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Biomedical subjects

Y Nagase

Publications and source records attributed to Y Nagase.

At least 19 recordsLinked to original sources

Electron microscopic observation of synaptic connections of jaw-muscle spindle and periodontal afferent terminals in the trigeminal motor and supratrigeminal nuclei in the cat.

Previous studies indicate that the trigeminal motor nucleus (Vmo) and supratrigeminal nucleus (Vsup) receive direct projections from muscle spindle (MS) and periodontal ligament (PL) afferents. The aim of the present study is to examine the ultrastructural characteristics of the two kinds of afferent in both nuclei using the intracellular horseradish peroxidase (HRP) injection technique in the cat. Our observations are based on complete or near-complete reconstructions of 288 MS (six fibers) and 69 PL (eight fibers) afferent boutons in Vmo, and of 93 MS (four fibers) and 188 PL (four fibers) afferent boutons in Vsup. All the labeled boutons contained spherical synaptic vesicles and were presynaptic to neuronal elements, and some were postsynaptic to axon terminals containing pleomorphic, synaptic vesicles (P-endings). In Vmo neuropil, MS afferent boutons were distributed widely from soma to distal dendrites, but PL afferent boutons predominated on distal dendrites. Most MS afferent boutons (87%) formed synaptic specialization(s) with one postsynaptic target while some (13%) contacting two or three dendritic profiles; PL afferents had a higher number of boutons (43%) contacting two or more dendritic profiles. A small but significant number of MS afferent boutons (12%) received contacts from P-endings, but PL afferent boutons (36%) received three times as many contacts from P-endings as MS afferents. In Vsup neuropil, most MS (72%) and PL (87%) afferent boutons formed two contacts presynaptic to one dendrite and postsynaptic to one P-ending, and their participation in synaptic triads was much more frequent than in Vmo neuropil. The present study indicates that MS and PL afferent terminals have a distinct characteristic in synaptic arrangements in Vmo and Vsup and provides evidence that the synaptic organization of primary afferents differs between the neuropils containing motoneurons and their interneurons.

Animals

Light microscopic observations of the contacts made between two spindle afferent types and alpha-motoneurons in the cat trigeminal motor nucleus.

Previous studies indicate that cat jaw-muscle spindle afferents can be divided into two types (type I and II) on the basis of their axonal trajectories. The present study examined the relationship between spindle afferent fibers and their target masseter alpha-motoneurons in the cat by using the intracellular horseradish peroxidase (HRP) injection technique, and provided several new findings on the synaptic organization generated between the two. Five type I afferent fiber-motoneuron pairs and nine type II afferent-motoneuron pairs were well stained with HRP. The following conclusions were drawn: 1) A motoneuron received contacts from only one collateral of any given spindle afferent. 2) The number of contacts made between an afferent and a motoneuron ranged from one to three. 3) The contacts made by a spindle afferent were on the same dendrite or dendrites branching from the same primary dendrite. 4) The vast majority of the contacts made by an afferent on a motoneuron were distributed in the dendritic tree within 600 microns from the soma, i.e., in the proximal three fourths of the dendritic tree. The differences observed between the two afferent types were as follows. First, type II afferent terminals made contacts on more distal dendrites of the motoneurons than did type I afferent terminals. Second, the contacts made between a type I afferent and a motoneuron were clustered together, but those made between a type II afferent and a motoneuron were widely dispersed. The present results provided the general rules of synaptic contacts between the spindle afferents and masseter alpha-motoneurons, and demonstrated that the spatial distribution of synaptic contacts on the dendritic tree was different between type I and type II afferents.

Animals

Electroencephalography in schizophrenic patients: comparison between neuroleptic-naive state and after treatment.

Electroencephalography of 12 schizophrenic patients was recorded in a neuroleptic-naive state and after 6.2 +/- 1.1 months of treatment, when they were on medication and in partial remission. Compared with age- and sex-matched controls, the neuroleptic-naive schizophrenics had less alpha 2 power. In the medicated state, alpha 2 power and slow-wave power were reduced as compared with the neuroleptic-naive state. The reduction in alpha 2 power may occur from the early stage of the disease and progress even though the patients are medicated and clinically improved.

Adult

Age-related changes in alpha 1-adrenoceptors in rat prostate.

The age-related changes in the density of alpha 1-adrenoceptors in the dorsolateral lobe of the rat prostate were evaluated in Wistar rats at 8, 52, and 104 weeks of age. [3H]YM617, a newly synthesized alpha 1-adrenergic blocker, was used as the ligand. The mean maximum number of binding sites, or alpha 1-adrenoceptor density (Bmax) +/- SE of 104-week-old rats (11.0 +/- 1.2 fmol/mg protein) was significantly lower than that in the 8-week-old rats (37.0 +/- 4.3 fmol/mg protein) and 52-week-old rats (37.2 +/- 3.4 fmol/mg protein) (respectively, P < 0.01). In contrast, mean affinity (Kd) values +/- SE of these groups showed no significant differences (8-week-old rats, 115.8 +/- 9.1; 52-week-old rats, 100.5 +/- 5.8; and 104-week-old rats, 116.4 +/- 9.8 pM). Mean volumes +/- SE of muscle cells of the prostate were 3.7 +/- 1.1 x 10(3) microns3 at 8 weeks, 30.0 +/- 6.2 x 10(3) microns3 at 52 weeks, and 18.6 +/- 8.2 x 10(3) microns3 at 104 weeks. Volumes for 8-week-old rats were significantly smaller than those for 52-week-old (P < 0.01) and 104-week-old rats (P < 0.05). However, the mean area density of the muscle cells showed no difference among the three groups: 20.1 +/- 2.2% at 8 weeks, 27.3 +/- 2.9% at 52 weeks and 20.3 +/- 3.4% at 104 weeks. In conclusion, the density of YM617-binding sites (alpha 1-adrenoceptors) in 104-week-old rats was lower than in 8- and 52-week-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists

Purification and functional properties of soluble forms of membrane cofactor protein (CD46) of complement: identification of forms increased in cancer patients' sera.

Normal human sera contained 10-60 ng/ml of soluble membrane cofactor protein (MCP, CD46) whereas sera of > 50% of the cancer patients contained > 60 ng/ml. MCP purified by immunoaffinity chromatography from both normal and cancer patients' sera consisted of three bands of 56, 47 and 29 kDa on SDS-PAGE/immunoblotting. The upper two components were increased in cancer patient sera. The 56 and 47 kDa soluble forms served as a cofactor for factor I-mediated cleavage of C3b. MCP expressed on Chinese hamster ovary (CHO) cells protects host cells from human C3 deposition and complement-mediated cytolysis, especially by activation of the alternative pathway. In this same assay system, exogenously added soluble MCP also protected untransfected CHO cells; however, its potency was much less than that of the endogenous membrane form. For example, 8 micrograms/ml of soluble MCP was equal to 10(4) copies/cell of the expressed MCP. Recombinant soluble forms possessed similar activity to the naturally occurring soluble forms and high doses (> 150 micrograms) blocked Arthus-like reaction induced in guinea-pigs by anti-Forssman antibody. These data establish that soluble forms of MCP are present in human sera that possess cofactor activity and their concentrations, especially the 56 and 47 kDa forms, are increased in sera of cancer patients. High doses of the recombinant soluble forms may be therapeutically useful for suppressing inflammatory responses.

Animals

[Histochemical study of biotinylated lectins in prostatic cancer].

We examined the staining pattern of various lectins in the malignant and benign prostatic tissues to clarify the difference of sugar residues of mucosubstances between them. The binding of different lectins (Concanavalia ensiformis [Con A], Triticum vulgaris [WAG], Ricinus communis [RCA-I], Arachis hypogaea [PNA], Ulex europaeus [UEA-I], Glycine max [SBA], and Gliffonia simplicifolia II [GSA-II]) to cells of benign prostatic tissues (17 cases) and adenocarcinoma (54 cases) was evaluated immunohistochemically. SBA which was negative in benign epithelial cells, showed tendency to the binding to prostatic carcinoma (42.6%). UEA-I was significantly bound to the adenocarcinoma (68.5%) compared to the benign prostatic tissue (35.3%). We also examined histochemically 25 pairs of tissues obtained from prostatic adenocarcinoma before and after the various therapies with various lectins. The histological responsiveness on the post-therapeutic specimens showed a significant correlation to the clinical responsiveness to therapy. But the staining pattern of these 7 lectins on the pre-therapeutic specimens did not show a significant correlation to the clinical responsiveness to therapy. In summary, the staining pattern of some lectins in the prostatic cancers is different from that in the benign prostatic tissues.

Adenocarcinoma

[Evaluation of advanced bladder tumor].

Ninety-two cases of advanced bladder tumor treated at the University of Tokyo and branch hospital from January 1977 to December 1992 were analyzed. The advanced bladder tumor was defined as that of higher than pT2 (according to the General Rule for Clinical and Pathological Studies on Bladder Cancer) or that with distant metastases. The following variants were evaluated, the therapeutic methods, the histological type, grade, stage, type of infiltration. The evidence of lymphatic infiltration, vessel infiltration, and lymph node metastases were also reviewed. The survival rate was calculated using Kaplan-Meier's method. In the cases with lymph node metastases, the survival rate was significantly lower than in the cases without metastases (p < 0.01), while no other factors affected the survival rate.

Combined Modality Therapy

[Histochemical expression of proliferating cell nuclear antigen (PCNA) for pre and post chemotherapeutic bladder cancer].

We examined whether the staining of proliferating cell nuclear antigen (PCNA) could be useful as a marker of chemotherapeutic effectiveness in nine patients with invasive bladder cancer treated by bilateral internal iliac artery infusion of cisplatin (CDDP). Two types of monoclonal antibodies PC-10, 19A2 were used for immunohistochemical staining in formalin-fixed, paraffin-embedded tissue sections. There was no difference between positive rates of PC-10 and 19A2. The mean positive rates between pre-chemotherapeutic specimens (15.4 +/- 6.7%) and post-chemotherapeutic specimens (4.2 +/- 3.1%) showed statistically significant difference (p < 001). The immunohistochemical evaluation of PCNA has value for investigation of cell's turnover. Therefore, the changes of PCNA-positive rate could be a historical parameter for the evaluation of chemotherapeutic effects.

Aged

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