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Biomedical subjects

A T Hasegawa

Publications and source records attributed to A T Hasegawa.

At least 19 recordsLinked to original sources
PubMed2001

Mechanisms of calcium oxalate crystal attachment to injured renal collecting duct cells.

BACKGROUND: Renal cell or tissue injury results in a loss of membrane lipid asymmetry and/or loss of cell polarity, and both events lead to changes on the surface of the cell membranes that enhance crystal attachment. We have proposed two distinct mechanisms of crystal attachment following membrane changes induced by various modes of injury. METHODS: Annexin V was used to determine whether phosphatidylserine (PS) exposure on the cell membrane surface plays a role in calcium oxalate monohydrate (COM) crystal attachment to cells that have lost their polarity as well as to cells that have lost their lipid asymmetry. We utilized two different experimental models of injury to renal epithelial cells in culture. The first model used calcium ionophore A23187 to induce a loss of lipid asymmetry, and the second model used EGTA to break down tight junctions and lose cell polarity. RESULTS: Inner medullary collecting duct cells that have lost lipid asymmetry demonstrated an increase in the number of cells that bound annexin V. However, when cells lost their polarity, they did not bind annexin V. In addition, the attachment of crystals to cells following a loss of cell polarity was not inhibited by annexin V. CONCLUSIONS: This study indicates that both individual cell injury (loss of lipid asymmetry) and generalized cell monolayer injury (loss of cell polarity) result in the presentation of different cell surfaces and that both forms of injury result in an increased affinity for crystal attachment. Both mechanisms could be important independently or collectively in the retention of microcrystals to renal collecting duct cells in urolithiasis.

Animals↗
PubMed2000

[A case of patent urachus in an adult male].

A 31-year-old man was referred to our hospital for evaluation of urachal rest. The history of his present illness dated back to birth, when the umbilicus was projected and urinary discharge was noted. At that time, the symptom of discharge had spontaneously subsided. At the age of 22, however, the patient again experienced discharge from the umbilicus. Although he did not seek treatment, after six years this symptom disappeared. Around this time, however, pyuria was revealed during medical examination, and abdominal ultrasonography (US) suggested the presence of urachal rest. At the time of hospitalization, physical examination revealed that the patient's right testis was not palpable. He was diagnosed with patent urachus with hemilateral aplasia and monorchism by US, computed tomography, magnetic resonance imaging and cystoscopy. The patient subsequently underwent radical operation. Patent urachus in adults is very rare, and only a few cases have been reported. To our knowledge, only one previously reported case involved a recurrence after spontaneous healing. Further, this is the first report of a patient with patent urachus with hemilateral aplasia and monorchism. Radical operation is generally recommended, based on the fact that very few cases heal conservatively.

Adult↗
PubMed1999

Oxalate-induced exposure of phosphatidylserine on the surface of renal epithelial cells in culture.

A molecular mechanism of crystal attachment to renal cells after injury has been proposed in which the exposure of phosphatidylserine (PS) on the cell membrane surface following injury provides attachment sites for calcium-containing crystals. Annexin V was used to determine whether injury to kidney cells by oxalate in culture resulted in PS exposure on the cell surface. When continuous cultures of intermedullary collecting duct cells were exposed to various levels of oxalate, a dose-dependent increase in PS exposure was observed on the cell surfaces. Initially, only scattered cells expressed PS on the surface. However, as the level of oxalate increased, groups of cells began to express PS, suggesting that the injured cells may have an influence on neighboring cells. Exposure of PS on the cell membrane surface correlated with a corresponding increase in calcium oxalate monohydrate crystal attachment to the cells. This indicates that damage to kidney epithelial cells by elevated concentrations of urinary components, in this case oxalate, could result in exposure of PS on cells, which could provide a point of fixation or nucleation for calcium-containing crystals.

Annexin A5↗
PubMed1987

The effect of some urinary stone inhibitors on membrane interaction potentials of stone crystals.

The effect of stone growth inhibitors (citrate, pyrophosphate, ethane diphosphonate, methane diphosphonate, chondroitin sulfate A, chondroitin sulfate C, heparin and ribonucleic acid) on crystal-membrane interactions of whewellite, weddellite, apatite, brushite, struvite, uric acid, monosodium urate and quartz (control) stones was quantitated. As a model for the initial retention of microcrystals by kidney epithelial membranes, crystal-induced membranolysis of red blood cells served as a measure of crystal-membrane interactions. The inhibitors induced changes in hemolytic potential from approximately 320 per cent enhancement to 80 per cent inhibition. No inhibitor behaved the same way for all crystals studied. However, some crystals showed consistent trends in altered hemolytic potential in the presence of inhibitors. These crystals included weddellite and sodium urate, which were inhibited consistently, and apatite and quartz, which were enhanced consistently. Whewellite, uric acid, brushite and struvite exhibited mixed patterns in the altered hemolytic potentials owing to the inhibitors.

Calcium Oxalate↗
PubMed1982

Initial methadone dose in treating opiate addiction.

Intramuscular administration of naloxone was used to precipitate the narcotic withdrawal syndrome in opiate-dependent patients. Objective signs of withdrawal were rated according to a previously developed scale. Based upon naloxone-induced withdrawal scores, 76 patients were given a dose of methadone, either low, medium, or high, in a randomized double-blind manner on 2 consecutive days. The adequacy of the methadone dose was evaluated by assessing the patients' physical responses after each treatment. Results indicate that the medium dose of methadone in each naloxone-induced withdrawal score range provides optimal control of narcotic deprivation. It is concluded that a correct initial dose of methadone can be administered when the degree of opiate dependence is established by the naloxone test.

Dose-Response Relationship, Drug↗
PubMed1982

Clinical comparison of propoxyphene napsylate and methadone in the treatment of opiate dependence.

In this double-blind comparison of propoxyphene napsylate (PN) 800 mg in two divided doses versus methadone 20 mg, methadone 10 mg or placebo methadone, it was found that PN: 1) did not alleviate withdrawal symptoms in patients previously maintained on methadone 20 mg; 2) produced a slightly overmedicated effect in the detoxified group of exmethadone patients; and 3) compared favorably to methadone 10 mg in suppressing withdrawal symptoms without producing evidence of overmedication in those patients previously stabilized on a methadone maintenance dose of 10 mg.

Adult↗
PubMed1981

Propoxyphene napsylate compared to methadone for opiate dependence.

When high single doses of propoxyphene napsylate (PN) were given to patients on a methadone maintenance program, results indicated that, to avoid undesirable side effects, the dose should not exceed 600 mg. However, when PN was given in divided doses (800 mg/day in two equal doses), no significant adverse reactions were noted. In the double-blind comparison of 800 mg PN in two divided doses versus 20 mg methadone, 10 mg methadone, or placebo methadone, it was found that PN (1) did not alleviate withdrawal symptoms in patients previously maintained on 20 mg methadone, (2) produced a slightly overmedicated effect in the detoxified group of ex-methadone patients, and (3) compared favorably to 10 mg methadone in suppressing withdrawal symptoms without producing evidence of overmedication in those patients previously stabilized on a methadone maintenance dose of 10 mg. It is concluded that on a mg for mg basis, PN at a dose of 80-times that of methadone will relieve withdrawal symptoms in the treatment of mildly addicted patients requiring 10 mg methadone or less per day.

Adult↗
PubMed1980

Enterohepatic circulation of l-alpha-acetylmethadol in the rat.

The enterohepatic circulation of the biliary metabolites of l-alpha[3H]acetylmethadol ([3H]LAAM) was studied in rats. Bile was collected for 48 hr from a biliary-cannulated donor rat after s.c. administration of [3H]LAAM. This bile containing tritium-labeled LAAM metabolites was then infused into the small intestine of a recipient rat for 48 hr and the appearance of radioactivity in bile formed in the liver of the recipient rat was monitored. Forty-eight hours after the start of infusion, 40% of the infused radioactivity had been excreted into the bile of the recipient rat, indicating extensive enterohepatic circulation of the biliary metabolites of LAAM. The data indicated that only a small percentage of the infused [3H]LAAM metabolites were present in the systemic circulation at any one time. This was further investigated by comparing the plasma levels of tritium with time and the tissue concentrations at 24 and 48 h after s.c. [3H]LAAM administration in biliary-cannulated and sham-operated control rats. Complete diversion of the bile did not significantly decrease the levels of [3H]LAAM or its metabolites in the systemic pool. These findings tend to minimize the contribution of enterohepatic circulation in the recirculation of active metabolites of LAAM and ultimately in its long duration of opiate-like action.

Animals↗
PubMed1976

Role of metabolism in the biliary excretion of methadone metabolites.

The biliary excretion of the major methadone metabolites was studied after the administration of purified 14C-labeled metabolites of methadone. The three methadone metabolites administered to rats were the pyrrolidine and pyrroline metabolites and the glucuronide conjugate of the hydroxylated pyrroline metabolite. We found that the excretion of 14C into bile was greater after administration of the metabolites which underwent fewer metabolic steps prior to biliary excretion. Phenobarbital pretreatment of rats increased the biliary excretion of 14C after the administration of the 14C-labeled pyrrolidine and pyrroline metabolites, both of which undergo further metabolism. Phenobarbital pretreatment did not change the biliary excretion of 14C-labeled glucuronide of the pyrroline metabolite which does not undergo further metabolism in the liver. Analysis of bile samples showed that the increased biliary excretion of 14C in phenobarbital-pretreated rats after administration of the labeled pyrrolidine and pyrroline metabolites was due primarily to increases in the biliary excretion of methadone metabolites which resulted from further in vivo metabolism of the injected metabolites. These data confirm our earlier suggestion (Roerig et al., Biochem. Pharmacol. 24: 355-362, 1975) that phenobarbital pretreatment increases biliary excretion of methadone metabolites by increasing hepatic metabolism of methadone. Furthermore, it can be concluded from these studies that metabolism is a rate-limiting process in the excretion of methadone metabolites in bile.

Animals↗