Biomedical subjects
Publications and source records attributed to S Takada.
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The study of the mechanism of pressure transmission is important for the treatment of rapid deterioration of a patient's condition with increased intracranial pressure (ICP) from a space taking lesion in neurosurgical practice. The aim of this experiment is to clarify the mechanism of pressure transmission during supratentorial balloon inflation, by continuously monitoring local shiftings of the brain using strain gauge sensors. Mongrel dogs and macaca fuscatas were fixed in stereotaxic head frames with light anesthesia. Brain shiftings were evaluated by sensors discriminating two dimensional directions, sagittal and coronal planes, at the cerebrum. Brain stem shift was measured as displacement from the midline at the midbrain and ventro-dorsal shifting in the pons. ICP was raised by inflation of a supratentorial balloon located in the frontal lobe in one group or the temporal lobe in other group. As parameters detecting the changes in the functions of the brain stem, systemic blood pressure (SAP), respiration and pupil size were simultaneously monitored. Shifting of the brain stem occurred in four staged in both groups. During a minimum increment of ICP shifts to the antiballoon side were observed at the occipital lobe and the midbrain. The pons showed no shift in stage I. During the further inflation of the balloon stage II, the pons started to shift to the ventral side. In this stage the temporal lobe, in addition to the occipital lobe, shifted to the antiballoon side. There was a tendency for stage II to last longer for the frontal balloon than for the temporal balloon.(ABSTRACT TRUNCATED AT 250 WORDS)
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Human stomach adenocarcinomas containing alpha-1-antichymotrypsin (ACT) in their cell nuclei were transplanted into nude mice. The presence of ACT was monitored using an immunohistochemical technique with horseradish peroxidase-labeled rabbit anti-ACT Fab' as well as single radial immunodiffusion. Two weeks after transplantation, ACT could be found neither in transplanted carcinoma cells nor in the sera of carcinoma-bearing nude mice. However, if human ACT was injected i.v., it could be detected in the transplanted carcinoma cell nuclei 2 h after injection. The ACT was detected immunohistochemically and was confirmed by biochemical fractionation using 125I-labeled ACT. On the other hand, the amount of ACT production was not sufficient to indicate biosynthesis. These results demonstrated that ACT detected in stomach carcinoma cell nuclei was not synthesized in carcinoma cells but was incorporated from the blood circulation.
Karyotypes of Myotis siligorensis, Myotis mystacinus, Pipistrellus pulveratus, Tylonycteris robustula, Miniopterus schreibersi fuliginosus, Hipposideros fulvus and Aselliscus stoliczkanus from Thailand are investigated.
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Biological activities of a variety of synthetic human (h) and rat (r) atrial natriuretic peptide (ANP) and related peptides as assessed by receptor binding and cyclic GMP response, and regulation of vascular ANP receptors were studied in rat aortic vascular smooth muscle cells (VSMC) in culture. alpha-hANP1-28 and alpha-hANP7-28 equally inhibited the binding of 125I-labeled-alpha-hANP to its vascular receptors, whereas Met(O)12-alpha-hANP1-28 was less potent and reduced and carboxymethylated (RCM)-alpha-hANP1-28 was ineffective. rANP5-27 and rANP5-28 were equipotent in receptor binding, whereas rANP5-25 had somewhat less potent effect and rANP8-28 fragment was ineffective. alpha-hANP1-28, alpha-hANP7-28, rANP5-27 and rANP5-28 similarly stimulated intracellular cyclic GMP formation, whereas rANP5-25 showed less stimulatory effect, and RCM-alpha-hANP1-28, Met12-sulfoxide and rANP fragment were ineffective. Pretreatment with unlabeled alpha-hANP (3.2 X 10(-9) and 3.2 X 10(-8)M) for 24 hrs resulted in a substantial reduction (55 and 75%) of total receptor number without changing the affinity of ANP receptors. These results suggest that the common ring structure formed by the disulfide bond in the molecule is critical for receptor binding and subsequent biological actions, and that a hydrophobic amino acid located at the position of 12, and (24-26) residues at the C-terminal side, but not (1-6) at the N-terminal side, of the disulfide bridge may play a part in modulating receptor binding and/or biological functions. The present study also indicates "down-regulation" of vascular ANP receptors by homologous ligand.
The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Upon stimulation by autologous non-T cells, OKT4+ cells produce interleukin 2 (IL2); cells contained within both OKT4+ and OKT8+ cell populations can also be activated by autologous non-T cells to become sensitive to IL2. Once these activated OKT4+ and OKT8+ cells are exposed to IL2 produced by OKT4+ cells, they will proliferate and go on to differentiate into effector cells. Patients with systemic lupus erythematosus (SLE) have a defect in the AMLR. The ability of OKT4+ cells to produce IL2 in the AMLR is impaired. Upon triggering with autologous non-T cells, their OKT8+ cells become sensitive to proliferative signals of IL2; however, their OKT4+ cells fail to express IL2 receptors. These defects are a consistent feature in patients with SLE. AMLR-induced immunologic processes which require cell interactions between OKT4+ cell subpopulations are not correctable even by the addition of normal IL2. However, the immunologic processes mediated through OKT4+-OKT8+ cell interactions can be corrected with normal IL2. The latter finding suggests that the partial correction of the AMLR-induced immunologic processes with IL2 might lead to suppressed B cell hyperactivity of patients with SLE.
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In vitro viable cell count studies of sustained release preparations of cefaclor (CCL) conclude that the mixture of nonenteric and enteric coated granules of CCL in the ratio of 4 to 6 is the most appropriate form (4:6 form) for the sustained release preparation of CCL. In order to clinically confirm the above conclusion, comparative double blind clinical studies of 3 mixtures forms (2:8, 4:6 and 6:4 forms) with a regular preparation (CCL form) were conducted in dental infections regarding efficacy, safety, and usefulness of the 4 forms. Evaluable cases for efficacy and usefulness were 364 in total (96 cases for the 2:8 form group, 89 cases for the 4:6 form group, 89 cases for the 6:4 form group, and 90 cases for the CCL form group). Evaluable cases for safety were 404 cases in total (102 for the 2:8 form, 100 for the 4:6 form, 102 for the 6:4 form, and 100 for the CCL form). Daily dose of the 3 forms of sustained release preparations was 375 mg b.i.d. after breakfast and dinner and that of the CCL form 250 mg t.i.d. after breakfast, lunch and dinner. Following are the results of the clinical studies: There were no significant differences among the 4 patient-groups (2:8 form, 4:6 form, 6:4 form, and CCL form) regarding background factors of the patients and findings of their subjective and objective symptoms before the initiation of the administration, and it was therefore confirmed that there were no problems in conducting the comparative double blind clinical studies. Overall clinical effective rate determined by the efficacy evaluation criteria of the Japanese society of oral surgery (JSOS) were 89.5% at day 3 and 94.8% at day 5 in the 2:8 form group, 87.4% at day 3 and 95.5% at day 5 in the 4:6 form group, 86.4% at day 3 and 91.0% at day 5 in the 6:4 form group, and 93.3% at day 3 and 96.7% at day 5 in the CCL form group. The effective rate determined by the physicians who actually treated the patients were 84.4% in the 2:8 form group, 87.6% in the 4:6 form group, 84.1% in the 6:4 form group, and 87.8% in the CCL form group. In both judgments by the efficacy evaluation criteria of JSOS and the physicians, there were no significant differences among the 4 forms regarding overall clinical efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)
Normal immunoregulation depends on a complex set of cellular interactions in which interleukin 2 (IL 2) appears to play an important role. We have examined the IL 2 activity in patients with systemic lupus erythematosus (SLE). IL 2 production by phytohemagglutinin (PHA)-stimulated T cells for 48 hr was measured by the ability of their culture fluid to induce proliferation of normal human T cells that had been activated for more than 20 days by PHA plus IL 2. To measure IL 2 responsiveness, T cells were blasted by preincubation with concanavalin A for 96 hr and stimulated for another 72 hr with lectin-free standard IL 2. SLE T cells failed to produce normal levels of IL 2 in vitro compared with normal control T cells. This failure resided in both OKT4+ and OKT8+ cells. Furthermore, the abnormality was due neither to soluble inhibitory factors produced by SLE T cells nor to active suppressor cells that might be induced by PHA-stimulation. Responsiveness to IL 2 of T cells from some, but not all, SLE patients was decreased significantly from that of normal controls. Absorption studies as well as studies with anti-Tac antibody demonstrated that the impaired responsiveness of T cells in the specific patients with SLE was due to inadequate expression of IL 2 receptors on the T cells upon activation. This defect was exclusively ascribed to the dysfunction of OKT4+, but not OKT8+, cells. The above defects in production of and responsiveness to IL 2 observed in patients with SLE were present at all times regardless of the disease activity or of corticosteroid therapy. Thus, the deficient IL 2 activity may be intrinsic to SLE lymphocytes and may contribute to impaired immunoregulation and to the development of SLE.
To assess early bilirubin toxicity, a study was made of auditory brainstem responses in relation to total bilirubin levels as well as unbound bilirubin levels in 56 hyperbilirubinemic infants (total bilirubin greater than or equal to 15.0 mg/dL) and 24 infants who did not have jaundice. The latencies of wave I at 85 dB HL (hearing level) in hyperbilirubinemic infants were significantly greater than those in the control group. The latencies of wave I and V in hyperbilirubinemic infants with unbound bilirubin levels greater than or equal to 1.0 microgram/dL (group C) were greater than those in the control group and in the hyperbilirubinemic infants with unbound bilirubin levels less than 0.5 microgram/dL (group A) and with unbound bilirubin levels less than 1.0 microgram/dL (group B). There were no significant differences of the wave I-V interpeak latency between the control infants and the hyperbilirubinemic infants. Thirty of the 80 infants showed prolonged peak latencies (greater than the mean +/- 2 SD for the control infants) of wave I and/or V in one or both ears. The incidences of the prolonged peak latencies in group B (42%) and group C (89%) were significantly greater than that in the control group (12%). The serial determinations of auditory brainstem responses in infants treated with exchange transfusions revealed that the prolonged peak latencies before exchange transfusion improved at 48 and 96 hours after the procedure for wave I, and at 24, 48, and 96 hours after the procedure for wave V. The interpeak latency of wave I-V did not change with exchange transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
The studies of changes in regional blood flow (rCBF) have been reported on different clinical courses in the five cases (mean 57.4 y.o.) showing bilateral occlusion or stenosis of internal carotid arteries. Values of rCBF using Fg (fast component in gray matter) were closely correlated with their clinical courses. The three patients (2 males and 1 female) showed bilateral focal decreased patterns of rCBF and their uneventful clinical courses except for mild attacks of transient cerebral ischemia. However, the rest two male patients showed bilateral decreased pattern of rCBF and moderate hemiparesis including attacks of loss of consciousness. The one died suddenly because of the thalamic hemorrhage and the other died also suddenly from the unknown etiology. Such differences between the classification of clinical course and hemodynamics evaluated by rCBF was discriminated more clearly by Fg (fast component in gray matter) than by F mean (mean rCBF). The authors concluded that the evaluation by Fg may be valuable to estimate prognosis of patients with bilateral occlusion of internal carotid artery. There are two patterns of decreased rCBF in our study. The patients with bilateral diffuse decreased patterns of rCBF should be followed up more carefully because of the sudden death from cerebral hemorrhage.
Rats were immunized by intraperitoneal injection of ovalbumin (egg albumin) emulsified in Freund's incomplete adjuvant, and then the effect of an intravenous challenge with ovalbumin on salicylic acid absorption from the small intestine was examined by means of an in situ recirculation technique. The disappearance of salicylic acid from the luminal solution was significantly decreased in rats treated with ovalbumin compared with control groups treated with saline. The decreased absorption of salicylic acid in ovalbumin-immunized rats was related to the anti-ovalbumin antibody responses examined by passive cutaneous anaphylactic reactions. On the other hand, the decreased absorption of salicylic acid was not found in ovalbumin-immunized rats challenged intravenously with bovine gamma-globulin. Similar results were also noted in rats immunized via the footpads with ovalbumin. However, no significant change was observed in the intestinal absorption of salicylic acid in normal (nonimmunized) rats challenged intravenously with ovalbumin. Furthermore, intestinal absorption of sulfadimethoxine and sulfanilamide was significantly decreased during systemic anaphylaxis, whereas no change was observed in the absorption of sulfisoxazole, quinine, sulfanilic acid, and phenolsulfonphthalein. This suggests that the intestinal absorption of rapidly absorbed drugs, including salicylic acid, is more sensitive to systemic anaphylaxis than that of poorly absorbed drugs.