[Circadian rhythms of the pancreatic ductal pressure and E.M.G. of the papillary sphincter in Japanese monkey].
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Biomedical subjects
Publications and source records attributed to Y Sakamoto.
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A 3-year and 5-month old boy presented with the chief complaint of painless swelling in the scrotum, which had been noticed since birth. Under the diagnosis of intrascrotal tumor, an operation was performed. As the testis and epididymis were intact, the tumor was removed. The pathological diagnosis of the resected tumor was a well-encapsulated benign lipoma.
Since 1974, approximately 200 fresh cancer tissues obtained from various types of cancer patients were inoculated into athymic BALB/c nude mice, of which 30 percent were taken and grown in the subcutaneous space of mice. Among them 15 lines of gastrointestinal and breast cancer xenografts were selected for experimental single agent chemotherapy. The response rates of 14 drugs examined in this xenograft system were compared with the cumulative clinical response rate of each drug in the same type of cancer. Drugs which were clinically effective against one type of tumor were found to be also effective against the corresponding xenograft in nude mice. Thus the human cancer-nude mouse system was considered useful as a predictive secondary screening method for new drugs. This evidence suggested to us the feasibility of utilizing the system as a chemosensitivity test for determining the drugs effective for an individual human malignancy. In our present study, the responses to 15 experimental chemotherapies with single agent or drug combination of 11 lines of cancer xenografts in nude mice were directly compared with the clinical response in each donor patient to the corresponding chemotherapy. Good correlation was obtained between these respective results, the overall predictive accuracy of the experimental results being 93%. Therefore, if the rate of transplantability to nude mice were to be improved, this nude mouse system would become a promising tool for the individual chemosensitivity test. The subrenal capsule (SRC) assay recently introduced by Bogden and his colleagues has excited much attention among Japanese clinical oncologists. In our study, cancer tissues implanted under the renal capsule 6 days after inoculation, did not show marked proliferation and a high percentage of implants was almost replaced by host reactive tissue. It therefore seems necessary to solve some fundamental problems before we can apply this assay method to clinical chemosensitivity trial.
A renocolonic fistula, complicated by a renal stone, was diagnosed in two women, 53 and 63 years old. The first patient had had a previous history of surgery when she underwent exploratory laparotomy for a right perinephric abscess, but the attempt to remove the right kidney was abandoned due to complications and a drainage tube was left. Six years after the first admission, an increased purulent discharge brought her in for further evaluation, fistulography then disclosed the presence of a renocolonic fistula. The second patient had a staghorn stone in the non-functioning left kidney. Retrograde pyelography revealed a fistulous tract between the renal collecting system and the colon. Subsequently, both patients underwent surgery in one stage to remove the infected kidney and the involved colon. The postoperative course was uneventful in each case, and they have since led comfortable lives without any febrile episodes. These two cases are the 17th and 18th cases of renocolonic fistulas reported in the Japanese literature.
This is a report of two cases of adenomatoid tumor on the epididymis. Both patients presented with the chief complaint of an intrascrotal mass. One patient, 56 years old, had a tumor on the left epididymis and underwent left epididymectomy. The other patient, 65 years old, had a tumor on the right epididymis and underwent resection of the tumor. Subsequently histological diagnosis confirmed an adenomatoid tumor. From the Japanese literature, 103 cases of adenomatoid tumor including the present cases were reviewed. The tumor was located on the epididymis in 83 cases with a mean age of 39.6 years and on the testicular tunica in 11 cases with a mean age of 27.5 years. These tumors originated from two sites, from the serosal lining of the genital tract and from the Müllerian remnant. The former type is called by Yasuma the Mesotherial type and the latter, the adenomatoid type. The present two cases are of the adenomatoid type, which is usually found on the tail of the epididymis in men from 30 to 50 years of age.
Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of human glioma cell lines into nude mice. The tumor growth was steady and fast in MG nude mice if 10(7) cells were implanted. Median survival time (MST) of nude mice inoculated with tumor cells was inversely related to the number of cells inoculated. There was a correlation between in vitro and in vivo (MG models) growth rate, which means that the cell kinetics in vitro are reflected in vivo. The clinicopathological features observed in nude mouse MG models were similar to those seen in diffuse leptomeningeal involvement of gliomas in humans. The models will be useful for investigating the pathophysiology of meningeal gliomatosis and the efficacy of chemotherapeutic agents.
A retrospective study was conducted on 22 patients with renal pelvic tumor treated at our University Hospital between 1970 and 1984. The patients included 18 males and 4 females, from 31 to 81 years of age. The left kidney was involved in 14 cases, and the right in 8. More than 60% of them also presented gross hematuria. IVP abnormalities included filling defects in 9 cases and non-visualizing kidney in 8 cases. Pretreatment urinary cytology was positive in 65.7%. Radical nephroureterectomy was performed in 18 cases, followed by adjuvant therapy in 10 cases; radiation in 5 cases, chemotherapy in 4 cases, and radiation/chemotherapy in one case. Histology revealed transitional cell carcinoma in all cases. On diagnosis, simultaneous urothelial tumors were identified in one case in the ureter and the bladder, and in one case in the bladder. Tumor development after surgery was observed in 9 cases, 8 in the bladder and one in the ipsilateral renal pelvis. The 5-year actual survival rate was 58.2% over all: that of the low-grade group was 100%; that of the high-grade group, 45.1%; that of the low-stage group, 100%; that of the high-stage group, 19%. In conclusion, the prognosis in our series was significantly influenced by the stage and grade of the tumor.
From clinical studies on T-2588, an oral ester type cephem, the following results were obtained. Ten patients with acute tonsillitis, 3 with acute pharyngolaryngitis, 2 with acute sinusitis, 1 with acute exacerbation of chronic sinusitis and 2 with acute exacerbation of chronic otitis media were treated with T-2588 at a daily dose of 300 or 600 mg. Clinical responses were excellent in 12, good in 4, fair in 1 and poor in 1. Clinical efficacy was 88.9%. Bacteriologically, all isolates except one strain of S. aureus were eliminated. Clinical efficacies classified by clinical isolates correlated well with bacteriological efficacies. The MICs of T-2525 against clinical isolates were determined and compared with those of cephalexin, cefaclor and amoxicillin. The T-2525 showed potent antibacterial activity against Gram-positive and Gram-negative bacteria including S. pneumoniae, H. influenzae and beta-Streptococcus, but the activity of T-2525 against S. aureus was similar to that of the other antibiotics examined. Neither side effect nor abnormal laboratory finding was observed.
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Significant increase in the activity of an acetyl-CoA hydrolase (ATP-stimulated, ADP-inhibited enzyme) in the supernatant fraction of rat liver was observed after 44-68 h of starvation (about 2-fold), and in the early stage of diabetes (about 1.6-fold), but not in the chronic stage of diabetes. The increased enzymatic activity in starved rats returned to the control level within 20 h when the animals were given laboratory chow, but not when they were given fat-free diet with a high carbohydrate content, and the enzyme activity was increased by the latter diet containing 1% thyroid powder. A single intraperitoneal injection of 3,3'5-triiodo-L-thyronine or 3,3',5,5'-tetraiodo-L-thyronine resulted in twice the normal enzyme activity two days later, and conversely 7 days after thyroidectomy, the enzyme activity was about 60% of the control level. A single subcutaneous injection of alpha-(p-chlorophenoxy)isobutyric acid, a hypolipidemic drug, doubled the enzyme activity in euthyroid rats, but not in thyroidectomized rats. Of the various tissues tested besides the liver, only the kidney had detectable ATP-stimulated and ADP-inhibited enzyme activity (5% of the activity in liver cytosol). The kidney enzyme had similar kinetic and immunochemical properties to the liver enzyme. Changes in the enzyme activity in the liver in various states were closely related to the amount of enzyme present, judging from results obtained by enzyme-linked immunosorbent assay. The physiological role of this enzyme (which hydrolyzes acetyl-CoA to acetate and CoASH) may be in maintenance of the cytosolic acetyl-CoA concentration and CoASH pool for both fatty acid synthesis and oxidation.
The activity of acetyl-CoA hydrolase (dimeric form) purified from the supernatant fraction of rat liver was shown to have a half-life (t1/2) of 3 min at 0 degree C, but to stable at 37 degrees C (t1/2 = 34 h) [Isohashi, F., Nakanishi, Y. & Sakamoto, Y. (1983) Biochemistry 22, 584-590]. Incubation of the purified enzyme with L-ascorbic acid (AsA) at 37 degrees C resulted in inactivation of the enzyme (t1/2 = 90 min at 2 mM AsA). The extent of inactivation was greatly enhanced by addition of transition metal ions (Cu2+, Fe2+, and Fe3+). Thiol reducing agents, such as reduced glutathione and DL-dithiothreitol, protected the hydrolase from inactivation by AsA. However, these materials did not restore the catalytic activity of the enzyme inactivated by AsA. When AsA solution containing Cu2+ was preincubated under aerobic conditions at 37 degrees C for various times in the absence of enzyme, and then aliquots were incubated with the enzyme solution for 20 min, remaining activity was found to decrease with increase in the preincubation time, reaching a minimum at 60 min. However, further preincubation reduced the potential for inactivation. Catalase, a hydrogen peroxide (H2O2) scavenger, almost completely prevented inactivation of the enzyme by AsA plus Cu2+. Superoxide dismutase and tiron, which are both superoxide (O2-) scavengers, also prevented inactivation of the enzyme. A high concentration of mannitol, a hydroxyl radical (OH) scavenger, partially protected the enzyme from inactivation. These results suggest that inactivation of the enzyme by AsA in the presence of Cu2+ was due to the effect of active oxygen species (H2O2, O2-, OH) that are known to be autoxidation products of AsA. Valeryl-CoA, a competitive inhibitor of acetyl-CoA hydrolase, greatly protected the enzyme from inactivation by AsA plus Cu2+, but ATP and ADP, which are both effectors of this enzyme, had only slight protective effects. These results suggest that inactivation of this enzyme by addition of AsA plus Cu2+ was mainly due to attack on its active site.
On amino acid analysis of urine of histidinemic patients, an unidentified compound was eluted in a position between beta-aminoisobutyric acid and gamma-aminobutyric acid. This compound was purified to homogeneity from the urine by a combination of extraction with 80% ethanol, repeated column chromatography on Bio-Rad AG-50, and high performance liquid chromatography on a strongly cationic ion exchanger. The compound yielded free histidine on hydrolysis in an evacuated sealed tube with 0.1-6.0 M HCl at 145 degrees C for 5 h, but not at 100 degrees C for 24 h. This compound was determined to be N tau-ribosylhistidine by 1H and 13C NMR spectroscopies. The urinary content of this material in normal and histidinemic children was 17.8 +/- 13.4 (n = 10) and 126 +/- 51 (n = 14) mumol/g creatinine (mean +/- S.D.), respectively, and were closely correlated with those of urinary histidine. The renal clearance value of N tau-ribosylhistidine in humans was 96% of that of creatinine. When rats were fed on diets rich in histidine, the urinary excretion of N tau-ribosylhistidine increased greatly and was well correlated with the intake of histidine.
Paper electrophoresis and Bio-Gel P-4 column chromatography of the oligosaccharides released from mouse kidney gamma-glutamyltranspeptidase by hydrazinolysis gave fractionation patterns quite distinct from those of the bovine and rat kidney enzymes. Structural studies of the fractionated oligosaccharides by sequential exoglycosidase digestion in combination with methylation analysis showed that mouse kidney gamma-glutamyltranspeptidase contains a series of bisected complex-type asparagine-linked sugar chains with the following oligosaccharides as their outer chain moieties: GlcNAc beta 1----, Sia alpha 2----Gal beta 1----4GlcNAc beta 1----, Gal beta 1----4(Fuc alpha 1----3)GlcNAc beta 1----, and sialylated N-acetyllactosamine repeating sugar chains. Some of these sugar chains were found for the first time in glycoproteins.
Administration of either D- or L-thyroxine (T4) significantly increased the glucocorticoid binding capacity of cytosol of the livers of adrenalectomized adult rats. Administration of up to 0.5 mg/100 g body wt. of L-T4 was more effective than that of D-T4, but higher doses (0.8-3 mg/100 g body wt.) of D-T4 increased the binding capacity markedly to more than that with L-T4. T4- administration did not alter the apparent dissociation constant of glucocorticoid binding proteins for glucocorticoid binding, or their behavior on DEAE-cellulose chromatography either before or after thermal activation (23 degrees C for 40 min). Thus the increased binding capacity seemed to be due to increase in the level of glucocorticoid receptor in rat liver.
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The effect of about one hundred compounds on the activity of histidine decarboxylase partially purified from whole bodies of fetal rats was determined. Most of them at their 10 mM concentration had little effect on the enzyme activity; but 12 compounds inhibited the enzyme to a greater extent than 30%. Among these, except for alpha-methylhistidine that has been known to be a strong and specific inhibitor, DOPA, homocysteine, cysteine, methionine and urocanic acid were the best inhibitors; beta-phenyllactic acid, phenylpyruvic acid and carnosine were less strong inhibitors; valine, oxaloacetic acid and N tau-methylimidazole acetic acid were weak inhibitors. Histamine had no inhibitory action. Thus, the substrate binding site of histidine decarboxylase is very rigid and specific for L-histidine.
Experimental allergic orchitis (EAO) was induced in cyclophosphamide (CY)-pretreated C3H/He mice by immunization with viable testicular cells (TC) without any adjuvants. The pathological changes such as hypospermatogenesis in the seminiferous tubules and mild cellular infiltration in the interstitium were observed in most mice thus treated. Delayed footpad reaction (DFR) against testicular antigen and anti-sperm antibody in sera were detected in those mice. This murine model of orchitis is new and simple in that no adjuvants are used for induction and can be useful in further studies on mechanisms of induction and maintenance of EAO.
The number of postmenopausal women colposcopically diagnosed has markedly increased during the last 15 years. In some of them, a clear colposcopic impression, required for planning an appropriate therapy, was disturbed by severe senile cervicocolpitis, when examined by the conventional technique using acetic acid. With a 5-year experience of 79 paired colposcopies, it was concluded that estrogen administration is necessary as a routine precolposcopic procedure in such cases and oral administration of conjugated estrogens at 1.25 mg/day for 14 days is adequate for this purpose.