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Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 865 records · Page 48Linked to original sources

Evaluation of cerebral collateral circulation by technetium-99m HM-PAO brain SPECT during Matas test: report of three cases.

Three cases with cerebral ischemic symptoms and an intracranial aneurysm are presented. Using [99mTc]hexamethyl-propyleneamine oxime (HM-PAO) single photon emission computed tomography imaging before and during the Matas test, a quantitative measurement method was developed for evaluating brain collateral circulation. The evaluation correlated well with findings of contrast carotid angiography. This noninvasive method seems to be useful for selection of patients for appropriate surgical treatment.

Aged↗

Regulation of two ion channels by a common muscarinic receptor-transduction system in a vertebrate neuron.

In bullfrog sympathetic ganglion cells, muscarine produced an inward current (Imus) through the activation of a subtype (M1) of muscarinic acetylcholine receptor (mAChR) by suppressing an outward M-current (IM), and/or activating cation-selective current (ID; see below). The former was induced with a potency (Kd = 0.5 microM) higher than the latter (Kd = 5 microM) before and after blocking a fraction of the receptor with an irreversible blocker. Activators of protein kinase C mimicked muscarine's actions. Blocking IM by Ba2+ increased ID. These results suggest that activation of M1-mAChR both closes M-channel and opens cation-selective D-channel through phosphoinositide breakdown and the subsequent activation of protein kinase C and that a difference in potency at the last step of the cascade determines the order in which channels are regulated.

Animals↗

Variability of initial cortical sensory evoked potentials to posterior tibial nerve stimulation.

Scalp topographies and distributions of initial cortical positive-negative components of somatosensory evoked potentials (SEPs) to posterior tibial nerve stimulation were studied in 12 normal controls in order to investigate the generator sources of the cortical SEPs. There are three variations in topographies and distributions of early cortical SEPs in normal subjects. In 5 of 12 cases initial cortical positive-negative components were distributed over the centro-parietal areas ipsilateral to the stimulation site or midline parasagittal areas. The origins of these components are speculated to be vertical dipolar generators located at the contralateral interhemispheric fissure. In 5 of 12 cases P37/N36, and N45/P43 showed a phase reversal between the left and right hemispheres and may be generated from horizontal dipoles located at the contralateral interhemispheric fissure. In 2 of 12 cases N36 and P43 were distributed predominantly over the contralateral hemisphere. Oblique dipolar generators located at the contralateral interhemispheric fissure may be oriented prominently to the contralateral hemisphere. Normal variations of initial cortical positive-negative components of SEPs to posterior tibial nerve stimulation should be considered in their clinical applications.

Adolescent↗

Misoprostol-induced changes in gastric mucosal hemodynamics. A double-blind parallel study in human volunteers.

The effects of misoprostol on human gastric mucosal hemodynamics were examined in a double-blind, placebo-controlled, parallel study in 12 healthy male volunteers. Six subjects received 200 micrograms of misoprostol and six received placebo. The index of mucosal blood volume and mucosal blood hemoglobin oxygen saturation (Hb-SO2) were measured at 20 locations in the stomach using reflectance spectrophotometry during endoscopy prior to and after administration of the study drug. Mucosal blood volume index increased by approximately 10 to 25 percent throughout the stomach without a significant change in mucosal Hb-SO2 following treatment with misoprostol. The increase in mucosal blood volume index was statistically significant for 16 of the 20 locations (p less than or equal to 0.05). Placebo produced no significant change in mucosal blood volume and mucosal Hb-SO2. These findings suggest that misoprostol may have the potential effect of accelerating gastric ulcer healing by improving gastric mucosal hemodynamics, in addition to its gastric acid antisecretory activity.

Adult↗

Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A.

Twelve complementary DNA clones for human lysosomal alpha-galactosidase A were isolated from an Okayama-Berg library constructed from SV40-transformed human fibroblasts. The identity of these clones was confirmed by complete colinearity of the nucleotide-deduced amino acid sequence with that determined by direct chemical sequencing of human placental alpha-galactosidase A. Hybridization of the alpha-galactosidase A cDNA to genomic DNA from individuals with varying numbers of X chromosomes as well as from interspecies somatic-cell hybrids showed only a single locus in the genome at Xq 13.1-Xq 22. One cDNA clone (pcD-AG210) contained the complete coding sequence for both the signal peptide and mature alpha-galactosidase A. The signal peptide of 31 amino acids contains the expected hydrophobic domains consisting of Leu-Gly-Cys-Ala-Leu-Ala-Leu and Phe-Leu-Ala-Leu-Val and has Ala at the signal peptidase cleavage site. Twelve out of fifteen G residues flanking the 5' end of the cDNA in pcD-AG210 were removed and the truncated fragment was ligated into the original vector. This construct, pcD-AG502, encoded enzymatically active human alpha-galactosidase A in monkey COS cells.

Amino Acid Sequence↗

A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease.

To search for a genetic marker for type 2 Gaucher's disease (acute neuronopathic form), we compared the nucleotide sequence of a cloned glucocerebrosidase gene from a patient with Gaucher's disease with a normal gene. We found only a single base substitution (T----C) in exon X. This mutation results in the substitution of proline for leucine in position number 444 and produces a new cleavage site for the NciI restriction endonuclease. We analyzed NciI enzymatic digests of genomic DNA from 20 patients with type 1, 5 with type 2, and 11 with type 3 Gaucher's disease, and 29 normal controls for a restriction-fragment-length polymorphism (RFLP). Four of 5 patients with type 2 disease and all 11 with type 3 disease had at least one allele with the mutation. Two of 5 patients with type 2 disease and 7 of 11 with type 3 were homozygous for this mutation. Only 4 of 20 patients with type 1 Gaucher's disease had the mutant allele and were heterozygous for it. None of the 29 normal controls had the mutant allele. The high frequency of this mutation (444leucine----proline) in patients with neuronopathic Gaucher's disease, detectable by the NciI RFLP, may be of value in the identification of patients who will have the neurologic sequelae of Gaucher's disease.

Adolescent↗

Chicken ornithine transcarbamylase: its unexpected expression.

Ornithine transcarbamylase (OTC), one of the enzymes of the urea cycle, is detectable in some strains of chickens, although they have no functional urea cycle. The enzyme consists of three identical subunits of 36 kd and is present in mitochondria of the kidney. Using immunoabsorbent column chromatography, we found further evidence that the enzyme is detectable as a precursor form (40 kd) in chicken brain, heart, liver, pancreas, gizzard, small intestine, and breast muscle. When an extract of small intestine containing only precursor OTC was treated with a kidney extract, the precursor was converted into OTC. This suggests that there is a tissue-specific processing protease in the kidney which splits a peptide off the precursor, causing the expression of OTC activity in this organ. However, the reason why the enzyme or its precursor is expressed in these organs is not known. The results of this study suggest that, unlike mammals, chickens are more organ specific with regard to the ability to incorporate precursor OTC into mitochondria.

Animals↗

Chromosomal instability in mutagen-sensitive mutants isolated from mouse lymphoma L5178Y cells. I. Five different genes participate in the formation of baseline sister-chromatid exchanges and spontaneous chromosomal aberrations.

In a search for cell mutants that show an increase or a decrease in the frequency of baseline sister-chromatid exchanges (SCEs) or spontaneous chromosomal aberrations (CAs), large numbers of mutagen-sensitive clones previously isolated from mouse lymphoma L5178Y cells were analyzed. In addition to two SCE mutants (ES 4 and AC 12) previously reported, three other mutants were identified as an SCE mutant. An ethyl methanesulfonate-sensitive mutant ES 2 and an alkylating agent-sensitive mutant MS 1 exhibited, respectively, 1.4-fold and 1.8-fold higher baseline SCE frequencies than did the parental L5178Y. In contrast, M10, which is sensitive to X-ray and 4-nitroquinoline 1-oxide, showed a reduced frequency of baseline SCEs (0.65-fold). These 5 mutants including ES 4 and AC 12 had 3--9-fold increases in spontaneous CA frequencies. Measurement of baseline SCE formation in inter-mutant hybrids revealed that M10 mutation is dominant, MS 1 and ES 4 mutations are semidominant, and ES 2 and AC 12 mutations are recessive. Because SCE frequencies in hybrids formed between pairs of 4 mutants (ES 2, MS 1, ES 4 and AC 12) were significantly lower than those in the tetraploid mutant cells, these 4 mutants probably belong to different complementation groups. Since M10 behaved dominantly with respect to SCE phenotype, it was not possible to determine by complementation test whether it belongs to a different group from the other mutants. However, the finding that M10 is complemented by other mutants for EMS sensitivity indicates that the M10 mutation is different from the other mutations. From these results, it is concluded that at least 4 different genes participate in the formation of high levels of baseline SCEs. The defects in ES 2, MS 1, ES 4, and AC 12 produce common lesions responsible for the formation of both SCEs and CAs. In contrast, the defect in M10 is associated with a high increase in spontaneous CA frequency, but conversely associated with a decrease in baseline SCE frequency. This suggests that M10 is defective in the process involved in the formation of baseline SCEs.

Animals↗

Chromosomal instability in mutagen-sensitive mutants isolated from mouse lymphoma L5178Y cells. II. Abnormal induction of sister-chromatid exchanges and chromosomal aberrations by mutagens in an ionizing radiation-sensitive mutant (M10) and an alkylating agent-sensitive mutant (MS1).

To determine the mutual relationships between cell survival and induction of sister-chromatid exchanges (SCEs) as well as chromosomal aberrations (CAs), mutagen-induced SCEs and CAs were analyzed in an ionizing radiation-sensitive mutant (M10) and an alkylating agent-sensitive mutant (MS 1) isolated from mouse lymphoma L5178Y cells. The levels of CA induction in both mutants strictly corresponded to the sensitivity to lethal effects of mutagens, except that caffeine-induced CAs in M10 are considerably lower than those in L5178Y. The results clearly indicate that except for caffeine-induced CAs in M10, mutagen-induced lethal lesions are responsible for CA induction. In contrast, SCE induction in mutants was complicated. In M10, hypersensitive to killing by gamma-rays, methyl methanesulfonate (MMS), and 4-nitroquinoline 1-oxide (4NQO), but not sensitive to UV or caffeine, the frequency of SCEs induced by gamma-rays was barely higher than that in L5178Y, and the frequencies of MMS- and UV-induced SCEs were similar to those in L5178Y, but 4NQO- and caffeine-induced SCEs were markedly lower than those in L5178Y. MS 1, which is hypersensitive to MMS and caffeine, but not sensitive to UV or 4NQO, responded to caffeine with an enhanced frequency of SCEs and had a normal frequency of MMS-induced SCEs, but a reduced frequency of UV- and 4NQO-induced SCEs. Thus, susceptibility to SCE induction by mutagens is not necessarily correlated with sensitivity of mutants to cell killing and/or CA induction by mutagens. Furthermore, the spontaneous levels of SCEs are lower in M10 and higher in MS 1 than that in L5178Y (Tsuji et al., 1987). Based on these results, we speculate that M10 may be partially defective in the processes for the formation of SCEs caused by mutagens. On the other hand, MS 1 may modify SCE formation-related lesions induced by UV and 4NQO to some repair intermediates that do not cause SCE formation. In addition, MMS-induced lethal lesions in MS 1 may not be responsible for SCE induction whereas caffeine-induced lethal lesions are closely correlated with SCE induction. Thus, the lesions or mechanisms involved in SCE production are in part different from those responsible for cell lethality or CA production.

4-Nitroquinoline-1-oxide↗

[Islet cell carcinoma associated with concurrent Zollinger-Ellison syndrome and Cushing's syndrome].

A tissue specimen taken from the pancreatic tumor of a patient suffering from Zollinger-Ellison syndrome associated with a concurrent Cushing's syndrome was investigated both morphologically and immunohistochemically. Histologically, the tumor cells were found to be arranged in a cord or ribbon pattern. An immunohistochemical study revealed that the tumor nodule contained both gastrin and ACTH. Further, double stainings of the same section disclosed that the same tumor nodule possessed both hormones simultaneously, thus confirming the concurrent presence of Zollinger-Ellison syndrome and Cushing's syndrome. An electron micrograph of the tumor cell showed the presence of numerous endocrine-type granules in the cytoplasm. These findings substantiate the concurrent presence of the two characteristic clinical syndromes.

Adenoma, Islet Cell↗

Immunohistochemical studies on the expression of pulmonary surfactant apoproteins in human lung carcinomas using monoclonal antibodies.

To reevaluate the expression of pulmonary surfactant apoproteins in lung carcinomas, cancerous tissues from 47 cases were immunohistochemically examined by the avidin-biotin peroxidase complex method using monoclonal antibodies. These antibodies recognized apoproteins in type II pneumocytes in normal and in hyperplastic alveoli and nonciliated columnal cells (Clara cells) in terminal bronchioles of noncancerous tissues. Cancer cells positive for surfactant apoproteins were observed in 11 out of 33 adenocarcinomas, including 1 case of bronchioloalveolar carcinoma. Interestingly, two cases of adenocarcinomas with ultrastructural features of Clara cells, which had metastatic lesions, were positively stained both in the primary and the metastatic sites. Two out of 4 adenosquamous carcinomas showed positive reaction, which was exclusively localized in the cells with papillary structure. The present study indicates that the expression of surfactant apoproteins in cancer cells occurs ubiquitously in adenocarcinomas, which are considered to be derived from the terminal air way.

Adenocarcinoma↗

A new noninvasive quantitative assessment of cerebral blood flow using N-isopropyl-(iodine 123)p-iodoamphetamine.

The use of a nomogram is described as a new noninvasive quantitative assessment of cerebral blood flow using N-isopropyl-(123I)p-iodoamphetamine (IMP) and single-photon emission computed tomography. The nomogram was constructed from a computer analysis of the flow value relative to varying washout rate of brain activities between early and late tomographic images, and partition coefficient between brain tissue and blood. The validity of this method was evaluated in normal volunteers and in patients with cerebrovascular disorders by comparing the cortical flow values (Y) estimated from the IMP-nomogram with initial slope indices (X) by the 133Xe inhalation method. A significant correlation (N = 42, r = 0.88, P less than .001) was demonstrated between them, and the regression line was Y = 1.6X-7. A development and confirmation of this method made it possible to measure flow values noninvasively with the use of IMP.

Adult↗