Experimental approach to using extrinsic fluorine-19 in magnetic resonance imaging.
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Biomedical subjects
Publications and source records attributed to M Itoh.
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Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Nine monoclonal antibodies (MAbs) directed to F protein of Sendai virus were obtained and characterized for their protective ability against Sendai virus infection in mice. None of the MAbs showed hemagglutination-inhibition (HI), hemolysis-inhibition (HLI), or neutralization (NT) activities in vitro when assayed by standard methods. Some of the MAbs, however, showed complement-requiring NT (C-NT) and complement-requiring hemolysis (C-HL) activities when assayed in the presence of complement. Passive immunization experiments revealed that the MAbs with higher C-NT and C-HL activities showed protective activity against Sendai virus pneumonia in mice, and that some MAbs with IgG1 isotype having neither C-NT nor C-HL activity also showed the protective activity. Digestion of the MAbs with pepsin which split immunoglobulin molecules into F(ab')2 and Fc fragments greatly suppressed the protective activity. These results suggest that not only complement-mediated immunological responses such as immune virolysis but also antibody-dependent cellular cytotoxicity (ADCC) and/or immune phagocytosis, in which complement system is not necessarily involved, play an important role in the protection of mice from Sendai virus infection.
The binding of [3H]pyrilamine, a selective ligand of histamine H1 receptors, to guinea pig brain in vivo was compared with its binding to a brain homogenate. The pharmacological properties (regional distribution, saturability, and stereoselectivity) of the [3H]pyrilamine binding in vivo were similar to those of the in vitro binding to brain homogenate. A dynamic four-compartment model was proposed for the analysis of the kinetics of [3H]pyrilamine binding in vivo. The receptor constants in vivo were determined by a computer-fitting method after correcting the radioactivity of arterial plasma and brain for the presence of radioactive metabolites. The in vivo association and dissociation were 213 and 42 times, respectively, slower than those of in vitro binding at 37 degrees C. A possible mechanism for slow association and dissociation in vivo is discussed.
Polysulfides formed through the breakdown of elemental sulfur or other sulfur compounds were found to be reduced to H(2)S by the hyperthermophilic archaebacterium Pyrococcus furiosus during growth. Metabolism of polysulfides by the organism was dissimilatory, as no incorporation of S-labeled elemental sulfur was detected. However, [S]cysteine and [S]methionine were incorporated into cellular protein. Contact between the organism and elemental sulfur is not necessary for metabolism. The sulfide generated from metabolic reduction of polysulfides dissociates to a strong nucleophile, HS, which in turn opens up the S(8) elemental sulfur ring. In addition to H(2)S, P. furiosus cultures produced methyl mercaptan in a growth-associated fashion.
A protease-activation mutant of Sendai virus, TCs, was isolated from a trypsin-resistant mutant, TR-5. TCs was activated in vitro by both trypsin and chymotrypsin. TCs was, however, less sensitive to trypsin and chymotrypsin than were the wild-type virus and TR-5, respectively. F protein of TCs had a single amino acid substitution at residue 114 from glutamine to arginine, resulting in the appearance of the new cleavage site for trypsin and the shift of the cleavage site for chymotrypsin. Activation of TCs in the lungs of mice occurred less efficiently than that of the wild type, and TCs caused a less severe pneumopathogenicity than did the wild-type virus, which supports our previous view that the in vitro trypsin sensitivity of Sendai virus can be a good indication of pneumopathogenicity in mice.
Rex protein of human T-cell leukemia virus type 1 (HTLV-1) induces cytoplasmic expression of unspliced gag/pol mRNA and singly spliced env mRNA and thus is essential for replication of the virus. This regulation requires a cis-acting rex-responsive element (RXE), located in the 3' region of the viral RNA. By external deletion, we have identified RXE composed of 205 nucleotides. The secondary structure of RXE was confirmed by studies on its susceptibility to nuclease digestions to consist of four stem-loops and a long stretch of stem structure. Substitution and deletion mutations revealed that two regions of the stem-loops and their secondary structures are essential for rex regulation. Similar secondary structures were found in the corresponding regions of HTLV-2, bovine leukemia virus and human immunodeficiency virus. Furthermore, a sequence of 11 nucleotides in the RXE was found to be conserved in the secondary structures of HTLV-1, HTLV-2, and bovine leukemia virus. These observations suggest that the secondary structure as well as the conserved sequence may be important in expression of unspliced RNA even with diverged sequences as observed in these viruses.
Cerebral blood flow and oxygen metabolism in aged normal subjects were measured with positron emission tomography and their relationship with brain atrophy was evaluated. Brain atrophy progressed in a linear fashion during aging while cerebral blood flow and oxygen metabolism were well preserved. The finding suggests that brain atrophy is an aging process less dependent on cerebral blood flow and metabolism over the course of normal aging.
Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats (SHRSP) were investigated. Betaxolol was provided in a dose of 33 +/- 1.8 mg/kg/day, orally in drinking water, throughout the experimental period. The chronic treatment with betaxolol inhibited the development of hypertension in SHRSP and reduced values of blood urea nitrogen, creatinine, total cholesterol, free cholesterol, triglyceride, phospholipid and HDL-cholesterol in serum. Treatment with betaxolol apparently inhibited the incidence of hypertensive lesions such as cardiac fibrosis, mesenteric vasculitis, proliferative and/or necrotic vasculitis and glomeruli showing collapse or vasculitis in the kidneys. To shorten the time before the onset of hypertension and the subsequent stroke, SHRSP were kept on a SP diet containing 0.39% Na instead of the F-2 diet. When the SHRSP were kept on the SP diet, all of the control SHRSP had cerebral apoplexy and severe hypertensive lesions in the heart and kidney. When betaxolol was chronically administered to SHRSP, cerebral apoplexy and hypertensive lesions in the heart and kidney were inhibited, but the effect on blood pressure was slight. Treatment with betaxolol reduced serum creatinine levels. Our observations show that betaxolol reduces blood pressure and potently inhibits hypertensive complications in SHRSP.
Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[18F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p less than 0.01 and p less than 0.05) and basal ganglia (p less than 0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain.
A case of malignant ependymoma with extracranial metastases is reported. A 59-year-old male was admitted to our hospital with vomiting and ataxia. Following computed tomographic (CT) scanning indicating a ring-like enhanced mass in the cerebellum, the tumor was subtotally removed in December, 1985. Histological diagnosis was malignant ependymoma. A second operation was performed in February, 1987, due to recurrence of the tumor in the fourth ventricle. Postoperative radiation therapy at a total dose of 7780 rads was given over 2 years. Eleven months after radiation therapy was completed, he reported cough and multiple skin metastases. Chest x-rays showed metastases at the right hilus. Repeated CT scans revealed separate frontal cerebral metastatic tumors. He died of respiratory insufficiency. Extracranial metastases of infratentorial ependymoma to the skin and lung are rare pathological entities.
Interleukin 2 (IL2) responsiveness of ovalbumin (OVA)-stimulated lymphocytes from patients with hen-egg allergy was studied. The number of viable cells of 5-day cultured lymphocytes stimulated with OVA was increased by an additional three days incubation with recombinant IL2. This phenomenon was not observed when the lymphocytes of patients allergic to OVA but not to Dermatophagoides farinae extract antigen (Df) were stimulated with Df. Normal lymphocytes stimulated with OVA expressed Tac antigen (low affinity IL2 receptor) but, in contrast to those from the allergic patients, did not absorb nor respond to IL2. The induction of OVA-specific IL2 responsiveness in patient lymphocytes was markedly suppressed on the addition of culture supernatant from OVA-stimulated normal T cells, but Df-specific IL2 responsiveness of the lymphocytes from Df-sensitized patients with bronchial asthma was not suppressed by the same supernatant. The supernatant of lymphocytes from allergic patients did not show such suppressive effect. The patient lymphocytes whose IL2 responsiveness was suppressed with the supernatant from normal lymphocytes still expressed Tac antigen. These observations suggest that the culture supernatant of normal T lymphocytes stimulated with OVA contained an antigen-specific factor suppressing the induction of IL2 responsiveness of OVA-stimulated patient lymphocytes. The production of such a suppressive factor was impaired in the patient, and further, the factor may have inhibited the triggering signal of IL2 receptors having absorbed IL2. The existence of some allogeneic barrier between the factor(s) and patient lymphocytes was suggested, since the supernatant from OVA-stimulated normal T cells did not necessarily suppress the response of all patients tested.
A nitrocellulose membrane strip dotted with crude antigens of trematodes, such as Paragonimus miyazakii, P. westermani, Fasciola sp., Clonorchis sinensis and Schistosoma japonicum was applied for serodiagnosis of trematodiasis. With peroxidase conjugated anti-human IgG and 4-chloro-1-naphthol as a substrate, antibodies in trematodiasis patient sera were clearly detected on the strip as bluish purple spots. Densities of the spots correlated well with values obtained by standard micro-ELISA. Cross-reactions among the trematode antigens, which is occurred more frequently than by ELISA, were observed with this method. However, the darkest spot correlated with the infecting parasite in all cases. With the high reliability and advantage that crude antigens can be used, this simple method, multi-dot ELISA, is considered to be useful for serodiagnosis of trematodiasis.
A 53-year-old woman was admitted with complaints of edema in the lower legs. The patient had developed polyarthralgia in 1982 and had been treated with D-penicillamine and prednisolone under the diagnosis of rheumatoid arthritis. She then had developed sclerosis of skin as well as dry eyes and dry mouth. In November 1987, bucillamine treatment had started and proteinuria had appeared in February 1988. Her blood showed hypoproteinemia and was positive for anti-Scl-70 antibody test and for anti-SS-A antibody test. The skin biopsy and labial salivary gland biopsy revealed the increased collagen fibers in the subcutaneous tissue and the round cell infiltration around the salivary ducts. We diagnosed her as progressive systemic sclerosis (PSS) with Sjögren's syndrome (SjS) complicated by nephrotic syndrome. Subsequently a renal biopsy was performed. There were the granular deposition of IgG and complements in the glomerular capillary wall and electron dense deposits in the subepithelial region. These findings suggested that she had membranous nephropathy. Since such a renal lesion was rarely observed in PSS and SjS, it was highly probable that bucillamine induced the nephropathy. The bucillamine treatment was discontinued about 2 months after the nephrotic syndrome had developed. However, the nephrotic syndrome has continued for additional 8 months. Thus it is concluded that the renal damage is one of the important side effect caused by bucillamine.
To make clear the characteristics of cerebral glucose uterization in dementia, PET studies with 18F-FDG were carried out. Taking the pattern of 18F-FDG uterization, dementia can be subdivided into two types. One type shows a simultaneous and symmetrical reduction glucose uterization in the posterior part of neocortex covering the temporal, parietal and occipital association cortices. This is referred to as type I. Although this type constitutes only about 1/5 of all dementia patients, it is considered the fundamental type of dementia. Aside from this, there is type wherein a simultaneous and symmetrical reduction in glucose uterization of the neocortex. This is type II. It constitutes about 4/5 of all dementia patients which is far more type I. There are no essential difference in the characteristics of cerebral glucose uterization in AD and MID. However, with regards the mean, AD is lower than MID. Various organic defect in neocortex do not correlate with the global reduction in glucose uterization in dementia patients. These results suggest that the reduction in glucose uterization in dementia may be functional disorder.
A new dosage form of mitomycin C (MMC-CH) comprising 0.75 mg/ml of activated carbon particles adsorbing mitomycin C at 124 micrograms/mg and 7 micrograms/ml of mitomycin C in a free state was injected intraperitoneally to male rats of Donryu strain transplanted intraperitoneally with 10(7) cells/rat of Yoshida sarcoma 4 days before injection. The rats were subjected to autopsy within 60 min after injection. MMC-CH adhered selectively to the tumor surface of Yoshida sarcoma growing intraperitoneally rather than to the surface of organs such as small intestines which the surface cancer did not affect. Within 120 min after injection, mitomycin C concentration in the tissue samples was bioassayed. Intraperitoneally injected MMC-CH distributed high levels of mitomycin C to the tumor rather than to the unaffected organ located intraperitoneally. Animals killed by cancer after the treatment of MMC-CH were autopsied. Histological effects of MMC-CH were studied microscopically. Mitomycin C adsorbed on activated carbon particles induced degenerative changes in the tissues of tumors to which the activated carbon particles had adhered.
Using a total of 60 human extracted first deciduous molars (30 upper molars and 30 lower molars), we contrived a variety of ideal cavities having dentin thicknesses below the cavity (subcavitary dentin) that measure approximately 1 mm in thickness from the pulp chamber at any point of measurement and also having a retentional groove prepared in such a way that detachment of a filling material is prevented. The transparent specimens prepared from the cavity-containing teeth were cut into serial sections of 93 microns. These sections were reconstructed using a personal computer. The thickness of dentin below the cavity was measured in randomly selected sections. Results obtained were as follows: 1. An ideal thickness of the subcavitary dentin was preserved for upper first deciduous molar by preparing a retentional groove lingually or by providing a dovetail-like shape to mesio-distolingual sides in the cavity; for lower first deciduous molar, any form of cavitation worked. 2. In the upper first deciduous molars, the margins of the cavity were displaced medially to the summits of the respective cusps 1.9 mm at the buccal side and 1.2 mm at the lingual side. In the lower first deciduous molars, the buccal margin medially measured 0.9 mm and the lingual margin measured 0.6 mm at the mesial side. At the distal side, the buccal and lingual margins measured 1.2 mm and 1.0 mm, respectively. 3. The ratio of cavity width to the distance between the summits of the buccal and lingual cusps was 1/3 in upper deciduous first molars and 2/5 in the lower first deciduous molars. 4. In the upper first deciduous molars, the depths of the buccal and lingual walls of the cavity at the center of the central groove were both 1.1 mm. In the lower first deciduous molars, the cavity formed with its center at the middle of the transverse ridge had a depth of 1.5 mm at the buccal wall and a depth of 1.7 mm at the lingual wall. The cavity formed with its center at the central fossa had a depth of 1.2 mm at the buccal wall and 1.1 mm at the lingual wall. 5. The width of the gingival wall in the proximal box measured 0.6-0.7 mm in upper and lower first deciduous molars.
This study was designed to devise configuratively ideal cavity formations using 49 second deciduous molars, consisting of 25 extracted from the maxilla and 24 from the mandible. A cavity having at least 1 mm subcavitary (below the cavity) dentin thickness at any point of measurement and having an appropriately formed and positioned retention was defined as an ideal cavity. The same methods were used as in our previous study of first deciduous molars. The following results were obtained: 1. In upper second deciduous molars, the subcavitary dentin thickness was thin at the mesiobuccal side of the cavity; it measured 0.9 mm. In lower second deciduous molars, the subcavitary dentin thickness was thin at the mesiobuccal, distolingual sides of the cavity, and central fossa, where the retentional groove was provided; it measured 0.8-0.9 mm. The other measured values exceeded 1.0 mm. All thickness measurements were very close to the values considered as ideal. 2. In upper second deciduous molars, the margins of the cavity were positioned medially to the summits of respective cusps, 1.8-2.0 mm at the buccal side and 1.5 mm at the lingual side. The entire cavity was located lingually. 3. In lower second deciduous molars, the buccal margin of the cavity was positioned 1.7 mm medially to the summit of the distobuccal cusp and 1.2-1.3 mm medially to the summits of the other buccal cusps. The lingual margin was positioned 1.4-1.5 mm medially to the summits of respective cusps. medially to the summits of respective cusps. 4. The buccolingual width of the cavity amounted to 1/3 of the distance between the summits of the buccal and lingual cusps in both upper and lower second deciduous molars. 5. At the mesial side, the depth of cavity was 1.4 mm at the buccal wall and 1.5 mm at the lingual wall in upper second deciduous molars, and 1.4 mm at the buccal wall and 1.6 mm at the lingual wall in lower second deciduous molars. 6. The width of gingival wall in the proximal box measured 1.0 mm in both upper and lower second deciduous molars.