Sparsomycin analogs. V. Synthesis and antitumor activity of (E)-beta-(pyrimidin-5-yl)acrylamides.
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Biomedical subjects
Publications and source records attributed to S Fukuda.
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The effect of inoculation of cytomegalovirus (CMV) into the endolymphatic sac was examined in CMV-seronegative and seropositive animals. Seronegative animals developed hearing loss, infection in the epithelial cells of the endolymphatic sac and perisaccular connective tissue, and endolymphatic hydrops. Control animals inoculated with inactivated CMV showed no hearing loss, viral infection, or endolymphatic hydrops. Seropositive animals showed complete protection from hearing loss and viral infection, yet a monocytic infiltrate was seen surrounding the endolymphatic sac. Associated with this localized immune response was mild evidence of endolymphatic hydrops in 40% (2/5) of the animals. Control seropositive animals inoculated with inactivated CMV showed no hearing loss or morphological changes. CMV then, can infect cells of the endolymphatic sac resulting in hearing loss and endolymphatic hydrops. The immune response to CMV in seropositive animals is protective, but is associated with endolymphatic sac inflammation.
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The comparative biological activities of intracerebroventricular (icv) injection of alpha-rat and alpha-human atrial natriuretic peptide (rANP and hANP, respectively) in the arginine vasopressin (AVP) release in conscious rats and the binding properties of these peptides to their specific receptors have been investigated. An icv injection of 5 micrograms rANP inhibited the AVP release induced by osmotic and hemorrhagic stimuli. In contrast, 20 micrograms of hANP was needed to exert an inhibitory effect on the AVP release. The receptor binding studies were carried out by using rat hypothalamic membrane preparations. The binding studies revealed that the potency of rANP was greater than that of hANP in displacing radioligand from its binding sites. Scatchard analysis revealed that the dissociation constant for rANP was significantly lower than that for hANP (0.52 +/- 0.04 vs 1.20 +/- 0.16 nM, P less than 0.01). The binding capacity of these peptides was similar. These results suggest that the greater biological potency of rANP compared with hANP in the inhibition of AVP release is caused by the difference in the binding potency of these peptides.
Fluctuations in serum levels of testosterone (T) within a day, both with age and as a result of sexual stimulation, were examined in male beagle dogs. Eighty male dogs aged between 3 months and 16 years and bred in our laboratory were used under strictly controlled breeding conditions (temperature: 22 +/- 1 degree C, relative humidity: 55 +/- 5%, lighting time: 8:00 a.m.-8:00 p.m.). The level of T was measured by an RIA method. In order to examine the fluctuation in T level within a day, blood samples were obtained at 0:00, 6:00, 12:00 and 18:00 in each of five dogs aged 1.7 and 2.1 years. T levels fluctuated with a regular pattern that was lowest at 12:00, and increased to a peak at 18:00-6:00, thereafter decreasing until 12:00. In order to examine the change in T level with age, blood samples were obtained at 9:00, 12:00 and 16:00 from 70 dogs aged between 3 months and 16 years. The regular diurnal pattern of T level was usually seen, and the levels at 12:00 were always low and did not fluctuate at any age except for 6 months, and 13, 14 and 16 years. The T level at 9:00 increased to reach a peak at 4 years, whereas that at 16:00 did so at 2 years. T levels at 9:00 were significantly higher at 4-12 and 14 years than at 3 months, and were higher at 4 years than at 9 months.(ABSTRACT TRUNCATED AT 250 WORDS)
The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.
Superoxide anion (O2-) production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL) was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6) neutrophils, p less than 0.05). In 10 patients with myelodysplastic syndrome (MDS), however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01), but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.
Guinea pigs were inoculated with mumps virus (Torii strain) by the intralabyrinthine or intravascular route and their cochleas were examined by immunofluorescence and electron microscopy. In these animals, viral antigen was detected in the cochleas, most often in the stria vascularis. However, viral infection was produced only in those with intralabyrinthine inoculation. The cochlear lesion commonly observed in this study was severe degeneration of the organ of Corti, which was usually found in the basal turn. Morphological evidence of viral infection, as depicted by intracellular strands of nucleocapsids and budding of the virus at the endolymphatic surface, was prominent in both the stria vascularis and Reissner's membrane. The cochlear location of mumps infection correlated closely with that of the viral antigen formerly reported in newborn hamsters.
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B-cell human lymphoblastoid cell line, BALL-1, produced interferon-alpha (IFN-alpha) and cytotoxic factors by the stimulation of hemagglutinating virus of Japan (HVJ). These cytotoxic factors were identified to be tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on the basis of molecular level analysis. In the kinetic study, it was found that the maximum production of IFN-alpha was reached at 16-20 hr and that of TNF-alpha was at 10-16 hr after the stimulation by HVJ, whereas the maximum production of TNF-beta was at 40-50 hr, suggesting that the regulation of TNF-alpha and TNF-beta genes are different. These cytokines were purified by monoclonal antibody linked column chromatography, respectively. IFN-alpha was further separated into 9 subspecies on the basis of the difference of isoelectric point by FPLC chromatofocusing method. From the N-terminal amino acid sequence analyses of the 7 species of 9 subspecies, these subspecies were classified into 3 subtypes according to the Weissmann's notation. On the other hand, the amino acid sequence of the tryptic peptides of purified TNF-alpha and TNF-beta coincided well with the parts of the complete amino acid sequences which had been deduced from complementary DNA of TNF-alpha and TNF-beta of BALL-1 cell.
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Regression of hyaline membrane disease was studied with light and electron microscopy, immunohistochemistry using the factor VIII-related antigen, lysozyme, alpha 1-antichymotrypsin and surfactant apoprotein antisera, and biochemical quantitation of surfactant disaturated phosphatidylcholine. The repair of hyaline membrane disease occurred by two processes; expansion of atelectatic alveoli and absorption of the hyaline membrane. Regenerative type II pneumocytes containing numerous organelles and lamellar inclusion bodies could be seen three days following birth. Disaturated phosphatidylcholine content also increased three days after birth. Absorption of the hyaline membrane occurred on part of several types of cells such as intra-alveolar macrophages and spindle-shaped cells appearing below or above the hyaline membrane. Intra-alveolar macrophages showed positive immunoreactivity with lysozyme and alpha 1-antichymotrypsin antisera. The spindle-shaped cells indicated negative immunoreactivity with these antisera, though some of them showed positive immunoreactivity with surfactant apoprotein or factor VIII-related antigen antisera. It thus appears that cells of different origin may possibly participate in the absorption of hyaline membrane.
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