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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 541 records · Page 30Linked to original sources
PubMed1991

On the transforming growth factor beta-like activity of synthetic polypeptides comprising the amino-terminal sequence of human parathyroid hormone-related peptide.

Purified native forms of human parathyroid hormone-related peptide (PTHrp) have recently been reported to display biological activities characteristic of transforming growth factor beta (TGF-beta). The TGF-beta-like property of PTHrp may reside within the amino N-terminal PTH-receptor binding region of the polypeptide, since a synthetic analog corresponding to amino acids 1-36 of human PTHrp is as active as purified native PTHrp in bioassays specific to TGF-beta. Complete lack of structural similarity between PTHrp and TGF-beta prompted us to address the question whether copresence of the TGF-beta-like and PTH-like biological activities in the N-terminal sequence of the PTHrp molecule is a general phenomenon observable with different N-terminal PTHrp peptides of varying amino acid chain length in a variety of target cells that respond in defined ways to TGF-beta in vitro. Two forms of synthetic N-terminal human PTHrp, PTHrp-(1-34) and [Tyr40]PTHrp-(1-40), which are fully active in conventional assays for PTH/PTHrp, were tested for effects in three in vitro bioassay systems for TGF-beta: 1) stimulation, and 2) inhibition, respectively, of epidermal growth factor-dependent soft-agar colony formation of either normal rat kidney-derived fibroblasts (NRK 49F) or human lung carcinoma cells (A549); and 3) biosynthesis of metabolically labeled fibronectin in both NRK 49F cells and clonal osteoblastic rat osteosarcoma cells (ROS 17/2.8). Human TGF-beta over the dose range of 2.5-80 pM significantly stimulated or inhibited soft-agar colony formation of either NRK 49F or A549 cells, respectively, and caused a severalfold increase in biosynthetically labeled [35S]fibronectin in NRK 49F and ROS 17/2.8 cells. In contrast, none of PTHrp-(1-34), [Tyr40]PTHrp-(1-40), and synthetic human PTH-(1-34), each tested at 0.1-10 nM, displayed detectable biological activity in any of the three assay systems. In addition, covalent cross-linking of intact NRK 49F and ROS 17/2.8 cells with either [125I]TGF-beta or 125I-[Tyr40] PTHrp-(1-40) revealed the presence of several distinct affinity-labeled receptor species for TGF-beta in both cell types and the 80K PTH/PTHrp receptors in ROS 17/2.8 cells. The affinity-labeled TGF-beta receptor species were insensitive to excess PTHrp and PTH peptides, and the 80K PTH/PTHrp receptors were insensitive to excess TGF-beta, indicating that PTHrp and TGF-beta do not cross-react with respect to receptor binding for interaction with these cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Affinity Labels↗
PubMed1991

Possibility of heat sterilization of liposomes.

Several kinds of liposomes were sterilized at 121 degrees C for 20 min. They tended to aggregate after heat sterilization (HS) in saline, while no aggregation was observed in an isotonized sugar or polyol solution. The dispersions containing egg phosphatidylcholine (EggPC) with a high peroxide value (POV) turned slightly yellowish after HS. This color change was prevented by using EggPC with a low POV, hydrogenated EggPC (H-EggPC) or dipalmitoylphosphatidylcholine (DPPC). Nitrogen gas bubbling at neutral pH also prevented the color change, but vitamin E did not. The particle size of the EggPC liposomes extruded through a 0.4 micron membrane filter did not change significantly after HS, whereas the H-EggPC or DPPC liposomes extruded through a 0.8 micron membrane filter tended to be reduced in size. On this change the type of medium had a considerable influence. The anionic 6-carboxyfluorescein leaked from the negatively charged liposomes (EggPC/cholesterol (Chol)/egg phosphatidylglycerol) during HS, while no leakage was observed from the positively charged liposomes (EggPC/Chol/stearylamine) not only during HS but also during a long period of storage. It was suggested that sterilization of liposomes by heating was practicable as well as that by filtration, if the liposomes were prepared as follows: the charged liposomes made of lipids with low POV's were dispersed in a sugar or polyol solution adjusted to nearly pH 6.5, where the amount of dissolved oxygen was minimized. An ionic water-soluble drug had to be encapsulated in the oppositely charged liposomes.

Color↗
PubMed1991

Hemodynamic study of posterior circulation using hydraulic vascular model--critical stenosis of the vertebrobasilar artery and tolerance to occlusion therapy.

A hydraulic vascular model with glass and silicone tubes of the intracranial portion of the vertebro-basilar artery was used to determine the critical stenosis causing vertebrobasilar insufficiency, and the minimum diameter of the posterior communicating arteries (PComAs) necessary to tolerate therapeutic vertebrobasilar occlusion for unclippable aneurysms. The critical stenosis of one vertebral artery (VA) or basilar artery (BA) differed greatly depending upon the anatomical variations of the PComA and the posterior cerebral artery (PCA): 1.14 mm diameter when the artery supplies 80 ml/min to the cerebellum and brainstem only, 1.33 mm when 140 ml/min to these structures and one PCA, and 1.56 mm when 200 ml/min to these structures and both PCAs. The minimum PComA diameter to tolerate therapeutic occlusion depended largely upon the occlusion site: one PComA with 1.54 mm diameter for bilateral VA occlusion and 1.25 mm for BA occlusion distal to the branching of the superior cerebellar arteries. The total volume of collateral flow through both PComAs can be estimated by summing the squares of the diameters. These values cannot be applied rigidly to clinical cases, but are useful standards to evaluate the stenotic lesion or tolerance to occlusion.

Blood Flow Velocity↗
PubMed1991

Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats.

Cerebral arterial bifurcations in rats were treated to induce cerebral aneurysms experimentally, and flow patterns of latex particles introduced under a constant flow rate were analyzed with a 16-mm cine-camera and videocassette recorder. Cerebral aneurysms were produced by ligating one common carotid artery, inducing experimental hypertension, and feeding the animals beta-aminopropionitrile. After perfusion and fixation, samples of cerebral arterial bifurcations with shallow invaginations and with small aneurysms were obtained and used for analysis. Bifurcations in rats without experimental treatment were used as control specimens. Flow studies in the control bifurcations showed that the apical intimal pad, not the apex itself, acted as the flow divider. Small particles tended to accumulate at the region just distal to the apical intimal pad, where the initial aneurysmal changes are known to occur. This indicates stagnation of flow at that site. In the bifurcations with shallow invaginations and small aneurysms, a marked pressure gradient was present at the proximal end of the aneurysm orifice. A tendency for stagnation of small particles near the aneurysm wall was also observed. The wall shear stress was highest at the distal end of the aneurysmal orifice, which may be responsible for the development of these lesions.

Animals↗
PubMed1991

Possible roles of basic fibroblast growth factor in the pathogenesis of moyamoya disease: an immunohistochemical study.

Prominent features of moyamoya disease are fibrocellular thickening of the intima and enhanced angiogenesis. The pathogenesis of moyamoya disease is, however, unknown. Basic fibroblast growth factor (FGF) is an angiogenic factor as well as a potent mitogen for a number of cell types including vascular endothelial and smooth-muscle cells. In order to test the possibility that basic FGF takes part in the pathogenesis of moyamoya disease, the authors tested for the presence of this factor using a mouse monoclonal antibody against human recombinant basic FGF. The surgical specimens studied included two sections of the superficial temporal artery (STA) and four samples of dura mater from four patients with moyamoya disease. Surgical specimens were obtained from three patients with other diseases as control tissue. Sections of the STA obtained from the patients with moyamoya disease showed strong basic FGF immunoreactivity in endothelial and smooth-muscle cells, while control sections had only faint and scattered immunoreactivity. All sections of the dura mater obtained from the patients with moyamoya disease also revealed more intense immunohistochemical staining of basic FGF in meningeal and vascular cells than did control sections. These observations indicate that the amount of basic FGF is increased in the tissues of patients with moyamoya disease; thus, basic FGF may play an important role in the pathogenesis of moyamoya disease.

Adult↗
PubMed1991

[Immunomodulatory effects of interferons on target human gliosarcoma cells in the tumor-specific CTL- and LAK-mediated cytolysis].

We compared the regulatory effects of interferon (IFN)-beta and IFN-gamma on the susceptibility of a human gliosarcoma line GI-1 to the attack of autologous cloned tumor-specific cytotoxic T-lymphocytes (CTL) and lymphokine-activated killer (LAK) cells. Preincubation of GI-1 cells with IFN-gamma caused augmented susceptibility to the cytotoxic attack of two autologous CTL clones, whereas IFN-beta exhibited no such marked effect. On the other hand, preincubation with either IFN-beta or IFN-gamma made the GI-1 cells resistant to the attack of autologous LAK cells. Both IFNs augmented the surface expression of HLA class-I molecules on GI-1 cells. A monoclonal anti-HLA class-I antibody blocked the cytolysis by one CTL clone, but not by the other one. These results suggest that IFN-gamma exerts some different effect (s) from that of IFN-beta on the target GI-1 cells in their susceptibility to the CTL-mediated cytolysis, and that recognition mechanisms of target cells by the CTL are different from those by LAK cells. This draws our attention to IFN administration in adoptive immunotherapy against brain tumors using CTLs and LAK cells.

Brain Neoplasms↗
PubMed1991

[Changes in cerebral energy and calcium metabolisms on focal cerebral ischemia].

Changes of brain tissue calcium in the focal ischemia model of Wistar rat were investigated by three different methods; atomic absorption spectrophotometer, calcium stain with alizarin red S, and new histochemical method using aequorin, a calcium ion sensitive photoprotein. Tissue pH and tissue ATP were concomitantly investigated by histochemical method. Rat brain was frozen in situ at 15, 60 or 240 minutes after left middle cerebral artery was occluded. Coronal brain sections of 16 microns thickness was made and the brain slices applied for calcium stain and histochemical studies. The residual brain block was applied for atomic absorption spectrophotometric study. Tissue calcium content of left hemisphere increased from 1.34 +/- 0.09 (mean +/- SEM) (n = 7) to 1. 54 +/- 0.16 (n = 12), 2.07 +/- 0.12 (n = 9). 1.69 +/- 0.11 (n = 10) mumol/g wet weight after 15, 60 and 240 minutes respectively. Calcium stain with alizarin red S showed that the increase of calcium was observed in the peripheral part of the ischemic lesion where ATP was left in a spotty fashion, and calcium deposits disappeared with correspondence to exhaustion of ATP. Tissue calcium ion content studied by newly histochemical method, showed heterogeneous change. At an early stage of the ischemia, the increase of tissue calcium ion was shown only in the peripheral part of the ischemic lesion, and it gradually extended to the central part. Calcium ion increased in density in an area corresponding to that of the ATP decrease. Within the area of calcium ion increase, regional differences were noted; a greater increase at the border with the intact area and in the parts where ATP was heterogeneously preserved. In the non-ischemic area close to the ischemic area, where ATP was preserved with mild acidosis, calcium ion decreased more than in the surrounding area where ATP was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Effects of several volatile anesthetics on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pig.

The effects of various volatile anesthetics on intramuscular Ca(2+)-related functions were studied with the skinned fiber technique in guinea pig skeletal muscles. All the volatile anesthetics tested significantly enhanced Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) at clinical concentrations with negligible effects both on Ca2+ sensitivity of the contractile system and on Ca2+ uptake by the SR. A comparison was made of the enhancing effect of several volatile anesthetics on CICR at clinical concentrations. Halothane was the most potent, followed by methoxyflurane, isoflurane, enflurane, sevoflurane and diethyl ether. If CICR plays an important role in triggering MH, this order of volatile anesthetics on their enhancing effect on CICR, also corresponds to their potency in triggering MH.

Anesthetics↗
PubMed1991

[Left atrial myxoma with cerebral oncotic aneurysms with special reference to the importance of serial angiography].

A case of atrial myxoma with cerebral oncotic aneurysms was presented. A 37 year-old woman was admitted complaining of right hemiparesis, and episodes of syncope. Neurological examination on admission revealed a right arm monoparesis, a right hemisensory disturbance, and a motor aphasia. Computed tomography (CT) demonstrated low density areas in the left fronto-parietal region, and multiple discrete enhancing high density spots scattered bilaterally in the parietal lobes. Cerebral angiography showed multiple fusiform peripheral aneurysms especially in the distribution of the bilateral middle cerebral arteries. Cerebral emboli from the cardiac source were suspected, and an echocardiography was performed, which disclosed a huge villous mass in the left atrium. The cardiac mass was resected uneventfully under cardiopulmonary bypass. It proved to be a left atrial myxoma. Postoperatively, her neurological deficit persisted. After the resection of the cardiac tumor, follow-up angiographies were undertaken twice. The second angiography performed 6 months later revealed spontaneous resolution or stabilization of most of the aneurysms detected before. On the other hand, newly-developed aneurysms were seen at the sites which had seemed normal previously on the first angiography. No remarkable changes were seen on the third one except the slight enlargement of one of the aneurysms in the middle cerebral territory. At 3 years she was neurologically stable. Because of the paucity of knowledge concerning the natural history of cerebral oncotic aneurysms and lack of definite treatment for them, long-term follow-up including serial angiography is mandatory after the resection of left atrial myxoma.

Adult↗
PubMed1991

[Successful reinduction of complete remission in a patient with ALL associated with multiple liver abscesses who relapsed after 6 years].

We reported on a 35 year-old patient suffering from ALL with multiple liver abscesses (Journal of Kyusyu Hematological Society, Vol. 31, No. 3 & 4, Dec., 1983). He experienced six years of complete hematological remission from 1983 to 1989, with low fever, positive CRP, polyclonal gamma-globulinemia and elevated alkaline phosphatase. A relapse occurred in June of 1989. A subsequent biopsy revealed fibrosis of the liver attributed to inflammation. At present, he has returned to the complete remission stage with no exacerbation of the liver abscesses.

Adult↗
PubMed1990

Increase of tyrosine hydroxylase-like immunoreactive neurons in the nucleus accumbens and the olfactory bulb in the rat with the lesion in the ventral tegmental area of the midbrain.

A small number of neurons in the nucleus accumbens of the rat showed tyrosine hydroxylase-like immunoreactivity (TH-LI). These TH-LI neurons had medium-sized cell bodies with several spiny dendrites. When a lesion was produced in the ventral tegmental area of the midbrain by injecting 6-hydroxydopamine, TH-LI neurons in the nucleus accumbens, as well as those in the olfactory bulb, were increased in number on the side ipsilateral to the lesion. The results indicated that expression of TH might be enhanced in some neurons deprived of dopaminergic afferent fibers.

Animals↗
PubMed1990

Origins and distribution of cerebrovascular nerve fibers showing calcitonin gene-related peptide-like immunoreactivity in the major cerebral artery of the dog.

The origins and overall distribution of perivascular nerve fibers showing calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in the major cerebral arteries were investigated immunohistochemically in the dog by using whole-mount preparations of the arterial trees around the circle of Willis. Perivascular nerve fibers with CGRP-LI were seen most abundantly in the basilar artery, vertebral artery, common anterior cerebral artery, proximal part of the anterior cerebral artery, and terminal part of the internal carotid artery. They were far less numerous in the middle cerebral artery, posterior cerebral artery, superior cerebellar artery, and distal part of the anterior cerebral artery. Neuronal cell bodies with CGRP-LI were observed in the trigeminal, nodose, superior cervical, and dorsal root ganglia. CGRP-LI fibers in the large pial arteries in the circle of Willis were eliminated ipsilaterally after unilateral transection of the ophthalmic division of the trigeminal nerve, and slightly reduced in number ipsilaterally after unilateral transection of the maxillary division of the trigeminal nerve. They did not show any noticeable changes after unilateral transection of the mandibular division of the trigeminal nerve. On the other hand, CGRP-LI fibers in the basilar and vertebral arteries did not show any appreciable changes after unilateral transection of the trigeminal nerve, but they were eliminated after bilateral ganglionectomy of the dorsal root ganglia of the first, second, and third cervical nerves. After ganglionectomy of the ciliary, pterygopalatine, otic, nodose, or superior cervical ganglion, no changes were observed in perivascular nerve fibers with CGRP-LI in the major cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Regional changes of tissue pH and ATP content in rat brain following systemic administration of kainic acid.

Regional metabolic alterations induced by systemic administration of kainic acid were investigated in rat brains. The histochemical study revealed that an acidic pH shift preceded an ATP decrease in the limbic structures. In the hippocampal Ammon's horn, it was noted that a selective decrease of ATP occurred in the dendritic subfield, such as the stratum radiatum and/or the stratum oriens. It was suggested that this selective ATP decrease in the dendrite is directly related to kainate neurotoxicity.

Adenosine Triphosphate↗
PubMed1990

Infiltrative and cytolytic activities of lymphokine-activated killer cells against a human glioma spheroid model.

In the present study, we investigated not only the cytotoxic effects of lymphokine-activated killer (LAK) cells on a tumor mass but also the ultrastructural cell-to-cell interaction between LAK effector cells and tumor cells during the cytolytic process within a three-dimensional solid tumor. A multicellular tumor spheroid of a human glioma cell line (U-251MG) was utilized as a solid tumor model. LAK cells were generated from peripheral blood lymphocytes of a healthy donor after stimulation by interleukin 2. Multicellular tumor spheroids with diameters of 500 microns were cocultivated with either LAK cells or nonactivated peripheral blood lymphocytes at the effector:target cell ratio of 20:1, and then time-sequential kinetic, morphological, and ultrastructural analyses were carried out. Morphological and kinetic studies showed that LAK cells directly infiltrated toward the inner areas of multicellular tumor spheroids and caused a progressive tumor destruction. In contrast, peripheral blood lymphocytes hardly exhibited such activities. Ultrastructurally, it was found that the infiltrating LAK effector cells were composed of heterogeneous subpopulations, T-like cells, and large granular lymphocyte-like cells. Both types of lymphocytes tightly adhered to the tumor cells and showed typical morphological features of killing them.

Cell Line↗