[Nursing of a patient with esophageal cancer and loss of voice].
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Biomedical subjects
Publications and source records attributed to A Ito.
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Morphological and immunohistochemical studies of cerebellar tumor induction with neonatal administration of N-ethyl-N-nitrosourea (ENU) were conducted in four strains of rats and their hybrids, i.e., noninbred Wistar, Fischer (F344), Long-Evans, Wistar/Furth, and hybrids of Long-Evans and Wistar/Furth. Neonatal s.c. injection of 40 mg ENU/kg body weight produced 53 cerebellar tumors in 46 (8.4%) rats among 550 animals. There was no sex difference in the incidence (male = 9.6%; female = 7.0%). Histological examination showed that most of the tumors (83%) were oligodendrogliomas and the neoplastic cells were positively stained immunohistochemically with anti-Leu-7 monoclonal antibody. In examining the location of cerebellar tumors, 22 (42%) were located in the vermis, 11 (21%) in the hemisphere, 9 (17%) in the flocculus, 6 (11%) in the peduncle, and 5 (9%) in other sites. When their origins were examined in relation to their location to the internal granular layer of the cerebellum, 40 (75%) tumors were found just under the internal granular layer (subcortical region) and 9 (17%) in the white matter or cerebellar nuclei. Only 2 (4%) subependymal tumors were observed. Ontogenic study of the rat cerebellum revealed the presence of an aggregation of primitive glial cells in the subcortical region during the neonatal period, and the [3H]thymidine pulse-labeling index of these cells was 13.7%. Electron microscopic study showed the primitive nature of these cells and they reacted positively with anti-Leu-7 monoclonal antibody. These results indicate that cerebellar tumors are induced in an appreciable incidence with neonatal injection of ENU in rats and that cerebellar target cells in the subcortical region are present after ENU carcinogenesis.
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A method for measuring antibodies which inhibit the binding of 125I-alpha-bungarotoxin to the acetylcholine receptor was developed. The procedure allows the detection of inhibitory activity in 70% of sera from the patients with myasthenia gravis. Kinetic analysis showed that (1) a linear dose-response exists between logarithmic concentrations of any test serum and inhibitory activity, (2) the slope of the inhibition line is identical among various myasthenic sera and, (3) the slope of line induced by various cholinergic ligands was comparable to that obtained by myasthenic sera. The inhibitory activity correlated with the titer of anti-acetylcholine receptor antibody measured by an immunoprecipitation method (r = 0.76, p less than 0.01).
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The neoplastic cells from a patient with B-cell prolymphocytic leukemia exhibited sheep red blood cell (SRBC) rosette formation. Immunochemistries revealed no reactivity with T-cell monoclonal antibodies OKT 3, 4, 8, and 11. However, the neoplastic cells expressed characteristics of B-cells including surface IgM and IgD associated with lambda light chains, Ia-like antigenicity, and reactivity to monoclonal antibodies against B-cell antigens B1, B2, and B4. Inhibition procedures revealed that SRBC rosette formation was the result of binding activity of surface immunoglobulin to SRBC. Pretreatment of the leukemic cells with antihuman IgM or lambda antisera, or pronase or trypsin blocked rosette formation with SRBC. Circulating antibody to SRBC was also suspected by the fact that preincubation of SRBC with heat-inactivated patient's serum resulted in agglutination of the SRBC.
An enzymatic method using 4-hydroxyproline 2-epimerase (EC 5.1.1.9), D-amino acid oxidase (EC 1.4.3.3.), and a colorimetric reagent of the mixture of Ti(IV) and 4-(2-pyridylazo)-resorcinol was found to be useful in the spectrophotometric assay for hydroxyproline in collagenous tissue hydrolysates. It was possible to determine free hydroxyproline in 250 microliter of tissue hydrolysates at concentrations ranging from 1 to 12.5 micrograms. The coefficient of variation was less than 3%, and the correlation between the proposed method and the colorimetric method (K.I. Kivirikko, O. Laitinen, and D. J. Prockop (1967) Anal. Biochem. 19, 249-255) was 0.973. Thus, this method is convenient because it requires less time than the above colorimetric method, and is also reproducible and sensitive.
Serum levels of estrogens and testosterone were measured in 25 male patients with hepatocellular carcinoma and associated cirrhosis of the liver and in another 25 male patients with cirrhosis only. The two groups were statistically comparable in terms of age distribution, duration of liver disease, incidence of alcohol abuse, incidence of hepatitis B surface antigenemia, and grade of hepatic dysfunction. Estrone was significantly elevated in both groups of patients. Estradiol concentrations were above normal in 10 patients with hepatocellular carcinoma and in 11 with cirrhosis only. All patients had normal concentrations of estriol. There were no statistical differences between the two groups in either individual or total estrogen levels (estrone 0.05 less than p less than 0.1). Eight of the patients with hepatocellular carcinoma and 5 of the cirrhotics had lower testosterone levels than normal, but this difference was not significant. However, the estrone to testosterone ratios were significantly higher in the hepatocellular carcinoma group than in the cirrhosis group (p less than 0.05). The present study seems to indicate that hyperestrogenemia commonly seen in male patients with liver cirrhosis may play some role in hepatic carcinogenesis of cirrhotic livers. Further studies are needed to determine if the estrone to testosterone ratio is implicated in hepatocarcinogenesis in cirrhotic men.
The androgen receptor content of normal human liver, hepatocellular carcinoma, and surrounding liver tissue was determined in patients with chronic liver disease. Androgen receptor was detected in all six normal livers obtained from 4 men and 2 women. The androgen receptor content in these 6 individuals ranged from 5.0 to 10.2 fmol/mg protein (Kd 10.6-31.8 X 10(-10) M). The livers from 2 patients with chronic active hepatitis and from 10 cirrhotic patients with hepatocellular carcinoma had detectable amounts of androgen receptor ranging from 2.0 to 14.8 fmol/mg protein (Kd 4.0-30.9 X 10(-10) M). Androgen receptor was found in the cytosol of 14 of 19 men with hepatocellular carcinoma. The titer ranged from 3.7 to 45.4 fmol/mg protein (Kd 3.2-21.4 X 10(-10) M). Hepatocellular carcinoma had a significantly higher concentration of androgen receptor than did the surrounding cirrhotic liver tissue. In 2 men and 1 woman, androgen receptor was detected in the cirrhotic liver but not in the tumor. In the remaining 3 men, both tumor and cirrhotic liver were negative for androgen receptor.
[3H]Dihydrotestosterone (DHT) binding to a specific protein in the cytosol of bovine ovarian capsule was studied in vitro. The specific androgen-binding protein in the cytosol was analyzed by chromatographic and ultracentrifugal techniques. From Scatchard analysis, the dissociation constant was 7.4 nM and the number of binding sites was 58.8 fmol/mg protein. Testosterone and 17 alpha-methyltrienolone (R1881) compete for [3H]DHT binding. In the presence of sodium molybdate and at low salt concentrations, the steroid-protein complex sediments as a 9S form, while in the presence of high salt, it sediments at 3.5S. In the absence of molybdate or in the presence of high salt, the 9S form dissociates in a temperature-dependent manner into smaller units. These properties are consistent with the presence of a typical androgen receptor in the bovine ovarian capsule.
The influence of increased gastric pH on induction of intestinal metaplasia in the stomach of male JCL/SD rats was examined following surgical procedures of pyloroplasty or pyloroplasty and vagotomy. Twelve months after pyloroplasty plus vagotomy serum gastric concentrations were significantly higher (group II) than in rats receiving only pyloroplasty (group I) or in sham operated animals (group III). Additionally, trehalase activity was also higher in group II than in groups I and III. The incidence of intestinal metaplasia was significantly higher in groups I and II compared with the sham operated control animals (group III). This study indicates that intestinal metaplasia could be induced by surgical procedures such as pyloroplasty with or without vagotomy. Furthermore, elevation of the pH on gastric mucosa by such procedures may play a significant role in the subsequent development of metaplasia in the stomach.
One common and characteristic feature of the extension peptides of mitochondrial enzyme precursors is the presence of repeating short stretches of uncharged amino acids linked by basic amino acids. We synthesized several model peptides having this particular feature of the extension peptides. The peptides contained arginine or lysine as a basic amino acid residue linking sequences of two to four residues of leucine and alanine. We examined the effects of the peptides on the import of the precursors of two mitochondrial enzymes, cytochrome P-450(SCC) and adrenodoxin, and found that the peptides were generally inhibitory to the import of the precursors into mitochondria. The effective concentrations of some of the inhibitory peptides were as low as a few microM. The peptides containing lysine instead of arginine had an essentially similar inhibitory effect on the import. The peptides did not inhibit the binding of pre-P450(SCC) to the surface of mitochondria. The synthetic model peptides uncoupled oxidative phosphorylation of mitochondria prepared from either rat liver or bovine adrenal cortex, and induced leakage of enzymes from the inner compartments of mitochondria. However, the synthetic model peptides did not solubilize membrane-bound enzymes from mitochondria, suggesting that their effect on the membranes is different from that of detergents. The synthetic model peptides seem to bind to the membranes causing significant perturbation in the membrane structure, which is possibly related to the functions of the particular common sequence found in the extension peptides of mitochondrial enzyme precursors.
The biogenesis of a microsomal NAD(P)+-dependent aldehyde dehydrogenase (AlDH) in rat liver was studied using specific antibody raised against the purified enzyme prepared by the method of Nakayasu et al. (Nakayasu, H., Mihara, K., & Sato, R. (1978) Biochem. Biophys. Res. Commun. 83, 697-703). The antibody raised against purified AlDH inhibited the activity of microsome-bound AlDH as effectively as that of the detergent-solubilized enzyme, suggesting that AlDH molecules are present on the outer surface of microsomal vesicles and that a major portion of each molecule, including the active site, is exposed. The cell-free translation of RNA preparations extracted from free and membrane-bound polysomes showed that AlDH was exclusively synthesized on free polysomes. The in vitro synthesized AlDH had the same molecular weight as the authentic enzyme. When a single intravenous injection of [3H]leucine was given to rats, there was no detectable difference in the specific radioactivities of AlDH in rough and smooth microsomes even at the shortest time point, suggesting random incorporation of newly synthesized AlDH molecules into rough and smooth endoplasmic reticulum.