4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents.
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Action Potentials↗
Biomedical subjects
K Miyake
Publications and source records attributed to K Miyake.
The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins.
The present study was undertaken to determine the relationship between the hyaluronate receptor and CD44 (H-CAM), cell-surface glycoproteins of similar molecular weights that have been implicated in cell adhesion. In initial experiments, a panel of monoclonal antibodies directed against CD44 were tested for their ability to cross react with the hyaluronate receptor. These antibodies immunoprecipitated [3H]hyaluronate binding activity from detergent extracts of both mouse and human cells, indicating that the hyaluronate receptor is identical to CD44. In addition, one of these antibodies (KM-201 to mouse CD44) directly blocked the binding of labeled hyaluronate to the receptor and inhibited hyaluronate dependent aggregation of SV-3T3 cells. CD44 has also been implicated in lymphocyte binding to high endothelial venules during lymphocyte homing. Interestingly, the monoclonal antibody Hermes-3, which blocks lymphocyte binding to the high endothelial venules of mucosal lymphoid tissue, had no effect on the binding of labeled hyaluronate. Furthermore, the binding of lymphocytes to high endothelial cells of lymph nodes and mucosal lymphoid tissue was not significantly affected by treatment with agents that block the binding of hyaluronate (hyaluronidase, excess hyaluronate and specific antibodies). Thus, CD44 appears to have at least two distinct functional domains, one for binding hyaluronate and another involved in interactions with mucosal high endothelial venules.
Animals↗
The A-factor-binding protein of Streptomyces griseus negatively controls streptomycin production and sporulation.
A-factor, 2-(6'-methylheptanoyl)-3R-hydroxymethyl-4-butanolide, is an autoregulator essential for streptomycin production and sporulation in Streptomyces griseus. S. griseus 2247 that requires no A-factor for streptomycin production or sporulation was found to have a defect in the A-factor-binding protein. This observation implied that the A-factor-binding protein in the absence of A-factor repressed the expression of both phenotypes in the wild-type strain. Screening among mutagenized S. griseus colonies for strains producing streptomycin and sporulating in the absence of A-factor yielded three mutants that were also deficient in the A-factor-binding protein. Reversal of the defect in the A-factor-binding protein of these mutants led to the simultaneous loss of streptomycin production and sporulation. These data suggested that the A-factor-binding protein played a role in repressing both streptomycin production and sporulation and that the binding of A-factor to the protein released its repression. Mutants deficient in the A-factor-binding protein began to produce streptomycin and sporulate at an earlier stage of growth than did the wild-type strain. These mutants produced approximately 10 times more streptomycin than did the parental strain. These findings are consistent with the idea that the intracellular concentration of A-factor determines the timing of derepression of the gene(s) whose expression is repressed by the A-factor-binding protein.
4-Butyrolactone↗
Effects of portal infusion of hypertonic solution on jejunal electrolyte transport in anesthetized dogs.
Jejunal electrolyte absorption was measured in the jejunal loops of anesthetized dogs during infusions of hypertonic solutions via the portal vein. The net Na absorption was not influenced by the 9% NaCl infusion into the inferior vena cava, although it was significantly attenuated by the portal 9% NaCl infusion. This effect may not be due to the osmotic stimulus, since the portal 50% glucose or 6.5% LiCl infusion had no significant influence on the net Na absorption. To determine the mechanism of the decrease in the net Na absorption during the portal hypertonic NaCl infusion, the net Na absorption was measured after the section of anterior and posterior hepatic nerves (SAPH) or intravenous atropine injection. Both SAPH and the intravenous atropine injection completely blocked the effect of the portal 9% NaCl infusion on the net Na absorption. These results indicate that 1) net Na absorption in dog jejunum is depressed by the hypertonic NaCl infusion via the portal vein; 2) the effect is NaCl specific and may not be due to the osmotic stimulus; and 3) the afferent limbs of this effect are the anterior and posterior hepatic nerves, and the efferent limb of this effect is the vagus nerve. Thus the hepatojejunal reflex may play an important role in the regulation of body fluid homeostasis.
Absorption↗
[Toxicity of bis (tri-n-butyltin) oxide on learning and development in the rat].
The toxicity of bis (tri-n-butyltin) oxide (TBTO) was studied in THA rats. Doses of 0 (control), 10 or 15 mg/kg/day of TBTO were administered to adult rats for 12 consecutive days, and 0, 5 or 10 mg/kg/day was given to pregnant rats from day 6 to day 20 of gestation by gastric intubation. In the adult rat exposure experiment, the 15 mg/kg group showed slightly decreased body weight and spontaneous motor activity, and a low avoidance rate in the Sidman avoidance test in the early stage of administration. In the pregnant-rat exposure experiment, no effect of TBTO was seen in either the 5 mg/kg or 10 mg/kg groups in dams while all pups in the 10 mg/kg group died by postnatal day 3. Little effect of TBTO on body weight, pinna detachment, incisor eruption, eye opening, surface righting, cliff avoidance, pivoting, negative geotaxis and auditory startle was found in the 5 mg/kg pups. In the Sidman avoidance test, the avoidance rate of the 5 mg/kg pups was lower than that of control pups in the early stage of the session. In a water E-maze test, the swimming time to the goal and the number of errors were increased in the 5 mg/kg pups. In a reversal water E-maze test, increases of the swimming time to the goal and the number of errors made by the 5 mg/kg pups were marked. These results suggest that TBTO administration disrupts the learning acquisition of rats, and that the toxicity of TBTO is greater in prenatally exposed pups than in adult rats.
Animals↗
[Sex difference in operant behavior following single exposure to carbon monoxide in adult rats].
Sex difference of effects of single exposure of carbon monoxide (CO) on operant behavior was studied in adult rats. The animals were obtained by continued selective breeding and have a high level of avoidance ability and small individual differences (THA rat: Tokai high avoider rat). Experiments were conducted as follows: Exposure were carried out at the concentrations of 50, 100, 200 and 400 ppm of CO gas for 4 h in THA rats, and their operant behavior was studied by Sidman avoidance test conducted 1 h before and after CO exposure. Rats whose carboxyhemoglobin (COHb) in blood was determined after the termination of CO exposure were of the same strain and age as those that underwent operant behavior test. Exposure of CO 50 ppm did not produce any marked change in operant behavior. In male rat groups, response counts in the Sidman avoidance test decreased after exposure to CO 100, 200 and 400 ppm when compared to the value before exposure, but increase in shock counts was observed only by exposure to CO 400 ppm. In female rat groups, response counts decreased after the exposure to CO 200 and 400 ppm, but shock counts did not show any marked change at all the CO exposure concentrations. COHb concentrations immediately after the exposure to CO 50, 100, 200 and 400 ppm for 4 h were 9.1 +/- 1.2, 13.5 +/- 0.5, 24.3 +/- 0.7 and 43.6 +/- 1.6%, respectively, in males, and 9.2 +/- 1.1, 13.7 +/- +/- 0.8, 24.0 +/- 1.0 and 42.0 +/- 1.4%, respectively, in females.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Statistical evaluation of determinants of progression of superficial bladder cancer by proportional hazards model].
To evaluate clinical and pathological factors present at the initial consultation which affect disease progression, we reviewed data from 223 patients with superficial bladder cancer (pTa and pT1) who were initially treated at Nagoya University Hospital between January 1973 and December 1987. The factors included in the present analysis were age, sex, symptoms, interval between initial symptoms and first consultation, location of tumor, size, number, endoscopic shape, histological pattern of growth, grade and stage. The median duration of the follow-up after initial treatment was 46 months. Of the 223 patients, 17 died: 8 (3.6%) of bladder cancer and the remaining 9 (4.0%) of unrelated causes. Disease progression developed in 12 patients (5.4%): muscle invasion of the bladder wall in 11 and lung metastasis in one. The interval between initial treatment and progression ranged from 4 to 108 months, with a median of 11.5 months. Of the 12 patients, 9 (75%) had disease progression within 2 years. Progression was significantly associated with poor prognosis (p less than 0.001): the 5-year actuarial survival rates were 47.1% and 92.8% in patients with and without progression, respectively. Univariate analysis by Cox's proportional hazards model demonstrated that characteristics such as irritative bladder symptoms, higher-grade tumors, invasion into lamina propria, and nonpapillary growth seen at initial consultation were significantly related to disease progression. Cox's proportional hazards model produced hazard ratios of 10.2 in irritative bladder symptoms (yes vs. no), 6.3 in histological grade (grade 3 vs. grades 0-2), 4.9 in stage (pT1 vs. pTa), and 4.7 in pattern of growth (papillary vs. nonpapillary).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Transurethral incision of the prostate and bladder neck for the treatment of outflow obstruction caused by a small benign prostate].
Transurethral incision of the prostate and bladder neck (TIPBn) was compared with transurethral resection of the prostate (TURP) followed by bladder neck incision in the treatment of 22 patients with outflow obstruction caused by a small prostate adenoma (below 15 gm). Eleven patients underwent TIPBn and another 11 TURP. An evaluation of the urodynamic findings and subjective symptoms was undertaken before the operation and 3 months afterwards. Urodynamic findings were evaluated, based upon uroflowmetry, i.e., in terms of maximum flow rate, average flow rate, voiding time, initiation time and residual rate. All patients in the TIPBn group revealed an improvement in every urodynamic parameter (MFR: from 6.1 to 10.8 ml/sec, AFR: from 3.1 to 5.8 ml/sec, Voiding time: from 95.5 to 24.2 sec/100 ml, Initiation time: 34.3 to 10.2 sec, Residual rate: 31.6 to 17.8%, in mean value). Ten out of the 11 in the TIPBn group subjectively considered the result to be good. The improvements in the urodynamic parameters in the TIPBn group were statistically comparable to those in the TURP. The improvements in voiding time and initiation time, however, tended to be much better in the TIPBn group. We conclude that TIPBn can be the operation of choice in the treatment of outflow obstruction caused by a small prostate.
Aged↗
[Effects of alpha-1-blocking agent in the treatment of detrusor sphincter dyssynergia].
Effects of adrenergic alpha-1-blocking agent, prazosin, in the treatment of detrusor external-sphincter dyssynergia (DSD) were evaluated in both experimental and clinical aspects. Experimentally, in the urethral pressure profile in dogs, the maximum urethral closing pressure was depressed after intravenous injection of 1 mg prazosin. When experimental DSD was obtained in dogs by stimulating electrically the unilateral 2nd sacral root, intra-venous injection of 1 mg prazosin inhibited contraction of the external urethral sphincter. Clinically, 74 patients with DSD based on neurogenic bladder from cerebral vascular attack (CVA) (13 cases) and spinal cord injury (61 cases) were retrospectively surveyed in terms of therapeutical effects of prazosin for DSD. Spinal cord injury was subdivided to 4 groups for clinical evaluation; cervical cord injury (C) with complete paralysis, thoracic cord injury (Th) with complete paralysis, lumbar cord injury (L) with complete paralysis and spinal cord injury with incomplete paralysis. Patients with CVA and spinal cord injury with incomplete paralysis showed good response rates in subjective improvement, 69% and 60% respectively. However, those with spinal cord injury with complete paralysis showed a poor response (28% for C, 23% for Th and 14% for L). The amount of residual urine significantly decreased after treatment, in all the groups except that of lumbar cord injury with complete paralysis. In all the groups, however, even after the drug treatment the amount of residual urine ranged from 80 to 170 ml and the rates of needing clean intermittent catheterization unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Clinical experience with ESWL with new Dornier lithotripter MPL 9000].
In June 1988, the new type of the lithotripter MPL 9000 (Dornier), which was the first interdisciplinary lithotripter for treatment of urinary and biliary calculi, was installed at the Shakai Hoken Chukyo Hospital. MPL 9000 has some features which enable one to treat with low range of shock wave energy and without anesthesia due to the enlarged aperture of the ellipsoid (210 mm), and locate the stone by computerized two ultrasound probes (coaxial, lateral). Unlike HM-3, the water bath is not used: shock wave is shot through the water cushion. From June to November 1988, 35 patients suffering from 64 urinary calculi were treated. The majority represented caliceal (75%) and pelvic (17%) stones, whereas 5 calculi were treated in the upper and lower ureter. Twenty-four patients were treated in one session and 11 patients needed additional sessions. The given number of shock waves was between 1337 and 3050 per one session and averaged 2403 with low generator voltage (15-18 kv). Twenty sessions (42%) were given without any medication and other 28 sessions (58%) were under analgesia (Pentazocine, i.v.) for the pain complained during the treatment. The rate of successful disintegration (less than 5 mm) was 88%. After the 1-month followup, 47.1% were free of stone, and 62.1% were free after the 3-month. Four patients had arrhythmia and one patient was with a subcapsular renal hematoma. We have concluded that this lithotripter is useful to treat upper and lower urinary tract calculi, in particular radiolucent ones in high risk patients because it is applicable without anesthesia.
Adult↗
[Clinical importance of microhematuria as an initial sign of bladder tumor].
To investigate the role of microhematuria for the diagnosis of bladder tumor, the retrospective study of 156 patients with bladder tumor was done. Among the 156 cases, asymptomatic microhematuria was observed in 15 cases (9.6%) as an initial sign of the disease. According to the process to the final diagnosis, these 15 cases were classified into 4 groups; the Group 1 comprised 4 patients who consulted the urologist just after health examination; the Group 2 comprised 6 patients who consulted the urologist by the introduction of the general practitioner; the Group 3 comprised 2 patients who disregarded the sign and consulted the urologist after the appearance of symptoms; the Group 4 comprised 3 patients whose general practitioner overlooked the sign and who consulted the urologist after the appearance of the symptoms. The mean duration between the initial sign and the final diagnosis of each group was 2, 2, 8 and 62 months, respectively. Three of the 5 patients (60%) in groups 3 and 4 were treated by total cystectomy, while only 2 of the 10 patients (20%) in groups 1 and 2 totally cystectomized. High grade tumor was observed more frequently in groups 3 and 4 than in groups 1 and 2. Since the negative rate of urinary cytologic examinations of these 15 cases was 33.3%, cystoscopic examination was necessary for screening of bladder tumor.
Adult↗
[Statistical study of tumors of the renal pelvis and ureter].
We reviewed data from 62 patients with epithelial tumors of the renal pelvis and ureter who were hospitalized and treated at Nagoya University Hospital between July, 1970 and June, 1988. Of the 62 patients, 50 were males and 12 were females, the ratio being 4.2:1. The mean age was 62.1 years, the ages ranging from 41 to 87 years. The peak incidence of tumors was marked in the sixth decade for the males and in the seventh decade for the females. Eighty-two percent of the patients were 50 years of age or older. Smoking habits were noted in 76.0 percent of the males and in 16.7 percent of the females. Asymptomatic macrohematuria, found in 43 patients, was the most frequent symptom. Ninety percent of the 62 tumors were transitional cell carcinoma. Twenty-five patients (40.3%) had concomitant bladder cancer, which was previously diagnosed in 3, simultaneously found in 9, and subsequently developed in 16. Twenty-nine patients had tumors localized in the renal pelvis and eighteen in the ureter; the remaining fifteen had tumors localized in two or three organs, including the renal pelvis, ureter and bladder. Histological grades of ureteral tumors were significantly higher than those of renal pelvic tumors. The sensitivity of urinary cytology was 57.8 percent. High-grade tumors had higher sensitivity than low-grade tumors. Larger tumors (greater than 3 cm in diameter) were significantly associated with high-stage tumors, whereas no apparent correlation was found between tumor size and histological grade. Nonpapillary growth of tumor and vascular invasion were significantly related with high-stage and high-grade tumors; diffuse pattern of tumor infiltration was associated with high-stage tumors.
Adult↗
[Clinical study of urinary cytology in bladder tumors--analysis of factors related with positivity of urinary cytology].
To clarify the clinical and pathological determinants affecting the sensitivity of urinary cytology, we reviewed cytological findings from 119 patients with bladder cancer who were initially treated between January 1982 and March 1988. Cytological specimens obtained from voided urine were stained by the Giemsa and Papanicolaou techniques, and were classified into three categories of malignant cells: positive, suspicious, and negative. Of 311 specimens examined, 114 (37%) were positive, 81 (26%) were suspicious, and the remaining 116 (37%) were negative. The overall positive rate, or sensitivity, was 50% (60 out of 119 patients). The sensitivities were 7% for patients with grade 1 tumors, 42% for grade 2 tumors, and 97% for grade 3 tumors. Univariate analysis by logistic regression analysis revealed that grade, stage, histological pattern of growth, size and number of tumors, and patient age were significantly related with the positivity of voided urinary cytology. The logistic regression model, as a multivariate analysis, demonstrated that grade was the most important determinant affecting the positive cytologic finding, followed by number of tumors with statistical significance. We conclude that the lower sensitivity in conventional urinary cytology for low-grade tumors necessitates new adjuncts, including immunocytochemistry and flow cytometry, to lower the false-negative rate.
Adult↗
[Serum level of vascular basement membrane associated collagen by the sandwich ELISA with monoclonal antibodies and its clinical significance in various diseases].
A sandwich ELISA system for detecting vascular basement membrane associated collagen (BAC) was developed. Serum levels of BAC were determined in patients with liver diseases (N = 53), various cancers (N = 65) and other diseases (399). Serum levels of procollagen type III (PIIIP) amino propeptide, type IV collagen.7s domain (7s domain) and other parameters (TP, ALB, GOT, GPT, CHE, gamma-GTP, ALP, LDH, CHE, TG, GLU) were also determined in those patients. In the whole patients, serum concentrations of BAC showed a weak correlation with GOT, GPT, ALB and CHE but not with gamma-GTP and ALP. There was no correlation between BAC and PIIIP or 7s domain. Although serum levels of BAC were elevated in both liver diseases and cancers, the increase in liver diseases was more marked. Markedly increased serum levels of BAC with low levels of CHE were found only in liver cirrhosis and liver cirrhosis plus hepatocellular carcinoma. Increased BAC may reflect capillarization of the liver sinusoid or remodeling of the vascular basement membrane which is observed in the progression of liver fibrosis. Serum BAC is thought to be a promising new marker, different from PIIIP or 7s domain for diagnosing fibrosis state in the organs, particularly in the liver.
Antibodies, Monoclonal↗
[Antibody response to P-fimbriae of Escherichia coli in patients with genitourinary infections].
The serum antibody response to P-fimbriae of Escherichia coli in patients with genitourinary infections was investigated with enzyme linked immunosorbent assay (ELISA) for P-fimbriae-specific IgG antibody. 1) Female patients with acute pyelonephritis had a significantly (P less than 0.01) higher titer of serum IgG antibody by ELISA, compared with patients with acute cystitis or control subjects. The prevalence of positive serum IgG antibody response was 65% in patients with acute pyelonephritis. 2) Patients with epididymitis with high fever had a significantly (P less than 0.01) higher titer of serum IgG antibody by ELISA, compared with patients with epididymitis without fever or control subjects. The prevalence of positive serum IgG antibody response was 60% in patients with epididymitis with high fever. Therefore, 65% of female patients with acute pyelonephritis and 60% of patients with epididymitis with high fever are infected with P-fimbriated E. coli. The measurement of serum antibody response to P-fimbriae must be helpful for the diagnosis and the antibiotic therapy of epididymitis.
Acute Disease↗
[Clinical evaluation of bunazosin hydrochloride for the treatment of voiding disturbances due to neurogenic bladder--a double-blind study].
The therapeutic utility of bunazosin hydrochloride was evaluated by a multi-center (67 hospitals) double-blind controlled study in patients who complained of voiding disturbances due to neurogenic bladder. For means of comparison, bethanechol chloride and placebo were used as reference drugs. Bunazosin hydrochloride was orally administered 1.5 mg per day for the first week and 3.0 mg per day for two weeks thereafter (Group E). Bethanechol chloride 15 mg (Group B) and placebo (Group P) were orally administered three times daily for three weeks. Three hundred and twenty-three cases were subjected to this study. The global improvement rating was analyzed for 244 cases (83 in Group E, 78 in Group B and 83 in Group P). The global utility rating (GUR) was analyzed for 252 cases (84 in Group E, 81 in Group B and 87 in Group P). Three hundred and twenty cases (107 in Group E, 104 in Group B and 109 in Group P) were analyzed with respect to overall safety rating (OSR). The global improvement ratings (excellent and good) were 32.5% in Group E, 28.2% in Group B and 21.2% in Group P. In the evaluation of GUR, Group E was superior to Group P. In addition, the incidence judged to be useless in Group E was significantly lower than that in Group B. There were no differences in OSR among these three groups. In the total evaluation of the subjective symptoms, the rates of improvement were not different among these three groups. In the total evaluation of the objective findings, the improvement rate in Group E was significantly higher than that in Group P. In addition, the deterioration rate in Group E was significantly lower than that in Group B. In objective findings before and after administration of bunazosin hydrochloride (Group E), the volume of residual urine, the rate of residual urine and the average flow rate improved significantly However, the bladder capacity, the maximum resting bladder pressure and the maximum urethral pressure did not change significantly. Bunazosin hydrochloride improved the objective findings regardless of the bladder capacity and the maximum resting bladder pressure. These significant improvements were marked in the neurogenic bladder patients who were able to urinate and in the patients whose urethral pressure was high. There were no differences in the incidence of side effects or in the appearance of abnormal values of laboratory findings in these three groups. Neither specific signs nor serious clinical side effects except those reported previously were observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenergic alpha-Antagonists↗
[A case of a 46XX male].
A 37-year-old man consulted our hospital with a complaint of male infertility. He was masculine but 159.9 cm in height. His beard, axillary hair and pubic hair were all normal. The penis and scrotum were also normal, but bilateral testes were very small (1 ml. respectively). Semen analysis revealed azoospermia. Endocrinological examination showed elevated serum lactating hormone and follicle stimulating hormone level, and extremely low level of serum testosterone. Testicular biopsy disclosed severely hyalinized seminiferous tubules and hyperplasia of Leydig cells. No ovarian tissue could be detected. The chromosomal analysis revealed a karyotype of 46 XX. This case was diagnosed as a case of 46XX male. The Japanese literature of 46XX male is reviewed.
Adult↗
[Malignant pheochromocytoma presenting as an acute abdomen: a case report].
A case of right adrenal malignant pheochromocytoma was reported. The patient was a 16-year-old boy who complained of severe right side abdominal pain due to spontaneous hemorrhage into the retroperitoneal space. Right adrenalectomy was performed on Feb. 22, 1988 but the preoperative high serous catecholamine level did not drop to the normal level. Postoperatively bone and liver metastasis were detected by a 131I-MIBG scan. He was treated with a combination chemotherapeutic regimen consisting of cyclophosphamide, vincristine and dacarbazine in 2 repeated cycles but there was no effect. He died 5 months after the operation.
Abdomen, Acute↗