[A case of "non specific multiple ulcers of the small intestine" with perforation as a presenting sign].
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Biomedical subjects
Publications and source records attributed to Y Satoh.
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Xeroderma pigmentosum (XP) is an autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. There are nine genetic complementation groups of XP, groups A-H and a variant. We have cloned the mouse DNA repair gene that complements the defect of group A, the XPAC gene. Here we report molecular cloning of human and mouse XPAC complementary DNAs. Expression of XPAC cDNA confers ultraviolet-resistance on several group A cell lines, but not on lines of other XP groups. Almost all group A lines tested showed abnormality or absence of XPAC messenger RNAs. These results indicate that a defective XPAC gene causes group A XP. The human and mouse XPAC genes are located on chromosome 9q34.1 and chromosome 4C2, respectively. Human XPAC cDNA encodes a protein of 273 amino acids with a zinc-finger motif.
Phosphoenolpyruvate carboxykinase from chicken liver mitochondria and rat liver cytosol catalyzes the phosphorylation of alpha-substituted carboxylic acids such as glycolate, thioglycolate, and DL-beta-chlorolactate in reactions with absolute requirements for divalent cation activators. 31P NMR analysis of the reaction products indicates that phosphorylation occurs at the alpha-position to generate the corresponding O- or S-bridged phosphate monoesters. In addition, the enzymes catalyze the bicarbonate-dependent phosphorylation of hydroxylamine. The chicken liver enzyme also catalyze the bicarbonate-dependent phosphorylation of hydroxylamine. The chicken liver enzyme also catalyzes the bicarbonate-dependent phosphorylation of fluoride ion. The kappa cat values for these substrates are 20-1000-fold slower than the kappa cat for oxaloacetate. Pyruvate and beta-hydroxypyruvate are not phosphorylated, since the enzyme does not catalyze the enolization of these compounds. Oxalate, a structural analogue of the enolate of pyruvate, is a competitive inhibitor of phosphoenolpyruvate carboxykinase (Ki of 5 microM) in the direction of phosphoenolpyruvate formation. Oxalate is also an inhibitor of the chicken liver enzyme in the direction of oxaloacetate formation and in the decarboxylation of oxaloacetate. The chicken liver enzyme is inhibited by beta-sulfopyruvate, an isoelectronic analogue of oxaloacetate. The extensive homologies between the reactions catalyzed by phosphoenolpyruvate carboxykinase and pyruvate kinase suggest that the divalent cation activators in these reactions may have similar functions. The substrate specificity indicates that phosphoenolpyruvate carboxykinase decarboxylates oxaloacetate to form the enolate of pyruvate which is then phosphorylated by MgGTP on the enzyme.
Paneth cells in the following species were observed under an electron microscope: human, rhesus monkey, hare, guinea pig, rat, nude rat, mouse, golden hamster, and insect feeder bat. Secretory granules containing homogeneous electron-dense materials were observed in the Paneth cells of humans, monkeys, hares, guinea pigs, and bats; mouse Paneth-cell granules were bipartite (central core and peripheral halo), and the Paneth cells in rats and golden hamsters had secretory granules showing various electron densities. In humans, monkeys, and bats, immature granules near the Golgi apparatus sometimes showed bipartite substructure. The number and size of secretory granules were also diverse among various animal species. Some lysosome-like bodies were commonly observed in peri- or supranuclear regions, though the size and shape of the bodies differed from cell to cell. In apical cytoplasm, small clear vesicles (100-200 nm diameter) were more-or-less observed in all species examined, and it was especially note that rat Paneth cells contained many clear vesicles. Small dense-cored vesicles (150-200 nm diameter) were rare. It is unlikely that the various ultrastructural features of Paneth cells correlate with the phylogenetical classification.
To determine the effect of cholinergic secretagogue on the Harderian gland of rats, several light- and electron-microscopic parameters were morphometrically assessed at different time intervals after carbamylcholine injection. In controls, two types of glandular cells (type A cells having 40-55 large vacuoles per cell profile and type B cells containing 30-38 smaller vacuoles per cell profile) and myoepithelial cells were recognized. At 5 min after injection of carbamylcholine, when rats secreted "bloody tears", many alveoli showing narrower lumina and exocytotic figures in both types of cells were observed. Some vacuoles, which were covered by thin cytoplasmic sheets, protruded into the alveolar lumina. However, there was no evidence of apocrine or holocrine secretion. At 30 min and 120 min after injection, most of the alveolar lumina were dilated, and a pronounced decrease in the number of vacuoles in the glandular cells was observed. At 300 min after injection, the secretory vacuoles in both cell types reaccumulated. Transitional forms between the two cell types were not observed. The two types of Harderian gland cells can therefore be considered independent populations rather than different secretory stages of the same cell. It appears that the secretory process of the Harderian gland of rat is affected by cholinergic stimulation of the two types of glandular cells and of myoepithelial cells.
Nine patients with severe dysuria caused by prostatic cancer received prostatic microwave coagulation under intraoperative real-time ultrasonic scanning. During the procedure, the microwave applicator was clearly observed, and the coagulation region appeared as an hyperechoic area compared to the noncoagulated region. Intraoperative real-time ultrasonic scanning allowed safer and more efficacious application of prostatic microwave coagulation.
The mode of action of T-cell-suppressor factor (TsF) induced by ultraviolet B (UVB) preirradiation in terms of interaction with several cytokines was studied. Suppression of murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) by preirradiation of the sensitizing site to low doses of UVB was caused by antigen-specific suppressor T cells (Ts) and was not associated with the generation of efferent limb-acting suppressor cells. TsF released by Ts inhibited the proliferation of immune lymph node (LN) cells in vitro and reduced interleukin (IL)-2 production of these cells in an antigen-specific fashion without affecting the IL-2 receptor (IL-2R) expression. Both rIL-2 and rGM-CSF have the ability to restore CPS responses in the UVB-preirradiated mice when administered after but not before photosensitization. However, rIL-2 but not rGM-CSF counteracted the in vivo inhibitory effect of TsF. rGM-CSF did not affect the density of I-A+ epidermal Langerhans cells (LCs). It was suggested that TsF inhibited IL-2-mediated immune T-cell proliferation, while rGM-CSF reconstituted the CPS by enhancing the function of photodamaged LCs. These results indicate multiple steps of the UVB-induced immunosuppression circuit, each of which seems to be controlled by different immunomodulators.
The molecular basis of group A xeroderma pigmentosum (XP) was investigated by comparison of the nucleotide sequences of multiple clones of the XP group A complementing gene (XPAC) from a patient with group A XP with that of a normal gene. The clones showed a G----C substitution at the 3' splice acceptor site of intron 3, which altered the obligatory AG acceptor dinucleotide to AC. Nucleotide sequencing of cDNAs amplified by the polymerase chain reaction revealed that this single base substitution abolishes the canonical 3' splice site, thus creating two abnormally spliced mRNA forms. The larger form is identical with normal mRNA except for a dinucleotide deletion at the 5' end of exon 4. This deletion results in a frameshift with premature translation termination in exon 4. The smaller form has a deletion of the entire exon 3 and the dinucleotide at the 5' end of exon 4. The result of a transfection study provided additional evidence that this single base substitution is the disease-causing mutation. This single base substitution creates a new cleavage site for the restriction nuclease AlwNI. Analysis of AlwNI restriction fragment length polymorphism showed a high frequency of this mutation in Japanese patients with group A XP: 16 of 21 unrelated Japanese patients were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 Blacks with group A XP did not have this mutant allele. The polymorphic AlwNI restriction fragments are concluded to be useful for diagnosis of group A XP in Japanese subjects, including prenatal cases and carriers.
Twenty-five cases of lumbar spinal canal stenosis were investigated by dynamic myeloscopy to explain the pathophysiologic mechanism of intermittent claudication, one of the characteristic signs of the disorder. Myeloscopic examination revealed that, in accordance with postural alteration, the diameter of blood vessels on the cauda equinae showed significant changes in many patients in the stenosis group, but showed no changes in control group. In this series, it was suggested that the microcirculatory disturbance of vessels on cauda equinae might play an important role in the development of intermittent claudication.
The DNA repair of ultraviolet (UV)-induced damages in primary cultured melanocytes from xeroderma pigmentosum (XP) patients and normal subjects were studied by measuring unscheduled DNA synthesis (UDS) on autoradiographs. Melanocytes were cultured in alpha-minimum essential medium (alpha-MEM) supplemented with 10% fetal calf serum (FCS), 12-O-tetradecanoyl-phorbol-13 acetate (TPA), and geneticin. The levels of UDS in XP melanocytes were compared with those in normal melanocytes. In both normal and XP melanocytes, post-UV-UDS increased dose-dependently at doses of 5-10 J/m2. XP melanocytes exhibited various levels of defect in DNA repair, depending on the type of XP. Melanocytes from XP-A patients displayed very low levels of UDS, only 6.2-8.4% that of the normal melanocytes. However, UDS values in melanocytes from intermediate groups, XP-D, XP-E, and XP-F, were relatively high, 37.2-53.5% of the control in XP-D, 50.0-66.5% in XP-E, and 38.2-46.7% in XP-F, respectively. Melanocytes from XP-variant patients exhibited almost normal levels of UDS, 87.7-91.6% of those from normal subjects. The levels of UDS in XP melanocytes were very similar to those in fibroblasts isolated from the same specimens.
Expression of mRNAs of carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) genes in colorectal carcinomas and adenomas was investigated by in situ hybridization (ISH) with specific biotinylated probes. Hybridization was clearly detected throughout the cytoplasm of 7 out of 15 adenomas and 13 out of 15 carcinomas with the CEA cDNA probe, and in 6 out of 15 adenomas and 10 out of 15 carcinomas with the NCA cDNA probe. The intensity of signal appeared to be stronger in carcinomas than that in adenomas, and the CEA and NCA mRNAs were expressed together in most of the positive tissue specimens. On the other hand, noninvaded tissues adjacent to the carcinoma did not show any signal except for 4 cases faintly stained with the NCA probe. This finding was partly confirmed by Northern blot analysis which indicated that the specific bands for the CEA and NCA mRNAs were more intense in RNAs from carcinoma tissues than in those from adjacent noninvaded tissues. These data suggest that the ISH technique with biotinylated probes could be of use for analyzing expression and localization of CEA and related genes on tissue sections.
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A filtered QRS (fQRS) was recorded by signal averaging in 7-day-old myocardial infarction (MI) in dogs to detect late potential (LP). The criteria for the LP included a duration of fQRS (D) greater than or equal to 60 msec and a voltage in the last 15 msec (V15) less than or equal to 10 microV. These parameters were determined from the control data from 15 dogs without infarction (D: 45 to 60 msec and V15: 12.0 to 83.6 microV). On the seventh day of infarction, the D had increased from 53.5 +/- 4.7 to 62.2 +/- 9.6 msec (P less than 0.05) and the V15 decreased from 38.6 +/- 19.5 to 18.4 +/- 16.0 microV (P less than 0.01). Of 23 dogs, 14 met the LP criteria (group A) and 9 did not (group B). Sustained ventricular tachycardia (SVT) was induced in 12 group A dogs and in none of the group B dogs. The delayed epicardial activation (DEA) was recorded after the end of QRS at 5.1 +/- 4.7 sites in group A dogs and 1.3 +/- 1.8 sites in group B dogs (P less than 0.05). The maximum value of epicardial activation time was more prolonged in group A than in group B (70.0 +/- 28.3 vs 44.4 +/- 9.8 msec, P less than 0.01). The area of MI was more extensive in dogs with DEA than those without (24.9 +/- 5.8% vs 10.3 +/- 9.0% of the total left ventricular weight, P less than 0.01). In 72 of 90 sites with DEA, the thickness of the surviving epicardial muscle was less than or equal to 1 mm. The sensitivity and specificity of the criteria for LP in detecting DEA were 71.4% and 55.6%, and 100% and 81.8% for predicting inducibility of SVT. It was thus concluded that LP, reflected the DEA, was identified from infarct areas of slow conduction within a reentry circuit of SVT.
A 35-year-old Japanese female patient with xeroderma pigmentosum (XP), registered as XP114TO, was assigned to complementation group D by the cell fusion complementation test. The patient had manifested moderate solar sensitivity and freckles by the age of 6 years. The skin phototest using 290- and 300-nm monochromatic ultraviolet (UV) light revealed slightly lowered minimal erythema doses at 24 h after irradiation. The XP114TO skin fibroblasts exhibited about the 6-fold higher sensitivity to the lethal effect of 254-nm UV as did normal cells. Unscheduled DNA synthesis (UDS) induced in XP114TO cells by 254-nm UV (10 J/m2) was 33% of normal, falling into the group D range of 25-50% UDS. The patient developed lentigo maligna on the right side of the nose. Unlike the typical XP group D cases in the West, she showed no neurological abnormalities.
It is widely accepted that expression of protooncogenes is coupled with cellular proliferation and differentiation. Since ACTH stimulates not only steroidogenesis but also cellular proliferation, we investigated whether ACTH affects the expression of c-fos, c-myc, and beta-actin genes. The effect of ACTH on adrenal glands was studied in hypophysectomized rats. Changes in the mRNA levels were studied by Northern and dot blot analyses. It was demonstrated that ACTH induces increases in mRNAs encoding c-fos and beta-actin in adrenal glands of hypophysectomized rats. When stimulated by ACTH (5 IU/100 g BW), the mRNA levels of both genes increase rapidly; the maximum levels are observed at 30 min for c-fos and 6 h for beta-actin. Both mRNAs declined to near-control levels by 6-24 h. The levels of mRNAs encoding cholesterol side-chain cleavage cytochrome P-450 and 21-hydroxylase cytochrome P-450 began to increase 3 and 12 h after ACTH administration, respectively. This increase continued for 24 h after ACTH treatment. Increases in total adrenal RNA and adrenal weight occurred slowly after ACTH treatment. On the other hand, the levels of c-myc mRNA were very low and were not increased by ACTH administration. These results suggest that increased expression of c-fos and beta-actin genes by ACTH may have important roles in mediating its action on adrenals.
Epidermal growth factor (EGF) receptor mRNA expression in livers of newborn, adult control and partially hepatectomized rats 1 and 3 days post-operation was examined by Northern blot analysis. A human EGF receptor cDNA (P 64-1, Ullrich et al., 1984) was hybridized to RNA species of 10, 6 and 3 kb. These mRNAs were profoundly decreased in livers from newborn rats and relatively decreased in regenerating rat livers. beta-Actin mRNA in these tissues showed a tendency to increase over that of the adult controls.
The changes in steady-state levels of mRNA for cholesterol side-chain cleavage cytochrome P-450 (P-450scc) and steroid 21-hydroxylase cytochrome P-450 (P-450c21) caused by hypophysectomy and ACTH treatment were determined in rat adrenals. Hypophysectomy caused marked decreases in adrenal weight and total RNA per gland. Administration of ACTH resulted in increases in adrenal weight and total RNA. A significant correlation between the amount of RNA and adrenal weight was observed. Both P-450scc and P-450c21 mRNAs were decreased by hypophysectomy and increased by ACTH treatment. P-450scc mRNA decreased to 20% and P-450c21 mRNA to 76% of control values 1 day after hypophysectomy. ACTH caused a significant increase in P-450scc mRNA after 3 h. However, a significant increase in P-450c21 mRNA was observed 12 h after administration of ACTH. These results are concordant with previous studies in vitro utilizing cultured adrenocortical cells. Moreover, the induction of steady-state levels of P-450scc mRNA was faster than that observed by other investigators in studies in vitro. These results may indicate that integrity of the adrenal gland in vivo is important for the action of ACTH.
High-strength denture teeth (HS teeth) were developed in order to improve the hardness and wear resistance of conventional plastic denture teeth (PL teeth), while retaining their feature of easy occlusal adjustment. The objective of this study was to evaluate the abrasive wear resistance of HS teeth. We conducted wear tests and measured surface roughness using six types of anterior artificial teeth, i.e., three types of HS teeth and three types of PL teeth, the latter serving as the control. The results of the toothbrush abrasion test revealed that the HS teeth had about 5 times greater wear resistance than the PL teeth. It was also found that the type of artificial teeth and the number of abrasive wear-testing strokes had a significant (P less than 0.05) influence on the surface roughness of artificial teeth.