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Biomedical subjects

Y Kojima

Publications and source records attributed to Y Kojima.

At least 199 records · Page 11Linked to original sources

[Transurethral incision for ureterocele in children].

Transurethral incision (TUI) was performed as the initial treatment in 10 children with ureteroceles. Three patients had ureteroceles associated with a single ureter. TUI relieved hydronephrosis and preserved renal function in all 3 cases. Urinary tract infection developed in no patients. However, all the patients required an antireflux operation because of postoperative vesicoureteral reflux (VUR). Seven children had a total of 8 ureteroceles associated with a duplex system. TUI resulted in preservation of the upper pole function in 6 of the 8 ureteroceles. Urinary tract infections and VUR developed in 3 and 7 patients, respectively. Common sheath reimplantation was performed in 2 ureteroceles. TUI relieves obstruction before the onset of devastating infections although it carries the risk of postoperative VUR. We recommend TUI as the initial treatment for ureteroceles associated with both single and duplex systems.

Adolescent↗

Adenosine 3',5'-cyclic monophosphate-stimulated Ca++ efflux and acetylcholine release in ileal myenteric plexus are mediated by N-type Ca++ channels: inhibition by the kappa opioid receptor agonist.

Adenosine 3',5'-cyclic monophosphate (cAMP) is an important second messenger involved in cholinergic transmission. The aims of this study were to characterize the calcium channels associated with cyclic AMP-mediated acetylcholine release and Ca++ efflux in ileal myenteric plexus. We also examined if this process can be inhibited by agents such as opioids that inhibit N-type calcium channels via a pertussis toxin-sensitive G protein. Application of a cell permeant analogue, 8-bromoadenosine cyclic AMP (8Br-cAMP) (1 mM), and an activator of the adenylyl cyclase system, forskolin (0.1 mM), in a superfusion system resulted in both Ca++ efflux and 3H-acetylcholine (ACh) release from the dispersed myenteric ganglia. A preferential N-type Ca++ channel blocker, omega-Conotoxin GVIA (omega-CgTx, 10-100 nM), significantly inhibited 3H-ACh release stimulated by 8Br-cAMP. 10 nM omega-CgTx also totally inhibited 8Br-cAMP-induced Ca++ efflux, whereas the L-type Ca++ channel blocker, nifedipine (1 microM), and the T-type Ca++ channel blocker, nickel (100 microM), both had no effects on the action of 8Br-cAMP. 3H-ACh release during 0.1 mM forskolin stimulation was inhibited by pretreatment with a kappa receptor agonist, U50488H at 1 to 100 nM. In addition, U50488H significantly inhibited 3H-Ach release and Ca++ efflux elicited by 8Br-cAMP. Inhibition of 3H-ACh release by U50488H was reversed by 3 hr pretreatment with 300 ng/ml pertussis toxin. These results suggest that, in the myenteric plexus, cyclic AMP-stimulated Ca++ efflux and Ach release were mediated by N-type calcium channels. This process may be inhibited by activation of the kappa opioid receptor through pertussis toxin-sensitive G protein(s).

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

[Effect on 5'-deoxy-5-fluorouridine (5'-DFUR) of pyrimidine nucleoside phosphorylase (PyNPase), matrix metalloprotease and serum IAP values. Hokuriku Colorectal Cancer Chemotherapy Study Group].

PyNPase activity, MMPs activity and serum IAP values were measured in tumor tissues from colorectal cancer patients who had been divided into two groups, one given preoperative 5'-DFUR and the controls. PyNPase activity of the preoperative administration group was approximately equivalent to that of the controls. In the control group, correlations were assessed between PyNPase activity and activities of MMP1 and MMP3. To assess the effect of 5'-DFUR on the activity of MMPs, we divided patients into two groups, a high and a low PyNPase activity group. Although there was no correlation with MMPs activity of the preoperative administration group and the control group in the low PyNPase activity group, the activities of MMP1 and MMP9 of the control group were significantly higher in the high PyNPase activity group. Moreover, the serum IAP value of the administration group was significantly lower than that of the control group. These results indicated that PyNPase activity was thus suggested to be somehow related to MMPs activity and serum IAP values.

Adult↗

[A case of lung carcinoid].

A 78-year-old female was pointed out an abnormal shadow in left lung field. For 4 years this shadow was followed up as benign tumor. Chest CT scan revealed growing tumor and new tumor in right lung. Tumor resection was performed. Until operation time carcinoid syndrome was not found. This case was diagnosed histopathologically typical carcinoid of peripheral lung.

Aged↗

[Radiation therapy for adrenal metastases].

PURPOSE: To evaluate the role of radiation therapy for adrenal metastases. MATERIALS AND METHODS: Fourteen patients, 13 with primary lung carcinoma and one with primary unknown carcinoma, received radiation therapy for adrenal metastases from 1984 to 1995 at the Hyogo Medical Center for Adults. Total dose ranged from 16 Gy to 60 Gy, and fractional dose from 1.6 Gy/ Fr to 3 Gy/Fr. RESULTS: Partial response of the local tumor was recognized in 2 of 7 patients by CT imaging. Pain relief was obtained in 7 of 8 patients. Median survival was 3 months, and 6-month survival was 28.6% in all patients. Among patients in the symptomatic group, who had complaints of pain due to adrenal mass, survival was even worse (12.5% at 6 months). There were no severe complications, but 4 patients (29%) had gastrointestinal symptoms. CONCLUSION: Radiation therapy is useful for the purpose of pain relief in adrenal metastases.

Adrenal Gland Neoplasms↗

[A randomized study on intravesical pirarubicin (THP) chemoprophylaxis of recurrence after transurethral resection of superficial bladder cancer].

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of tetrahydropyranyladriamycin (THP) following complete transurethral resection (TUR) of superficial bladder cancer. A total of 80 patients were randomized into "THP" or "control" group. In the THP group, 20 mg of THP dissolved in 40 ml saline (or 5% dextrose) was administered intravesically once a week for 10 weeks, starting from about 7 days after TUR. In the control group, 40 ml saline was given with the same schedule. The patients were followed up by cystoscopy and urinary cytology every 3 months. The number of evaluable patients was 36 for the THP group and 37 for the control group. The non-recurrence rates in the THP group and control group were 79.4% versus 63.2% at 1 year and 69.8% versus 47.4% at 3 to 5 years, respectively. These figures were not statistically significant. However, THP instillation significantly reduced tumor recurrence rates for multiple tumors, and also tended to decrease recurrence rates for primary and pT1 tumors. Adverse effects were observed in 53.6% of the patients in the THP group, but they were tolerable. Our results suggest that intravesical THP instillation would not be effective for all patients with superficial bladder cancer. Further study is warranted in a selected group of patients.

Administration, Intravesical↗

Fas/APO-1-mediated apoptosis of human renal cell carcinoma.

We have investigated the Fas-mediated apoptosis of cultured human renal cell carcinoma OUR-10. OUR-10 cells express Fas antigen on their cell surface and showed apoptotic cell death by stimulation with anti-Fas agonistic antibody. Cell proliferation of OUR-10 was reduced to 62% by the addition of anti-Fas antibody. The cytotoxic effect of anti-Fas antibody on OUR-10 was augmented by the pretreatment of these cells with interferon-gamma, not with interferon-alpha or with interleukin-2. Flow cytometry demonstrated that preculture of Our-10 cells with interferon-gamma increased the cell surface Fas antigen. Immunohistochemical analysis of resected tissues from the patients with renal cancer revealed stronger expression of Fas antigen on the surface of cancer cells than that of normal cells. These data suggest that Fas may be one of the possible targets for a novel approach to human kidney cancer, and the efficiency of this Fas-mediated treatment for kidney cancer could be augmented by the treatment with interferon-gamma.

Apoptosis↗

Binding sites for blood coagulation factor Xa and protein S involving residues 493-506 in factor Va.

Inactivation due to cleavage of Factor Va (FVa) at Arg 506 by activated protein C (APC) helps to downregulate blood coagulation. To identify potential functional roles of amino acids near Arg 506, synthetic overlapping pentadecapeptides comprising FVa heavy chain residues 481-525 were tested for their ability to inhibit prothrombin activation by prothrombinase complexes [Factor Xa (FXa):FVa:phospholipids:Ca2+]. The most potent inhibition was observed for peptide VP493 (residues 493-506), with 50% inhibition at 2.5 microM. VP493 also inhibited FXa in plasma in FXa-1-stage clotting assays by 50% at 3 microM. When the C-terminal carboxamide group of VP493 was replaced by a carboxyl group, most prothrombinase inhibitory activity was lost. VP493 preincubated with FXa inhibited prothrombinase with a pattern of mixed inhibition. Homologous peptides from Factor VIII sequences did not inhibit prothrombinase. Affinity-purified antibodies to VP493 inhibited prothrombinase activity and prolonged FXa-1-stage clotting times. VP493 also blocked the ability of protein S to inhibit prothrombinase independently of APC. Immobilized VP493 bound specifically with similar affinity to both FXa and protein S (Kd approximately 40 nM), but did not measurably bind prothrombin or APC. These studies suggest that FVa residues 493-506 contribute to binding sites for both FXa and protein S, providing a rationale for the ability of protein S to negate the protective effect of FXa toward APC cleavage of FVa. Possible loss of this FVa binding site for FXa due to cleavage at Arg 506 by APC may help explain why this cleavage causes 40% decrease in FVa activity and facilitates inactivation of FVa.

Amino Acid Sequence↗

A malignant granular cell tumor of the stomach: report of a case.

We report herein what to our knowledge is the first documented case of a malignant granular cell tumor of the stomach. A 64-year-old woman was admitted to our hospital for investigation of gastric submucosal tumor. Endoscopy disclosed a large hemispherical mass located on the lesser curvature at the gastric antrum with a normal mucosal surface, and computed tomography (CT) revealed a solid tumor about 7 cm in diameter with clear margins. A laparotomy was carried out under the preoperative diagnosis of leiomyosarcoma of the stomach. A tumor was found in the gastric antrum, with extragastric extension to the hepatic hilum, and a distal partial gastrectomy was performed. However, a follow-up CT scan performed 21 months postoperatively revealed a solid tumor of about 10 cm in diameter with clear margins, situated between the liver and the transverse colon. This was subsequently diagnosed as local recurrence and a resection was carried out. Microscopic examination of both the first and second specimens showed that the tumor cells were large and polygonal, with medullary proliferation and finely granular eosinophilic cytoplasm. Mitotic figures were also present. Thus, the lesion was diagnosed as a malignant granular cell tumor of the stomach from the clinical and pathological findings.

Cell Division↗

Roles of the conserved serines of metallothionein in cadmium binding.

The sequence of six amino acid residues -Ser-Cys-Cys-Ser-Cys-Cys- is present in all mammalian metallothionein sequences and has been highly conserved during evolution, although the metallothioneins have divergent primary sequences. To determine whether two serines in the sequence play a crucial role in metal-binding of metallothioneins, a mutant metallothionein with these two serines replaced by leucines was obtained using an Escherichia coli expression system. The expressed protein was analyzed for its chemical and spectroscopic properties. It was confirmed that the mutant metallothionein (MT) bound cadmium through a metal-thiolate complex and that there was no strong difference between the mutant and the wild-type MTs in retaining the metal-binding cluster. However, the metal-binding cluster of the mutant metallothionein was more unstable than that of the wild-type metallothionein. The two conservative serines could play a role in the stability of metal-binding ligands.

Amino Acid Sequence↗

Abnormal excitability of the corticospinal pathway in patients with amyotrophic lateral sclerosis: a single motor unit study using transcranial magnetic stimulation.

The pathophysiology of corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) was investigated by studying the effect of transcranial magnetic stimulation on discharge characteristics of single motor units during voluntary activation. The motor units were recorded from the first dorsal interosseus muscles of 12 patients with ALS, 14 healthy subjects, 12 patients with upper motor neuron lesions and 9 with pure lower motor neuron diseases. More than 100 magnetic stimuli were delivered over the scalp during minimal muscle contraction. The occurrence of motor unit discharges was plotted in a peristimulus time histogram. An increase in discharge probability at latencies of 20-30 msec, that represents monosynaptic activation (primary peak) was found in normal units. Motor units from ALS patients with short disease durations had significantly increased discharge probabilities in the primary peak (P < 0.001). Motor units from 4 ALS patients with upper motor neuron signs showed double primary peaks: an initial synchronized peak followed by a dispersed peak. The latter was ascribed to a slow corticospinal pathway, which remains undetected or is functionally insignificant in healthy subjects. We conclude that the excitabilities of the surviving corticospinal tract pathways are abnormally increased in ALS, especially in the early stage.

Adolescent↗

Metallothionein in the ovaries of laying hens exposed to cadmium.

The presence of metallothionein (MT) and its mRNA in the ovaries of laying hens is reported. In laying hens injected with cadmium (Cd), Cd accumulated in the follicle walls of the ovaries not in the follicle yolks. In the follicle walls, (Cd, Zn)-MT and its mRNA were found. This indicates that MT bound to Cd is biosynthesized in the follicle walls. We suggest that MT might play a role in sequestering Cd. On the other hand, zinc (Zn) was found in the follicle walls and yolks in the Cd-treated laying hens. The relationship between Zn and (Cd, Zn)-MT is also discussed.

Animals↗

Disaccharide analysis of human skin glycosaminoglycans in sun-exposed and sun-protected skin of aged people.

The total amount of main disaccharide units of skin glycosaminoglycans was compared between sun-exposed (n = 12) and sun-protected skin (n = 14) of aged people using high performance liquid chromatography after labeling with 1-phenyl-3-methyl-5-pyrazolone. The total amount of main disaccharide units in sun-exposed skin was comparable to sun-protected skin presumably due to the diversity of individuals. Consequently, we compared sun-exposed skin with sun-protected skin in identical individuals (n = 6). The total amount of main disaccharide units in sun-exposed skin was significantly greater than that in sun-protected skin (P < 0.05). In addition, the ratio of delta Di-HA (hyaluronic acid, HA)/delta Di-4S (dermatan sulfate, DS) in sun-exposed skin showed a decreasing trend as compared with sun-protected skin in four of six individuals. These results are in agreement with our previous results obtained in animal experiments of photoaging, i.e., hairless mouse skin exposed to repeated UV irradiation showed an increase in total amount of main disaccharide units and a decrease in the ratio of delta Di-HA(HA)/delta Di-4S(DS). We could confirm similar changes in skin glycosaminoglycans both in human and murine photoaging supporting the appropriate rationale for using the hairless mouse as an animal model for photoaging. Again, disaccharide analysis should provide a useful method to examine the biochemical changes of skin glycosaminoglycans in human photoaging.

Aged↗

Nucleotide sequence of the uricase gene from Bacillus sp. TB-90.

The nucleotide sequence of the uricase gene from the thermophilic bacterium Bacillus sp. TB-90 was determined. The primary structure of the uricase deduced from the nucleotide sequence comprised 332 amino acids, with a total molecular mass of 37,994 Da. The molecular mass of the subunit of the uricase produced by the transformant of Escherichia coli agreed well with this value. However, the molecular mass of a subunit of the uricase produced by Bacillus sp. TB-90 was found to be 34,000 Da by SDS-PAGE. The difference between these molecular masses was attributed to processing of the C-terminal 13 amino acid residue in Bacillus sp. TB-90. Comparison of the enzymatic properties of both uricases showed that the thermostability of the uricase produced by the transformant was enhanced by about 10 degrees C in comparison to that produced by Bacillus sp. TB-90.

Amino Acid Sequence↗

Independent self-assembly of cadmium-binding alpha-fragment of metallothionein in Escherichia coli without participation of beta-fragment.

We examined the independent self-assembly of the alpha- and beta-fragments of human metallothionein (MT) into cadmium-binding conformation in an Escherichia coli expression system, in addition to wild-type MT expression. The expressed alpha-fragment formed independently the structure of a metal-binding cluster without the aid of the beta-fragment. The alpha-fragment and wild-type MT expressed in E.coli were purified and analyzed for their biochemical and spectroscopic properties. The apparent cadmium binding of the alpha-fragment was approximately 12-fold greater than that for the wild-type MT, whereas in other respects the studied biochemical properties were similar. In contrast, we were unable to obtain any independently expressed beta-fragment as the cadmium-binding form in this study. Possible explanations for this phenomenon are discussed.

Amino Acid Sequence↗

Case report: portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt.

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 micrograms/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.

Aged↗

Impaired intracellular signal transduction in gastric smooth muscle of diabetic BB/W rats.

The pathophysiological mechanisms responsible for diabetic gastroparesis remain unclear. Diabetes mellitus occurs spontaneously in 90% of a partially inbred colony of BB/W rats. This animal model resembles human insulin-dependent diabetes and is suitable for investigating the mechanism of diabetic gastroparesis. Diabetic BB/W rats were killed 6 mo after the onset of diabetes. Muscle contraction experiments and [3H]acetylcholine release studies were performed with muscle strips of the gastric body. Biochemical measurements of inositol trisphosphate (IP3) and protein kinase C (PKC) in gastric muscle were performed to characterize abnormalities of the intracellular signal transduction system in gastric myocytes. Circular muscle contractions in response to direct myogenic stimulants, carbachol (10(-7) - 10 (-3)M) or substance P (10(-7) - 10(-5)M), were significantly impaired in diabetic BB/W rats compared with controls. Similarly, muscle contractions in response to NaF (10 mM), a direct stimulant of G proteins, were also impaired in diabetic BB/W rats. In contrast, muscle contractions in response to KCl (25-75 mM) were similar between control and diabetic BB/W rats, indicating normal voltage-dependent Ca2+ entry in muscle strips obtained from diabetics BB/W rats. [3H]acetylcholine release from gastric myenteric plexus in response to electrical transmural stimulation remained intact in diabetic BB/W rats. In separate studies, we demonstrated that carbachol (10(-6) - 10(-4)M) -induced IP3 responses were significantly reduced in diabetic rats compared with control. In addition, there was also impairment of translocation of PKC in diabetic BB/W rats. These observations indicate that myogenic impairment occurred in diabetic BB/W rats. This resulted from altered intracellular signal transduction involving abnormal IP3 production and PKC translocation.

Acetylcholine↗