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Biomedical subjects

Y Nagase

Publications and source records attributed to Y Nagase.

At least 55 records · Page 3Linked to original sources

Immunohistochemical localization of glucose transporters in human renal cell carcinoma.

The localization of 2 isoforms of glucose transporters (GLUT1 and GLUT4) in 75 patients with renal cell carcinoma was examined immunohistochemically. Paraffin sections were immunostained with either anti-GLUT1 or GLUT4 antibody by the avidin-biotin-peroxidase complex method. In 55 of 75 patients, GLUT1 staining was demonstrated at the plasma membrane of the cancer cells. In the clear cell subtype, 44 of 52 (84.6%) patients were positive for GLUT1. We did not detect positive staining for GLUT1 in the spindle cell type. In the mixed cell subtype, positive staining was recognized in only the areas of clear cell carcinomas (10 of 13; 76.9%). Positive staining for GLUT1 did not show any significant correlation with tumor grade or extent. Heterogeneous expression of GLUT1 was observed in tumor cell mass: some tumor cells were positive for GLUT1, while other cells were not. In adjacent normal tissue, GLUT1 staining was only recognized at the plasma membrane of some renal tubules. GLUT4 staining was not recognized in either tumor or normal tissues.

Carcinoma, Renal Cell↗

Morphology and synaptic connections of slowly adapting periodontal afferent terminals in the trigeminal subnuclei principalis and oralis of the cat.

Previous studies suggest that sensory information from primary afferent fibers is processed in a distinct manner in the individual subnuclei of trigeminal sensory nuclear complex. The present study has addressed this issue by using intra-axonal labeling with horseradish peroxidase to examine the ultrastructure and synaptic organization of axon terminals from slowly adapting (SA) periodontal afferents in the ventral subdivision (Vpv) of principalis and the rostro-dorsomedial part (Vo.r) of oralis. Our observations are based on complete or near-complete reconstructions of 139 synaptic boutons in Vpv and 105 in Vo.r. All the labeled boutons contained clear, spherical, synaptic vesicles and were presynaptic to unlabeled dendrites, and they were frequently postsynaptic to unlabeled axon terminals containing pleomorphic synaptic vesicles (P-endings). The P-endings frequently formed axodendritic synapses on dendrites which received axodendritic synapses from labeled boutons (synaptic triads). On the basis of the number of contacts, synaptic arrangements associated with the labeled boutons could be subgrouped into simple (one or two contacts), intermediate (three or four contacts), and complex (five or more contacts) types. The labeled boutons varied from round to elongated forms with smooth to more irregular or scalloped contours. The boutons with scalloped contour were much more frequent in the complex type. The boutons of the intermediate type were significantly smaller than the complex type and larger than the simple type. The SA periodontal afferent terminals participated in each type of synaptic arrangements in Vpv, but were mostly of the simple type in Vo.r. The size of labeled boutons was significantly larger in Vpv than in Vo.r. The total number of axodendritic and axoaxonic contacts per labeled bouton was significantly higher in Vpv than in Vo.r. Another difference was the more frequent occurrence of synaptic triads in Vpv than in Vo.r. These observations provide evidence that sensory information from primary afferent fibers is processed in a different manner in the two subnuclei.

Adaptation, Physiological↗

Central terminations of low-threshold mechanoreceptive afferents in the trigeminal nuclei interpolaris and caudalis of the cat.

Previous studies indicate that vibrissa, nonvibrissa, guard hair, hairy skin, and periodontal ligament afferents give rise to morphologically distinct terminal arbors in the trigeminal nuclei principalis (Vp) and oralis (Vo) in the cat. The present study describes the extent to which morphological and functional relationships exist in the nuclei interpolaris (Vi) and caudalis (Vc). Twenty-two fibers were physiologically characterized and stained by intra-axonal HRP injection techniques. The fast adapting (FA) vibrissa (VF) afferents gave rise to compact and circumscribed arbors in Vi and Vc. These tended to be larger in Vc than in Vi. The slowly adapting (SA) vibrissa (VS) afferents in Vi and Vc had more widespread and larger arbors than those of the VF afferents. The VS arbors in Vc tended to be larger and less circular than those in Vi. Guard hair (GH) afferents gave rise to circumscribed arbors in both nuclei, but those in Vc tended to have larger and more circular arbors than those in Vi. Down hair (DH) afferents gave rise to small, circumscribed arbors or a few distinct patches of boutons within a small area in Vi; arbors in Vc were less extensive and "stringy." Unlike other afferents, DH arbors were larger in Vi than in Vc, but smaller than those of GH afferents in either nuclei. The SA hairy skin (SS) afferents had arbors that were widespread with a few distinct patches of boutons; the arbors in Vc were larger than those in Vi. The arbors of SS afferents were smaller than those of VS and GH afferents in both nuclei. Like GH afferents, FA periodontal ligament (PF) afferents gave rise to large and circumscribed arbors in Vi, although the arbors in Vc were smaller and less dense. The present study demonstrated significant functional and morphological relationships for primary afferents in Vi and Vc, thus suggesting that sensory information from each of the distinct fiber or functional classes is processed in a characteristic manner in the individual nuclei.

Afferent Pathways↗

Multidirectional contraction of human hypertrophied prostate.

1. The purpose of the present investigation is to evaluate muscle contraction in two directions (longitudinal and circumferential to urethra) physiologically and morphologically for alpha-adrenoceptor agonists. 2. Norepinephrine (10(-7)-10(-4) M), phenylephrine (10(-7)-10(-4) M) and clonidine (10(-7)-10(-4) M) induced contractions in a dose-dependent manner on human prostate from patients with benign prostatic hypertrophy (BPH). 3. No significant differences were observed between longitudinal and circumferential directions of human prostate in 50% of the maximal muscle contraction (EC50 values) and the maximal muscle contractions caused by any agents used. 4. Morphometric analysis for muscle in prostates was performed using formalin-fixed, paraffin-embedded sections stained by the Mallory-Azan method. 5. There was no significant difference in the density of the muscle area between longitudinal and circumferential directions of prostatic strips. 6. These results suggest that there are no significant differences in responsiveness of alpha-adrenoceptor agonists and the smooth muscle contents in longitudinal and circumferential directions to urethra, for human hypertrophied prostate.

Adrenergic alpha-Agonists↗

NADPH-diaphorase in the spinal trigeminal nucleus oralis and rostral solitary tract nucleus of rats.

NADPH-diaphorase histochemical staining demonstrated a distinct neural group that might synthesize nitric oxide in the lower brainstem of rats. The NADPH-diaphorase stain revealed a Golgi-like network in the dorsomedial spinal trigeminal nucleus oralis and rostrolateral solitary tract nucleus, whereas this network was more dense in the latter nucleus. The distribution of NADPH-diaphorase-positive neurons in these areas overlapped with parts of central terminations from the chorda tympani nerve, as demonstrated with transganglionic transport of wheatgerm agglutinin conjugated horseradish peroxidase. The number of NADPH-diaphorase-positive neurons changed after chorda tympani nerve lesion relative to the contralateral side. The control value (%) was 106.0 +/- 4.9 (mean +/- S.E.M.). One hour after the nerve lesion, the value increased to 115.2 +/- 9.1 (P > 0.05). It then decreased to 83.9 +/- 5.2 two days after the lesion (P < 0.05), and remained at this reduced level for one or two weeks, 83.2 +/- 3.0 (P < 0.01) and 83.7 +/- 2.3 (P < 0.01), respectively. This statistically significant reduction recovered to control level 103.4 +/- 2.9 four weeks after the lesion. These results show that NADPH-diaphorase-positive neurons in the lower brainstem could be regulated trans-synaptically by primary afferents, possibly gustatory inputs.

Animals↗

Lower interhemispheric coherence in a case of agenesis of the corpus callosum.

Interhemispheric coherence and relative power were compared in a patient with total agenesis of the corpus callosum and age and sex matched controls. The patient showed lower interhemispheric coherence than normal controls in F3-F4, C3-C4, and in P3-P4 especially in the higher theta, lower alpha, and beta bands. Differences in relative power were much less marked. These results seem to reflect that interhemispheric connection is degraded because of callosal agenesis.

Adolescent↗

[Two-color flow cytometric analysis of lymphocytic subsets in renal cell carcinoma].

The subsets of tumor infiltrating lymphocytes (TILs) in 17 patients with renal cell carcinoma were studied by two-color flow cytometry and immunohistochemistry. In grade 1 tumors, CD4-positive cells were significantly increased compared to grade 2 and 3 tumors (35 +/- 7% vs 25 +/- 10%) (p < 0.05). In 10 of 14 patients, CD8-positive cells were predominant over CD4-positive cells, resulting in less than one in CD4/CD8-ratio. Regarding CD4 cells in all 17 cases, the helper T-cells (CD4-positive and CD45RA-negative) were statistically predominant over the inducer T-cells (CD4-positive and CD45RA-positive) (p < 0.01). When CD8 cells were investigated in 16 out of the 17 cases, the cytotoxic T-cells (CD8-positive and CD11b-negative) were found also significantly predominant over the suppressor T-cells (CD8-positive and CD11b-positive) (p < 0.01). Immunohistochemically, the infiltrating pattern of TILs in the 17 patients was classified into cluster (N = 4), separate (N = 6), and mixed types (N = 7). The tumor in the cluster and mixed type had a tendency to be dominant in low grade tumors, and had the prominent CD8-positive cells (more than 90% were cytotoxic T-cells) over CD4-positive cells. However, no statistical significance was noted in this finding. The advanced tumor tended to show the single type of TIL infiltration. These results suggest that cytotoxic T-cells consisted of most of TILs in cluster and mixed types play an immunoreactive role against renal cell carcinoma.

Adult↗

Synaptic connections of a periodontal primary afferent neuron within the subnucleus oralis of the cat.

The central axon of a primary afferent neuron that responded to light mechanical stimulation of the lower premolar teeth in a fast adapting fashion was intra-axonally injected with horseradish peroxidase in the cat. The labeled terminals within the rostrodorsomedial (Vo.r) and dorsomedial (Vo.dm) parts of subnucleus oralis were examined electron microscopically. The labeled ending had pale axoplasm, contained clear spherical synaptic vesicles, and formed multiple synapses with dendrites and/or unlabeled axonal endings with pleomorphic vesicles (P-endings). In these synaptic contacts, the labeled primary ending was presynaptic to dendrites and postsynaptic to P-endings. Labeled endings simultaneously synapsing with both dendrites and P-endings were more frequent in Vo.dm (28%) than in Vo.r (8.3%).

Animals↗

Nucleus ambiguus of the rabbit: cytoarchitectural subdivision and myotopical and neurotopic representations.

The cytoarchitectural subdivisions of the nucleus ambiguus of the rabbit and its myotopical and neurotopical representations were investigated with HRP labeling. The nucleus was subdivided into the compact cell group (CoG), the medial and lateral scattered cell groups (SGm and SGl), and the diffuse cell group (DiG). The CoG was formed by esophageal, pharyngeal constrictor, and palatal motoneurons in the rostral half of the nucleus. The SGm and SGl were located medial and lateral to the CoG, respectively, in the rostral one-third of the nucleus. Stylopharyngeal and cricothyroid motoneurons were located in the most rostral one-fifth of the SGm and the remaining four-fifths, respectively, whereas the SGl was not labeled with HRP injections into the palatal, pharyngeal, esophageal, and laryngeal muscles. The DiG was formed by recurrent laryngeal motoneurons in the caudal two-thirds of the nucleus. Neurons of origin for the glossopharyngeal nerve occupied the stylopharyngeal region, with a few of them scattered in the CoG and SGl. Neurons giving rise to axons in the superior laryngeal nerve occupied the cricothyroid region, with a few of them scattered in the pharyngeal constrictor region; whereas the pharyngeal vagal branch originated from the pharyngeal constrictor and palatal regions. Neurons of the DiG, SGl, and esophageal region contributed to the infranodosal vagus nerve; esophageal fibers of the recurrent laryngeal nerve originated from the dorsal esophageal region. Laryngeal fibers of the recurrent laryngeal nerve originated from the DiG, the caudal neurons of which had axons traversing the cranial accessory root.

Accessory Nerve↗

The central projections of the monkey tooth pulp afferent neurons.

Transganglionic transport of horseradish peroxidase conjugated to wheatgerm agglutinin (HRP:WGA) entrapped in hypoallergenic polyacrylamide gel was used to study the patterns of termination of primary afferents that innervate the upper and lower tooth pulps within the trigeminal sensory nuclear complex (TSNC) of the monkey. HRP:WGA injections were also made into the lower incisors and molars, in order to examine the topographic arrangement of pulpal afferent projections. HRP-labeled pulpal afferents innervating lower and upper teeth projected ipsilaterally to the rostral subnucleus dorsalis (Vpd) and caudal subnucleus ventralis (Vpv) of the nucleus principalis (Vp); the rostrodorsomedial (Vo.r) and dorsomedial (Vo.dm) subdivisions of the nucleus oralis (Vo); the dorsomedial subdivision of the nucleus interpolaris (Vi); and laminae I-II and/or V of the nucleus caudalis (Vc) at its rostralmost level. The HRP-labeled terminals from upper and lower pulpal afferents formed a rostrocaudal column from the midlevel of Vp to the rostral tip of Vc. The label in Vp and Vo was considerably dense, but the column of terminals was interrupted at the Vpd-Vpv transition. The label in Vi and Vc was much less dense compared to that in the rostral nuclei, and the column of terminals was interrupted frequently. The representation of the upper and lower teeth in TSNC was organized in a somatotopic fashion that varied from one subdivision to the next, though their terminal zones overlapped within Vpd. The upper and lower teeth were represented in Vpv, Vo.r, Vo.dm, Vi, and Vc in a ventrodorsal, dorsoventral, lateromedial, lateromedial, and lateromedial sequence, respectively. Topographic arrangement was also noticed for the projections of pulpal afferents from the lower incisors and molars: The representations of the lower incisors and molars in Vpv, Vo.r, Vo.dm, Vi, and Vc were organized in a lateromedial, dorsoventral, ventrodorsal, ventrodorsal, and lateromedial sequence, respectively. The present results indicating sparse projections from pulpal afferents in the monkey's Vc are in good correspondence with a clinical report that trigeminal tractotomy just rostral to the obex has no significant effect on dental pain perception in patients. Furthermore, the present study indicates that projection patterns of pulpal afferents--which include the termination sites, the density of terminations between nuclei, and topographic arrangement--differ among animal species.

Afferent Pathways↗

EEG coherence in unmedicated schizophrenic patients: topographical study of predominantly never medicated cases.

Electroencephalographic (EEG) power and coherence were compared in 11 unmedicated schizophrenics (including 9 never mediated patients) and in 15 normal controls. There was no significant difference in power between the two groups. However, interhemispheric coherence between O1-O2 was higher in the schizophrenics in the delta and beta bands, and interhemispheric coherence between T5-T6 was higher in the delta band. These results suggest that coherence is more sensitive than power for comparison of these two groups, and that cerebral function is less lateralized in schizophrenics.

Adult↗

Topographical changes in alpha power in medicated and unmedicated schizophrenics during digits span reverse matching test.

The topographical distribution of alpha power reduction was compared in nine unmedicated schizophrenics (predominantly never-treated), 17 medicated schizophrenics, and 15 normal controls. The task involved four procedures: (1) listening to signal sound, (2) listening to digits for memorization, (3) after listening, and (4) listening to digits for recognition. The electroencephalograms (EEGs) during each procedure were analyzed with Fast Fourier Transformation and compared with EEGs at rest. While listening to the digits, medicated schizophrenics showed less alpha power reduction than normal controls and unmedicated schizophrenics. In addition, there were correlations found between the degree of alpha power reduction and medication dose, and score of chronic symptoms. These suggest that patients with different clinical backgrounds have differing cerebral activity.

Adult↗

An HRP study of the location of the motoneurons supplying the tensor veli palatini muscle of the rabbit.

Location of the motoneurons supplying the tensor veli palatini muscle of the rabbit was examined with the retrograde labeling technique following intramuscular injection of HRP. Labeled motoneurons were ipsilaterally located in the ventral or ventromedial portion of the rostral two-thirds of the motor trigeminal nucleus at the level of about 6.0 to 8.5 mm rostral to the obex. The location of the labeled motoneurons was ventromedial to the region supplying the masseter, the temporalis, and the medial pterygoid muscles and ventral to the region supplying the anterior digastric and the mylohyoid muscles, the location which coincided with the lateral pterygoid region. The labeled motoneurons were scattered around or in this region.

Animals↗

Soluble forms of membrane cofactor protein (CD46, MCP) are present in plasma, tears, and seminal fluid in normal subjects.

We have established an ELISA for determination of membrane cofactor protein (MCP, CD46) both solubilized from cell membranes and released in body fluids. In this assay, mouse MoAbs against MCP, M177 and M160 whose epitopes were different, were used as capture and detection antibodies, respectively. The NP-40 concentration in samples for MCP to be measured must be less than 0.05%. The detection limit of this MCP assay was 0.5 ng. The assay was used to quantify solubilized membrane MCP, and soluble MCP in normal human plasma, serum, urine, saliva, tears, and seminal fluid, and culture media of tumour cell lines. Soluble MCP was barely detected in the conditioned media of the cell lines. The levels of sMCP in plasma and serum were 10-60 ng/ml and that in tears, 0-50 ng/ml. Seminal fluid contained about 10-fold more soluble MCP than serum. Soluble MCP was not detectable by this assay in the other body fluids, suggesting that their MCP levels were less than the detection limit, if any.

Anticoagulants↗

Preparations of cyclic sulfoxide derivatives and their evaluation as transdermal penetration enhancers.

Novel cyclic sulfoxides, such as 2-octyl, 2-dodecyl and 2-hexadecyltetrahydrothiophene-1-oxide were prepared by the alkylation of tetrahydrothiophene-1-oxide. Additionally, 2-methyl, 2-ethyl and 2-propyl-5-dodecyltetrahydro-thiophene-1-oxide were conducted by further alkylation. Their enhancing activity on the penetration of indomethacin through rabbit skin was evaluated in in vitro experiments, and the effect of the alkyl length on the enhancing activity was discussed. Among the 2-alkyl-tetrahydrothiophene-1-oxides, the compounds containing dodecyl and hexadecyl groups promoted a much greater penetration of the drug through the skin than the compound containing an octyl group. A stronger effect was observed in the experiment using 2-dodecyl-5-alkyltetrahydrothiophene-1-oxide, as compared with the that of 2-dodecyl-tetrahydrothiophene-1-oxide. The substitution of the alkyl groups to the next position of the sulfoxide group seemed to make the enhancing activities large.

Animals↗

Synaptic connections of a low-threshold mechanoreceptive primary neuron within the trigeminal subnucleus oralis.

The central axon of a primary afferent neuron that responded to indentation of the glabrous skin of the lower lip in a slowly adapting fashion was intra-axonally injected with horseradish peroxidase. The labeled terminal within the subnucleus oralis was examined electron microscopically. The labeled ending had a pale axoplasm and contained clear spherical synaptic vesicles. The labeled ending formed a synaptic triad with a dendrite and an unlabeled axonal ending with pleomorphic vesicles (a mixture of oval, flattened and dense core vesicles). The labeled primary ending was presynaptic only to the dendrite, while the unlabeled ending was presynaptic to both the dendrite and the labeled primary ending.

Animals↗

Location of the motoneurons supplying the rabbit pharyngeal constrictor muscles and the peripheral course of their axons: a study using the retrograde HRP or fluorescent labeling technique.

The location of the motoneurons supplying the rabbit pharyngeal constrictor muscles (the superior and the middle constrictors, and the thyropharyngeus and the cricopharyngeus; the last two collectively compose the inferior constrictor) was investigated with intramuscular injection of HRP or the fluorescent tracer nuclear yellow into the individual muscles. Moreover, the peripheral course of their axons was investigated by injection of HRP into all of the pharyngeal constrictors in conjunction with intracranial severing of either the vagus or the glossopharyngeal nerves. The pharyngeal constrictor motoneurons were ipsilaterally located within a subdivision of the nucleus ambiguus which is formed by a compact arrangement of the smallest neurons of the nucleus and situated in the rostral half of the nucleus. We named that subdivision the compact cell group (CoG). Axons of the pharyngeal constrictor motoneurons traversed the vagal rootlets. The rostrocaudal extent of the pharyngeal constrictor motoneurons covered almost the entire length of CoG at a level from about 500 to 2,900 microns rostral to the obex, with their number being most numerous in the middle one-third level of the CoG. Although the motoneurons of the superior constrictor, those of the middle constrictor, and those of the thyropharyngeous and the cricopharyngeus overlapped considerably in location, they tended to be arranged rostrocaudally in that order. At the middle one-third level of the CoG, where the CoG is subdivided into dorsomedial and ventrolateral subgroups of neurons, the superior and the middle constrictor motoneurons were confined to the medial portion of the dorsomedial subgroup, while the inferior constrictor motoneurons were distributed throughout its entirety.

Animals↗

[Lymphocytic subsets of tumor tissue, non tumorous kidney, and the peripheral blood in primary renal cell carcinoma].

Lymphocyte subsets were examined in renal cell carcinoma (TILs), adjacent non-tumor renal tissue and peripheral blood (PBLs) by flow cytometry and histochemistry in eighteen patients with renal cell carcinoma. CD5-positive cells were predominant in the TILs in 14 patients. In the renal cell carcinoma tissue, CD8-positive cells were predominant over CD4-positive cells, resulting in a less than unity ratio of CD4/CF8-positive cells. The lymphocyte number was significantly in adjacent normal renal tissue than in renal cell carcinoma. However, lymphocyte subsets ratios were not significantly different between these two tissues. PBLs showed the same proportions (CD4/CD8 mean 1.9 +/- 0.8) as the previously published healthy controlled data. The proportions of CD8-positive cells were significantly increased (p less than 0.05) and those of CD4-positive cells were also significantly decreased (p less than 0.01) in the TILs. The infiltrating pattern of TILs in 17 patients was divided histochemically into cluster (N = 7), single (N = 4), and mixed types (N = 6). The cluster and mixed types were significantly more common in grade 1 tumors and the single type was more common in the grade 2 tumors (p less than 0.05). The pT3 tumors showed the single type of TIL infiltration pattern, but showed no significant difference. In the cluster pattern of TILs, CD8-positive cells were surrounded by CD4-positive cells. Non-tumorous kidneys showed no infiltration of lymphocytes, except in 2 patients of pyelonephritis. These results suggest that cytotoxic T-cells stained as CD8 play an immunoreactive role against renal cell carcinoma.

CD4-CD8 Ratio↗