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Biomedical subjects

H Fujioka

Publications and source records attributed to H Fujioka.

At least 343 records · Page 19Linked to original sources

On the intracellular transport and the nuclear association of human cytomegalovirus structural proteins.

In cells productively infected with human cytomegalovirus (HCMV) AD169, large amounts of two viral proteins, the 150K major capsid and the 68K major matrix proteins, are continuously produced during the late phase of infection. In the present study, the mechanism for the intracellular transport of the 150K and 68K proteins was investigated. Infected cells were labelled for 30 min at 72 h post-infection with [35S]methionine, chased for various periods of time at 37 degrees C, and fractionated into cytoplasmic and nuclear fractions. Immediately after 30 min of labelling, the 68K protein was already associated with the nuclear fraction. In contrast, the major proportion of the 150K protein remained in the cytoplasm for more than 1 h; the migration of the 150K protein was much slower than that of the 68K protein. Both the 150K and the 68K proteins were associated with the perinuclear cytoskeletal fraction in the process of migration. After migration into the nucleus, these proteins were resistant to extraction with DNase and high salt, indicating that they were associated with the nuclear skeleton (nuclear matrix). Effects of various inhibitors on the migration of the 150K protein showed that cycloheximide inhibited the transport of the 150K protein, but other inhibitors such as arabinosyl cytosine, cytochalasin D, colchicine or sodium azide did not. The results suggest that the cytoskeletal structure may play a role in the intracellular transport of HCMV structural proteins from the cytoplasm into the nucleus.

Biological Transport↗

Pharmacokinetics of spironolactone and potassium canrenoate in humans.

Plasma concentrations and urinary excretion of canrenone (III), canrenoic acid (IV) and canrenoic acid glucuronide (V) were determined by means of high performance liquid chromatography (HPLC) and fluorometry after oral administration of spironolactone (I) and potassium canrenoate (II) to human subjects. Comparison of both assays for III in plasma as well as in urine after administration of I showed marked differences. Plasma concentrations of III were significantly higher after administration of II than I, Cmax and AUC from II being 3--5 times larger than those from I by means of HPLC assay, while the fluorometrically determined values for III in plasma after administration of I and II did not differ as much from each other. On the other hand, in contrast to plasma, the amount of III excreted in urine after administration of I was much larger than that after II, i.e. 3--4 times greater by means of HPLC and over 10 times greater by means of fluorometry. These results strongly suggest that precursors of III are formed which have a higher renal clearance than that for III alone after oral administration of I. Considering the relative biological potency ratio of I and II, it is presumed that their pharmacological activities may relate to the urinary excretion of III. Plasma concentrations of IV were definitely higher after administration of II compared to those after I. Canrenoic acid (IV) was excreted mainly as glucuronide (V) in urine.

Adult↗

[Clinical observation on in situ carcinoma of the bladder and related conditions].

Clinical course and histological findings of 692 patients with bladder tumor were reviewed to reveal the statistics and clinical profile of carcinoma in situ and its related conditions in the urinary bladder. Primary papillary intraepithelial lesions were found in 83 cases (12.0%), whereas flat intraepithelial carcinoma was found in 16 cases (2.0%), 10 as primary and 6 as secondary tumors. In 35 cases (3.5%), the bladder lesion was flat and rather difficult to find by cystoscopy, and initially considered as chronic cystitis or flat carcinoma in situ. Post-operative histological diagnosis, however, revealed micro- or apparent invasion beyond the basement membrane. Thus they were tentatively classified as clinical carcinoma in situ. The result of the radical surgical treatments for the clinical carcinoma in situ was very poor with a rough 5-year survival of 19%. The management of primary or secondary flat intraepithelial carcinoma was carried out by radical surgery or bladder sparing operation followed by intravesical instillation of cytotoxic agents. The results of these procedures remain uncertain. Some confusion in terminology of carcinoma in situ is discussed and the term "flat carcinoma" was recommended to indicate carcinoma in situ and its related conditions.

Adult↗

Anesthetics block excitation with various effects on inhibition in MRF neurons.

The effects of isoflurane and halothane on the behavior of mesencephalic reticular neurons in the rat were studied by long-term extracellular microelectrode recording. Both anesthetics always suppressed the excitatory responses with simultaneous blocking or augmenting effects on the inhibitory responses of the reticular neurons. The blocking effects on the inhibitory responses were more frequently noticed during light anesthesia than during the deep stage.

Action Potentials↗

Hormone receptor in renal cell carcinoma and correlation with clinical response to endocrine therapy.

Analyses of hormone receptors in cytosols from 41 renal cell carcinoma specimens were performed by the dextran-coated charcoal technique, using estradiol, synthetic progestin R5020 and synthetic androgen R1881. Binding data were calculated according to the method of Scatchard. Of 41 renal cell carcinomas estradiol receptor was detected in 11, R5020 receptor in 11 and R1881 receptor in 13. No significant correlation between histopathological findings and hormone receptors was observed. Patients were classified into those positive and negative for receptors. The clinical response of endocrine therapy for 17 with advanced residual or metastatic lesions after nephrectomy was studied in regard to the survival rates. Although there was no complete or partial regression in tumor size, the survival rate of patients with 1 or more receptors was significantly higher than that of patients negative for receptors (p less than 0.01). In conclusion, hormonal manipulation in patients with renal cell carcinoma cannot induce an antitumor effect but seems to increase survival in patients with receptors.

Adenocarcinoma↗

Autologous mixed lymphocyte tumor cell culture in patients with renal cell carcinoma.

Cell-mediated immunity was studied by measurement of lymphocyte response to autologous tumor cells in 19 surgically treated patients with histologically proved (mixed lymphocyte tumor cell culture) renal cell carcinoma. Tumor stage was low in 9 patients and high in 10, while grade was low in 11 and high in 8. Of 8 patients in whom a positive lymphocyte response was detected 6 had high and 2 had low stage tumors (p less than 0.05), while the grade of disease was low in 7 and high in 1 (p less than 0.05). Furthermore, the more advanced and undifferentiated the tumor the more significant the decrease in lymphocyte response (p less than 0.05). Lymphocyte response was positive in 5 of 8 patients with low stage and low grade tumors but negative in 7 with high stage and high grade disease. However, no correlation between the lymphocyte response and the degree of microscopic lymphocytic infiltration in and around the tumor was found. This study confirms that the specific immunological defense mechanism of patients with renal cell carcinoma against the tumors remains well at an earlier stage of tumor development, especially in cases with well differentiated malignancy, and showed attenuation in parallel with pathological spread or in poorly differentiated tumors.

Adenocarcinoma↗

Anesthetics and excitatory/inhibitory responses of midbrain reticular neurons.

The effects of nitrous oxide, halothane, ether, isoflurane, thiopental, and thiamylal on the excitatory as well as inhibitory responses of single neurons in the midbrain reticular formation (MRF), believed to be one of the most important sites for the regulation of wakefulness, were studied by long-term, extracellular microelectrode recording in cats and rats. All anesthetics except nitrous oxide suppressed the excitatory responses of MRF neurons evoked by somatosensory stimulation. The inhibitory responses markedly were potentiated by both barbiturates but variously affected by other inhalation anesthetics. Blockade of the inhibitory responses (disinhibition) was observed more frequently with the inhalation agents during the light state of anesthesia. Thus, suppression of excitatory responses is likely to be a general feature of the anesthetic state in terms of the behavior of MRF neurons. Further, potentiation of the inhibitory responses might be characteristic of barbiturate anesthesia.

Anesthetics↗

Abortive infection of L cells by influenza B virus: defect in bud formation.

Host-dependent restriction of influenza B virus replication in L cells was analysed in comparison with productive infection in MDCK or 1-5C-4 cells. The synthesis and intracellular distribution of virus-specific proteins and the production of cytoplasmic ribonucleoproteins in nonpermissive L cells were similar to those in permissive MDCK cells. However, an electron microscopic study of infected L cells showed neither extracellular virions nor budding virus particles on the cell surface, in contrast to MDCK cells which produced numerous virus particles. PAGE analysis of the plasma membrane isolated from the cells demonstrated no significant difference in the composition of viral polypeptides between permissive 1-5C-4 and nonpermissive L cells. It was noted that the abortiveness of influenza B virus infection in L cells may be due to a defect in host cell function involved in the initiation of virus budding.

Animals↗

Enhancement of Newcastle disease virus-induced fusion of mouse L cells by sodium vanadate.

Sodium vanadate enhanced Newcastle disease virus (NDV)-induced cell fusion in L cells, and there was a direct correlation between the degree of cell fusion and the dose of vanadate added. When anti-F protein of NDV monospecific antiserum was added to the culture fluid of L cells infected with NDV, the enhancement of cell fusion was suppressed. In contrast, neither anti-HN nor anti-M protein monospecific antiserum inhibited the enhancement. Incubation at low temperature (4 C) and addition of sodium azide to the culture fluid suppressed the enhancement. The suppression by azide was seen only when the drug was added within 5 min after the beginning of incubation of NDV-infected L cells with vanadate. On the other hand, incubation at low temperature inhibited the enhancement at any time during incubation with vanadate. Cytochalasin D also inhibited the enhancement if it was added at any time during incubation with vanadate.

Animals↗

Spontaneous regression of pulmonary metastases after nephrectomy for renal cell carcinoma.

A case of spontaneous regression of pulmonary metastases from renal cell carcinoma after nephrectomy is presented. In a 57-year-old Japanese male who had already had pulmonary metastases at the time of nephrectomy, the metastatic lesions disappeared without adjuvant therapy 8 years after nephrectomy. He is still surviving without recurrence or any signs indicative of new metastasis at the present. The clinical aspects of this interesting phenomenon are discussed briefly.

Adenocarcinoma↗

Late recurrence of renal cell carcinoma after nephrectomy.

Late recurrence of renal cell carcinoma is unusual. Of 43 patients who underwent curative nephrectomy more than 10 years before, 2 cases (4.7%) had late recurrence. The 2 cases, both female patients, had late recurrence 12 and 19 years from the date of nephrectomy. The clinical aspects of late recurrence are discussed briefly.

Adenocarcinoma↗

Biopharmaceutical studies on hydantoin derivatives. IV. Factors affecting bioavailability of 5,5-diphenylhydantoin in dog.

Several factors affecting the bioavailability of 5,5-diphenylhydantoin (I) and its sodium salt (I-Na) were examined in dogs in relation to meal and following results were obtained. The bioavailability of I was not appreciably affected by the volume of coadministered water in the range of 30-120 ml. The bioavailability of I was most excellent when I was administered 0.5 h after meal. Food intake 0.5 h after drug administration enhanced appreciably the bioavailability, but that 2 h after drug administration did hardly affect the bioavailability. The extent of bioavailability of I-Na was almost 100% of the dose in the range of 100-400 mg/dog when it was administered 0.5 h after meal. While, when I-Na was administered in the fasting state, the extent of bioavailability was about 60% of the dose. Food-induced enhancement of the bioavailability of I was independent of the food constituents. The bioavailability of I was increased about 1.5-fold and 2-fold with 10-fold increase in the specific surface area of I, in the nonfasting and the fasting states, respectively. In the experiments using the dogs with the chronically implanted fistula in the common bile duct, it was found that the bile was not a major factor contributing to the food-induced enhancement of the bioavailability of I. There was a good correlation between the bioavailability of I in dog and that in man.

Adult↗