A study of pyloric function after pylorus-preserving pancreatoduodenectomy in the canine model.
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Biomedical subjects
Publications and source records attributed to M Okajima.
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The disulphate ester of ursodeoxycholyl-p-aminobenzoic acid (PABA-UCDA) was synthesised and compared with PABA-UDCA for its use in detection of intestinal bacteria. This compound, PABA-UDCA disulphate, had characters in common with PABA-UDCA in that it was deconjugated by cholylglycine hydrolase to release free PABA and bacteria that split glycocholic acid deconjugated PABA-UDCA disulphate. Further, in rat experiments urinary excretions of PABA were measured for six hours after oral administration of 15 mg PABA-UDCA disulphate. Ten control rats excreted (mean (SE) 188.2 (13.6) micrograms of PABA; 10 rats with an intestinal stagnant loop excreted more (530.1 (30.1) micrograms; p < 0.001): whereas 10 rats in each of three groups pretreated by oral administration of various antibiotics excreted less (polymixin B+tinidazole, 4.9 (1.6) micrograms; kanamycin, 31.0 (4.7) micrograms; clindamycin 40.9 (5.5) micrograms; p < 0.001). By contrast with PABA-UDCA, PABA-UDCA disulphate was not actively absorbed from any part of the small intestine in everted gut sac experiments, and showed poor recovery from bile after its intraileal instillation in rats. This indicated that PABA-UDCA disulphate is a single pass type substance in the gut and its oral administration test reflects the sum of the activities of bacteria in the small intestine and colon. The disulphate was easily soluble in water and this allowed its application in an in vitro test involving PABA-UDCA disulphate incubation with intraperitoneal pus (PABA-UDCA disulphate incubation test) from patients with peritonitis. This test was carried out on six patients with peritonitis, and the severity of bacterial peritonitis was expressed quantitatively. From the results obtained PABA-UDCA disulphate was considered a good material to detect intestinal bacteria.
The development of dermal ridges, ridge configurations, and volar pad contours was investigated in the volar skin of the rat (Rattus norvegicus). The ridged structures corresponding to the epidermal ridges of primates exist only at the epidermal-dermal junction in the rat. Dermal specimens were prepared by treatment with alkaline solution and examined by toluidine blue staining and scanning electron microscopy, together with histological sections. Differentiation of dermal ridges began on day 18 of gestation on the palm followed by the sole. Ridges increased in number with advancing age. The process was complete approximately 2-3 days after birth, and sweat ducts began to develop simultaneously. As dermal ridges present various configurational patterns on palmar interdigital pad III, pattern formation on this pad was inspected in fetuses of three inbred strains possessing different pattern types, and in the hybrid progeny derived from them. Patterns and pad forms appeared to be under genetic control. It was revealed that the ridge arrangements, i.e., whorls, triradii, comb-like patterns, and others, are closely related to the pad contours during the developmental period, as hypothesized in primates.
A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 +/- 13.8 micrograms (mean +/- SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 +/- 70.2 micrograms; P less than 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P less than 0.001; polymixin B + tinidazole, 14.0 +/- 2.5 micrograms; polymixin B, 224.9 +/- 23.5 micrograms; tinidazole, 42.7 +/- 8.6 micrograms; kanamycin, 50.3 +/- 5.8 micrograms; clindamycin, 57.4 +/- 7.4 micrograms; vancomycin, 70.4 +/- 8.5 micrograms; and paromomycin, 160.4 +/- 16.4 micrograms). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 +/- 15.9 micrograms; P less than 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 +/- 34.5 micrograms and 386.7 +/- 61.2 micrograms, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 +/- 2.02 mg in controls (n = 5) and 12.20 +/- 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P less than 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment.
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Body surface potential maps differ considerably in their pattern even among normals, depending upon torso configuration. Thus individualized modelling of the heart-torso model is certainly desirable for a forward problem if it can be achieved without much effort. In this paper such a heart-torso model which is flexible enough to adapt to different body shapes with ease will be reported. As its basic structure, the innermost sphere represents the electromotive force of the heart, the outermost ellipsoid surface representing the torso surface and nine similar ellipsoid surfaces intervening between the two with step-wise increasing diameters were considered. We made 98 radiating penetration points for the innermost sphere as well as the 10 intervening ellipsoid surfaces. By making use of neighboring points of penetration as corners, the heart-torso model was divided into 4992 tetrahedral elements for a finite element method calculation. Once this basic structure was established, it was found to be very easy to be modified in a computer in order to make it fit to individual torso configurations quite faithfully by deforming the outermost ellipsoid. Individualized torso-heart models were built and their maps were simulated using data obtained from several healthy subjects. This paper discusses the results of two individuals, one muscular and the other slender, who exhibited considerably different body surface potential maps.
Previous studies from this laboratory have reported on the characteristics of a molecule which make it inhibitory. These findings were based on studies using the T cell-independent haptenated polymer, 2,4-dinitrophenyl-polyacrylamide (DNP-PA). The present study was undertaken to determine whether the same molecular properties which defined the inhibitory potentials of DNP-PA were characteristic of other haptenated polymers as well. The molecules studied here consisted of a series of five diverse fluoresceinated polymers with varying molecular mass and hapten valence. In agreement with the previous findings on DNP-PA, definable molecular forms of fluoresceinated dextrans. Ficolls, polyacrylamides, carboxymethyl celluloses and polyvinyl alcohols were each found to be capable of inhibiting the anti-fluorescein response to immunogenic forms of haptenated polymers of either the same or different carrier chemistry. This inhibitory ability was relatively independent of the chemical composition and conformation of the carrier polymer. These studies allow some logical generalizations to be made as to which quantitative molecular properties of haptenated type 2 T cell-independent antigens determine whether they will be stimulatory or inhibitory of an anti-hapten immune response.
Murine T helper type 2 clones were stimulated with immobilized anti-CD3 antibody or with recombinant lymphokines to compare the expression of T-cell activation genes induced by these stimuli. Immobilized anti-CD3 antibody, recombinant interleukin 2 (IL-2), and recombinant interleukin 4 (IL-4) all induced proliferation of the T helper type 2 clones 10-5-17 and D10. Proliferation of these clones induced by anti-CD3 antibody was completely inhibited by cyclosporine A, whereas cyclosporine A had little effect on proliferation induced by recombinant IL-2 or recombinant IL-4. Both immobilized anti-CD3 antibody, and recombinant IL-2 induced the expression of the protooncogenes c-myc and c-myb. Immobilized anti-CD3 antibody also induced expression of the lymphokine genes IL-4, interleukin 5 (IL-5), and granulocyte-macrophage colony-stimulating factor. In contrast, recombinant IL-2 induced IL-5 mRNA expression but did not induce detectable expression of IL-4 or granulocyte-macrophage colony-stimulating factor mRNA. Likewise, recombinant IL-4 induced expression of IL-5 but not IL-4 mRNA. Thus, the IL-4 and IL-5 genes appear to be differentially regulated after stimulation with recombinant lymphokines. Effects of cyclosporine A and the protein synthesis inhibitors cycloheximide and anisomycin on IL-4 and IL-5 gene expression suggest that these genes are activated by different pathways after anti-CD3 stimulation. Cyclosporine A completely inhibited anti-CD3-induced expression of IL-4 mRNA but not of IL-5 mRNA, and protein-synthesis inhibitors completely inhibited induction of IL-5 mRNA but not of IL-4 mRNA. Together, our data show that T-cell receptor-mediated and lymphokine receptor-mediated signals induce different patterns of lymphokine gene expression and provide strong evidence that the IL-4 and IL-5 genes are differently regulated.
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The outline of the Nagoya Program, the most representative software package for computerized electrocardiography in Japan, is described. First, the history and current status of research and its transfer to commercial products for computerized interpretation of electrocardiograms is briefly reviewed. Second, development and testing of the Nagoya Program is depicted, referring to a gold standard for evaluation and the database being used for this purpose, and to its participation in the CSE study. Third, a description of signal acquisition and wave identification is given, followed by the detection of rhythm disturbances. Next, algorithms for contour classification, which consist of decision-tree logic established through trial and error and making use of the database of ECGs, are described. Finally, special features and future plans of the Nagoya Program are mentioned.
T cell-independent Ag are believed to stimulate antibody formation in the relative absence of Ag processing and T cell help. Previous studies on the type 2 T cell independent (TI-2) Ag DNP-polyacrylamide, have shown that when one systematically varies the molecular mass and hapten valence, the immunogenic potential of this type of molecule depends on definable molecular characteristics. It was found that to be immunogenic, these molecules had to exceed a threshold molecular mass of 100,000 Da and a threshold hapten valence of 20. The present study was undertaken to determine whether such findings could be generalized to other molecules belonging to the TI-2 class of Ag. The molecular characteristics of five chemically different fluoresceinated (FL)-polymers were systematically varied, and their ability to stimulate an IgM antihapten immune response was measured. The polymers used as carriers were carefully size-fractionated and consisted of one natural polymer (dextran), one modified natural polymer (carboxymethyl cellulose), and three synthetic polymers (Ficoll, polyvinyl alcohol, and polyacrylamide). The carriers varied in physical structure from the highly cross-linked Ficoll, to the somewhat branched dextran, to the linear polyacrylamide, carboxymethyl cellulose, and polyvinyl alcohol. Polymers were haptenated with FL and size-fractionated so as to yield a panel of molecules with varying molecular mass, hapten valence, and hapten density. Anti-FL IgM response to these haptenated polymers was measured in vivo after i.p. injection of the FL-polymer in saline, and measured in vitro after culture with unfractionated spleen cells from naive mice. In agreement with the previous studies on DNP-polyacrylamide, it was found that to be immunogenic, each of the FL-polymers had to exceed a comparable threshold value of molecular mass and of hapten valence. Optimal immunogenicity occurred when the FL-polymers had values of mass and hapten density lying within a predictable range. Immunogenicity decreased when these optimal parameters were substantially increased or decreased. We conclude that the immunogenicity of soluble haptenated polymers depends on predictable physical molecular characteristics, and is relatively independent of the chemical composition and conformation of the carrier polymer.
To clarify the physiological role of the mechanism that adrenergic nerve inhibits Ach release from intramural cholinergic nerve endings, the influence of Midaglizole, alpha 2-adrenergic receptor antagonist, to postprandial gastrointestinal motilities in conscious dogs was investigated. Postprandial motilities of gastric antrum, duodenum, ileum, and colon were significantly enhanced by Midaglizole (3.0-5.0 mg/kg body weight, i.v.). These excitatory responses were abolished by atropine (0.05-0.1 mg/kg body weight, i.v.). On the other hand, in most cases (29 cases out of 32), when Midaglizole was administered during quiesent phase of IMC, no change occurred in gastrointestinal motility. However, after subliminal dose of pentagastrin or cisapride, which stimulated Ach release from intramural cholinergic neuron without development of motility, was administered, Midaglizole induced phasic, postprandial motility-like contraction in gastrointestinal tract. Even in the fasted state, when Midaglizole was administered intragastrically, irregular contractions with high amplitude occurred in every regions from gastric antrum to colon. And these excitatory responses were abolished by atropine. Similar reaction was observed also in truncal vagotomized dogs. These results suggest that it is the physiological mechanism that adrenergic nerve presynaptically inhibits Ach release from intramural cholinergic neuron, which is the main mechanism of development of postprandial motility, acting on alpha 2-adrenergic receptor, and has tonic control of postprandial motility.
Development of the dermal ridges in volar skin was investigated in 28 pigtailed macaque (Macaca nemestrina) fetuses of known gestational age, ranging from 51 days postconception to newborn. Histology, scanning electron microscopy, and staining of the abraded dermal surface were used in the study. Morphological features of the dermal-epidermal system and their changes with advancing age are described. Chronology was established for stages in the development of the volar skin, i.e., the differentiation of the primary and secondary epidermal ridges (PER and SER) at the undersurface of the epidermis corresponding to the formation of primary and secondary dermal ridges (PDR and SDR) and the development of the dermal papillae. PDRs were first seen at 55 gestational days and SDRs at 93 days. Differentiation of sweat ducts occurred over the period between 60 and 119 gestational days. A regional sequence of differentiation starting with the digital apices of the hand and ending in the calcar area and the phalanges of the foot was documented. Generally, morphogenesis in the macaque was accelerated relative to that in the human fetus by approximately 3 weeks.
The action of cisapride on physiological and disturbed gastrointestinal motor function was investigated in conscious and anesthetized dogs and the mechanism of action involved. Regardless of the presence or absence of vagal innervation, administration of cisapride (0.2 mg approximately 1.0 mg/kg body weight, i.v.) during the quiescent period of interdigestive migrating contractions (IMC), induced non-migrating IMC-like motility in the entire gastrointestinal tract from gastric body to distal colon. Administration of cisapride in the digestive state resulted in the excitatory response of increased amplitude of digestive peristalsis and strong IMC-like motility was not observed. All of these excitatory responses in gastrointestinal motility disappeared by the administration of atropine (0.5 mg approximately 0.1 mg/kg body weight, i.v.). Furthermore, the excitatory response in gastrointestinal motility induced by cisapride in anesthetized dogs disappeared by the administration of TTX (10 micrograms/kg of body weight, i.v.). These results suggest that the excitatory action of cisapride on the gastrointestinal motility is based on its mechanism in which cisapride acts on the cholinergic neurones in the gastrointestinal wall to stimulate ACh release, resulting in the increase in gastrointestinal motility. Cisapride caused powerful IMC-like motility in the ileum of animal with pseudo-obstruction-like motor disturbance which had been seen after preparation of Thiry loop (ileum). This motility migrated from the proximal ileum to the Thiry loop and then to the distal ileum. Trimebutine maleate also demonstrated this effect, but metoclopramide and domperidone were ineffective. Administration of cisapride at the doses (0.2 mg approximately 1.0 mg/kg body weight, i.v.) causing stimulated motor response in the gastrointestinal tract did not induce significant secretion of gastric acid, pancreatic juice and bile.
Dermatoglyphic abnormalities are often observed in patients with chromosome aberrations, but no similar observations have been made in animals. In the present study, palmar dermatoglyphics were examined in 4 rats with chromosome anomalies. Reciprocal translocations were induced by gamma-irradiation; the animals used were obtained from among offspring with abnormal karyotypes that were derived from the original mutant rats. As the epidermal surface of the volar pad of the rat is flat, dermatoglyphic characteristics were observed on the dermal surface following staining with toluidine blue. Unusual ridge configurations were found in some of them, suggesting that dermatoglyphic development in the rat reflects, to some extent, an abnormal chromosome constitution.
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Ambulatory electrocardiographic monitoring was performed on 360 healthy children, from newborn infants to junior high school students. They were divided into five groups by age: group A, 63 newborn infants on the first day of life; group B, 50 infants aged 1-11 months; group C, 53 kindergarten pupils aged 4-6 years; group D, 97 primary school pupils aged 9-12 years; and group E, 97 junior high school students aged 13-15 years. The maximal and minimal heart rates were significantly greater in infants than in older children. Sinus arrhythmia was recorded in every child. One boy in group E had an episode of sinus arrest for three seconds without any symptoms. First-degree and Wenckebach type second-degree atrioventricular blocks were not detected in group A and group B, but were most frequent in group E, especially during sleep. Supraventricular premature contractions (SVPCs) were the most common type of arrhythmia detected in this study. More than half of the children had at least one SVPC per 24-h monitoring period, and there were many children with frequent SVPCs in group E. The incidence of ventricular premature contractions (VPCs) in children of groups A and E was rather higher than in the other groups. Ventricular tachycardia was not recorded in any child except one newborn infant who had a couplet of VPCs without symptoms. Each group had different types and incidences of arrhythmias. There was a rising incidence of arrhythmias with advancing age, except in the neonatal period.