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Biomedical subjects

H Nakada

Publications and source records attributed to H Nakada.

At least 127 records · Page 7Linked to original sources
PubMed1986

[A subacute oral toxicity study of T-2588 in juvenile rats].

A subacute toxicity study on T-2588 was carried out in juvenile rats (6 days-old 48 males and 48 females) by oral administrations at dose levels of 250, 500 and 1,000 mg/kg/day for 1 month. The results obtained were summarized below. During the study, there were no clinical signs considered to be related to the treatment. There were no T-2588-related abnormalities in urinalysis, hematological examinations, biochemical examinations and ophthalmological examinations. Slight increases in relative liver and kidney weights were observed in the 1,000 mg/kg-treated group and slight increases in relative kidney weight were detected in the 500 mg/kg-treated female group. Histologically, however, T-2588-related abnormality was not observed. The maximum safety dose of T-2588 was estimated to be 250 mg/kg/day. In addition to the above examinations, male reproductive performance was examined in the group administered with a dose level of 1,000 mg/kg/day. No adverse effects were observed in male fertility and F1 generation.

Administration, Oral↗
PubMed1985

Electron microscopic examination of the catecholaminergic innervation of neurophysin- or vasopressin-containing neurons in the rat hypothalamus.

The ultrastructural relationships between neurophysin (NP)- or vasopressin (VP)-containing neurons and catecholamine terminals in the paraventricular nucleus and supraoptic nucleus of the rat were observed by means of a technique combining immunocytochemistry using NP I/II or VP antiserum with autoradiography after [3H]noradrenaline (NA) injection or 5-hydroxydopamine (5-OHDA) uptake. NP- or VP-like immunoreactive nerve cell bodies and fibers received synaptic contacts from a large number of immunonegative axon terminals. The presynaptic elements that innervate the neurosecretory neurons were studied. Axon terminals labeled with [3H]NA or 5-OHDA made synaptic contacts with NP- or VP-like immunoreactive nerve cell bodies and fibers. Furthermore, axodendritic and/or axo/axonic and axosomatic synapses occurred between the same NP- or VP-like immunoreactive neurons. These findings suggest that at least NA- and 5-OHDA-containing neurons play some important role in the control of neurosecretion in the NP- or VP-producing neurons of the rat hypothalamus and that the axon collaterals of NP- and VP-containing neurons make synaptic contacts with the same kind of neurons to form a recurrent collateral circuit.

Animals↗
PubMed1985

Phosphorylation of the rat hepatocyte asialoglycoprotein receptor.

Phosphorylation of asialoglycoprotein receptor was investigated by using rat hepatocytes. Analysis of the purified receptor by SDS-PAGE and autoradiogram revealed that the 64 and 54 Kd polypeptides of the receptor were phosphorylated but the 43 Kd one was not and that phosphorylation took place at the cell surface. These results are compatible with the fact that the 64 and 54 Kd species exist predominantly at the cell surface. The sites of phosphorylation were identified as Ser and Thr with no detectable radioactivity in phosphotyrosine.

Amino Acids↗
PubMed1985

Intracellular transport of a newly synthesized asialoglycoprotein receptor in rat liver.

Intracellular transport of a newly synthesized asialoglycoprotein receptor was studied biochemically using a monospecific antibody for the receptor. Pulse-labeling by intravenous injection of [3H]leucine and pulse-chasing after 10 min by cycloheximide injection resulted in the maximal labeling of the receptor in the rough microsomes at 15 min, in the smooth microsomes and the heavy Golgi subfraction (GF3) at 25 min and in the intermediate plus light Golgi subfraction (GF1+2) at 30 min. By 60 min, the labeling in GF1+2 had decreased and leveled off. In the plasma membrane fraction, the labeled receptor first appeared at 20 min, increased rapidly and also reached a constant level at 40-60 min. Intracellular movement of the newly synthesized receptor in the GF1+2 and plasma membrane fractions was also investigated by purifying the receptor protein from the GF1+2 and plasma membrane fractions by affinity chromatography. It was revealed that the specific radioactivities of the receptor in the two fractions become equilibrated after 60-120 min. The receptor of the various membrane fractions was also pulse-labeled in vivo for 20 min simultaneously with [3H]glucosamine and [14C]leucine, and pulse-chased for the following 40 min. After pulse-labeling for 20 min, the ratio of the radioactivity of [3H]glucosamine or [3H]sialic acid to [14C]leucine of the receptor from the rough and smooth microsomes, and GF3, GF2, and GF1 increased in that order. That of the receptor from the plasma membrane fraction was infinitely higher, because, while a significant amount of 3H-radioactivity was incorporated into the receptor in the Golgi apparatus, only a negligible amount of 14C-radioactivity was incorporated into the same receptor in the plasma membrane due to the delay in the arrival of [14C]leucine labeled receptor to the plasma membrane. After chasing for 40 min, however, the same radioactivity ratios of the GF1 and plasma membrane fractions approached each other. All these results strongly suggest that the distribution of the newly synthesized receptor becomes rapidly equilibrated between the trans-Golgi components and plasma membranes probably by repeated recycling of the receptor protein between the two membranes.

Animals↗
PubMed1985

Monocyte chemiluminescence and macrophage precursors in the aged.

Age-related alterations in the host defense system have been vigorously investigated because of increased susceptibility to infection and neoplasms in the aged. Although monocyte-macrophages form a major part of the cellular defense against microorganisms, the majority of investigations has been limited to neutrophils and lymphocytes. The present study, designed to determine the influence of age on mononuclear phagocytes, revealed no significant decrease in the absolute number of blood monocytes, but did reveal a tendency for the chemiluminescence of blood monocytes to decrease (p less than 0.10) and a significant decrease in the numbers of macrophage precursors (p less than 0.05) in the aged (over 70 year old), in comparison with controls (under 40 years old). On the basis of these findings, functional alterations of monocyte-macrophages seem to participate in the increased susceptibility to infection in the aged.

Adult↗
PubMed1985

[Phase I-II study of recombinant interferon gamma].

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.

Adult↗
PubMed1985

[Evaluation of ototoxic effect of micronomicin by intravenous drip infusion].

Ototoxic effect of micronomicin (MCR) in intravenous drip administration was investigated in guinea pigs (300--400 g) receiving MCR for 30 days at dose of 50 and 100 mg/kg, respectively. MCR was dissolved in physiologic saline and 1.5 ml of the solution was infused through polyethylene tube into the left external jugular vein with Perista mini-pump for 60 minutes every day after measurement of body weight. Auditory impairment was monitored by pinna reflex audiometry. Pinna reflex loss was not detected in any animal in frequency range (0.5 to 20 kHz). Cochlear hair cell damage generally was of mild degree. Two out of 6 animals treated with MCR 50 mg/kg (Table 1) showed outer hair cell loss confined to unilateral basal end and posterior 3/4 of the first turn, respectively. Outer hair cell loss was noticed in 4 of 9 animals receiving MCR 100 mg/kg (Table 2); much less extensive in 3 animals, unsymmetrical slightly extensive in remaining 1. Unilateral circumscribed loss of inner hair cells was noticed at lower part of the hook in the latter one. Vestibular hair cell loss was scattered and less extensive and occurred in 4 of the 6 50 mg/kg given animals and in 7 of the 9 100 mg/kg ones. Comparison in incidence and extension of the outer hair cell loss of the cochlea (Tables 3, 4) in the present study and previous ones on the ototoxic effect of MCR in intramuscular and intravenous administration suggests that there was no distinct difference in enhancement of the ototoxic effect in the intravenous drip administration.

Aminoglycosides↗
PubMed1985

[Breast cancer and hematological malignancy in the same patients].

Ten women with breast cancer and hematological malignancy (nine with double malignancy and one with triple malignancy) were analyzed. Mastectomy was performed on all patients in our hospital between July 1959 and June 1982 (23 years). Diagnoses of hematological malignancy were seven acute leukemias (five AML, two AMMoL), one CML, two lymphomas and one myeloma. Irradiation and chemotherapy were postoperative treatments in eight and three patients, respectively. The median interval between the first diagnosis and the second was four years and 10 months (one year and five months to 21 years and seven months). The median survival time from the first diagnosis was five years and eight months, while that from the second was six and a half months. In a clinical setting, it is difficult to ascertain the causative factors of multiple malignancy. Accumulation of additional patients is needed for further analysis.

Adult↗
PubMed1985

[A combination chemotherapy using mitomycin C, vincristine and cisplatin (MVP) for advanced cervical cancer].

Nine patients with advanced cervical cancer were treated with a combination chemotherapy (MVP) consisting of mitomycin C 8 mg/m2 i.v. days 1 and 8, vincristine 1 mg/m2 i.v. days 1 and 8, and cisplatin 15 mg/m2 i.v. days 1 to 5. The regimen was repeated at 4-week intervals. Of nine patients with measurable metastatic disease, there was 1 complete response (CR), 4 partial responses (PR), and 4 with no change, with an overall response rate (CR + PR) of 56% (5/9). The median duration of responses was 6 months, ranging from 1.8 to 9.1 months. The median survival time from initiation of the chemotherapy was 11 months for responders, and 15+ months for non-responders, respectively. Patients with no prior chemotherapy had a 60% (3/5) response rate and 2 patients out of 4 who had received prior chemotherapy responded; furthermore, metastatic lesions in extrapelvic regions (lung) responded well. Leukopenia less than 3,000/mm3 occurred in 68% of cases and the median nadir was 1,900/mm3 (700-2900). Thrombocytopenia less than 10 X 10/mm3 occurred in 37% of cases and the median nadir was 5.15 X 10/mm3 (3.2-9.0). Non-hematological toxicities were nausea and vomiting, renal dysfunction and peripheral neuropathy, but these were reversible and tolerable.

Adenocarcinoma↗
PubMed1985

[A case of renal cell carcinoma developing from a dysplastic kidney].

A case of renal cell carcinoma developing from a unilateral dysplastic kidney is reported. A 33-year-old woman was admitted to our hospital because of lumbago due to metastatic cancer to the bones. She was treated with interferon and combination chemotherapies, but died nine and a half months after initiation of the therapy. Autopsy revealed a widely metastasized renal cell carcinoma originating from a dysplastic left kidney. This is the second such case in the literature. Clinical management of renal dysplasia should take into consideration the possibility of developing malignancy.

Adult↗
PubMed1984

Glycosylation of a receptor specific for asialoglycoproteins in rat liver.

Glycosylation of a rat receptor specific for asialoglycoproteins was investigated in vivo by using monospecific antibody. After intravenous injection of [3H]mannose, the receptor protein was immunoprecipitated from various subcellular fractions and the glycopeptide and oligosaccharide chains of the protein were prepared by treatment with pronase and endo-beta-N-acetylglucosaminidase H. The glycopeptides thus prepared from the rough and smooth microsomes and Golgi heavy fraction (GF3) were all sensitive to endo H and most of the endo H-sensitive oligosaccharides were eluted at the position considered to correspond to Man8GlcNAc on high-resolution Bio-Gel chromatography. Endo H-resistant forms were first detected in the Golgi intermediate fraction (GF2) and significantly in the light Golgi fraction (GF1), suggesting the formation of the complex-type oligosaccharide chains in the latter fraction. This view was also supported by the almost exclusive addition of the terminal sugars such as N-acetylglucosamine, galactose, and sialic acid in GF1. These results suggest that the major form of the oligosaccharide chains from the endoplasmic reticulum to the Golgi apparatus is Man8GlcNAc2 and that the processing of these large mannosyloligosaccharide chains and subsequent addition of terminal sugars to them are performed successively in the trans-Golgi region.

Animals↗
PubMed1984

Topology of asialoglycoprotein receptor in rat liver subcellular fractions: a ferritin immunoelectron microscopic study.

Direct ferritin immunoelectron microscopy was used to visualize the asialoglycoprotein receptor in various rat liver subcellular fractions. The cytoplasmic surfaces of cytoplasmic organelles such as the rough and smooth microsomes, Golgi cisternae and lysosomes showed hardly any ferritin label exception for the slight labeling of secretory granules found mainly in the light Golgi fraction (GF1). Occasionally, however, open membrane sheet structures, smooth vesicular or tubular structures heavily labeled with ferritin, were present in all these subcellular fractions. These structures probably correspond to fragmented sinusoidal or lateral hepatocyte plasma membranes recovered to these subcellular fractions. When the limiting membranes of the secretion granules were partially broken by mechanical force, a number of ferritin particles frequently were seen attached in large clusters to the luminal surface of the membrane, the cytoplasmic surface of the corresponding domain being slightly labeled. These observations are strong evidence that the receptor protein is never translocated vertically throughout the intracellular transport from ER to plasma membrane via Golgi apparatus and from plasma membrane back to trans-Golgi elements and also in lysosomes, always exposing the major antigenic sites to the luminal or extracellular surface and the minor counterparts to the cytoplasmic surface of the membranes. The receptor protein also is suggested to be concentrated in clusters on the luminal surface of secretion granules when they form on the trans-side of the Golgi apparatus.

Animals↗
PubMed1984

Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma.

The pathogenesis of hyperasialoglycoproteinemia in cirrhosis and liver cell carcinoma was investigated by measuring the amount of asialoglycoprotein receptor in hepatic tissues from 30 patients with either cirrhosis or a malignancy. The asialoglycoprotein receptor activity in the cirrhotic liver was 770 +/- 423 U/g liver, i.e., 28% of the control value (2770 +/- 731 U/g liver). Receptor activity was negligible in tissues from patients with either liver cell carcinoma or metastatic tumor. The receptor levels in noncirrhotic and cirrhotic tissues in close proximity to liver cell carcinoma were 2281 +/- 659 and 1134 +/- 473 U/g liver, respectively. There was a close correlation between serum asialoglycoprotein levels and the size of the tumor mass in patients with liver cell carcinoma. Our results suggest that decreases in the asialoglycoprotein receptor levels may lead to an accumulation of serum asialoglycoproteins in patients with cirrhosis or liver cell carcinoma, or both.

Asialoglycoprotein Receptor↗