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Biomedical subjects

K Onoe

Publications and source records attributed to K Onoe.

At least 19 recordsLinked to original sources

Brain activation study by use of positron emission tomography in unanesthetized monkeys.

A system for the measurement of brain activity in conscious monkeys by positron emission tomography (PET) was established in the present study. The signal/noise ratio was maximal around 40 s for data acquisition in the PET scan with 15O-labeled water. When the monkey was stimulated by vibration and subtraction images of the data sets from regional cerebral blood flow (rCBF) changes in paired stimulation and control were superimposed on magnetic resonance images obtained from the same specimens, a somatotopic map corresponding to the sites stimulated was clearly demonstrated. Visual stimulation with a photic stimulator activated the corresponding regions of the primary visual cortex. Comparison of the activated sites and extents under the conscious state with those under anesthesia assured that the study is controllable; there was little unpredictable activation due to unlimited subject movement or to psychological effects.

Animals

Light microscopical immunohistochemical study on parathyroid adenoma in primary hyperparathyroidism.

Fifteen adenomatous parathyroid glands obtained from 15 patients with primary hyperparathyroidism were examined both pathologically and immunohistochemically and connected with the clinical data for each patient. Four consecutive sections of the largest section surface of each resected adenomatous parathyroid gland were utilized for 4 kinds of stains, that is, hematoxylin-eosin, Grimelius and the immunohistochemical stains for parathyroid hormone (PTH) and chromogranin A. The results were as follows: (1) The large adenomatous parathyroid glands showed strong reactions to PTH as well as chromogranin A and Grimelius. On the other hand, the parathyroid adenoma obtained from a 9-year-old boy with hypercalcemic crisis showed almost no stain-positive cells for both PTH and chromogranin A. It is assumed that the former phenomenon reflects a substantial storage of secretory granules, while the latter reflects exhaustion of these granules. (2) The normal parathyroid cells in the neoplastic parathyroid glands generally showed stronger reactions to PTH and chromogranin A than neoplastic parathyroid cells. This suggests that normal cells in the neoplastic parathyroid glands may have their release of PTH rather than its synthesis suppressed, and also might support the hypothesis of some authors that chromogranin A or SP-I might contribute to stabilization of PTH or the secretory vesicle.

Adenoma

A hole in the T cell repertoire specific for a pigeon cytochrome c related peptide associated with amino acid substitutions on I-Ab molecules.

When C57BL/10(B10) mice were immunized with a pigeon cytochrome c related peptide, 50V (AEGFSYTVANKNKGIT), two helper T cell populations with different specificity were activated. A major T cell population reacted with a 50V analog, 50V54A (AEGFSYTVANKAKGIT), more potently than with the immunogen, 50V, in a heteroclitic fashion, whereas the other minor T cell population responded only to 50V. By contrast, when bm12 mice were immunized with 50V, the minor T cell population responding only to 50V could hardly be demonstrated. The apparent deletion of the minor T cell population in bm12 mice seems to be attributable to negative selection under the influence of I-Abm12 molecules, since the minor T cell population was undetectable in both I-Ab and I-Abm12 restricted T cells from (B10 x bm12)F1 mice. Thus, three mutant points on the I-A molecule in bm12 mice appear to be involved in the seemingly negative selection of the certain T cell repertoire. The present finding demonstrates that a T cell repertoire generated under the influence of a MHC product (Ab) on one parental strain is eliminated by a different MHC product (Abm12) on the other parental strain of F1 cross. The mechanism underlying the apparent negative selection is discussed.

Amino Acid Sequence

In vivo recording of electrical activity of canine tracheal smooth muscle.

Electrical activity of the tracheal smooth muscle was studied using extracellular bipolar electrodes in 37 decerebrate, paralyzed, and mechanically ventilated dogs. A spontaneous oscillatory potential that consisted of a slow sinusoidal wave of 0.57 +/- 0.13 (SD) Hz mean frequency but lacked a fast spike component was recorded from 15 dogs. Lung collapse accomplished by bilateral pneumothoraxes evoked or augmented the slow potentials that were associated with an increase in tracheal muscle contraction in 26 dogs. This suggests that the inputs from the airway mechanoreceptors reflexly activate the tracheal smooth muscle cells. Bilateral vagal transection abolished both the spontaneous and the reflexly evoked slow waves and provided relaxation of the tracheal smooth muscle. Electrical stimulation of the distal nerve with a train pulse (0.5 ms, 1-30 Hz) evoked slow-wave oscillatory potentials accompanied by a contraction of the tracheal smooth muscle in all the experimental animals. Our observations in this in vivo study confirm that the electrical activity of tracheal smooth muscle consists of slow oscillatory potentials and that tracheal contraction is at least partly coupled to the slow-wave activity of the smooth muscle.

Action Potentials

[Effects of tiropramide on the activity of lower urinary tract in dogs and its interpretation].

The rhythmic contractions of urinary bladder under constant volume condition were evoked in decerebrate and de-anesthetized dogs, while various myogenic and nerve-mediated electrical and mechanical activities of smooth muscles were recorded from in vivo pelvic viscera. The vesical rhythmic contractions were transiently and partially blocked by intravenous application of tiropromide. This 'partial' block showed a good contrast to the 'complete' block of identical contractions, which was observed after application of oxybutynin, known as a potent anti-muscarinic drug. The bladder voiding cycles were observed in other decerebrate dogs, while the warmed Ringer solution was infused at a steady rate into the dome of the bladder until principal voiding contraction occurred in cystometric recordings. The initiation of voiding contraction was markedly delayed after intravenous injection of tiropramide. The delay of principal contraction was found to be due to successive appearance of falling waves in cystometric recordings. As a evident contrast, terodiline caused a significant reduction of voiding contraction height and shortening of clonic discharge phase of external urethral sphincters during voiding cycle. It is concluded that tiropramide does not reveal anti-muscarinic action which oxybutynin or terodiline does really show, instead tiropramide acts principally on bladder detrusor itself, especially on its relaxation phase of premature contraction to be prolonged. The evidences were also presented for electrophysiological identification of bladder detrusor and urethral smooth muscle.

Action Potentials

[Electrical activities of urethral circular muscle and bladder detrusor and their control, examined by in vivo dogs].

While the micturition reflex was induced in dog by infusion of Ringer solution into the bladder, the following four types of electrical activity were picked up by two bipolar wire electrodes, embedded in the posterior wall of bladder and in the prostatic part of male urethra; 'intravesical ureter potential' and 'detrusor spike' by bladder electrode, and 'slow wave' and 'external sphincter spike' by urethral electrode. The relative size, respective rhythm and timing of discharge during voiding cycle were specific for each of them and they were readily identifiable for their own sources. The 'ureter potential' was not actively related to the voiding cycle but its triphasic wave form was dissociated at the maximum contraction phase of the bladder. Unexpected finding was the 'quasi-synchronization' of discharges between detrusor and external sphincter. The entire discharges in both muscles were consisted of 'initial burst', 'intermittent inhibition' and 'prolonged after-discharge'. The initial burst of detrusor was definitely delayed in comparison with that of external sphincter, but the end of prolonged after-discharges was again synchronized in both muscles. The possible mechanism for synchronization was discussed. The 'slow wave' was sometimes superposed on the tonic discharge of external sphincter recorded by same wire-electrode in urethral wall, therefore, their properties were analyzed under the condition of 'immobilization' of external sphincter. The sustained waxing and waning 'slow waves', observed in all female urethrae and one-fifth of male urethrae, were markedly suppressed by elicitation of isovolumetric rhythmic contractions of bladder with fall of intraurethral pressure. This bladder-dependent behavior of 'slow wave' was interpreted as a sign of 'urinary' sphincteric activity of urethral circular muscle. On the other hand, 'spontaneous' cyclic activation of 'slow wave' which was seen in about four-fifths of male urethrae and was not dependent upon the state of bladder, was interpreted as a sign of 'genital' sphincteric activity of the same circular smooth muscle.

Action Potentials

Activation of Ca(2+)-dependent K+ channel and Cl- conductance in canine pancreatic acinar cells through a cyclic AMP pathway.

Effects of adenosine 3',5'-cyclic monophosphate (cAMP) on Ca(2+)-dependent K+ channel and Cl- conductance in the plasma membrane of isolated canine pancreatic acinar cells were studied by patch-clamp methods. In whole-cell current recordings on isolated cells dialyzed with K(+)-rich solution containing 0.5 mM EGTA, addition of 0.5 mM dibutyryl cAMP (dbcAMP), or 50 microM forskolin to the bath increased outward K+ and inward Cl- currents associated with depolarizing and hyperpolarizing voltage jumps, respectively. In intact cells (cell-attached configurations), addition of 0.5 mM dbcAMP or 50 microM forskolin to the bath increased the opening of single K+ channel. In Ca(2+)-free external solution (bath and pipette) 50 microM forskolin or 0.5 mM dbcAMP application evoked an increase in the opening of single K+ channel in intact cells. Addition of 0.5 mM dbcAMP to the bath solution containing 10 mM EGTA without Ca2+ increased the currents of whole-cell dialyzed with K(+)-rich solution containing 10 mM EGTA. When cell was dialyzed with 20 mM EGTA, dbcAMP, or forskolin application did not increase the whole-cell currents. In excised inside-out patches, addition of the catalytic subunit of cAMP-dependent protein kinase (16 U/ml) in the presence of 0.3 mM ATP to the cytoplasmic face of membrane activated the K+ channel, but 0.1 mM cAMP did not. These results suggest that cAMP-dependent phosphorylation can activate Ca(2+)-dependent K+ channels without increase in intracellular free Ca2+ and cAMP-dependent mechanism can activate Ca(2+)-dependent Cl- conductances without the increase in Ca2+ in canine pancreatic acinar cells.

Animals

Patch-clamp studies of K+ and Cl- channel currents in canine pancreatic acinar cells.

K+ and Cl- channel currents in the plasma membrane of isolated canine pancreatic acinar cells were studied by patch-clamp single-channel and whole-cell current recording techniques. In excised inside-out patches, we found a Ca(2+)-activated (control range 0.01-0.4 microM) and voltage-activated K(+)-selective channel with a unit conductance of approximately 40 pS in symmetrical K(+)-rich solutions. In intact cells, addition of acetylcholine (1 microM) or bombesin tetradecapeptide (0.1 nM) to the bath evoked an increase in frequency of K+ channel opening. In whole-cell recordings on cells dialyzed with K(+)-rich and Ca(2+)-free solution containing 0.5 mM EGTA, the resting potential was about -40 mV. Depolarizing voltage pulses activated outward K+ currents, which were blocked by 10 mM tetraethylammonium, whereas hyperpolarizing pulses evoked smaller inward currents. Acetylcholine or bombesin activated the K+ current and enhanced the inward current, which was reduced by a low Cl- (10 mM) intracellular solution at -90 mV holding potential. These results suggest that both Ca(2+)- and voltage-activated K+ channels and Ca(2+)-activated Cl- channels exist in the plasma membrane of canine pancreatic acinar cells.

Acetylcholine

[A resected case of gastric carcinoma with complete remission of Virchow's node metastasis by 5'-DFUR administration].

5'-DFUR was administered orally at 800 mg/day, for total dosage of 57.6 g to the gastric cancer patient, classified Borrmann Type 2, with Virchow's node metastasis. Gastric tumor had diminished in size on the fluoroscopy and the endoscopy. We then made distal gastrectomy. The resected stomach showed moderately differentiated tubular adenocarcinoma on the pathological examination. Side effect was diarrhea.

Adenocarcinoma

Oscillatory potentials recorded from walls of anal canal and urethrae in dogs.

1. Oscillatory potentials were recorded from internal anal sphincters and from internal urethral sphincters in similarity and difference in their characteristics. similarity and difference in their characteristics. 2. Unexpected finding was the appearance of burst-and-pause alternation in male urethrae in contrast to continuous oscillation in female urethrae. 3. Stimulation experiments revealed that the internal anal sphincter was controlled by reciprocal spinal outflow; lumbar accrelation and sacral inhibition. But the recto-anal reflex, constantly observable in decerebrate dogs, was predominantly inhibitory, which was identical with sacral action. 4. The effect of ventral root stimulation upon urethral oscillation was 'identical' for lumbar and for sacral activations, even if it was excitatory or inhibitory, depending upon ongoing level of activity and upon stimulus parameters. Nevertheless, reciprocal activation between detrusor spike and urethral oscillation was observed during 'isometric voiding contractions'. The reason for this inconsistency was discussed.

Anal Canal

Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells.

When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance.

Animals

Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice.

The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis.

Animals

Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism.

Thirty-seven nodular hyperplastic parathyroid glands obtained by subtotal parathyroidectomy from 11 haemodialysed patients with secondary hyperparathyroidism were examined both pathologically and immunohistochemically. Four consecutive sections of the largest section-surface of each gland were subject to 4 different stains (haematoxyline-eosin, Grimelius, and the immunohistochemical stains for parathyroid hormone and chromogranin A) for comparison of each nodule. It was found that the major part of each nodule consisted of a single cell type with a single pattern of cells. These reacted uniformly to each stain. The mechanism involved in the storage and secretion of the secretory granule appeared to be regulated at the nodule and not at the cell level. The results suggest that the nodules may come from a monoclonal proliferation of a single parathyroid cell. Our present light microscopic immunohistochemical study, failed to demonstrate completely identical immunoreactive positivity of each nodule or each parathyroid cell to PTH. Chromogranin A or secretory protein-I did not indicate the coexistence of PTH and SP-I in the same secretory granule, which was in good agreement with the electron microscopic immunocytochemical study of Arps using bovine parathyroid glands. Our present study, however, provides good evidence that chromogranin A positivity is demonstrable in the human parathyroid gland outside the adrenal medulla and sympathetic nerves.

Humans

[Clinical evaluation of serum neuron-specific enolase levels in patients with lung cancer].

Serum neuron-specific enolase (NSE) levels were studied in 105 patients with malignant neoplasms (lung cancer 38, others 67), 13 patients with various benign diseases and 7 healthy adults. The mean serum NSE level in adult control subjects was 7.4 +/- 0.8 ng/ml, and cut off level was decided 10 ng/ml. Serum NSE levels were elevated in 14/38 (37%) of patients with lung cancer and in 14/67 (21%) of patients with the other malignant neoplasms. In patients with benign diseases, serum NSE level was elevated only in one patient with pituitary adenoma. In 7 patients with small cell lung cancer, the positive rate was higher (86%) than in those with non-small cell lung cancer (26%), and serum NSE levels were higher than 25 ng/ml except one case. There was no correlation between serum NSE and CEA (carcinoembryonic antigen) levels in patients with small cell lung cancer, also in patients with lung cancer. The measurement of serum NSE level seemed to be useful for diagnosis in patients with small cell lung cancer.

Adult