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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 739 records · Page 41Linked to original sources

Functional supersensitivity of alpha 1-adrenergic system in spinal ventral horn is due to absence of an uptake system and not to postsynaptic change.

The excitatory effects of adrenoceptor agonists on ventral horn cells were compared using an extracellular recording technique in spinal cord slices isolated from non-treated and 6-hydroxydopamine (6-OHDA)-treated rats (intracisternally 14 days previously). In spinal cord slices isolated from 6-OHDA-treated rats, the concentration-response curves for the alpha 1-adrenoceptor-mediated facilitatory effects produced by noradrenaline and phenylephrine but not those produced by methoxamine and isoproterenol were shifted to the left. 6-OHDA pretreatment decreased the level and uptake of noradrenaline and increased the number of [3H]prazosin binding sites in the spinal cord. These results suggest that in 6-OHDA-induced denervation, functional supersensitivity of the alpha 1-adrenergic system in the spinal ventral horn is due to absence of an uptake system, and not to postsynaptic change.

Animals↗

Long-term cultivation of anchorage-independent animal cells immobilized within reticulated biomass support particles in a circulating bed fermentor.

Long-term cultivation of anchorage-independent animal cells immobilized within porous biomass support particles (BSPs) using a gas-stirred circulating bed fermentor (CBF) was investigated. Inoculation of mouse myeloma MPC-11 (ATCC CCL 167) cells into reticulated polyvinyl formal resin BSPs (3 x 3 x 3 mm; mean pore diameter, 60 microns; porosity, 0.88) and the repeated batch culture of inoculated cells were performed under gentle circulation of BSPs, induced by sparging air from the base of the fermentor. The glucose uptake rate of cells decreased in the initial period just after the start of circulation, since a relatively large number of cells leaked from the BSPs. After that period, the uptake rate gradually increased and the leakage of cells diminished. In the meantime, when inoculated cells were incubated statically by introducing air into days before circulating the BSPs, glucose consumption became very rapid and cell density in the BSPs reached at least 10(7) cells/cm3 BSP. Thus, a long-term cultivation without significant leakage of cells and with high cell density in BSPs was successfully achieved in the CBF-BSP system.

Animals↗

Midbrain stimulation inhibits the micturition, defecation and rhythmic straining reflexes elicited by activation of sacral vesical and rectal afferents in the dog.

Inhibition of the micturition, defecation and rhythmic straining reflexes by midbrain stimulation was compared with the inhibition of the jaw-opening reflex caused by tooth pulp stimulation in decerebrate dogs. All of the reflexes were inhibited by stimulation of the dorsal and ventral periaqueductal gray, dorsal raphe nucleus and central tegmental field with similar threshold intensities. After a hemisection of the spinal cord at the C2 segment, the midbrain stimulation still suppressed the micturition reflex as well as field potential changes which were evoked by stimulation of the pelvic nerve and recorded from the lateral funiculus just caudal to the hemisection, but did not influence the discharges of the vesical branch of the pelvic nerve which were elicited by stimulation of the lateral funiculus just rostral to the hemisection. The results suggest that stimulation of the neural elements in the 4 midbrain areas depresses the ascending activities from vesical and colorectal afferents of the pelvic nerve at the spinal level, and consequently inhibits the pelvic nerve reflexes. Systemic methysergide suppressed midbrain inhibition of the jaw-opening reflex, but did not affect the midbrain inhibition of the pelvic nerve reflexes. Systemic naloxone did not influence midbrain inhibition of the pelvic nerve reflexes or the jaw-opening reflex, but enhanced the micturition and rhythmic straining reflexes. Possible roles of the midbrain inhibition of the pelvic nerve reflexes are discussed.

Analgesia↗

Functional analysis of cis-elements, auxin response and early developmental profiles of the mannopine synthase bidirectional promoter.

The dual MAS1'-2' promoter regulating two divergently transcribed mannopine synthase genes has been widely employed in plant expression vectors. As part of an effort towards its rational design as a genetic engineering tool, we have undertaken a functional analysis of the promoter by deletion mutagenesis and by the use of hybrid promoter constructs. Our results indicate that the central region of the intergenic promoter is composed of at least four domains. Three of these contain complementary sequences, which can potentially hybridize to form alternative palindromic structures. These three domains can function cooperatively, and in an orientation-independent manner, in imparting a sevenfold higher expression level at the 2' end relative to the corresponding 1'. The remaining domain is characterized by tracts of repeated A/T-rich elements, and appears to confer the weak activity at the MAS1' promoter end. However, even though this A/T-rich DNA segment is functional, our deletion analysis provided strong evidence that it is completely dispensable for wild-type promoter activity. In addition, the relative distances between these enhancer domains and the 1'-2' TATA-proximal regions can have a pronounced influence on the level of expression in both directions. In young tobacco seedlings, the two promoter ends are expressed in similar, if not identical, tissues in the aerial parts of the plants, but major differences can be observed in roots. Transient expression assays using hybrid promoter constructs showed that cis-elements that can respond to auxin induction signals are redundant in nature, in that they are dispersed throughout the promoter and showed no obvious consensus sequence.

2,4-Dichlorophenoxyacetic Acid↗

Age-related changes in human D1 dopamine receptors measured by positron emission tomography.

The effects of age on the binding parameters of 11C-SCH23390, the highly selective ligand for central D1 dopamine receptors, at specific binding sites in the brain were studied. Seventeen healthy male volunteers (20-72 years old) participated. Regional radioactivity in the brain was followed for 40 min by positron emission tomography (PET). A high accumulation of radioactivity was observed in the striatum and there was a conspicuous accumulation in the neocortex. A two-compartment model was used to obtain quantitative estimates of rate constants of association (K3) and dissociation (k4). The binding potential (k3/k4) of the dopamine D1 receptors in the striatum and frontal cortex decreased by 35% and 39%, respectively, with age. The value of k3 decreased by 58% in the striatum and 83% in the frontal cortex, whereas the value of k4 decreased by 35% in the striatum and 72% in the frontal cortex with age.

Adult↗

Quantitative measurement of uptake of radiolabeled monoclonal antibody by means of planar data.

Data obtained from planar images were used to measure the uptake of monoclonal antibody in organs and tumors. Background counts included in the region of interest were eliminated, and the attenuation of the photons emitted by the radionuclide through the intervening tissues was compensated for. The background counts and the intensity of the attenuation were determined from the results of phantom studies and numerical integration with a personal computer. The quantitative uptake of 111In labeled anti-melanoma Monoclonal Antibody (ZME-018) in a melanoma lesion, the liver, and the bone marrow of a patient was measured by the planar method which we developed.

Antibodies, Monoclonal↗

An arterialised venous flap using the long saphenous vein.

Free arterialised venous flaps and an arterialised osteocutaneous venous flap, fed by an arterialised long saphenous vein, were used successfully in three cases. This flap has a larger skin territory than those previously reported and the incorporation of bone into such a flap has not been reported before.

Aged↗

Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists.

Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the cord tissue to 10 microM clonidine and tizanidine significantly reduced the release of substance P. The inhibitory effects of clonidine and tizanidine were attenuated by pre-exposure of the tissue to 10 microM piperoxane, which has alpha 2-antagonistic activity and the inhibitory effect of clonidine was attenuated by 10 microM yohimbine. Moreover, the inhibitory effects of clonidine and tizanidine were also blocked by a small dose of prazosin, an antagonist for alpha 1- and alpha 2B-receptors. None of the antagonists had any effect on release of substance P, when given alone. These results suggest that alpha 2B-adrenoceptors are involved in the inhibitory effects of clonidine and tizanidine on the release of substance P.

Adrenergic alpha-Antagonists↗

Quantitative in vivo analysis of benzodiazepine binding sites in the human brain using positron emission tomography.

Central-type benzodiazepine binding sites were characterized in a single normal human subject, using positron emission tomography (PET) and the radiolabelled benzodiazepine antagonist, carbon-11 labelled flumazenil ([11C] Ro 15-1788). The subject was scanned using tracer alone and tracer plus 4 different concentrations of unlabelled Ro 15-1788, including one concentration of unlabelled Ro 15-1788, chosen to produce maximum displacement of [11C] Ro 15-1788 from specific binding sites. Concentrations of free, unmetabolized [11C] Ro 15-1788 in plasma were estimated using a simple extraction and ultrafiltration method. Radioactivity in the regional exchangeable pool in brain was estimated under non-saturation conditions from the ratio of radioactivity in brain to plasma, under saturation conditions and the kinetics of free ligand in plasma. The specific binding was, then, estimated by the difference between the total radioactivity in brain and exchangeable pool radioactivity. Scatchard analyses were performed to yield Bmax and Kd values under pseudo-equilibrium conditions, which was observed as an increase of specific binding/free with reduction in specific binding. In cerebral cortex and cerebellum, the Bmax values were about 62-73 nmol/l and the Kd values were 3.6-6 nM in the estimation of free ligand in plasma and 12-15 nM in the estimation of exchangeable pool in brain, as free in brain.

Adult↗

Relationship between sialographic findings of parotid glands and histopathologic finding of labial glands in Sjögren's syndrome. Relation to clinical and immunologic findings.

We investigated a relationship between sialographic findings of parotid glands and histopathologic changes of labial glands, in relation to Sjögren's syndrome. We examined 107 patients, suspected to have Sjögren's syndrome because of dry mouth and dry eyes, in whom no other autoimmune diseases were diagnosed. Parotid sialography identified 37 patients with punctate, globular, cavitary, or destructive sialectasia (S-positive group). These sialographic findings were not seen in the other 70 patients (S-negative group). Among these patients, 54 demonstrated periductal lymphocytic infiltration in the labial glands (H-positive group), whereas the other 53 patients did not demonstrate this histologic finding (H-negative group). Significant differences in stimulated parotid salivary flow rate and incidence of keratoconjunctivitis sicca were observed between patients in the S-positive and the S-negative groups. Differences in the salivary flow rate and the incidence of keratoconjunctivitis sicca were also seen between patients in the H-positive and the H-negative groups, although the differences were not statistically significant. The rate of incidence of serum rheumatoid factor, anti-SS-A, and anti-SS-B antibodies were significantly higher in the S-positive and the H-positive groups than in their negative counterparts.

Antibodies, Antinuclear↗

Periductal lymphocytic infiltration of salivary glands in Sjögren's syndrome with relation to clinical and immunologic findings.

We studied 113 patients who were suspected to have Sjögren's syndrome (SS) because they had dry mouth and dry eyes, and who were determined as not having any other autoimmune disease, to clarify the relationship of periductal lymphocytic infiltration of salivary glands to clinical and immunologic findings in relation to SS. Periductal lymphocytic infiltrations were observed in the labial and/or the parotid glands of 57 patients (P-group). The salivary glands of the other 56 patients did not demonstrate obvious histologic changes (N-group). The stimulated salivary flow rate of parotid glands of the patients in both the P- and N-groups was significantly reduced when compared with healthy persons. However, no difference in the flow rate was observed between the P- and N-groups. In contrast, the percentage of patients in the P-group with keratoconjunctivitis sicca was significantly higher than that of patients in the N-group. Percentage of gamma-globulin fraction and IgG level in the sera of the patients in the P-group were both significantly higher than those in the N-group. The percentages of patients who demonstrated the serum rheumatoid factor, anti-SS-A, and anti-SS-B antibodies were also significantly higher in the P-group than in the N-group.

Antibodies, Antinuclear↗

Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin's lymphoma.

We have assessed levels of surface-expressed complement regulatory proteins, decay-accelerating factor (DAF) and membrane cofactor protein (MCP) on cells from patients with hematological malignancies. Neither malignant cells nor unaffected nucleated blood cells from the patients lacked MCP. On the other hand, complete deficiency of DAF was found in 2/10 of non-Hodgkin's lymphoma (NHL), while none of the 38 patients with acute nonlymphocytic leukemia (ANLL) (14 cases), chronic myelogenous leukemia (CML) (6 cases), acute lymphocytic leukemia (ALL) (12 cases) and chronic lymphocytic leukemia (CLL) (6 cases) lacked DAF. The two patients with DAF-negative NHL had no history of paroxysmal nocturnal hemoglobinuria (PNH), and their peripheral blood cells were DAF-positive. One DAF-negative NHL exhibited T cell markers and the other those of B cell. In both cases, treatment of the DAF-negative lymphoma cells with antibody against MCP (M177) followed by Mg(2+)-EGTA-serum resulted in efficient deposition of homologous C3. These results infer that some NHL specifically lack DAF and, through treatment with M177, are targeted by homologous C3.

Antibodies, Monoclonal↗

Study of biodistribution of enflurane in rats with in vivo 19F MRI.

In vivo 19F magnetic resonance imaging (MRI) of anesthetized rats enabled us to visualize the biodistribution of fluorinated anesthetics and to document the changes in MR signals in the body during the induction and the elimination phase of anesthesia. The authors examined in vivo 19F MRI in rats anesthetized with concentrations of 1.75-2.0% enflurane and demonstrated its in vivo distribution with concomitant 1H and 13C MRI to verify the anatomical correlation. Distinct 19F MR signals were acquired predominantly from the systemic adipose tissue and the liver. Additionally, the temporal changes in the tissue during and after anesthesia were characterized with in vivo 19F MRI in 6.4 min of the acquisition time. The 19F MR signals increased with time after anesthesia; however, the signals from the adipose tissue were apparently stronger than those from the liver. Following the discontinuation of inhalation, the MR signals in the liver decreased far more rapidly than those from the adipose tissue. When the animal woke up and began to move, the MR signals were still visible in the adipose tissue. These results confirmed the fact that enflurane dissolves preferentially in the adipose tissue and remains when the anesthetic effect disappears. Additionally, 19F MR signals of the liver during the elimination phase might reflect the concentration of enflurane in the blood.

Abdomen↗

Potential radiopharmaceuticals labeled with titanium-45.

The potential of some compounds labeled with cyclotron-produced titanium-45 (45Ti) as radiopharmaceuticals was studied. Properties of colloid formation of 45TiOCl2 or 45TiO-phytate in vivo resulted in the highest radioactivity uptake in the rat liver, followed by the spleen, suggesting potential for imaging the reticuloendothelial system. Three 45TiO-complexes with diethylenetriaminepentaacetic acid, citric acid and human serum albumin showed the highest radioactivity levels in the blood over 6 h. The binding of the 45Ti with plasma transferrin in vitro and in vivo suggested that these compounds can be used for estimating the blood volume. Also, potential as an indicator representing the breakdown of the blood-brain barrier in the rat was demonstrated by autoradiography.

Animals↗

The Bötzinger complex as the pattern generator for retching and vomiting in the dog.

To clarify the location of the pattern generator for the emetic act, the bulb was systematically stimulated and partially cut in decerebrate, paralyzed dogs. Stimulation of the following bulbar structures elicited the activities which could be recognized as retching and vomiting in the following muscle nerves. The bulbar structures were: the intra-bulbar bundle of the vagal afferents, the solitary tract and the medial subdivision of its nucleus (NTS), the area postrema, the commissural nucleus, the raphe area at the obex level, and the longitudinal reticular column which consists of 3 areas--the area between the caudal parts of the solitary complex (SC) and the nucleus ambiguus, the area ventromedial to the rostral part of the nucleus and the area dorsomedial to the retrofacial nucleus (RFN) which may correspond to the Bötzinger complex (BOT). The muscle nerves were: the phrenic branches to the dome and hiatal parts of the diaphragm, the abdominal muscle nerve, the pharyngo-esophageal branch of the vagus nerve, the mylohyoid muscle nerve, and the recurrent nerve branches to the adductors and abductor of the glottis. Emetic responses to stimulation of the vagal ventral trunk and the rostral SC still remained after cutting of the bilateral SCs at about 1 mm rostral to the obex, but disappeared after cutting at about 3.5 mm rostral to the obex. After the rostral cuts, stimulation of the SC part caudal to the cuts and the reticular column still induced the emetic act. Emetic responses to stimulation of the caudal SC remained after transection of the bulb at the rostral end of the RFN, but disappeared after transection at its caudal end or after partial cutting of the caudal BOT. The following hypothesis was proposed from these results. Emetic vagal afferents enter the rostral bulb, then descend through the SC to the area subpostrema. Subpostrema neurons project through the reticular column to the pattern generator of the emetic act in the BOT and activate it.

Animals↗

Actinomycosis of the larynx.

Actinomycosis is a disease characterized by a chronic suppurative and granulomatous process which tends to form multiple pyogenic draining sinus tracts. The most common site in which it occurs is the cervico-facial region, especially in the submandibular area. The exudates from the fistulous tracts usually contain yellow granules known as "sulfur granules," which can be considered as a hallmark of actinomycosis. We report a rare case of laryngeal actinomycosis which occurred in a 68-year-old male who had been irradiated 8 years before due to laryngeal carcinoma. During the admission, the patient was also diagnosed as being a myelodisplastic syndrome carrier. The patient was treated successfully with penicillin 10 million IU administered daily over 40 days. The etiologic agents, predisposing factors, diagnostic procedures, and available treatments are discussed, and the pertinent literature is reviewed herein.

Actinomycosis↗

DNA analysis of oral leukoplakia by flow cytometry.

DNA ploidy of 19 oral leukoplakias with and without epithelial dysplasia was investigated and the results were compared with 11 normal gingival biopsies, 14 oral benign tumours and 50 oral squamous cell carcinomas. The results suggest a possible relationship between DNA aneuploidy and oral leukoplakias or squamous cell carcinomas, as 32% of the oral leukoplakias and 48% of the oral squamous cell carcinomas were aneuploid although all the normal gingival biopsies and the benign oral tumours examined were diploid. No significant relationship was observed, however, between DNA ploidy and epithelial dysplasia in the leukoplakias.

Adult↗