Expression of three zebrafish Six4 genes in the cranial sensory placodes and the developing somites.

The homeobox gene Six4/AREC3 is a member of the vertebrate Six family of transcription factor genes. In this study we describe the cloning and expression of three zebrafish homologues of Six4/AREC3, six4.1, six4.2 and six4.3. These zebrafish Six4 proteins show high homology to the mammalian Six4/AREC3 proteins in the most C-terminal region in addition to the Six domain and homeodomain. Whole-mount in situ hybridization showed that six4.1 is expressed in the presumptive cranial placodal precursor cells, and later in the olfactory, otic and lateral line placodes. six4.2 is expressed in the presomitic mesoderm, somites and pectoral fin bud. six4.3 appears to be a unique member of the Six4 proteins and is expressed ubiquitously at gastrulation and later in the tectum.

Prostacyclin synthase gene transfer inhibits neointimal formation in rat balloon-injured arteries without bleeding complications.

OBJECTIVE: This study was designed to compare the effects of prostacyclin synthase (PCS) gene transfer with those of a systemic infusion of beraprost sodium (BPS), a prostacyclin analogue, on vascular smooth muscle cell (VSMC) proliferation and neointimal formation after arterial injury. METHODS: PCS gene (3 or 30 micrograms) was transfected into rat balloon-injured carotid arteries by a non-viral lipotransfection method. BPS (100 or 300 micrograms/kg/day) was subcutaneously infused with osmotic pumps after the injury. LacZ gene (30 micrograms) was used as a control. VSMC proliferation was estimated by the bromodeoxyuridine (BrdU) index (BrdU-positive nuclei/total nuclei) at day 7. Neointimal formation was evaluated at day 14. Each treatment group had six rats. RESULTS: PCS gene transfer prevented the increase in intimal/medial area ratio (3 micrograms: 46.6%, 30 micrograms: 61.1% reduction; P < 0.05, P < 0.01, respectively), as did BPS 300 micrograms/kg/day (49.8% reduction; P < 0.05). BPS 100 micrograms/kg/day, however, had no effects on the ratio. PCS gene transfer and BPS 300 micrograms/kg/day significantly suppressed the BrdU index. BPS 300 micrograms/kg/day group had more frequent hematoma and longer bleeding time. There were no significant differences in blood pressure, heart rate, or urinary volume among all groups. CONCLUSION: Both PCS gene transfer and BPS 300 micrograms/kg/day reduced neointimal formation after arterial injury by inhibiting VSMC proliferation. PCS gene transfer may be a safer therapeutic modality against neointimal formation than a systemic infusion of BPS because the former method resulted in fewer bleeding complications.

Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to evaluate the possible role of prostacyclin (PGI2) in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). METHODS: Measurement of mRNA and protein levels of PGH synthase (PGHS)-1, PGI2 synthase and the PGI2 receptor, in the thoracic aorta was performed in SHR aged 5, 10, 20, and 40 weeks old and in age-matched normotensive Wistar-Kyoto (WKY) rats with a competitive polymerase chain reaction method and immunoblotting. Aortic production of 6-keto-PGF1 alpha, the main metabolite of PGI2, was also measured. RESULTS: Compared with age-matched WKY rats, PGHS-1 mRNA and protein levels in the thoracic aorta of SHR increased with age, reaching three- and twofold higher than WKY rats at 40 weeks old, respectively. PGI2 synthase mRNA and protein levels in SHR were significantly higher than in WKY rats at 20 and 40 weeks old. In contrast, PGI2 receptor mRNA levels in SHR were consistently lower than in WKY rats at all ages. CONCLUSIONS: These results provide evidence that hypertension elicits alterations in levels of arachidonic acid metabolites, including PGH2 and PGI2. They also suggest that the decreased expression of PGI2 receptor mRNA in prehypertensive SHR could be one of the causes of hypertension in SHR.

Usefulness of enhanced insulin secretion during an oral glucose tolerance test as a predictor of restenosis after direct percutaneous transluminal coronary angioplasty during acute myocardial infarction in patients without diabetes mellitus.

To determine predictive factors of the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA), 25 nondiabetic nonobese patients aged <80 years old and 57 consecutive patients with successful direct PTCA with acute myocardial infarction were subjected to a 75-g oral glucose tolerance test (OGTT) and underwent follow-up coronary angiography 4 months later. The relation between the development of restenosis (late loss index: the decrease in the absolute minimal lumen diameter [MLD] at follow-up coronary angiography divided by MLD measured 1 day after PTCA) and the results of OGTT together with basic patient characteristics like age, body mass index, plasma levels of cholesterol, triglycerides, and high-density lipoprotein cholesterol were analyzed. Spearman's rank correlation analysis revealed that neither age, body mass index, nor plasma lipids correlated with late loss index, but only insulin area (p = 0.041) and insulin area/glucose area (p = 0.038) significantly correlated with the development of restenosis; a stepwise multiple regression analysis revealed that the insulin area was the only independent predictor of restenosis (p = 0.019). These results suggest that enhanced insulin secretion in response to glucose plays an important role in the development of restenosis after direct PTCA in non-diabetic patients, which may be through the direct action of insulin on smooth muscle cells of the coronary artery. This study also suggests the importance of performing OGTT for patients undergoing PTCA for the prediction of the development of restenosis.

Simultaneous intravascular two-dimensional plus Doppler ultrasound is useful for evaluation of postischemic vasodilatation: plasm NOx - levels determined by the Griess method may not reflect the extent of postischemic NO-induced vasodilatation.

Our objective was 1) to assess postischemic vasodilatation using simultaneous intravascular two-dimensional and Doppler ultrasound, and 2) to clarify whether plasma nitrite and nitrate (NOx-) levels change during postischemic vasodilatation. The vascular cross-sectional area (CSA) was evaluated in 18 mongrel dogs, and the average instantaneous peak velocity (APV) in the iliac arteries after the 5-min occlusion of blood flow was determined. Plasma NOx- levels were measured at the baseline, during the occlusion of blood flow, and 1.5, 3, and 10 min after recanalization. The %CSA significantly increased from 30 s to 7 min after the recanalization, and maximal vasodilatation was observed at 1.5 min after the recanalization (14.1 +/- 0.9 to 15.8 +/- 1.0 mm2, p< 0.0001 vs. baseline). Plasma NOx- levels were significantly reduced during the occlusion of blood flow and remained reduced at 1.5, 3, and 10 min after recanalization compared with the baseline values. We concluded that simultaneous intravascular two-dimensional and Doppler ultrasound is useful for assessment during postischemic vasodilatation, and that plasma NOx- levels assayed with the Griess reagent do not significantly increase, even when maximal vasodilatation is observed.

Localization of small renal tumor by dynamic computerized tomography.

Herein we report on 4 cases of renal tumor whose diameter was less than 3 cm. A mass lesion was suggested by renal echography in mass screening program. Renal dynamic computerized tomography (CT) with bolus injection can delineate a mass lesion clearer than ordinary plain and enhanced CT, and renal angiography. In renal dynamic CT, tumor lesion is well depicted because of the difference between the time density curve in the tumor lesion and that in the surrounding renal parenchyma. Renal dynamic CT is considered to be an especially versatile modality to diagnose small tumors which are hardly delineated by ordinary enhanced CT.

Severe hypertension in infant with unilateral hypoplastic kidney.

Unilateral renal hypoplasia unlike Ask-Upmark kidney (segmental renal hypoplasia) seldom causes hypertension. A case of an infant whose hypertension disappeared after removal of a hypoplastic kidney is reported. The removed kidney revealed no sign of Ask-Upmark lesion.

Preoperative computed tomography diagnosis of non-recurrent inferior laryngeal nerve.

OBJECTIVE: The non-recurrent inferior laryngeal nerve (NRILN) is a nerve anomaly that is associated with the developmentally aberrant subclavian artery. Thus, it is possible to predict NRILN by preoperative diagnosis of an aberrant subclavian artery. Preoperative recognition of the NRILN should be advantageous in the prevention of intraoperative nerve damage. The purpose of this study was to assess the possibility of diagnosis of an aberrant subclavian artery by computed tomography (CT) of the neck, which is often performed before thyroid surgery. METHODS: We retrospectively studied the preoperative CT films from 594 thyroid or esophageal surgery patients treated in our hospital between May 1995 and December 2000. An NRILN was identified intraoperatively in 6 of these patients, and a right recurrent inferior laryngeal nerve (RILN) was observed in 588 of these patients. We evaluated whether the brachiocephalic artery could be identified on the CT scan and classified the positional relationship between the right subclavian artery and the tracheoesophagus into three types. RESULTS: The brachiocephalic artery was identified on the CT films in 158 cases, all of which were cases of RILN. The right subclavian artery was detected on the ventral side of the membranous wall of the trachea in all 588 RILN cases, whereas it was detected on the dorsal side in all 6 NRILN cases. CONCLUSIONS: It was possible to predict an aberrant subclavian artery by identifying the brachiocephalic artery and position of the right subclavian artery on the CT film of the neck. When an anomaly of the subclavian artery is thus preoperatively detected, NRILN can be preoperatively predicted, which likely will enable prevention of vocal cord paralysis.

The apolipoprotein E genotype influences the risk for vasospastic angina.

It has been suggested that people with the epsilon4 allele of the apolipoprotein E (apoE) polymorphism and the deletion (D) allele of the insertion (I/D) polymorphism of angiotensin-converting enzymes, are at a greater risk for coronary artery disease. However, only a few studies have examined the relationships between vasospastic angina (VSA) and genotype, especially with the apoE polymorphism. In the present study, 76 patients with VSA without significant fixed coronary artery stenosis, 149 patients with ischemic heart disease (IHD) who had 75% or more luminal diameter narrowing and 213 healthy subjects were enrolled. The odds ratio for VSA of the epsilon4 allele carriers relative to the epsilon3/3 allele subjects compared with subjects with IHD and control subjects combined was 0.44 (95% CI 0.21 to 0.93, P=0.021), and that compared with control subjects alone was 0.36 (95% CI 0.17 to 0.78, P=0.005), implying that the presence of the epsilon4 allele indicates resistance to the development of VSA. In contrast, people with the epsilon2 allele showed a tendency to develop VSA more frequently than did patients with IHD (P=0.009), although the frequency of the epsilon2 allele did not differ between patients with VSA and control subjects. On the other hand, no recessive and dominant effects of the D alleles on VSA were found. These findings suggest that the risk of the occurrence of VSA may be reduced by the epsilon4 allele and increased by the epsilon2 allele. The ApoE polymorphism may be associated with IHD and VSA, probably due to the modulation of lipid metabolism.

[Study of the prostatic tissue cefbuperazone (CBPZ) level].

The concentration of Cefbuperazone (CBPZ) was determined in the prostatic tissue and serum of 23 patients with benign prostatic hypertrophy. One or 2 of CBPZ was injected intravenously prior to transurethral prostatectomy. The mean CBPZ level in prostatic tissue and tissue/serum ratio at 1 hour was 17.4 +/- 7.2 micrograms/g (28.9 +/- 9.1%) in 10 patients administered 1 g of CBPZ, and 34.7 +/- 1C.2 micrograms/g (35.7 +/- 13.2%) in 13 patients administered 2 g of CBPZ. Serum and prostatic tissue CBPZ levels responded satisfactorily to the dose of CBPZ. Weights of resected prostatic tissue were not correlated to the tissue CBPZ level. Judging from the inhibitory concentration of CBPZ (minimum inhibitory concentration 80), the prostatic tissue CBPZ level was sufficient against pathogenic bacteria, particularly E. coli, K. pneumoiae and P. mirabilis for a relatively long time. For this reason CBPZ is a very useful drug for treatment of bacterial prostatitis and postoperative infection of prostate.

[Treatment of organic impotence. Self-administered intracavernous injection of papaverin HCI (a preliminary report)].

Intracavernous injection of 40 mg papaverin HCI caused erection sufficient for intromission in all six cases of organic impotence. The patients were taught to self inject one corpus cavernosum just prior to coitus and reported that they were able to have coitus at home. No complications were encountered. This method should be tried first as an alternative to penile implant for patients with organic erectile failure.

[A clinical study of prostatic carcinoma].

Seventy seven patients with prostatic carcinoma were treated in our clinic between 1977 and 1986. Most of them were treated by a hormonal agent as the first therapy. None of the 9 stage A1 cases showed any reactivation, but 4 of the 5 stage A2 cases relapsed to metastatic disease. The chemotherapy performed in 3 of the 4 reactivated cases had no obvious effect on the disease. Seven of the 8 patients with stage B disease were alive without relapse. Relapse was seen in the other patient who had poorly differentiated carcinoma and chemotherapy in this case resulted in stable disease for the present. Four of the 15 stage C cases including 3 poorly differentiated carcinomas were hormone resistant or reactivated. For these resistant cases radiotherapy and/or the chemotherapy were performed, but a response was seen in only one case. Consequently, the first therapy for stage A2, B and C of poorly differentiated carcinoma must be improved. Of the 40 stage D cases, 4 patients who were treated by an early combination of hormonal therapy and chemotherapy had a better prognosis than the others. These 4 patients had poorly differentiated carcinomas with multiple bone metastases. Two of these 4 patients were alive without relapse for 17 and 72 months, and one of the 2 patients with relapse was also alive for 75 months. We believe that early chemotherapy is the key for better prognosis in stage D cases.

[Clinical study of ofloxacin (OFLX) on urinary tract infections].

Fifty-three patients with urinary tract infections (UTI) were treated with Ofloxacin, a new oral synthetic antimicrobial agent, and its clinical efficacy was studied. Ofloxacin (600 mg/day) was administered to 35 patients with acute simple cystitis for more than three days, and to 17 patients with complicated UTI for more than five days except a case in which the treatment was interrupted for side effects. Acute simple cystitis: In ten cases meeting the criteria of UTI committee, overall effectiveness rate was 100%. All of the 26 strains isolated from 26 patients disappeared after the treatment. In all of acute simple cystitis cases, 94.3% were evaluated as excellent or as moderate by attending doctors. Complicated UTI: In 11 cases treated during five or seven days, 63.6% of patients showed improvement on pyuria. Seven out of nine strains isolated from seven patients disappeared. However, two strains of P. aeruginosa and P. cepacia persisted after the treatment. In all of the complicated UTI cases, 38.9% of patients were evaluated as excellent or as moderate by attending doctors. Some slight side effects were observed in four out of 53 cases. This study showed that Ofloxacin is effective against urinary tract infections.

[A case of bladder amyloidosis].

Herein we report a case of bladder amyloidosis treated successfully with TUR & DMSO bladder instillation. A diagnosis was made by a biopsy of the bladder epithelium. Amyloid fibrils were confirmed in the biopsy specimen with polarization and electron-microscopy. The patient was treated with TUR. The residual lesion had disappeared with DMSO bladder instillations for 4 months (12X) without side effects after TUR. Thus DMSO bladder instillation with surgical resection seems to be an excellent therapy for bladder amyloidosis.

[Study of levels of latamoxef in prostatic tissue and bladder mucosal tissue].

The concentration of Latamoxef (LMOX) in the serum, prostatic tissue and bladder mucosal tissue of 20 patients with benign prostatic hypertrophy and bladder cancer was measured after intravenous infusion of 1 g or 2 g of LMOX. Serum, prostatic tissue and bladder mucosal tissue levels of LMOX responded satisfactorily to the dose of LMOX. The bladder mucosal tissue level was higher than the prostatic tissue levels. Judging from the inhibitory concentration of LMOX (MIC 80), the concentration was sufficiently effective against infections caused by gram-negative, gram-positive and anaerobic bacilli.

[Clinical effects of oxybutynin hydrochloride (Pollakis)--especially in the treatment of pollakisuria, urgency and urinary incontinence].

The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.

[Two cases of male infertility with pathological dilatation of ejaculatory duct].

Two cases of male infertility with pathological dilatation of ejaculatory duct are reported. In both cases, the dilatated wall of the ejaculatory duct was incised at the vermontanum with a cold knife endoscopically. After the incision, the findings of semen analysis of one case improved markedly and his wife became pregnant. In another case, semen analysis was not improved. Transurethral incision seemed to be a useful modality for the treatment of pathological dilatation of ejaculatory duct.

[Renomedullary interstitial cell tumor: a case report].

Renomedullary interstitial tumor is a common tumor in the renal medulla, present in 26-41% of consecutive autopsy specimens. However clinically evident case is infrequent because this lesion is usually small (less than 3 mm). We report a case of renomedullary interstitial tumor in a 76-year-old woman. Ultrasonogram incidentally revealed a mass in the left kidney while she visited to the hospital for hypertension and unstable angina. A CT scan showed a 2 cm mass that was not clearly enhanced. MR images showed low signal intensity in both T1 and T2 images. Arteriography demonstrated no neo-vascularity. Those findings showed that this lesion was benign one or hypovascular carcinoma. So Left nephrectomy was performed and histological examination revealed a renomedullary interstitial tumor.

[Intravesical oxybutynin hydrochloride in the treatment of urge incontinence in the elderly].

PURPOSE: This study was carried out to determine the effectiveness of intravesical oxybutynin hydrochloride on urinary urge incontinence in elderly people. METHODS: The subjects consisted of 13 patients with an average age of 75 years who demonstrated uninhibited detrusor contraction on cystometrogram. The trial protocol consisted of a pretreatment cystometrogram followed by the intravesical administration of 10 ml solution containing 5 mg oxybutynin hydrochloride (pH 5.85). The urodynamic studies were repeated one hour later. RESULTS: The mean bladder capacity before and after one hour of intravesical oxybutynin hydrochloride was 161 +/- 62 ml and 196 +/- 71 ml (mean +/- 1 S.D., n.s.). The rate of improvement was 15.4% (2 cases) in all 13 patients. Four patients out of 13 patients continued intravesical administration of the solution twice daily. Urinary incontinence disappeared in two patients and incontinence was markedly decreased in one. In the remaining patient, urinary incontinence did not change because of increased residual urine. Three patients have continued this therapy over one years and no side effects were observed. In these patients, residual urine volume did not increase. CONCLUSION: It is suggested that intravesical oxybutynin hydrochloride is an effective option of therapy for intractable urge incontinence in elderly people, however, the immediate posttreatment cystometrogram was not predictive of the response to intravesical therapy on overactive bladder in the elderly.

[Postoperative intravesical installation of tetrahydropyranyl-adriamycin (THP) and cytosine arabinoside (CA) for superficial bladder cancer: clinical results of prophylactic effects on recurrence].

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) and cytosine arabinoside (CA) was performed on 42 patients with superficial bladder cancer after transurethral resection (TUR) for the purpose of prophylaxis of recurrence. The instillation was carried out with 30 mg of THP dissolved in 30 ml of distilled water and 200 mg of CA (total 40 ml). These drugs were instilled 7 times for the initial 2 weeks after TUR, and then 7 times every two weeks, 8 times every month, and 4 times every three months. Cases eligible for evaluation of efficacy were 38 out of 42 patients. The cumulative non-recurrence rate at one, two and three years were 94%, 84% and 75%, respectively. These high non-recurrence rates were demonstrated regardless of the size, number and pathological grade of the tumors. Severe bladder irritability was demonstrated in 8 (19%) of 42 patients, but generalized side effects were not seen in any case. The reformed regimen with 20 mg of THP in 30 ml of physiological saline solution was then performed on trial in several patients and there were no severe symptoms. THP combined with CA seems to be remarkably effective for the prophylaxis of recurrence, while a high concentration of THP in distilled water may lead to severe bladder irritability.