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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 541 records · Page 30Linked to original sources
PubMed1988

Extraskeletal myxoid chondrosarcoma characterized by microtubular aggregates in the rough endoplasmic reticulum and tubulin immunoreactivity.

A case is reported of a 66-year-old female with an extraskeletal myxoid chondrosarcoma which had originated in the lateral region of the right knee. The tumour tissue of the primary, recurrent, and metastatic deposits in the lungs was examined by electron microscopy and immunohistochemistry. Almost all the sarcoma cells in every tumour specimen harboured immunoreactivity to both alpha- and beta-subunits of S-100 protein. A large population of cells in the subcutaneous tumour at autopsy had numerous parallel arrays of microtubules within the rough endoplasmic reticulum in addition to the well-described ultrastructural features indicative of chondroblastic origin. These structures were present in round to polygonal, but not in fibroblastic, tumour cells. Tubulin immunoreactivity in the tumour cells showed the same tendency, being frequently positive in the large cells of the subcutaneous tumour but weakly positive in the fibroblastic and medium-sized cells of the recurrent and metastatic tumours. The parallel arrays of intracisternal microtubules therefore may be composed of tubulin protein, as in ordinary cytoplasmic microtubules.

Chondrosarcoma↗
PubMed1988

Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain.

Tyrosine hydroxylase (TH) contents in the caudate nucleus, putamen, and substantia nigra from control and parkinsonism brains were measured for the first time by a sandwich enzyme immunoassay. Both the TH protein content and TH activity (Vmax) were decreased in parallel in the parkinsonian brains as compared with those of the control brains. In contrast, TH "homospecific activity" (activity per enzyme protein) was significantly increased in the parkinsonian brains. The results indicate that the decrease of TH activity in parkinsonian brains is due to the decrease of TH protein content as a result of cell death. The increase in the "homospecific activity" of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity.

Brain Chemistry↗
PubMed1988

Construction of protocellular structures under simulated primitive earth conditions.

We have developed experimental approaches for the construction of protocellular structures under simulated primitive earth conditions and studied their formation and characteristics. Three types of envelopes; protein envelopes, lipid envelopes, and lipid-protein envelopes are considered as candidates for protocellular structures. Simple protein envelopes and lipid envelopes are presumed to have originated at an early stage of chemical evolution, interaction mutually and then evolved into more complex envelopes composed of both lipids and proteins. Three kinds of protein envelopes were constructed in situ from amino acids under simulated primitive earth conditions such as a fresh water tide pool, a warm sea, and a submarine hydrothermal vent. One protein envelope was formed from a mixture of amino acid amides at 80 degrees C using multiple hydration-dehydration cycles. Marigranules, protein envelope structures, were produced from mixtures of glycine and acidic, basic and aromatic amino acids at 105 degrees C in a modified sea medium enriched with essential transition elements. Thermostable microspheres were also formed from a mixture of glycine, alanine, valine, and aspartic acid at 250 degrees C and above. The microspheres did not form at lower temperatures and consist of silicates and peptide-like polymers containing imide bonds and amino acid residues enriched in valine. Amphiphilic proteins with molecular weights of 2000 were necessary for the formation of the protein envelopes. Stable lipid envelopes were formed from different dialkyl phospholipids and fatty acids. Large, stable, lipid-protein envelopes were formed from egg lecithin and the solubilized marigranules. Polycations such as polylysine and polyhistidine, or basic proteins such as lysozyme and cytochrome c also stabilized lipid-protein envelopes.

Amino Acids↗
PubMed1988

Glucose tolerance in middle-aged Japanese males with uncomplicated hypertension.

Plasma glucose levels in 50 g oral glucose tolerance test (OGTT) were compared between uncomplicated hypertensives (n = 507, mean age = 48 +/- 0.3 years) and normotensives (n = 378, mean age = 46 +/- 0.3 years). The subjects were selected in a systematic way from 10,120 male employees in a work-site population in Japan. None of hypertensives took any antihypertensive drugs. Plasma glucose levels at each time point of OGTT were significantly higher in the hypertensives than in the normotensives when the differences in age, obesity, and other factors that might influence glucose metabolism were adjusted, using multiple linear regression analysis. Similarly, multiple regression analysis for subjects including both normotensives and hypertensives revealed a significant relationship between plasma glucose levels and blood pressure, which was independent of age and body mass index. These findings indicate a more direct association between hypertension and hyperglycemia, which is not mediated via aging or obesity.

Blood Glucose↗
PubMed1988

Deoxyribonucleic acid polymerase activity in the testes of infertile men with varicocele.

Activities of deoxyribonucleic acid (DNA) polymerase alpha, beta, and gamma were measured in extracts of testicular biopsy specimen obtained from 37 cases of male infertility with left varicocele and compared with those of 6 normal controls. It was observed that levels of DNA polymerase alpha, beta, and gamma were significantly lower in infertile men than normal controls on both sides of testes. Among three DNA polymerases, the level of DNA polymerase beta activity well correlated with the histological findings (Johnsen's score), i.e., the extent of differentiation of germinal cells. DNA polymerase beta activity appeared to be the lowest in the patients whose sperm density was less than 5 X 10(6)/ml. On the other hand, no correlation was apparent between levels of DNA polymerases and other clinical parameters, e.g., testicular volume, sperm motility, grade of varicocele, and serum hormone levels. These results suggest that the combined decrease in the DNA polymerase activities may be one of the factors that have deleterious effects on spermatogenesis in varicocele patients.

Adult↗
PubMed1988

Phospholipid modulates in vitro replication of autonomous replicating sequence from human cells.

A cloned plasmid, pmyc(H-K), containing sequences derived from human c-myc gene replicated in vitro in Raji nuclear extract in a semiconservative manner. Using this system, it was found that phosphatidylinositol and cardiolipin strongly inhibited the replication of pmyc(H-K) in vitro, whereas other phospholipids, i.e., phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, and sphingomyelin, had no appreciable effect. The concentrations of phosphatidylinositol and cardiolipin producing 50% inhibition of the replication were 4.6 and 5.4 microM, respectively. Phosphatidylinositol and cardiolipin inhibited the relaxation of pmyc(H-K) supercoiled DNA, but showed little or weaker effects on DNA polymerase alpha and topoisomerase II in Raji nuclear extract. These results suggest that phosphatidylinositol and cardiolipin antagonize the replication of pmyc(H-K) in vitro, through, at least in part, the interaction with topoisomerase I.

DNA Replication↗
PubMed1988

Isolation and Characterization of the Amyloplast Envelope-Membrane from Cultured White-Wild Cells of Sycamore (Acer pseudoplatanus L.).

To study the characteristic features of the amyloplast, a uniquely differentiated plastid-type which synthesizes and accumulates reserve starch, in comparison with those of the chloroplast, these two types of plastids were isolated from white-wild and green-mutant protoplasts of cultured sycamore (Acer pseudoplatanus L.) cells, respectively. The intactness of the isolated amyloplast preparations was 70%. Electron microscopic ultrastructural analysis of both plastid types revealed unique structural features of the green-mutant chloroplasts, including well developed grana membranes and abundant ribosomal particles and plastoglobuli. After osmotic rupture of the isolated amyloplasts and chloroplasts, a clear separation of the envelope-membranes was achieved by discontinuous sucrose density gradient centrifugation. Although the visible absorption spectra of the envelope lipid components were indistinguishable between the amyloplasts and chloroplasts, the envelope-membrane polypeptide patterns were clearly distinct as judged by denaturing electrophoresis. By immunoblotting analysis using the specific antiserum raised against the pea chloroplast 29-kilodalton Pi-translocator, the amount of this carrier-protein (31-kilodalton) in the white-wild amyloplast envelope-membranes was estimated to be at least 10-fold less than in the green-mutant envelopes.

Journal Article↗
PubMed1988

Establishment and characterization of resistant cells to etoposide (VP16) from a mouse breast cancer cell line, FM3A.

We established 4 cell lines resistant to VP16 from a mouse breast cancer cell line, FM3A. The IC50 values of all 4 resistant strains were approximately 2 micrograms/ml as measured by colony formation in soft agar; about 40 times higher than that of parent cell (0.05 microgram/ml). These cells showed a cross-resistance to VM26, a compound related to VP16, but not to a variety of other antitumor drugs including adriamycin, mitomycin C, cis-platinum, 5-fluorouracil, bleomycin, vincristine, 4-hydroperoxycyclophosphamide, methotrexate and cytosine arabinoside. Topoisomerase II, the putative target of VP16, was partially purified from cells, and was assayed using knotted P4 phage DNA as a substrate. However, no significant difference was observed between enzymes from resistant cells and from the parent cells in either activity per cell or sensitivity to VP16. On the other hand, the resistance of these cell lines to VP16 was greatly reduced by adding a calcium antagonist, verapamil, to the soft agar at a concentration as low as 5 microM, at which the viability of cells was hardly affected. A similar verapamil-induced reduction in the resistance of the cells to VM26 was also observed. These results suggest that the acquired resistance may be largely due to an altered membrane permeability to drugs, which may be overcome by verapamil, rather than to an altered topoisomerase II.

Animals↗
PubMed1988

Effects of systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mice on tyrosine hydroxylase, L-3,4-dihydroxyphenylalanine decarboxylase, dopamine beta-hydroxylase, and monoamine oxidase activities in the striatum and hypothalamus.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg subcutaneously per day for 8 days) to C57BL/6N mice were studied on tyrosine hydroxylase (TH), L-3,4-dihydroxyphenylalanine decarboxylase (DDC), and monoamine oxidase (MAO) activities in the striatum, and TH, DDC, dopamine-beta-hydroxylase (DBH), and MAO activities in the hypothalamus. Treatment with MPTP led to a large decrease in TH activity and a parallel decrease in DDC activity in the striatum, as compared with the saline controls. In contrast, MPTP administration did not cause a decrease of the activities of TH, DDC, and DBH in the hypothalamus. There was also no reduction in MAO activities of striatum and hypothalamus. These data indicate that MPTP administration to mice results in specific degeneration of the dopaminergic nigrostriatal pathway and that DDC in the mouse striatum may mainly be localized in the dopaminergic neurons with TH.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Lymphatic transport of recombinant human tumor necrosis factor in rats.

The lymphatic transport of recombinant human tumor necrosis factor (rHu-TNF) was investigated after its administration via various routes in anesthetized rats. After intravenous (i.v.) administration, the level of rHu-TNF in the lymph reached a peak at 2 h, and thereafter decreased exponentially in a pattern similar to that of the elimination from plasma. Intramuscular (i.m.) and subcutaneous (s.c.) administrations resulted in low levels of rHu-TNF both in the plasma and in the lymph. On the other hand, intraperitoneal (i.p.), intra-stomach wall (s.w.) and intra-gut wall (g.w.) administrations gave high lymph levels of rHu-TNF. After the s.w., g.w. and i.p. administrations, the ratios of rHu-TNF recovered from the thoracic duct to the cumulative amount estimated from the rHu-TNF concentration in plasma were about 25, 32 and 8 times higher than in the case of i.v. administration, respectively. These results suggest that the routes of local administration of rHu-TNF such as s.w., g.w. and i.p. may be highly effective for the treatment of lymphatic metastasis of cancer.

Animals↗
PubMed1988

Changes of enzymes involved in DNA synthesis in the testes of cryptorchid rats.

The activities of DNA polymerase alpha (EC 2.7.7.7) and topoisomerase I did not fluctuate up to 7 days after surgery to induce cryptorchidism and showed no significant difference from those in control testes (sham-operated). In contrast, the activity of DNA polymerase beta decreased by 43% at 5 days (P less than 0.01) and by 47% at 7 days (P less than 0.001). The activity of DNA polymerase gamma also decreased by 46% at 3 days (P less than 0.02) and by 78% at 7 days (P less than 0.01) after surgery. The amount of mRNA for DNA polymerase beta decreased in parallel with enzyme activity. Since the sensitivity to heat inactivation of testicular DNA polymerase beta was exactly the same as that from liver, the decrease in DNA polymerase beta activity may be, at least in part, due to reduced biosynthesis of enzyme protein. The morphological changes in cryptorchid testes suggested that the decrease in DNA polymerase beta and gamma activities might be related to the deleterious effects of elevated temperature on spermatogenesis.

Animals↗
PubMed1988

Decrease of topoisomerase I activity in the testes of infertile men with varicocele.

Topoisomerase I, which is involved in DNA metabolism, was measured in the testes of 37 infertile men with varicocele, using a minute amount of testicular biopsy specimen. In 38% of infertile men topoisomerase I activity was lower than that of normal men. Forty-six percent of patients with high grade varicocele (grade III) showed reduced topoisomerase I activity, while only 26% of patients with low grade varicocele (grades I and II) showed reduced levels of topoisomerase I. Johnsen's score of the patients with low topoisomerase I activity was lower than that of patients with normal levels of topoisomerase I. The decrease of topoisomerase I activity may be correlated with at least some fraction of hypospermatogenesis associated with varicocele.

Adult↗