Significance of taurine conjugation of bile acid in the biliary excretion of bilirubin.
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Biomedical subjects
Publications and source records attributed to T Tsujii.
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In the present study, the role of albumin and high-density lipoprotein (HDL) as endotoxin (Et)-binding proteins in chronically alcohol-fed rats was studied. In acute ethanol-loaded rats, the Et clearance in the blood was slightly prolonged, and the amount of albumin and HDL- bound Et in the blood was markedly increased. In chronic ethanol-loaded rats, the Et clearance was significantly faster than that in the control, and HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5 g/kg body weight of ethanol load, the Et clearance was much prolonged, and blood tumor necrosis factor and ALT was elevated, when HDL-bound Et was not further increased. Et-binding capacity of total proteins, albumin, and HDL in the hepatocyte culture medium were increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. In the culture experiment in the chronic ethanol-loaded rats, such increases were not observed. These results suggest that the increase in Et-binding capacity of HDL and albumin may serve as a protective mechanism against Et in chronic ethanol-loaded rats. An addition of high-dose ethanol to these rats may lead to impaired Et binding and inactivation, which may finally result in increased endotoxicity.
OBJECTIVE: The results of genitoplasty performed at our clinic for 41 female patients with congenital adrenal hyperplasia (CAH) were reviewed. PATIENTS: Among 57 females with CAH (56 with 21-hydroxylase deficiency and 1 with 11 beta-hydroxylase deficiency) diagnosed between 1961 and 1995, 41 underwent genitoplasty. For the rest of 16 patients, 1 received already clitorectomy, 11 (19%) needed no surgical reconstruction, 2 died before surgery, and 2 are in a waiting list for surgery. RESULTS: According to Prader's classification of virilized genitalia, 41 patients who received surgery included 8 of type I, 10 of type II, 17 of type III, and 4 of type IV. There was no patients of type V, and 2 were not classified because of previous surgery. Four patients underwent genitoplasty 7 times in total before visiting us. The age receiving initial genitoplasty at our clinic ranged from one year and 9 months to 20 years (median: 4 years and 5 months). Follow-up period averaged 17 years with the range of 2 months to 33 years. For enlarged clitoris, clitorectomy (amputation of clitoris) was carried out for 22 patients before 1975 and corporal resection for 17 after 1975. Two patients manifested recurrence of clitoromegaly after the surgery because of either incomplete resection of the clitoris or patient's ignorance of taking glucocorticoid regularly. Thirty-six patients needed labiovaginoplasty. Simple midline cutback was performed for 6 patients and Y-V plasty (skin flap labiointroitoplasty) for 30. Vaginal orifice was not identified in 5 patients at the initial surgery. Two patients received successful second introitoplasty at the older age than 10. Post-operative stenosis of vaginal orifice was confirmed in 6 patients and 3 underwent second introitoplasty. Among 23 patients older than 25 years at present, 7 got married and 4 raised 6 children with assistance of Caesarian section. CONCLUSIONS: Most of female patients with CAH needed genital plastic surgery including clitoroplasty and labiovaginoplasty. Corporal resection for enlarged clitoris with sufficient hormone therapy brought a satisfactory result. Y-V plasty for labiovaginoplasty proved to be an excellent method, especially from cosmetic viewpoint, but remained some problems as one stage operation including difficult identification of vaginal orifice and post-operative stenosis of introitus in some patients.
BACKGROUND: The objective of this study is to evaluate efficacy of en bloc cystourethrectomy with preservation of potency in patients with bladder carcinoma. METHODS: A total of nine patients underwent this procedure in 1991 and 1994. Following 2 cases of 1991 who were confirmed to recover potency and had no recurrence in the pelvis during 2-year follow up as a preliminary study, 7 cases underwent the same procedure in 1994. Erectile function was measured by the snap gauge band. RESULTS: Six of the 9 patients recovered erection adequate for sexual activity and 4 of them have practiced sexual intercourse. The remaining 3 patients experienced mild erection but inadequate. One of them failed to accomplish adequate erection because of perineal pain at erection. Three to eighteen months after surgery, the first erection was experienced. Surgical margins were pathologically negative in each of the 9 specimens. By the present, all of the 9 patients survive with no evidence of disease. CONCLUSION: The potency-sparing en bloc cystourethrectomy appears to preserve potency on the level comparable to the two-stage potency-sparing cystourethrectomy combined with delayed urethrectomy.
We retrospectively reviewed pretreatment levels of serum prostate specific antigen (PSA) in 138 newly diagnosed, untreated patients with prostate adenocarcinoma to evaluate the usefulness of serum PSA levels to predict results of radionuclide bone scans. All of the 24 patients with serum PSA levels above 200 ng/ml showed positive bone scans whereas those with serum PSA levels below 10 ng/ml included only three cases (3/51, 5.1%) positive for bone metastasis. All of the three had poorly differentiated adenocarcinoma of the prostate. In conclusion, bone scans may not be necessary in the cases with serum PSA levels less than 10 ng/ml except for those with poorly differentiated adenocarcinoma.
We studied the influence of EIS on the respiro-circulatory condition of patients with portal hypertension. Subjects were fifty patients with portal hypertension who were successfully injected more than 5.0 ml of sclerotant into varices. A prospective randomized controlled trial was proposed to elucidate the effect of prophylactic administration of pure oxygen. Twenty-five patients inhaled pure oxygen (O2), remaining twenty-five patients did not during EIS. Respiro-circulatory function of patients was evaluated by monitoring O2 saturation, pulse rate and blood pressure during EIS. PaO2 was measured before and after EIS in seven patients without O2. EIS by the 5% ethanolamine oleate with iopamidol (EOI) was performed under X-ray monitoring. O2 saturation in patients without O2 inhalation was lowered, whereas that in patients with O2 inhalation was stable during EIS. O2 saturation during injection of EOI and after EIS in patients without O2 inhalation was significantly lower than that in patients with O2 inhalation. Pulse rate was significantly lower and a rise in blood pressure was smaller in patients given O2. No significant differences of PaO2 was noted before and after EIS. In conclusion, the monitoring of O2 saturation, pulse rate and blood pressure is necessary during EIS. Prophylactic administration of pure oxygen may be useful for prevention of hypoxic state and respiro-circulatory stabilization during EIS.
In the present study, we evaluated the role of high-density lipoprotein (HDL) as an endotoxin-binding protein in chronically alcohol-fed rats. Although the blood endotoxin level was significantly elevated in chronic ethanol-loaded rats, compared with control rats, serum tumor necrosis factor (TNF), ALT, and lactate dehydrogenase were not elevated. Serum HDL and its endotoxin-binding capacity were significantly increased in chronic ethanol-loaded rats. When Kupffer cells isolated from control and chronic ethanol-loaded rats were cultured in the medium containing 3 to 30 mg/dl HDL and endotoxin (500 ng/ml), endotoxin uptake and TNF production of Kupffer cells were decreased in proportion to the concentration of HDL in the medium. These results suggest that the increase in endotoxin-binding capacity of HDL may serve as a protective mechanism against endotoxin in chronic ethanol-loaded rats.
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Pituitary adenylate cyclase activating polypeptide (PACAP) increases glycoprotein hormone alpha-subunit mRNA levels suggesting a role for PACAP in maintaining the high levels of alpha-subunit protein characteristic of the pituitary. The present study used primary pituitary cell cultures and the alpha T3-1 pituitary cell line to investigate how PACAP affects alpha-subunit mRNA transcripts. Stimulation of cultured pituitary cells with 10 nM PACAP38, 10 nM GnRH, or the combination, for 24 h increased alpha-subunit mRNA levels 1.5-fold, whereas GnRH more effectively (P<0.01) stimulated alpha-subunit protein release than did PACAP38 (3.2- vs. 2.0-fold). alpha-Subunit mRNA levels in alphaT3-1 cells were also increased by PACAP38 and by GnRH to maximum values at 12 h (P<0.05), and alpha-subunit protein secretion rose proportionately and in parallel with alpha-subunit mRNA levels. PACAP38 was a 100-fold more potent stimulator of alpha-subunit mRNA than was VIP, and a VIP-antagonist failed to block the stimulatory effect of PACAP38, suggesting an effect via type PACAP 1 receptors. Type I receptor mRNA transcripts were identified by Northern analysis in alphaT3-1 cells. Depletion of PCK activity by PMA failed to block the stimulatory effect of PACAP38, but prevented GnRH from increasing alpha-subunit mRNA levels and alpha-subunit secretion. PACAP38, like 8Br-cAMP and forskolin, stimulated (P<0.05) luciferase (LUC) activity in alphaT3-1 cells transfected with a plasmid containing the first 846 of 180 base pairs of the 5'-flanking region of the human alpha-subunit gene linked upstream to a LUC reporter gene. Finally, experiments using the transcription inhibitor DRB reveal that PACAP does not appreciably change alpha-subunit mRNA half-life. These findings are consistent with the proposal that PACAP contributes to the high levels of alpha-subunit protein characteristic of the pituitary by activating Type I receptors and stimulating alpha-subunit gene transcription in part by the cAMP/PKA pathway.
The effects of pituitary adenylate cyclase activating polypeptide (PACAP) administered intermittently on gonadotropin secretion and subunit mRNA levels in anterior pituitary cells from 7wk old intact and orchidectomized rats were studied. Cells were perifused for 9 h with hourly pulses of 2.5 nM GnRH or 10 nM PACAP, or with medium alone. Pulsatile PACAP initiated episodes of LH, FSH and alpha-subunit secretion, but was much less effective than GnRH. Responsiveness declined with repeated pulses of PACAP, although interpulse secretion increased gradually throughout the experiment. PACAP was a slightly more effective stimulator of LH release by pituitary cells from castrated than intact rats. At the completion of perifusion, pituitary RNA from castrated rats was extracted for measurement of gonadotropin subunit mRNA levels. Pulsatile PACAP stimulated alpha-subunit and LHbeta mRNA levels but did not affect FSHbeta mRNA. By contrast, continuous PACAP increased alpha-subunit mRNA levels, but suppressed FSHbeta mRNA without affecting LHbeta mRNA. We conclude that pulsatile PACAP is a relatively ineffective stimulator of gonadotropin secretion when administered alone, and regulates gonadotopin subunit gene expression quite differently than continuous PACAP. We propose that the mode of PACAP secretion in vivo may be a determinant of the differential expression of the gonadotropin subunit genes.
Human peripheral blood mononuclear cells (PBMC) cultured with or without concanavalin A (Con A) secrete soluble TCR alpha and TCR beta chains. Soluble TCR-like products of three different relative molecular masses--185,000 (Mr 185 kDa), 152 and 42 kDa--which are antigenically similar to those on T lymphocytes have been found in sera from healthy adult donors. These findings suggest that soluble TCRs, antigenically similar to cell surface TCRs, are secreted from T lymphocytes.
The endotoxin inactivating action of plasma was evaluated in 62 patients with cirrhosis and 10 healthy subjects. Endotoxin from E. coli 0111:B4 was added to each plasma sample to a final concentration of 250 pg/ml and the percentage loss of endotoxin activity by incubation (37 degrees C for 1 h) was calculated as the endotoxin inactivating rate. The plasma endotoxin inactivating rate in cirrhotics was significantly greater than that in healthy subjects, although patients with Child C cirrhosis and marked hyperbilirubinemia had a significantly lower endotoxin inactivating rate than other cirrhotics. The plasma endotoxin inactivating rate was positively correlated to serum HDL-cholesterol levels. In patients with Child A and Child B cirrhosis, the endotoxin inactivating rate was positively correlated to the endotoxin binding capacity of plasma albumin. The present results support the assumption that the plasma of cirrhotics has a high endotoxin inactivating capacity. Its decrease may augment endotoxicity in patients with advanced liver cirrhosis.
We report two cases of congenital adrenal hyperplasia (CAH) in which administration of chlormadinone acetate (CMA), a substituted progestational agent for prostatic disease, suppressed ACTH hypersecretion and lowered plasma testosterone levels. Case 1 was 83-year-old male with advanced prostatic carcinoma and CAH due to 21-hydroxylase deficiency. His plasma testosterone did not decrease in spite of a bilateral orchiectomy. Case 2 was 40-year-old female with CAH due to 21-hydroxylase deficiency suffering from virilization after the cessation of cortisol supplement therapy because of her breast carcinoma. In these two cases, oral administration of CMA at a daily dose of 75-100 mg suppressed ACTH and cortisol to subnormal levels and reduced testosterone levels. With the suppressive effect on ACTH excess and antiandrogenic action, CMA may be suitable for patients with CAH suffering from symptoms due to overproduced ACTH or adrenal androgen.
A 41-year-old female patient with muscle dystrophy, hepatosplenomegaly and tendinous xanthoma showed mild hypertriglyceridemia. The lipoprotein profile in blood showed increases in triglycerides in VLDL and LDL, and a marked decrease of cholesterol in HDL. Chylomicronemia was found, but was not severe. Both lipoprotein lipase and hepatic triglyceride lipase activities were reduced to a level that was only a few percent of the control. Immunoblotting study revealed that the IgG autoantibody in her serum was apparently reactable with hepatic triglyceride lipase and weakly with lipoprotein lipase. Hypertriglyceridemia in this patient is suggested to be due to the autoantibody to these lipases.
Single-stomal ureterostomy such as double barreled ureterocutaneostomy and cutaneous transureteroureterostomy have usually been performed by transperitoneal approach. However, extraperitoneal method is preferable since the patients for whom ureterocutaneostomy is indicated usually have a deteriorating general condition. We have reported single-stomal ureterocutaneostomy which can be done extraperitoneally. A total of thirteen patients, one man and twelve women, for whom permanent urinary diversion was indicated, have undergone this extraperitoneal ureterocutaneostomy for February 1988 to June 1994. Those with retroperitoneal lesions or with a history of paraaortic radiotherapy were excluded. The mean age was 61.7 (range: 42-76). The reasons for urinary diversion were vesicovaginal fistula in seven, obstructive nephropathy in four, rectovesical fistula in one and postoperative urine leak from the bladder in one. All patients had been treated for malignant diseases and had undergone transperitoneal surgery. Six patients had colostomy and ten had clinically evident recurrent diseases. In the operation, left ureter was dissected and severed extraperitoneally through left paramedian incision or left lumbotomy. The ureteral end was pushed to the right in a retroperitoneal tunnel created by blunt dissection. Then the ureter was picked up through the contralateral retroperitoneal approach. After both ureters were exposed, ureterocutaneostomy was made in right hypogastrium. Transureteroureterstomy with end-cutaneous ureterostomy, double barreled ureterocutaneostomy and ureteroureterostomy with loop ureterostomy were done in six, four and three patients, respectively. The mean operative time was 119 (range: 75-175) minutes and the mean intraoperative blood loss was 210 (range: 48-682) grams. Arrhythmia developed during retroperitoneal manipulation in one patient for whom the operation was done under spinal anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: The internal urethral ostium is usually closed both on the ejaculation and on the urine collection, although the difference of the closing characteristics have not been known. METHODS: The difference in closing style of bladder neck (internal urethral ostium) between on the phenylephrine administration corresponding state to the ejaculation and on the filling of urinary bladder corresponding state to the urinary continence was evaluated by Stereo-UPP method using mongrel dogs. RESULTS: On phenylephrine administration, the length between verumontanum and bladder neck was lengthened, and a remarkable pressure increase was observed in the area. On the urinary continence filling physiological saline in the bladder, the length of the urethra on the UPP curve of the anterior wall of urethra was lengthened (10%) and the base of bladder was gradually become flat. The pressure in the bladder neck was not relatively increased. CONCLUSIONS: The internal urethral ostium was closed both on the phenylephrine administration and on the urine collection, although the closing characteristics of each was very different. It was demonstrated that on the phenylephrine administration the area between the verumontanum and the bladder neck was lengthened, together with the rise of pressure in the area, whereas on the urine collection bladder neck was closed in low pressure by flattening the base of bladder.
In the field of gene therapy using retroviral vectors, it appears impossible to introduce a foreign gene into all target cells. Therefore adjacent cell killing, the socalled bystander effect, caused by genetically modified cells provides therapeutic advantages for gene therapy against cancers. We retrovirally transduced the herpes simplex virus thymidine kinase (HSV-tk) gene into murine and rat hepatocellular carcinoma (HCC) cells. These HSV-tk gene-transduced HCC cells were cocultured with the corresponding parental cells in the presence of ganciclovir, at a concentration not at all cytotoxic to the parental cells. When parental HCC cells were cocultured with their HSV-tk gene-transduced counterparts at a high density at which most cells were in contact with one another, they were markedly eliminated. Conversely, when cocultured at a low density at which none of the cells were in contact, a weak but statistically significant bystander effect was observed. Addition of lysates of HSV-tk gene-transduced cells in the presence of ganciclovir did not cause and killing of parental cells. Furthermore, media conditioned by transduced cells with ganciclovir exhibited weak cytotoxic effects on parental cells. These results indicate that cell-cell contact plays a major causative role in the bystander effect and that minor contributors to this phenomenon are some cytotoxic substance released from transduced cells. Importantly, the bystander effect was induced in vivo as well as in vitro. When mixtures of transduced and untransduced HCC cells were implanted into the flank region of mice, intraperitoneal ganciclovir administration considerably inhibited tumor development, indicating the feasibility of gene therapy with HSV-tk gene and ganciclovir against HCC.
We investigated whether an artificial neural network (ANN) could learn a chaotic pattern related to the time-course of some clinical laboratory data and predict its future pattern. Then, the patterns of serum ALT level over time in patients with chronic hepatitis were successively learned by ANN. Future patterns were also successively predicted. This procedure may be used to pick up an unexpected event in time-course of personal data, study the pathological background of disease, or application of prophylactic treatment.