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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 289 records · Page 16Linked to original sources
PubMed1998

[2-(omega-phenylalkyl)phenoxy]alkylamines: synthesis and dual dopamine2 (D2) and 5-hydroxytryptamine2 (5-HT2) receptor antagonistic activities.

A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their 5-hydroxytryptamine2 (5-HT2) and/or dopamine2 (D2) receptor antagonistic activities were examined in vitro. [2-(4-Phenylbutyl)phenoxy]alkylamines showed strong inhibition of both 5-HT2 and D2 receptors. In particular, [2-(4-Phenylbutyl)phenoxy]-methylpiperidine derivatives, 10b, 10i and 10q, exhibited potent inhibition. The structure-activity relationships in this series of compounds are discussed.

Amines↗
PubMed1998

[Identification of protein kinase C phosphorylation sites involved in desensitization of the histamine H1 receptor].

We studied whether direct phosphorylation plays a key role in protein kinase C-activating phorbol ester-mediated H1 receptor desensitization. Several potential protein kinase C-mediated phosphorylation sites were located in the third cytoplasmic loop form our cloning studies of H1 receptors. Ser396 and Ser398 were determined to be the phosphorylation sites by in vitro phosphorylation studies using synthetic peptides corresponding to the partial amino acid sequence of the third cytoplasmic loop. Mutant H1 receptors whose Ser396 or Ser398 were displaced by alanine were expressed in Chinese hamster ovary cells by site-directed mutagenesis. Characterization of these receptors revealed that Ser398, but not Ser396, was primarily responsible for protein kinase C-mediated H1 receptor desensitization.

Amino Acid Sequence↗
PubMed1998

Effects of lung volume reduction surgery on exercise pulmonary hemodynamics in severe emphysema.

STUDY OBJECTIVES: To clarify the effects of lung volume reduction surgery (LVRS) on pulmonary hemodynamics in severe emphysema and to evaluate the role of pulmonary circulation in the increased exercise performance after LVRS. DESIGN: In eight male patients with severe emphysema, we measured pulmonary artery (Ppa) and occlusion (Pop) pressures and cardiac output through a Swan-Ganz thermodilution catheter, and we calculated cardiac index (CI), pulmonary vascular resistance index, and driving pressure. The study was performed at rest and during exercise using a supine bicycle ergometer at 25 W, under room air and O2 inhalation. Exercise performance was expressed as endurance time in minutes. Pulmonary function tests were performed. The patients underwent an identical study before and 6 months after LVRS. RESULTS: The patients' exercise performance was significantly increased after LVRS (5.9+/-1.8 min) compared with that before LVRS (3.6+/-0.9 min). LVRS resulted in a significant increase in FEV1 and a significant decrease in residual volume. Before LVRS, Ppa was increased both at rest and during exercise. LVRS did not change rest or exercise Ppa. LVRS significantly decreased Pop during exercise from 24+/-10 mm Hg to 18+/-7 mm Hg. CI at rest and during exercise were significantly increased after LVRS. O2 administration significantly decreased Ppa during exercise both before and after LVRS. CONCLUSIONS: These findings suggest that LVRS does not improve pulmonary hypertension at rest or during exercise in patients with severe emphysema and that elevated Pop during exercise before LVRS is probably related to lung mechanic abnormalities.

Aged↗
PubMed1998

Basolateral pH-sensitive K+ channels mediate membrane potential of proximal tubule cells in bullfrog kidney.

The present study investigated basolateral K+ channels and their pH-sensitivity in isolated bullfrog proximal tubule cells by using the patch-clamp technique, and compared channel activity with the basolateral membrane potential (EM) and intracellular pH (pHi) monitored by using double-barreled H+-selective microelectrodes in perfused bullfrog proximal tubules. In the patch-clamp experiments, K+ channels with inward slope conductance of about 50 pS were observed in the basolateral membrane of isolated proximal tubule cells in cell-attached patches. Raising pH of the bath with HCO3(-)-free HEPES Ringer solutions from 7.7 (control) to 8.2 in the presence of an H+ ionophore, FCCP (2 micro M), enhanced channel activity to 126.4% of controls; lowering bath pH to 7.2 and to 6.7 reduced channel activity to 26.4 and to 1.7% of controls. Microelectrode experiments in bullfrog proximal tubules perfused with HCO3(-) -free HEPES Ringer solutions showed that EM and pHi in control conditions of peritubular pH 7.7 without FCCP were -52.6 mV and 7.45. Raising peritubular pH to 8.2 in the presence of FCCP (2 micro M) increased EM and pHi to -61.8 mV and 7.73; lowering it to 7. 2 and to 6.7 decreased EM and pHi to -28.6 mV and 7.25 and to -10.6 mV and 6.95. These results suggest that changes in EM in response to cellular alkalinization or acidification made by HCO3(-)-free HEPES solutions are produced primarily by changes in activity of the pH-sensitive K+ channels.

Animals↗
PubMed1998

Change in Ca2+ sensitivity of cerebrovascular smooth muscle in experimental chronic cerebral vasospasm.

The mechanism of chronic cerebral vasospasm was investigated by examining the relation between cytosolic Ca2+ level ([Ca2+]i) and muscle contraction in vascular smooth muscle after experimental vasospasm produced by the two-hemorrhage method in the canine basilar artery. [Ca2+]i and tension were recorded simultaneously with a fluorimeter using the arterial strips with a Ca2+ indicator, fura-2. High K+ concentration (72.4 mM) and U-46619 (thromboxane A2 analogue, 10(-8) M) were used as stimulants. The increase in contractile tension per [Ca2+]i per unit cross-sectional area was calculated, and compared for the vasospasm and the control groups. The increase in [Ca2+]i in the vasospasm group was smaller than that in the control group, so the increase in tension per [Ca2+]i per unit sectional area was larger in the vasospasm group. This value was much larger for the contraction induced by U-46619 than that induced by high K+ concentration in both groups. These results suggest that there is an increase in the basal Ca2+ sensitivity of the contractile elements in vasospastic vessels. In addition, the U-46619-induced increase in Ca2+ sensitivity seemed to be augmented in the vasospasm group.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Germinoma causing wallerian degeneration. Case report and review of the literature.

Germinomas occurring in the thalamus and basal ganglia sometimes cause atrophy of the cerebral hemisphere on the affected side. The authors present the case of a 12-year-old girl with a germinoma that developed in the basal frontal lobe and cerebral basal ganglia. Magnetic resonance imaging showed atrophy not only of the cerebrum but also of the brainstem. A T2-weighted image revealed an area of high intensity that proved to be wallerian degeneration extending from the corona radiata and internal capsule to the brainstem. The authors suggest that this pathological change may be involved in the development of the symptoms and hemiatrophy associated with germinomas in this region of the brain.

Brain Neoplasms↗
PubMed1998

Dietary supplementation of catechins and alpha-tocopherol accelerates the healing of trinitrobenzene sulfonic acid-induced ulcerative colitis in rats.

The effects of dietary catechins and alpha-tocopherol on inflammatory bowel disease in rats were examined. Male 9-week-old rats were intracolonically administrated trinitrobenzene sulfonic acid (TNBS) and fed the experimental diets containing 0.05% catechin and 0.025% alpha-tocopherol for 1 week, then dissected. The extent of colitis-induced TNBS was assessed macroscopically. The supplementation of catechins and alpha-tocopherol significantly decreased colonic damage compared with the group fed the basal diet (the disease control). In particular, catechin feeding completely inhibited the development of colon adhesions. Colonic myeloperoxidase (MPO) activity, which is a marker of neutrophil infiltration into the colonic mucosa, was lower in the groups that had been given catechins and alpha-tocopherol. The levels of thiobarbituric acid reactive substances in colon was highest in the disease control group; however, the differences among the groups were not significant. Plasma alkaline phosphatase activity was maintained at normal levels in the rats supplemented with catechins and alpha-tocopherol. These results suggest that catechins and alpha-tocopherol have anti-inflammatory effects on TNBS-induced rat colitis.

Alkaline Phosphatase↗
PubMed1998

[Superior sagittal sinus occlusion due to calvarial metastasis of renal cell carcinoma: 2 cases report].

We report two cases of superior sagittal sinus (SSS) occlusion due to calvarial metastasis of renal cell carcinoma. Both cases were presented with bulging of the skull. No stigmata of increased intracranial pressure was detected. Cerebral angiogram showed the occlusion of the SSS. Tumor cells did not penetrate into the dura mater nor the galea and the tumors were able to be removed easily in both cases. One case without collateral circulation showed recanalization of the SSS on the postoperative angiography. Another case with development of collateral circulation did not show recanalization of SSS on the postoperative magnetic resonance angiography. In the latter case, cortical veins flowed into the occluded portion. We consider that SSS should be preserved to prevent venous congestion in the cases where collateral circulation has not developed.

Aged↗
PubMed1998

[Successful treatment with end-to-end ureteral anastomosis for ureteral avulsion caused by abdominal blunt trauma: a case report].

Avulsion of ureter without renal injury is rarely caused by blunt trauma, only 28 cases having been reported in Japan. A 33-year-old male was admitted to our hospital 1 month after blunt abdominal trauma at work. He complained of left flank pain and macroscopic hematuria. Under the suspicion of renal or ureteral injury, drip infusion urography and abdominal computerized tomography revealed an extravasation from the left upper ureter and urinoma formation in the retroperitoneal cavity. In order to reduce the inflammation, the urinoma was drained. The retrograde pyelogram revealed complete obstruction at the left upper ureter, 20 cm from the left ureteral orifice. Urinary tract reconstruction, end-to-end ureteral anastomosis, was performed under the diagnosis of left ureteral avulsion. Drip infusion urography revealed normal ureteral healing without stricture formation at 2 years after reconstruction.

Abdominal Injuries↗
PubMed1998

[Mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery for severe emphysema].

To investigate the mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery (LVRS) for severe emphysema, we performed six-minute walk tests and pulmonary-function tests, and studied their correlation before and 3-to-5 months after LVRS in 7 patients with severe emphysema who underwent bilateral lung reduction via median sternotomy. Results of the tests showed a 59% increase in the 1-second forced expiratory volume (FEV1), a 25% reduction in the functional residual capacity (FRC), a 49% increase in the maximum voluntary ventilation (MVV), and a 20% increase in the distance walked in 6 minutes (6 MD). The degree of improvement in 6 MD correlated significantly with the degree of improvement in FEV1 (r = 0.97, p < 0.01), in FRC (r = 0.86, p < 0.05), and in MVV (r = 0.87, p < 0.05), and did not correlate with the degree of improvement in pulmonary gas exchange. These results support the hypothesis that an increase in lung elastic recoil after targeted emphysematous resection reduces airflow limitation, and thus leads to a short-term improvement in exercise tolerance after LVRS.

Aged↗
PubMed1998

[HR-CT evaluation of lung parenchymal alterations in patients following breast conservation therapy].

Twenty patients with early-stage breast cancer treated with breast conservation surgery and definite radiation, underwent computed tomography (added HR-CT) of the lungs before, immediately after, and at one, six, and twelve months after radiotherapy. During the follow-up period, 17 (85%) of the patients developed parenchymal alterations in the irradiated lung volume. We classified the parenchymal alterations into seven patterns: pattern 1 = septal line, 2 = nodular opacity, 3 = ground-glass opacity, 4 = consolidation, 5 = curvilinear opacity, 6 = aircyst accumulation, and 7 = irregularity of pleural surface. From one to six months after radiotherapy, 14 patients developed nodular opacities and ground glass opacities in the irradiated lung field. At 12 months after radiotherapy, fourteen patients were found to have aircyst accumulation and irregularity of the pleural surface. In this study, none of the patients presented any abnormal findings immediately after irradiation. There was no relationship between central lung distance or boost irradiation and the parenchymal alterations in the lung. On the other hand, there was a close relationship between oral anti-cancer agents and lung lesions. In conclusion, HR-CT was useful to evaluate morphologic changes in the irradiated lung.

Breast Neoplasms↗
PubMed1998

A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a genetic risk factor for cerebral hemorrhage but not for hypertension.

Platelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We previously found a higher prevalence of this mutation in patients with ischemic stroke. This fact suggests that the mutation might enhance the risk for stroke through its association with hypertension. We have addressed this hypothesis by analyzing the prevalence of the mutation in hypertension. We studied 138 patients with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9% homozygotes) in controls and 36.2% in hypertensives and the difference was not significant. The prevalence in patients with brain hemorrhage was significantly higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Primary hemangiopericytoma of the superior mediastinum: a case report.

We present a case of hemangiopericytoma arising in the superior mediastinum. A 48-year-old man demonstrated a superior mediastinal mass lesion on chest x-ray and was admitted to our hospital. A CT scan of the chest showed a well-circumscribed, heterogenously-enhanced mass, 7.0 x 6.5 x 6.5 cm in size, located in the right superior posterior mediastinum, compressing the trachea. The tumor was extirpated by surgical resection. Based on the histological findings, electron microscopic findings, and immunohistochemical studies, the tumor was diagnosed as hemangiopericytoma.

Diagnosis, Differential↗
PubMed1998

[Valproic acid relieved marked rigidity in three patients with end-stage parkinsonism].

We applied valproic acid (VPA) on the rigidity of three parkinsonian patients, two with Parkinson disease and one with striatonigral degeneration. They were all at Hoehn and Yahr's stage V and showed marked rigidity. In these patients, effect of L-DOPA had become limited or increasing the dosage of L-DOPA was difficult because of its side effects. Parkinsonian symptoms were assessed by using motor score of Unified Parkinson's Disease Rating Scale. The degree of rigidity in these three patients was markedly decreased with 300-600 mg/day of VPA. The blood level of VPA ranged from 24.8 to 66.5 micrograms/ml, which was relatively low compared with the effective blood level as an anti-epileptic agent. Parkinsonian symptoms other than rigidity, and the increased deep tendon reflexes which were present in the patient with striatonigral degeneration were not affected by VPA. Reduction of L-DOPA intensified rigidity again which had been under control. Trials of VPA on parkinsonism have been reported from two groups (Price PA, et al. 1978; Nutt J, et al. 1979), neither of which has observed any benefit of VPA. The difference of their results and ours seems to depend on the stage of patients; their patients had mild to moderate symptoms, whereas ours were in the end stage with marked rigidity. Since the effect of VPA upon parkinsonism is limited to rigidity, the end-stage patients whose care is difficult due to severe rigidity may obtain the best benefit of VPA. VPA is considered to take effect by activating gamma-aminobutyric acid (GABA) system. Because GABA is a common inhibitory neurotransmitter distributed in the wide areas of the central nervous system, it is difficult to locate the action site of VPA with regard to the amelioration of rigidity. The stretch reflex loop in the spinal cord does not seem to be the action site because no change was noted in deep tendon reflex. GABAergic striatal efferent neurons do not seem to be the sole action site either, because parkinsonian symptoms were not affected except for rigidity. The vestibular nucleus which receives strong GABAergic afferents from cerebellar Purkinje cells is an efficient tonus regulator. Since suppression of the function of the nucleus is known to reduce rigidity, it is at least a candidate for the action site of VPA. But there is no direct evidence for this matter. The exact action site of VPA remains to be elucidated.

Aged↗
PubMed1998

Pharmacokinetic characteristics of the novel anticancer agent CPT-11 and its active metabolite in plasma and lung lymph fluid following intravenous administration to sheep.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11, 100286-90-6) is one of the most promising novel anticancer agents, especially for lung cancer. 7-Ethyl-10-hydroxycamptothecin (SN-38), an active metabolic of CPT-11, has much stronger cytotoxicity than CPT-11. The present study was designed to evaluate the distribution and behavior of CPT-11 and SN-38 in lung lymph circulation following intravenous infusion. Awake sheep with chronically instrumented lung lymph fistulas were prepared. The concentrations of CPT-11 and SN-38 in plasma and lung lymph fluid were measured after intravenous infusion of 100 mg/body of CPT-11 for 90 min. SN-38 constantly showed higher lymph to plasma concentration ratios than those of CPT-11, and the % area under the curve (AUC) ratio of SN-38/CPT-11 in lymph fluid was significantly higher than that in plasma. These data indicated that SN-38 distributed in lung tissue moved more easily into lung lymph fluid than CPT-11, and might be more rapidly metabolized in lung tissue than plasma. CPT-11 may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Animals↗
PubMed1998

Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an omega-functionalized acyclic structure.

Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.

Allosteric Site↗
PubMed1998

[Bilateral aplasia of the internal carotid artery: a case report].

We report a case of bilateral aplasia of the internal carotid arteries. A 59-year-old man was admitted with generalized convulsions. Computed tomography and magnetic resonance imaging of the head showed normal findings. Three-dimensional computed tomography, angiography, and intra-arterial digital subtraction angiograms showed bilateral aplasia of the internal carotid arteries. The bilateral ophthalmic arteries were filled from the hypoplastic carotid arteries, and the anterior and middle cerebral arteries were filled from the basilar artery via the posterior communicating arteries. Associated with this bilateral aplasia of the internal carotid arteries, intracranial aneurysms and megadolicho-basilar anomaly were reported. Angiography is to be recommended if IC aplasia is suspected.

Carotid Artery, Internal↗