Biomedical subjects
Publications and source records attributed to N Hirota.
We report a case of renal cell carcinoma associated with angiomyolipoma in the same kidney without tuberous sclerosis. This rare situation indicates the need for careful diagnosis and management of renal tumors.
Progressive dementia had developed since the age of 55 in a male patient, who had worked as an aluminum refiner for 30 years. Balint's syndrome was observed from at 60 and he died of bronchopneumonia at 65. Neuropathological examination revealed characteristic features of Alzheimer's disease with marked atrophy of the occipito-temporal lobes and senile plaques of the cerebellum. Wavelength-dispersive X-ray microanalysis disclosed focal aluminum accumulation within the nucleus and cytoplasm of the tangle-bearing neurons. Microanalysis by the same method failed to disclose aluminum accumulation in the tangle-bearing neurons in a case of senile dementia of Alzheimer's type who had no possible inhalation of aluminum.
Although rare, mucinous cystadenocarcinoma of the pancreas is an established pathological entity. However, its characteristic features on diagnostic imaging have not yet been defined. Based upon clinicopathological studies on 5 cases, two subgroups of mucinous cystadenocarcinoma of the pancreas are proposed: the endophytic and the exophytic types. The former consist of large well-demarcated cystic tumors with numerous inward-growing cauliflower-like excrescences in mucinous material, which were characteristically demonstrated either by CT or ultrasonography. Tumors of this subtype were visualized as hypervascular masses in the capillary phase of angiography. Areas of malignant tissue were well-demarcated without capsular invasion, and tumors were free from lymph node or distant metastasis. Though cystic, the exophytic subtype had negligible inward-growing papillary projections. Corresponding to their macroscopic features, these tumors were demonstrated as cystic lesions lacking papillary projections on ultrasonography or CT. No tumor stains could be demonstrated by angiography. Despite of their smaller size than the former subtype, cancerous growth penetrated through the cyst wall and metastasized to lymph nodes, causing poorer prognosis than in the former.
To study the carcinogenic action of N-methyl-N-nitrosourea (MNU) on the stomach, MNU in distilled water at a concentration of 400 ppm was provided as drinking water to F344 male rats for 25 weeks (group I) or 15 weeks (group II). Twenty weeks following the cessation of the administration, invasive adenocarcinomas were found in the glandular stomach in 100% of 16 rats in group I and 38% of 21 rats in group II. Bone formation occurred within the stroma of carcinoma in 5 rats in group I. No neoplastic lesions developed in the esophagus, forestomach or duodenum of any rat. Thus, MNU in drinking water selectively induces glandular stomach carcinoma in high incidence in these rats.
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A single intravenous injection of methylazoxymethanol (MAM) acetate in doses of either 20 or 35 mg/kg body weight to male Sprague-Dawley rats induced altered liver cell foci and later, liver neoplasms in a dose related manner. Sequential observations in the rats given 35 mg/kg and thereafter fed an iron-loading diet revealed that the number of iron-excluding foci/cm2 increased with time. Partial hepatectomy (PH) before the high dose of MAM acetate resulted in 100% lethality while hepatectomy before the low dose carcinogen exposure lead to a higher incidence of neoplasms than in rats that received carcinogen alone. PH after either high or low dose carcinogen exposure did not result in a greater occurrence of liver neoplasms.
Methyl-accepting chemotaxis proteins (MCPs) were solubilized from the membrane of thermophilic bacterium PS-3 in the presence of Triton X-100. The solubilized MCPs could be methylated and demethylated. Methylation of the solubilized MCPs reached a steady state, at which the methylation and demethylation rates were equal. The solubilized MCPs were purified by anti-MCPs Sepharose 4B column chromatography. The purified MCPs could also be methylated and demethylated without reconstituting them into liposomes. As suggested by the results of sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the purified MCPs, ion-exchange chromatography showed that MCPs consisted of at least two components. Each component appeared on SDS gel electrophoresis as multiple bands in the 64K to 70K dalton range or in the 70K to 84K dalton range. The initial rate and level of methylation of the solubilized MCPs were increased by the addition of attractants: glutamate, L-serine, L-aspartate, D-glucose, etc. The threshold of the glutamate concentration for this increase was about 10(-7) M. The rate of demethylation was also increased by attractants.
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To investigate pre-synaptic influence of the descending noradrenergic system on the primary afferents containing substance P (SP), effects of noradrenergic manipulations on the in situ release of immunoreactive SP (iSP) from the dorsal horn were examined in the thalamic rabbit. Local application of noradrenaline (10 microM) to the dorsal horn produced complete inhibition of the noxious mechanical stimuli-evoked release of iSP. This effect was reversed by yohimbine (the more selective alpha 2-blocker, 10 microM) and partially antagonized by prazosin (the more selective alpha 1-blocker, 10 microM). The resting release of iSP was not affected by noradrenaline. The noxious mechanical stimuli-evoked release of iSP was significantly increased by acute spinal transection and local application of yohimbine (10 microM) alone to the dorsal horn. Prazosin (10 microM) slightly increased the evoked iSP release, and a beta-blocker metoprolol did not affect it. These results suggest that the nociceptive primary afferents containing SP are tonically inhibited by the descending noradrenergic system linked to alpha-adrenoceptors, and that such alpha-adrenoceptors located on the primary afferent terminals may be one of the sites of action of noradrenaline spinal analgesia. In contrast to the evoked iSP release, the resting iSP release was increased only by acute spinal transection and not by yohimbine, prazosin and metoprolol. All these observations suggest that tonic inhibition in propriospinal neurons containing SP is mediated by a non-noradrenergic system.
Antinociceptive effects of intrathecal injections of morphine, methionine-enkephalin, noradrenaline and serotonin were examined in rats, using 3 different methods: the tail-pinch, hot-plate and tail-flick tests. The order of sensitivity of the 3 methods to noradrenaline in the production of antinociception was tail-pinch greater than tail-flick greater than hot-plate, while that of morphine, methionine-enkephalin and serotonin was tail-flick greater than hot-plate greater than tail-pinch. These results indicate that intrathecal noradrenaline, but not methionine-enkephalin and serotonin, produces more potent inhibition of the mechanical nociception than does the thermal one, and suggest a closer relationship of the descending noradrenergic system to the mechanical nociceptive system, in the spinal cord of rats.
Effects of various types of natural skin stimuli on the in situ release of immunoreactive substance P and somatostatin from the rabbit dorsal horn were examined. Noxious mechanical or thermal stimuli specifically increased the release of immunoreactive substance P or somatostatin, respectively. Innocuous stimuli did not affect the release of these peptides. These results suggest that the nociceptive mechanical or thermal primary afferents contain substance P or somatostatin, respectively.
The effects of locally applied opioids on the release of immunoreactive Substance P (iSP), induced by mechanical stimuli, from the dorsal horn of the rabbit in situ, were investigated. Morphine and met-enkephalin (met-enk), but not dynorphin A (1-17) (DYN), in a concentration of 10 microM, significantly inhibited the evoked release. These inhibitory effects of morphine and met-enkephalin were antagonized by the local application of naloxone (10 microM) to the dorsal horn. These results suggest that the inhibition of the release of Substance P induced by noxious mechanical stimuli may be mediated by mu and delta, but not by kappa opioid receptors.
A sequential comparison was made between abnormal glycogen storage and other histochemical phenotypic changes in hepatocellular precancerous lesions (altered foci and neoplastic nodules) during various stages in the process of development of cancer in rat liver. N-2-fluorenylacetamide was fed to male rats for 8 weeks and groups of rats were killed at the end of carcinogen feeding and at 12 and 24 weeks on control diet. Foci rich in glycogen storage accounted for a majority of all foci over the course of experiment, while foci devoid of glycogen storage, which were absent at the end of carcinogen feeding, gradually increased in number during maintenance. Glycogen-deficient lesions that might appear to arise from glycogen-rich lesions displayed hyperbasophilia demonstrated by toluidine blue reaction, but often lacked gamma-glutamyl transpeptidase activity. Resistance to iron accumulation was consistently shown in all precursor lesions for hepatocellular carcinoma in the siderotic liver regardless of abundance or absence of cellular glycogen. It was suggested that properties such as loss of glycogen storing capacity, hyperbasophilia, and some cellular atypicality resembling those of carcinoma cells might be essential elements for malignant progression.
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Comprehensive studies of carcinogenesis in newborn or preweanling SD rats were conducted under various dose schedules of cycasin (CAS: 14901-08-7) administration. When cycasin was given sc to newborn rats at day 0, tumors were detected in more than 80% of rats of both sexes; kidney tumors were by far the most common. The incidences of tumors declined in the older groups, namely, over 60% in both sexes in the 7-day group, 55% in males and 8.3% in females in 14-day rats, and 0% in 21-day groups. By multiple administration, tumor incidences elevated considerably. Administration ip of cycasin also gave rise to tumor induction in newborn rats. A total of 435 kidney tumors found in the experiments were studied pathologically. Most of them were classified as mesenchymal tumor; some of them metastasized. A few other tumors were found in the liver and colon.
Depositing the thermophilic bacterium PS-3 on semi-solid agar plate containing rich medium, several chemotactic rings were formed as in the cases of Escherichia coli and Salmonella typhimurium, indicating that the bacterium is chemotactic. The cells were attracted to L-amino acids: L-alanine, tryptophan, L-aspartate, and glutamate; and to sugars: D-glucose, maltose, D-fructose, and sucrose. In order to find out some sort of methylatable proteins were present, which has been proven to be important in the case of Escherichia coli, the PS-3 cells were labeled with radioactive methionine under conditions in which the protein synthesis had been inhibited. The results showed that the cells contained methylatable proteins of 60,000 to 88,000 daltons. The banding pattern of these methylated proteins was very similar to that of Escherichia coli when the proteins were analyzed by SDS-polyacrylamide gel electrophoresis. In addition, the methyl groups attached onto the proteins were alkaline labile, indicating that the site of methylation was on carboxyl group. The methylation and demethylation reactions of these proteins were affected by the presence of attractants.