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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 523 records · Page 29Linked to original sources

Effects of diltiazem and noradrenaline on extracellular potassium changes in the globally ischaemic rat heart.

OBJECTIVE: The aim was to investigate the effects of a calcium antagonist (diltiazem) and a catecholamine (noradrenaline) on extracellular potassium accumulation during global ischaemia. METHODS: Extracellular potassium concentration ([K+]e) was measured during 30 min global ischaemia in the isolated rat heart using a valinomycin potassium sensitive electrode. Contracture development during ischaemia was measured throughout with an intraventricular balloon inserted into the left ventricle and myocardial adenine nucleotides were measured in separate series of hearts. RESULTS: In control hearts, [K+]e showed a characteristic triphasic change during 30 min global ischaemia. This consisted of an early rising phase followed by a transient falling phase after the initial peak of [K+]e, and then a late rising phase. Diltiazem suppressed the rate of rise of [K+]e during early ischaemia, but extended the time course of the early [K+]e rise with the higher dose, abolishing the transient falling phase of [K+]e. During late ischaemia, the rise in [K+]e was attenuated by diltiazem. Noradrenaline also suppressed the early extracellular potassium accumulation, but in contrast to diltiazem, hastened the time course of the late [K+]e rise. CONCLUSIONS: Although diltiazem suppresses the early potassium loss during ischaemia as previously described, the drug also decreases the [K+]e fall by some as yet unknown mechanism, so that the [K+]e level becomes higher than control during the falling phase.

Adenosine Triphosphate↗

Endothelin modulation of tissue plasminogen activator release from human vascular endothelial cells in culture.

To clarify a possible involvement of the vasoconstrictive peptide endothelin in the regulation of endothelial cell-mediated fibrinolytic system, confluent cultures of vascular endothelial cells from human umbilical vein were incubated in serum-free medium in the presence of endothelin-1 at 100 nM and below, and tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by enzyme immunoassay. Endothelin-1 at 1 nM and above significantly decreased the release of t-PA:Ag from the endothelial cells after a 24 h incubation. The t-PA:Ag release was also decreased by either endothelin-2 or endothelin-3 at 10 nM. The activity of lactate dehydrogenase in the medium was not changed by endothelin-1 at 100 nM and below, suggesting that the peptide did not cause nonspecific cell damage. The decrease in the t-PA:Ag release induced by endothelin-1 occurred in the presence or absence of 8-bromo cyclic AMP, which is an active congener of cyclic AMP; 3-isobutyl-1-methylxanthine, which is an inhibitor of phosphodiesterase; and forskolin, which is a stimulator of adenylate cyclase. These results strongly indicated that cyclic AMP which is known to down-regulate t-PA:Ag release was not involved in the endothelin-1 effect. However, endothelin-1 failed to decrease the t-PA:Ag release in the presence of either calcium ionophore A23187 or EGTA; the ionophore itself markedly decreased the release. The cytosolic calcium accumulation was significantly increased by endothelin-1. These results suggest that endothelin-1 decreases the release of t-PA:Ag from human endothelial cells through an excess accumulation of intracellular, especially cytosolic which would be mediated by an extracellular, calcium-dependent mechanism.

1-Methyl-3-isobutylxanthine↗

Analysis by step sectioning of early invasive bladder cancer with special reference to G3.pT1 disease.

Eighty cases of cystectomized and step-sectioned pT1 transitional cell carcinomas of various grades were analyzed. During the same period, 30 consecutive cases of pT2 carcinomas were also cystectomized and examined for comparison. This is a cross-sectional study of a variety of cases of bladder cancer, designed to delineate the characteristics of G3.pT1 disease. Tumors in this series had a full set of various pathological findings; grades 1 to 3, stages Ta-T1-T2, papillary-papillonodular-nodular tumor configuration, alpha-beta-gamma type of invasion, presence of lymphatic and venous involvement, and presence of associated carcinoma in situ/dysplasia. There is a distinct tendency of stepwise disease progression, such as grade 1-->3, stage T1-->T2, papillary-->nodular configuration, and alpha-->gamma invasion, these factors being mutually related. We noted a similarity between tumor groups containing G3 component, such as G2-3.pT1, G3 > 2.pT1, G3.pT1, G1-3.pT2, and G3.pT2. These tumors are different from groups such as G1-2.pT1, G2.pT1 and G2 > 3.pT1 in terms of tumor configuration and type of invasion. As regards pT1 having G3 components, early cystectomy seems to be the surest treatment. Whenever one adopts a conservative policy in treatment of these tumors, extreme care should be taken to monitor tumor progression.

Adult↗

Double ventricular responses to a single atrial depolarization in a patient with dual AV nodal pathways.

Electrophysiological study was performed in a patient with atrioventricular nodal reentrant tachycardia (AVNRT). Double ventricular responses through dual AV nodal pathways were observed by atrial extrastimulus technique followed by initiation of AVNRT. The difference in conduction time between the slow and fast AV nodal pathways was longer than 320 msec. A ventricular extrastimulus delivered during sinus rhythm, which was not followed by ventriculoatrial conduction, also induced AVNRT. These findings indicated the presence of an antegrade critical delay and retrograde block in the slow AV nodal pathway, criteria necessary for the occurrence of a double ventricular response.

Adult↗

Polymerase chain reaction-based detection of Trypanosoma cruzi DNA in serum.

DNAs prepared from chagasic patients' sera were amplified by the polymerase chain reaction using oligonucleotide primers which anneal specifically to a highly repetitive sequence of Trypanosoma cruzi nuclear DNA. Samples from both acutely and chronically infected patients yielded positive results by this method. No significant difference was observed when either whole blood or serum samples of the patients were used. These results indicate that serum instead of whole-blood samples could be used for polymerase chain reaction-based detection of T. cruzi in field studies without the need of applying any special chemical treatment to the specimens. This would represent a considerable advantage due to the easier handling and transportation of serum as compared with whole-blood samples, especially in tropical climates.

Adolescent↗

Biosynthesis of methylguanidine in the hepatic microsomal fraction.

We have investigated various synthetic mechanisms for the production of methylguanidine, a potent uremic toxin, and reported a role for active oxygen in its biosynthesis from creatinine in studies using isolated hepatocytes. In this study, we turn our attention to the hepatic microsomes. Liver homogenates were made from rats, and various organelles were obtained by centrifugation and incubated with creatinine. The results show that methylguanidine synthesis occurs only in the microsomal fraction in the presence of nicotinamide adenine dinucleotide phosphate, reduced form. The microsomal activity is inhibited by the addition of methimazole, metyrapone, superoxide dismutase, catalase or dimethylsulfoxide. These results suggest that methylguanidine is synthesized from creatinine by microsomes, and at least 2 enzymes are involved, an FAD-containing monooxygenase and a P-450-dependent oxidase based on the inhibitory effect of methimazole and metyrapone, respectively. Moreover, the inhibition by various scavengers of active oxygen suggests that active oxygen plays a role in the intermediate steps of the enzymatic reaction.

Animals↗

Epidermal growth factor in urine from the patients with urothelial tumors.

Epidermal growth factor (EGF) concentration in urine was measured with a radioimmunoassay in 40 untreated patients with urothelial tumors and a comparable control group of 25 normals. The concentration of EGF in urine from the patients with bladder, renal pelvic or ureter tumors was lower than normal (p less than 0.05). Patients with T4 tumors had lower concentrations of EGF compared with those of other stages. EGF concentrations after transurethral resection of bladder tumors were significantly elevated compared with the values before operation. These findings suggest that urothelial tumors are related to a low concentration of EGF and that a decrease of EGF is associated with invasion of tumors.

Carcinoma, Transitional Cell↗

Complement system in nutritional deficiency.

To break the vicious circle between malnutrition and severe infection which has been linked to the great magnitude of infant deaths worldwide, we have been searching by means of clinical and experimental studies for measures which provide for rapid enhancement of body defenses. Based on clinical observations of malnourished children and the sequence of recovery during nutritional rehabilitation, it is suggested that the complement system is a more important factor during the early stage of nutritional recovery than CMI. In animal experiments using malnourished rats, nutritional deprivation affected various components of the body defense system to various extents, CMI being the most susceptible to influence. The complement system acted to maintain host defense even when CMI was impaired. Also observed was the earlier recovery of serum complement to normal or higher levels as compared with that of CMI. The complement system responded to bacterial infection much earlier than other immunologic responses, even in malnourished rats with depressed CMI. The infected rats showed a much higher rate of de novo synthesis of complement proteins than noninfected rats, and this effect was predominant in the malnourished group. Based on these animal experiments, we attempted to induce rapid heightened resistance to infection in malnourished rats by enhancing the complement system. After administration of proper doses of lentinan or Zn-chlorophyllin, which are known to activate C3 in vitro, to malnourished rats, heightened resistance against bacterial infection was induced together with a heightened complement response. In contrast, after administration of cobra venom factor, which is known to reduce C3 activity both in vitro and in vivo, resistance against bacterial infection was reduced, even in well-nourished rats. In summary, we have analyzed in the malnourished state the mechanism of heightened resistance against bacterial infection after activation of C3 by lentinan or Zn-chlorophyllin. These C3 activators enhanced C3b formation and iC3b formation in vivo, eventually resulting in enhanced interaction of iC3b present on invaders with CR3 on phagocytic cells.

Animals↗

Stimulants from gardeniae fructus for cultured endothelial cell proliferation.

Bioassay-guided fractionation of Gardeniae Fructus extract (GFE), which stimulates the proliferation of cultured endothelial cells, led to the isolation of glycerol and D-mannitol. Both compounds significantly increased the incorporation of [3H]thymidine and [14C]leucine into the acid-insoluble fraction of bovine aortic endothelial cell layers in culture. This clearly indicated that glycerol and D-mannitol are active components of GFE on endothelial cell proliferation. On the other hand, they did not change the number of cultured vascular smooth muscle cells from bovine aorta. Glycerol and D-mannitol may be beneficial drugs for vascular disorders.

Animals↗

Purification and some properties of acidocin 8912, a novel bacteriocin produced by Lactobacillus acidophilus TK8912.

Acidocin 8912, a bacteriocin produced by Lactobacillus acidophilus TK8912, was purified by ammonium sulfate fractionation and successive chromatographies on CM-cellulose, Sephadex G-50, Sephadex G-25, and reversed-phase HPLC on Aquapore RP-300. The purified acidocin 8912 migrated as a single band on SDS-PAGE. The molecular weight was estimated to be 5200 by SDS-PAGE, and 5400 by HPLC gel filtration on TSKgel G3000PWXL. Both the amino acid composition and the N-terminal amino acid sequence analysis indicated that acidocin 8912 was a peptide composed of presumably 50 amino acids containing a Lys residue at the N-terminus. The purified acidocin 8912 showed a bactericidal effect on sensitive cells but not a bacteriolytic effect.

Amino Acid Sequence↗

Generalized resistance to thyroid hormone (GRTH) in a family: case studies.

A familial case of generalized resistance to thyroid hormone (GRTH) is described. A 17-year-old man (case 1), who had been treated with methimazole under the diagnosis of Graves' disease and his 11-year old sister (case 2) visited our clinic for the evaluation of their thyroid function. They lacked the signs and symptoms of thyrotoxicosis in spite of extremely high serum thyroid hormone levels. Their plasma TSH levels were not suppressed, but in fact markedly increased after TRH loading. Their peripheral indices of thyroid hormone were within normal limits and were not influenced by exogenous T3 administration. Even 150 micrograms T3 administration for 7 days did not fully suppress the TRH-stimulated TSH level in case 2. The two patients thus were diagnosed to have GRTH. Sera from their father and another sister showed identical abnormalities.

Adolescent↗

Chondroid chordoma presenting with hypopituitarism.

A 28-year-old man with chondroid chordoma, an uncommon variant of chordoma, is reported. The patient presented with visual disturbance and hypopituitarism. The latter is a rare complication of intracranial chordoma. The preoperative diagnosis of chondroid chordoma of the skull base was based on unique findings on computed tomography and magnetic resonance imaging studies. The development of the tumor over six years suggests that the prognosis of chondroid chordoma may be poor in younger patients, as recently reported. Although chondroid chordoma is very rare, it should be included in the differential diagnosis of hypopituitarism.

Adult↗

Surgical treatment of intrahepatic cholangiocarcinoma: four patients surviving more than five years.

BACKGROUND: To find the rational surgical strategy for the treatment of intrahepatic cholangiocarcinoma (ICC), clinical features of ICC were studied in 20 patients who underwent hepatic resection in the National Cancer Center Hospital from 1980 to 1990. METHODS: According to the morphologic pattern, we classified the ICCs into two subcategories, mass-forming and infiltrating, which correlated with their biologic behavior. RESULTS: Of 10 patients who underwent hepatectomy for mass-forming ICC, three survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 59.3%, 44.4%, and 44.4%, respectively. Of 10 patients who underwent hepatectomy for infiltrating ICC, one survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 72.0%, 27.0%, and 27.0%, respectively. The pathologic findings and recurrences indicated that the salient feature of the mass-forming type was its tendency for intrahepatic metastasis especially near a main lesion, and of the infiltrating type was the infiltrative spread via Glisson's capsule and hilar lymph nodal metastasis. CONCLUSIONS: An anatomic and extensive liver resection should be performed for mass-forming ICC, whereas a hepatectomy with excision of the extrahepatic bile duct and hilar lymph nodal dissection is recommended for infiltrating ICC.

Adenoma, Bile Duct↗

[A case of chronic toluene poisoning with myopathic changes].

We reported a 27-year-old man, who had inhaled toluene vapor for 11 years and developed both polyneuropathy and myopathy. He gradually developed progressive muscular weakness in the limbs 2 months after the last inhalation and became nonambulant. Neurological examination revealed distal dominant muscular weakness and hypoactive deep tendon reflexes, especially in the legs. The cranial nerves were intact and neither sensory disturbances nor cerebellar signs were observed. Laboratory studies demonstrated mildly elevated serum CK value, but serum electrolytes and urinalysis were normal. Electromyogram showed a neurogenic pattern in the limbs and also a myogenic in the gastrocnemius muscle. Motor nerve conduction velocities were delayed in the limbs. The sural nerve biopsy specimens showed demyelination, myelin avoids, and axonal swelling compatible with toxic neuropathy. The muscle biopsy of the gastrocnemius revealed necrotic muscle fibers, vacuolated muscle fibers, phagocytosis, a disordered intermyofibrillary network, and small group atrophy on light microscopy. On electron microscopy, two outstanding findings were observed; the first, dilatation and proliferation of the membrane system, and the second, appearance of irregular membrano lamellar structures and vacuoles associated with abnormal membrane system. These histological findings suggest that toluene may affect directly the membrane system of muscle fibers and consequently induce rhabdomyolysis.

Adult↗

Crystalloids in angiomyolipoma. 1. A previously unnoticed phenomenon of renal angiomyolipoma occurring at a high frequency.

We present a description of unique crystalloids in renal angiomyolipoma that have not previously been reported. The crystalloids cannot be identified by hematoxylin-and-eosin staining. Detailed observation after diastase treatment followed by PAS staining revealed needle- and rod-like crystalloids, which were clearly seen even by light microscopy, in 11 of 17 patients. Their appearance was characterized by the following phenomena: (a) They appeared mainly in large epithelioid smooth-muscle cells; (b) they appeared at a relatively high frequency at sites where smooth-muscle cells showed diffuse proliferation and where a hemangiopericytic pattern was observed; (c) they were often detected easily even at a site with a sarcomatous appearance; and (d) PAS-positive, diastase-resistant granules were often observed by light microscopy in the vicinity of crystalloids in all 17 patients. Electron-microscopic observation of one patient also revealed characteristic crystalloids. Prior to our study, only one patient had been reported to show crystalloids by electron microscopy, and the crystalloids were interpreted as renin. However, our study used Bowie's staining and immunohistochemistry to prove they were not renin. The nature of the crystalloids still needs to be elucidated. The fact that they closely resemble structures seen in alveolar soft part sarcoma provides one clue to their identification.

Adult↗

Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic inclusions comprising of aggregates of keratin.

A case of primary hepatic carcinoid tumor was recently encountered, which was argyrophil and showed positive reactions to serotonin, gastrin and pancreatic peptide in an immunohistochemical hormonal study. The tumor had unusual morphologic features. The neoplastic cells had a signet-ring cell appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma. Ultrastructural and immunohistochemical studies revealed the formation of the signet-ring cells to have been caused by the presence of cytoplasmic inclusions consisting of cytokeratins. Further investigation, using eight monoclonal antibodies recognizing cytokeratins of different molecular weights, showed the accumulated cytokeratins to be of low and medium molecular weights. The morphologic observations in this unusual case of hepatic carcinoid tumor are described and reported cases with similar features, for which we propose the term "signet-ring cell carcinoid," are reviewed.

Adult↗

[A study on the mass screening system for prostatic diseases].

Between 1984 and 1990, a mass screening for prostatic diseases was carried out on men over 55 years old in cities, towns and villages in Toyama Prefecture, Japan. The total number of subjects examined in the primary study was 1,232, which was 17.7% of the males over 55 years old in these areas. The primary study consisted of inquiry concerning urination, digital examination of the prostate, transabdominal ultrasonography, and determination of tumor markers. A secondary study was indicated for 100 subjects (8.9%) suspected to have prostatic cancer and 169 (15%) suspected to have benign prostatic hypertrophy, but only 92 (35%) of them were actually examined. Prostatic cancer was histologically diagnosed in 3 subjects (0.3%), and benign prostatic hypertrophy was established in 56 subjects (4.5%), who were referred to urologists. Though a high percentage of the population was covered by the primary study the percentage of subjects who received the secondary study among those in whom it was indicated was low. This probably was a reason for the low detection rate of prostatic cancer. An improved system is considered to be needed to increase the efficiency of mass screening for prostatic diseases.

Humans↗