Biomedical subjects
Publications and source records attributed to Y Oka.
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Twenty-six patients with unresectable gastric cancer, divided into two groups, were treated with combination chemotherapy of FEP (14 patients) or FAP (12 patients). The FEP regimen performed every 4 weeks was as follows: UFT 400 mg/m2 (p.o.) everyday, etoposide 50 mg/m2 (i.v.) and CDDP 30 mg/m2 (i.v.) on days 1, 8 and 15. FAP regimen was performed every 4 weeks was: UFT 400 mg/m2 (p.o.) everyday, adriamycin 10 mg/m2 (i.v.) and CDDP 30 mg/m2 (i.v.) on days 1, 8 and 15. In FEP group, (7 males and 7 females) the average age was 64 (range 53 to 75). Two patients were in PS 1, 4 in PS 2 and 8 in PS 3. In FAP group (7 males and 5 females) the average age was 55 (range 30 to 74). One patient was in PS 1, 5 in PS 2 and 6 in PS 3. No one in either group had prior chemotherapy. Response rates in FEP and FAP groups were 28.5% (4/14) and 33.3% (4/12), respectively. The median survival periods were 4.5 months in FEP group and 6.5 months in FAP group. As for side effects, myelosuppression appeared most frequently, being followed by alopecia and nausea, although the degree of alopecia was milder in FEP than in FAP. We conclude that new combination chemotherapies of either FEP or FAP are useful for advanced gastric cancer.
Malignant thymomas usually proliferate invasively and rarely metastasize to other organs. Since the metastases occur predominantly to the liver and kidneys, there have been only 16 cases with metastatic spreads of malignant thymomas to the central nervous system reported in the literature. A 59-year-old man was admitted with complaints of dizziness and vomiting. Three years and three months ago, he had been operated upon for mediastinal tumor, which was diagnosed as a predominantly lymphocytic type thymoma, and then followed by irradiation therapy of 3800 rads. The size of the tumor decreased markedly after the irradiation. Nine months after the operation, he complained again of dizziness and vomiting. Computed tomography scans showed a tumorous lesion in the right cerebellar hemisphere, which was thought to be a metastasis from the thymoma. He received radiotherapy of 4000 rads directed to the intracranial metastatic tumor, with the reduction of the tumor size and the relief of symptoms. On the present admission, he had cerebellar signs and symptoms. Neuroradiologically, there was a hypervascular tumor in the left cerebellar hemisphere and a hypovascular one in the right. At operation, a vascular and solid tumor with small necrotic areas were found in the left cerebellum, and a tumor with large liquefied clot within it in the right cerebellum. Pathologically, bilateral cerebellar tumors were confirmed as the metastases from the thymoma in the epithelial type.
A sensitive and simple two-site enzyme immunoassay was developed for rat epidermal growth factor (rEGF), which was purified from male rat submaxillary glands. This system is based on the sandwiching of the antigen between anti-rat EGF IgG antibody coated on a polystyrene bead and anti-rat EGF Fab' antibody-linked peroxidase, whose activity was stable at 4 degrees C for 6 months. In this system, the rat EGF was detectable at a concentration of 2 pg/tube. No interference was observed by addition of human plasma. There was no cross-reactivity with mouse EGF, human EGF, or other substances with similar chemical structures.
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In mid-August, 1986, a 50-year-old man underwent a detailed examination following the finding of a tumor in the upper abdominal region. The tumor was revealed to be a sigmoid colon cancer with multiple metastasis to both halves of the liver. Subsequent administration of FT-207 suppositories (750 mg X 2/day) resulted in a recognizable shrinkage of the metastatic lesions in the liver after one month, and a barium enema a month later indicated a decrease in the size of the original tumor. The pre-operative CEA value was 2,317 ng/ml, but this has reduced to 46.7 ng/ml to date March, 1987. In this report of single chemotherapy treatment with FT-207 of a sigmoid colon cancer involving metastasis to the liver, the prognosis obtained for the original and hepatic lesions has been good, and the patient's course to date healthy.
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Incubation of insulin-treated rat adipocytes with chloroquine, in a time- and concentration-dependent manner, was observed to inhibit the insulin-stimulated increase in insulin-like growth factor II (IGF-II) binding activity, whereas no significant change in IGF-II binding was observed in the absence of insulin. The incremental increase of insulin-stimulated IGF-II binding was inhibited 50% by 0.2 mM chloroquine within 15 min and was nearly completely abolished by 60 min. Interestingly, IGF-II binding was never observed to decrease below the binding value in cells without insulin treatment even when incubation was extended to 180 min. Scatchard analysis of IGF-II binding as well as the specific binding of an anti-IGF-II receptor antibody demonstrated that the loss of IGF-II binding in the insulin-stimulated chloroquine-treated adipocytes was due to a decrease in the number of cell-surface IGF-II receptors, whereas the total number of cellular IGF-II receptors was unaltered. The effect of chloroquine was observed to be reversible, temperature-dependent, and sensitive to the metabolic poison KCN. Furthermore, NH4Cl was also observed to inhibit insulin-stimulated increase in IGF-II binding. In contrast, chloroquine or NH4Cl did not inhibit the basal or insulin-stimulated glucose transport activity. Photoaffinity labeling of the glucose transporter with [3H]cytochalasin B also demonstrated that the basal and insulin-stimulated subcellular distribution of the glucose transporters was unaltered by chloroquine treatment. These results suggest that 1) insulin induces a constitutive, acidotropic agent-sensitive recycling of IGF-II receptor and 2) the glucose transporter and IGF-II receptor do not share the same insulin-regulated intracellular trafficking pathways.
We have studied the process by which purified Oxytricha macronuclear DNA associates with itself to form large aggregates. The various macronuclear DNA molecules all have the same terminal or telomeric DNA sequences that are shown below. 5' C4A4C4A4C4--mean length----G4T4G4T4G4T4G4T4G4 G4T4G4T4G4T4G4T4G4-----2.4 kb------C4A4C4A4C4. When incubated at high concentrations, these telomeric sequences cohere with one another to form an unusual structure--one that is quite different from any DNA structure so far described. The evidence for this is the following: 1) These sequences cohere albeit slowly, in the presence of relatively high concentrations of Na+, and no other cation tested. This contrasts with the rapid coherence of complementary single-chain terminals of normal DNA (sticky ends) which occurs in the presence of any cation tested. 2) If the cohered form is transferred into buffers containing a special cation, K+, it becomes much more resistant to dissociation by heating. We estimate that K+ increases the thermal stability by 25 degrees or more. The only precedent known (to us) for a cation-specific stabilization is that seen in the quadruplex structure formed by poly I. The thermal stability of double helical macronuclear DNA depends on the cation concentration, but not the cation type. Limited treatment with specific nucleases show that the 3' and 5'-ended strands are essential for the formation of the cohering structure. Once in the cohered form, the telomeric sequences are protected from the action of nucleases. Coherence is inhibited by specific, but not by non-specific, synthetic oligomers, and by short telomeric fragments with or without their terminal single chains. We conclude that the coherence occurs by the formation of a novel condensed structure that involves the terminal nucleotides in three or four chains.
It has been conventionally accepted that the anuran accessory nerve (nXI) only innervates the musculus cucullaris (C). However, we have found that the nXI of the Japanese toad innervated the musculus interscapularis (IS) in addition to the C. The motoneurons innervating these muscles were labelled by the intramuscular injection of horseradish peroxidase (HRP). In the accessory nucleus (XI), the motoneurons were somatotopically organized: the C motoneurons were localized more rostrally, while the IS motoneurons more caudally.
AT11-2, an Abelson virus-transformed cell line has DJH complexes on both chromosomes and is able to form functional variable region genes by the joins of VH genes to the DJH complexes during culture. Therefore we examined which VH gene family was used in functional VH to DJH recombinations in AT11-2. Surprisingly, of 32 independent functional VH to DJH recombinational events in AT11-2, 31 events used the VH segments of the VHQ52 family, and the remaining one used the VH segment of the VH7183 family. Thus, we describe here the first B precursor cell line that almost selectively uses the VHQ52 family in functional VH to DJH rearrangements. The selective use of the VHQ52 family in this B precursor cell line strongly indicates nonrandom use of VH gene families, and the existence of a stage at which the VHQ52 family is preferentially used during the normal development of early pre-B cells and has important implications for understanding the ontogeny of VH repertoire development. Furthermore, this cell line should prove extremely valuable in further studies of this kind.
The morphology and distribution of the cranial nerve motoneurons (except III, IV, and VI) and rostral spinal motoneurons were systematically studied in the Japanese toad (Bufo japonicus) by retrograde labelling with cobaltic lysine complex. The cobaltic lysine clearly labelled whole neurons, i.e., cell bodies, proximal and distal dendrites, and axons. The branchial motoneurons (V, VII, IX, and X) had similar morphological characteristics and formed a more-or-less continuous cell column through the brainstem. The dendrites could be grouped mainly into the dorsomedial and the ventrolateral dendritic arrays. The dorsomedial dendrites formed a dendritic plexus in the subependymal gray matter, which extended as far peripherally as beneath the ependymal layer. The ventrolateral dendrites formed a broom-like dendritic plexus in the lateral to ventrolateral white matter. They usually extended as far peripherally as the pial surface. The rostrocaudal extent of the dendritic field was also wide and usually exceeded the motor nuclear boundaries. The hypoglossal motoneurons were grouped into the dorsomedial and ventrolateral cell groups, and the latter was considered to be part of the rostral spinal motoneuron column, from their morphology and distribution. The former had well-differentiated dendrites and occupied a more medial position than the branchial motoneurons. Besides the equivalent of the dorsomedial and ventrolateral dendritic arrays of the branchial motoneurons, they had dorsal and commissural dendrites. The accessory motoneurons had morphological characteristics and a distribution pattern similar to those of the rostral spinal motoneurons rather than the branchial motoneurons. The rostral spinal motoneurons had morphological characteristics somewhat different from the branchial motoneurons and the hypoglossal motoneurons (dorsomedial group). Functional implications of the motoneuron morphology are discussed, mainly based on the present results and earlier anatomical and physiological studies of the spinal motoneurons. The present study also revealed the anatomical features of the preganglionic parasympathetic neurons supplying some cranial nerves. These neurons had small somata with less elaborate dendrites and formed an almost continuous cell column that occupied a more dorsal position than the motoneurons of the corresponding nerve. They are thought to be homologous to the salivatory nucleus and the dorsal motor nucleus of the vagus. The basic anatomical organization of the general visceral efferent column seems to be similar throughout vertebrates.
Coordinated activities of several muscles in the head region underlie the prey-catching behavior of anuran amphibians. As a step in elucidating the neural mechanisms generating these activity patterns in the Japanese toad, we labelled the motoneurons innervating 8 behaviorally relevant muscles using intramuscular (i.m.) injection technique of horseradish peroxidase (HRP), and examined their localization within the motor nuclei whose boundaries were determined by HRP application to the nerve trunk. All the motoneurons innervating the two jaw closer muscles (m. masseter major, m. temporalis) and m. submentalis were localized within the rostral subdivision of the trigeminal motor nucleus. The motoneurons innervating the only mouth opener muscle (m. depressor mandibulae) were scattered throughout the facial motor nucleus. The motoneurons innervating tongue (m. hypoglossus, m. genioglossus) and hyoid muscles (m. sternohyoideus, m. geniohyoideus) appeared within the hypoglossal nucleus with distribution patterns characteristic of the target muscles. Thus, we have revealed the neuroanatomical organization of the motoneurons relevant to the prey-catching behavior.
A variant was selected from an Abelson virus-transformed cell line with identifiable and distinguishable DJH rearrangements on both chromosomes. Southern blotting experiments suggested that this variant resulted from a secondary DJH complex formation accompanied with the deletion of one of the DJH rearrangements on the same chromosome. Furthermore, this variant started making mu-chains by the further functional join of a VH gene to the secondarily formed DJH complex. Thus, we describe here the first evidence of a secondary DJH complex formation.
We describe an improved method for correlative light and electron microscopic examination of synaptic organization of neurons extracellularly labelled by the axonal transport of cobaltic-lysine (Co-lys). After filling the neurons with Co-lys and precipitating the CoS, the brain is fixed in a double-aldehyde fixative, and thick slices are cut using a Microslicer. The slices are intensified using a physical developer, postfixed in OsO4 and embedded in resin. By cutting alternating semithin and ultrathin sections, it is possible to specify sites and types of synaptic contacts on labelled neuronal profiles.
Motoneurons supplying the accessory nerve (nXI) of the Japanese toad were retrogradely labelled by applying the cobaltic lysine to the cut end of the nerve. They had morphological characteristics and a distribution pattern similar to those of the rostral spinal motoneurons rather than the branchial motoneurons. We propose that the anuran nXI is equivalent to the so-called spinal portion of the nXI of other vertebrates, and both should be regarded as part of the rostral spinal nerves rather than the nerve accessory to the vagus nerve.
We labelled the preganglionic parasympathetic neurons of the facial, glossopharyngeal and vagus nerves of the Japanese toad by applying the cobaltic lysine to the cut end of the respective nerve, and examined their morphology and distribution. These neurons form an almost continuous cell column consisting of small neurons with less elaborate dendrites, and occupy a more dorsal position than the motoneurons of the corresponding nerves. The results suggest the presence of the amphibian homologues of the salivatory nucleus and the dorsal motor nucleus of the vagus.