans, gland density in the 2 regions was similar. The frequency of gland openings was determined in the ox, goat, pig, dog and sheep tracheas, and ranged from 0.3 per mm2 in the dorsal portion of the sheep trachea to 1.5 per mm2 in the ventral portion of the ox trachea. For these 5 species, the volume of gland acini per unit luminal surface area varied linearly with the numbers of gland openings, with the volume of individual glands being constant at approximately 120 nl.

Animals↗