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Biomedical subjects

K Kamiya

Publications and source records attributed to K Kamiya.

At least 217 records · Page 12Linked to original sources

1,5-Benzoxathiepin derivatives. III. Optical resolution of methyl (+/-)-cis-3-hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro- 2H-1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) with selective 5-hydroxytryptamine2(5-HT2)-antagonistic activity.

The selective 5-HT2-receptor antagonist, methyl (+/-)-cis-3-hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro-2H- 1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) was resolved in high optical purity using (R)-(-)- and (S)-(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphates ((R)-(-)- and (S)-(+)-BNP). The absolute configuration of (+)-CV-5197 was determined to be 3S,4R by X-ray crystallographic analysis. In the binding assay, it was demonstrated that (+)-CV-5197 was a more active isomer (IC50 = 23 nM +/- 6.3) for 5-HT2 receptor binding than the (-)-enantiomer (IC50 = 1600 nM +/- 82). (+)-CV-5197 completely inhibited the 5-HT-induced contraction of the isolated pig coronary artery at a concentration of 3 x 10(-7) M, whereas (-)-CV-5197 showed little antagonistic activity, even at 3 x 10(-4) M. Thus, the agreement between the results of the binding assays and the biological activities for the 3S,4R enantiomer of CV-5197 suggests that its physiological activity is probably exerted through 5-HT2-receptor antagonism.

Animals↗

Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer.

We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E2 without progesterone stimulates alveolar colony formation in the presence of cortisol and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E2, cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure.

Animals↗

Brain metastasis of thyroid papillary carcinoma--case report.

A rare case of brain metastasis of thyroid papillary carcinoma is reported. The cerebral metastasis was surgically treated without irradiation despite the presence of a spinal metastasis. No recurrence was demonstrated by computed tomography 1 year postoperatively. We suggest that surgery is indicated for a brain metastasis of thyroid papillary carcinoma even if other metastatic lesions are present.

Adenocarcinoma, Papillary↗

Investigation of normal pressure hydrocephalus by 123I-IMP SPECT.

We evaluated N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) as a method for identifying normal pressure hydrocephalic (NPH) patients eligible for shunting procedures. 123I-IMP SPECT scans were taken before and after cerebrospinal fluid (CSF) taps in NPH cases. Post-subarachnoid hemorrhagic (SAH) patients showed apparent frontal blood flow reduction but non-SAH cases did not. The frontal blood flow increased in comparison with the temporal flow after CSF tapping in SAH cases who benefited most from shunting. Cerebral blood flow study before and after CSF removal is a potential method for classifying NPH patients likely to benefit from the shunting operation.

Aged↗

Subdural hematoma due to ruptured intracranial aneurysm.

Subdural hematoma (SDH) was observed in 15 of 484 cases of aneurysmal subarachnoid hemorrhage (SAH). There were four males and 11 females, with ages ranging from 39 to 75 years. The clinical grades (Hunt and Hess) on admission were 11 in three cases, III in two, IV in four, and V in six. The ruptured aneurysms were located in the middle cerebral artery (MCA) in six cases, anterior communicating artery in three, internal carotid artery in two, and distal anterior cerebral artery (ACA) in two, with two cases unconfirmed. A high proportion of aneurysms occurred in the MCA and distal ACA. Aneurysmal neck clipping and removal of SDH were performed in the acute stage of seven cases, without intraoperative rerupture. The outcomes 1 year after SAH of the seven patients undergoing surgery were good recovery in five, but in two, vegetative state due to preoperative rerupture or medical complications. All eight patients without surgical intervention died. A good prognosis for patients with ruptured intracranial aneurysms accompanied by SDH can be expected with direct surgical intervention in the acute stage, even if the clinical grade on admission is poor.

Adult↗

[Intracranial tuberculoma with difficult preoperative diagnosis. Case report].

Intracranial tuberculoma is a relatively rare tumor in developed countries. A 41-year-old Japanese male with a personal history of pulmonary tuberculosis at the age of 20 was referred because of continuous headache. Computed tomography scan revealed multilocular ring-like enhancement in the right deep temporal region with massive brain edema. Angiography showed an avascular mass with narrowing of the carotid bifurcation. The preoperative diagnosis was glioblastoma. This mass was successfully removed and the histological diagnosis was tuberculoma. This case suggested that tuberculoma is still one of the differential diagnoses of an enhanced mass lesion even without any active extracranial tuberculous lesion.

Adult↗

Differential control of alveolar and ductal development in grafts of monodispersed rat mammary epithelium.

Multicellular secretory alveolar units (AU) develop in grafts of monodispersed mammary cells in intact recipient rats co-grafted with mammotropic hormone-secreting pituitary tumor (MtT). The cumulative evidence is consistent with a postulated clonal origin of these structures. Small numbers of multicellular structures of a second type, mammary ductal units (DU), were found in mammary cell grafts in intact Wistar/Furth recipients co-grafted with MtT W10 but not in intact F344 recipients co-grafted with MtT F4. Studies in (Wistar/Furth x F344) F1 hybrid recipients grafted with mammary cells from either parent strain demonstrated that this difference in DU formation is dependent on the strain of grafted MtT, and is not a genetic characteristic of the rat strain. DU formation is stimulated and AU formation is inhibited by elevation of mammotropic hormones from MtT coupled with glucocorticoid deficiency induced by adrenalectomy. cortisol treatment reverses this effect. Finally, in mammary glands in situ in intact rats, the total numbers of AU-forming clonogens decrease during 6 weeks after MtT transplantation. In contrast, during the same period, elevated mammotropins from grafted MtT coupled with glucocorticoid deficiency from adrenalectomy cause an increase in the total number of cells that are capable of AU formation when transplanted to intact recipients co-grafted with MtT. Thus, the same hormonal combination that stimulates DU formation in mammary cell grafts and has previously been shown to promote cancer in mammary glands in situ also stimulates an increase in the glandular content of assayable AU-forming cells in situ.

Adrenal Glands↗

[Surgical enucleation for renal cell carcinoma. A case report].

We present a case of bilateral synchronous renal cell carcinoma treated with surgical enucleation. Urological consultation was asked to evaluate masses of the kidneys, which were detected during a diagnostic imaging on a 58-year-old man with hepatic disorder. Excretory urograms showed definite bilateral upper pole renal masses. Bilateral selective renal angiograms disclosed neovascularity in the small masses. Surgical enucleation of the left renal tumor by a flank approach was performed. The surgical specimen being 3.5 by 2.5 by 2 cm (29 g) was pseudoencapsulated and was identified renal cell carcinoma of the clear cell type, grade 1. INF alpha, pathologically. Seven weeks after, a pseudoencapsulated tumor of 3 by 2.5 by 2 cm (16 g) in the right upper pole was removed by simple enucleation. The pathological diagnosis was renal cell carcinoma of clear cell type, grade 2, INF alpha. The patient is well without evidence of recurrent or any residual disease at 21 months after the second operation. Renal function remains with in normal limits (CCr 110 ml/min). Of our collected cases of bilateral synchronous renal carcinomas treated by bilateral conservative surgery, clinical data are available for 11. Including our case, a total of 12 cases are reviewed.

Carcinoma, Renal Cell↗

[A case of cranial and intracranial metastasis from testicular seminoma].

The case presented is of a 44-year-old man with skull and intracranial metastasis of seminoma. He was operated on for a testicular tumor at 41 years of age. Pathologically, it was pure seminoma. Coronal CT scan showed tumor invasion of the subcutaneous vault, and of the epidural and intraparenchymal region of the right parietal region. We treated him with a combination of surgical excision, radiation and PVB chemotherapy. He was neurologically disease-free for ten months after being discharged. However, he then succumbed to liver metastasis of seminoma. Seminoma mainly metastasizes via the lymph stream. CNS metastasis of seminoma is only 0.7% in Japan. We would like to stress that prophylactic chemotherapy would be essential even after patients get remission from CNS metastasis of seminoma.

Adult↗

Functional heterogeneity of human eosinophil chemotactic lymphokines.

We have previously isolated two OKT4-positive T lymphocyte-derived eosinophil chemotactic factors (LDECF) with MW of about 45-60 kDa of which production is different in antigen or mitogen dependency (1-4). The production of a LDECF from patients with parasite disease (LDECF-PD) is dependent on antigen or mitogen stimulation, whereas another LDECF from patients with hypereosinophilic syndrome (HES) is independent. Further purification of these LDECF with isoelectric focusing reveals that an isoelectric point of LDECF-HES is about 6.0 and that of LDECF-PD is around 7.0 to 8.0. Little or no activity of partially purified LDECF-HES and LDECF-PD is suppressed by treatment with monoclonal antibodies against GM-CSM, IL-3, and IL-5, which activate eosinophils. LDECF-HES and LDECF-PD attract eosinophils from healthy individuals. In contrast, eosinophils from patients with HES are attracted by LDECF-HES but not LDECF-PD. LDECF-HES enhances the expression of Fc epsilon receptor II (Fc epsilon RII) and Fc gamma receptor III (Fc gamma RIII) but not that of CR1 on eosinophils, whereas LDECF-PD enhances their CR1 and Fc gamma RIII expression but not Fc epsilon RII expression. Moreover, treatment with LDECF-PD suppresses the release of eosinophilic cationic protein (ECP) from eosinophils, whereas that with LDECF-HES fails. Treatment of eosinophils with phorbol myristate acetate enhances ECP release from eosinophils but it fails to enhance the intracellular ECP level. However, the intracellular ECP level is elevated by stimulation with phorbol myristate acetate if eosinophils were previously treated with LDECF-HES but not with LDECF-PD. These results suggest that various kinds of LDECF are produced according to the nature of diseases, and that each LDECF has functional heterogeneity on eosinophils.

Antigens, Surface↗

[A case of Morgagni's hernia: availability of CT scan, ultrasonography, and trans-abdominal surgical approach].

A 60-year-old obese woman was admitted to our hospital to receive surgical treatment for "slow-growing mediastinal lipoma". With the non-invasive examination such as CT scan and ultrasonography, she was revealed as Morgagni's hernia containing a greater omentum. With a trans-abdominal approach, we could take a good surgical field for the bilateral foramina of Morgagni. Several discussions were described for availability of CT scan, ultrasonography and a trans-abdominal approach.

Diagnosis, Differential↗

[Studies on intracellular kinetics of ara-C triphosphate in HL-60, human leukemia cells in relation to reasonable administration of ara-C].

To study the pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C), which is one of the main drugs used in chemotherapy for acute leukemia, its intracellular metabolism was investigated using HL-60 cells derived from human acute non-lymphocytic leukemia. The concentration of the drug and its metabolites in the cells were serially determined and the following results were obtained. 1) The uptake of ara-C into HL-60 cell (1 X 10(7)/ml) was very rapid when they were incubated with 2 microM ara-C. The total intracellular ara-C content per 10(9) cells exceeded the ara-C concentration in the extracellular fluid at about 7 minutes after the start of incubation. It reached about 4 times higher than the extracellular concentration after 60 minutes. 2) Conversion of ara-C to the active form, ara-CTP, was also rapid. The intracellular concentration of ara-CTP was about 3 times higher than the ara-C concentration in the extracellular fluid after incubation for 60 minutes. 3) Total accumulation of ara-C in the cells was dependent on the extracellular ara-C concentration up to a concentration of 100 microM. The production of ara-CTP occurred in such a way that, when the extracellular ara-C concentration was lower than 10 microM, more than 90% of the uptake of ara-C was converted to ara-CTP, while at concentrations above 10 microM the efficiency at production (the ratio of total ara-C to ara-CTP production) was decreased. The maximum intracellular ara-CTP concentration was estimated to reach to 45 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Arabinofuranosylcytosine Triphosphate↗

[Activities of enzymes converting 5-fluorouracil to 5-fluorouridine-5' monophosphate and 5-fluorodeoxyuridine-5' monophosphate in subcultured cell lines and solid tumor tissues].

The activities of five enzymes, orotate phosphoribosyltransferase (OPRTase), uridine kinase (UR kinase), thymidine kinase (TdR kinase), uridine phosphorylase (UR Prylase) and thymidine phosphorylase (TdR Prylase), were examined in subcultured human acute leukemia cell lines (HL-60, CCRF-CEM), subcultured human solid tumor cell lines (Colo-205, HeLa-S3) and human cancerous tissues with a view to compare the activation of 5-fluorouracil in them. There was no significant difference in the activity of any enzyme between HL-60 and CCRF-CEM, Colo-205 and HeLa-S3, and human lung cancerous tissue and human colon cancerous tissue. Compared between the acute leukemia cell lines and the solid tumor cell lines, the UR kinase activity was high in both cell lines. The OPRTase and UR Prylase activities were low in the solid tumor cell lines. In the cancerous tissues, both the UR kinase and TdR kinase activities were low, but the UR Prylase and TdR Prylase activities were markedly high. The results suggest that the intracellular activation of 5-fluorouracil varies with different human cancerous cells. When the anti-cancer activity of 5-fluorouracil is tested in vitro, the difference of fluoropyrimidine metabolism in subcultured cell lines from that in the cancerous tissue should be taken in account.

Fluorouracil↗

[Clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in a patient with acute non-lymphocytic leukemia with two CNS recurrences].

A case of two repeated CNS recurrences of acute non-lymphocytic leukemia (M2) was treated with intermediate dose Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-lymphocytic leukemia (M2) achieved complete remission by combination chemotherapy of Behenoyl-ara-C, Daunorubicin, 6-Mercaptopurine and Prednisolone in July, 1985. He subsequently received consolidation and intensification therapy with periodical intrathecal injection of Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of Ara-C and MTX. As he also relapsed systemically, Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of Ara-C is achieved throughout the CNS by this therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of Ara-C, which is enough concentrations for its cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including Behenoyl-ara-C, an analog of Ara-C, and was resistant to the intrathecal administration of Ara-C. These findings suggest that intermediate dose Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including Ara-C, and also, in some cases, more effective than intrathecal injection of antileukemic drugs for the treatment of CNS leukemia.

Cytarabine↗

Changes in epidural pulse pressure in brain oedema following experimental focal ischaemia.

This study was carried out to clarify the changes of pulse pressure of the intracranial pressure pulse wave in ischaemic brain oedema. Intracranial pressure and PP were measured in two groups of anaesthetized dogs; 1) increased volume of cerebrospinal fluid by cisternal saline injection (control group), 2) brain oedema caused by focal ischaemia (oedema group). Ischaemia was induced by 2 hours of occlusion of the anterior, middle cerebral and internal carotid arteries. The canine focal ischaemic model showed consistent ischaemic damage in the caudate nucleus and produced brain oedema successfully. PP increased linearly with rising ICP to 35 mm Hg, and PP in the oedema group was significantly smaller than that in the control group at the same ICP value. The slopes of the regression equation of ICP and PP were significantly different between the oedema and control group (oedema: 0.057 +/- 0.029, control: 0.106 +/- 0.009), mean +/- SD, P less than 0.005). These results suggest that PP is easily affected by ischaemic brain oedema, which indicates increase of the brain tissue in the cranium. We conclude that PP is affected even at the same ICP value when intracranial components have altered.

Animals↗

Two types of sodium channel block by class-I antiarrhythmic drugs studied by using Vmax of action potential in single ventricular myocytes.

The state-dependent sodium channel block by mexiletine, tocainide, lidocaine, OPC-88117, aprindine, quinidine, disopyramide and AN-132 was investigated in single ventricular myocytes isolated from guinea-pig hearts. A single conditioning clamp pulse with a duration from 10 ms to 1000 ms was applied from the resting potential (-82 mV) to 0 mV level using a suction pipette whole-cell voltage clamp technique, and the maximum upstroke velocity (Vmax) of a test action potential elicited 100 ms after termination of the clamp pulse was measured as an index of sodium channel availability. In myocytes treated with the eight drugs, such clamp pulse caused a significant decrease in Vmax. With mexiletine, tocainide, lidocaine, OPC-88117 and aprindine, the Vmax reduction was enhanced progressively as the clamp pulse duration was prolonged. With quinidine, disopyramide and AN-132, an appreciable Vmax reduction at the shortest clamp pulse was followed by an additional small enhancement of the Vmax decay. These findings suggest that the former group of drugs may block the sodium channel mainly during the inactivated state (inactivation blockers), whereas the latter one may do so mainly during the activated state (activation blockers). Multiple short clamp pulses caused a greater Vmax reduction than a single prolonged clamp pulse for the activation blockers, and vice-versa for the inactivation blockers. Molecular dimensions of the eight drugs, which were estimated by X-ray diffraction of crystals, did not satisfy a simple size criterion as proposed by Courtney (1988) to explain such different types of sodium channel block by Class-I drugs.

Action Potentials↗

Electrophysiological effects of AFD-21 and AFD-19, new antiarrhythmic compounds on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of AFD-21, a newly synthesized antiarrhythmic compound, and AFD-19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, AFD-21 10(-5) M caused a slight prolongation of action potential duration (APD), while AFD-19 above 10(-6) M shortened APD in a dose-dependent manner. 3. Both AFD-21 and AFD-19 above 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. 4. In the presence of AFD-21 or AFD-19, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. A time constant for the recovery of Vmax from the use-dependent block was 2.9 s for AFD-21 and 3.6s for AFD-19. 5. The curves relating membrane potential and Vmax were shifted by AFD-21 (10(-5) M), or AFD-19 (10(-5) M) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6. In single ventricular myocytes treated with AFD-21 (10(-5) M) or AFD-19 (10(-5) M), Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that both AFD-21 and AFD-19 have use- and voltage-dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics.

Action Potentials↗