Search PubMed⌕ Search

Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 307 records · Page 17Linked to original sources

Flow cytometric analysis of DNA content and Ki-67-positive fractions in the diagnosis of salivary gland tumors.

To explore the utility of flow cytometry (FCM) for the diagnosis of histopathology of salivary gland tumors, fresh materials taken at surgery from 23 Warthin's tumors, 57 pleomorphic adenomas, and 14 malignant tumors were analyzed for DNA ploidy and proliferative cell activities, including S-phase fraction (SPF), G2- plus M-phase fraction (G2M), and Ki-67-positive fraction. To facilitate this study, glands were taken from all major salivary sites and minor glands in the head and neck. DNA aneuploidy was not detected in the benign tumors. Nine of 14 malignant tumors showed DNA aneuploidy. The percentage of SPF or G2M of the malignant tumors was significantly higher than those of the benign tumors. The percentage of Ki-67-positive fraction of pleomorphic adenomas was comparable to that of malignant tumors and was significantly higher than that of Warthin's tumors. Ki-67 of 20% as a cut-off had a sensitivity of 88%, specificity of 100%, and accuracy of 91% for differentiating pleomorphic adenomas from Warthin's tumors. In analyzing DNA content and proliferative activities by FCM, we could distinguish among the three major histopathologies of salivary gland tumors. Warthin's tumors showed low SPF + G2M with low Ki-67, pleomorphic adenomas had low SPF + G2M with high Ki-67, and malignant tumor showed high SPF + G2M with high Ki-67. The high percentage of the Ki-67-positive fraction seen in pleomorphic adenomas may reflect their potential biological aggressiveness manifested as tumor recurrence or malignant transformation.

Adenolymphoma↗

A novel human glassy-cell carcinoma cell line producing IL-6 and IL-8 from uterine cervix.

A novel human cell line, TOM-2, was established from a rare uterine cervical cancer, glassy cell carcinoma (GCC). TOM-2 is the second established GCC cell line so far reported. The cells were intermediately or poorly differentiated with dysplastic nuclei and polygonal shape and secreted two tumor markers and cytokines, i.e., CA-125 and SCC, interleukin (1L)-1alpha, -6, and -8, and TNF-alpha. Growth of TOM-2 was so strongly dependent on population density that it was not possible to determine the plating efficiency. In mass culture, the following characteristics were observed: doubling time, 83 h; mode of chromosome number, 79; human papillomavirus type 18 DNA, detectable; tumorigenicity, easily transplantable into subcutis of nude mice; chemosensitivity in vitro, considerably sensitive to Cisplatin and 5-FU but not to 9 other antineoplastic agents. This novel cell line will be useful for developing new therapeutic strategies for the rare cancer, GCC.

Adult↗

Pharmacological effects of SA96 (bucillamine) and its metabolites as immunomodulating drugs--the disulfide structure of SA-96 metabolites plays a critical role in the pharmacological action of the drug.

SA96 (generic name, bucillamine) is a disease-modifying anti-rheumatoid arthritis (RA) drug with immunological effects. This compounds has two sulfhydryl groups in its molecule, and the differences and similarities between this drug and D-penicillamine, which is also a sulfhydryl group-containing anti-rheumatic drug, have frequently been discussed. To clarify the pharmacological differences between these two drugs, we examined the concentrations of the compounds and its metabolites in serum and synovial fluid, paying special attention to the metabolites of SA96 produced in vivo. SA96 was metabolized in a very short time to SA981 which is a disulfide compound formed by intramolecular binding of two sulfhydryl groups, and transferred to synovial fluid. In addition SA981 had significant suppressive effects on IL-6 and IL-8 production by synovial cells in vitro. These results demonstrate that SA96, which has two sulfhydryl groups, exhibits anti-rheumatic effects via a pharmacological action clearly different from that of D-penicillamine.

Adjuvants, Immunologic↗

Brainstem auditory evoked potentials during brainstem ischemia and reperfusion in gerbils.

To evaluate the reversibility of neural function in the brainstem following ischemia, we investigated the effect of transient brainstem ischemia on the brainstem auditory evoked potential in gerbils. Brainstem ischemia was produced by bilateral extracranial occlusion of vertebral arteries. Local cerebral blood flow was measured by quantitative autoradiography after 5 min of ischemia and was reduced to less than 3 ml/100 g per min in the pons and lower midbrain, indicating severe and reproducible brainstem ischemia. During brainstem ischemia, brainstem auditory evoked potential waveforms disappeared completely. After a brief ischemic insult (5 min), all four brainstem auditory evoked potential components recovered to normal. After longer ischemic insults (10-30 min), brainstem auditory evoked potential components never recovered to normal. Microtubule-associated protein 2 immunoreactivity revealed differential vulnerability of the acoustic relay nuclei in the brainstem. Neurons in the lateral lemniscus were most vulnerable, followed in order by neurons in the trapezoid body, the superior olive and the cochlear nucleus. We also demonstrated a close relationship between the reversibility of ischemia-induced changes on brainstem auditory evoked potential and ischemic lesions of these relay nuclei. These data may be useful for evaluating the therapeutic window of thrombolytic therapy during acute vertebrobasilar occlusion.

Animals↗

Altered cholinergic mechanisms and blood pressure regulation in the rostral ventrolateral medulla of DOCA-salt hypertensive rats.

We examined whether cholinergic transmission in the rostral ventrolateral medulla (RVLM) of deoxycorticosterone acetate-salt hypertensive rats (DHR) is enhanced and the enhancement is involved in the maintenance of hypertension in DHR, and whether cholineacetyltransferase (ChAT) activities and ChAT mRNA expression are enhanced in neurons intrinsic to the RVLM of DHR. Rats were anesthetized, paralyzed, and artificially ventilated. Unilateral microinjection of cholinergic agents into the RVLM produced a pressor response. The pressor response to physostigmine was greater in DHR than in control rats, whereas the response to carbachol was the same in both sets of rats. Bilateral microinjection of scopolamine into the RVLM produced a decrease in blood pressure. The depressor response was greater in DHR than in control rats. The number of ChAT-activity-detected neurons in the RVLM was greater in DHR than in control rats. The number of ChAT mRNA-expressing neurons in the RVLM was also clearly greater in DHR than in control rats. These results demonstrate that cholinergic transmission in the RVLM is enhanced in DHR, and this enhancement may play a role in the maintenance of hypertension in DHR. It is probable that enhanced activity of cholinergic neurons intrinsic to the RVLM is at least in part, responsible for the enhanced cholinergic transmission in the RVLM of DHR.

Animals↗

Neuron-glia interaction in the suprachiasmatic nucleus: a double labeling light and electron microscopic immunocytochemical study in the rat.

The morphological interactions between astroglial and neuronal elements were elucidated in the rat suprachiasmatic nucleus (SCN) by light and electron microscopic immunocytochemistry using antibodies against glial fibrillary acidic protein (GFAP), vasoactive intestinal peptide (VIP) and arginine-vasopressin (AVP). Throughout the SCN, particularly in its ventral portion, GFAP-like-immunoreactive (GFAP-LI) astroglial elements were found. These astrocytes displaying GFAP-like immunoreactivity occasionally contained fairly well-developed organelles. Some of these astrocytes were found as satellite cells in close contact with non-immunoreactive neuronal perikarya and processes. Around the neurons, GFAP-LI astroglial processes were also observed to cover some portions of presynaptic and postsynaptic elements. In addition, these astroglial elements were seen between two neuronal somata and pericytes of blood capillaries as glial endfeet. By double labeling immunoelectron microscopy using antibodies against GFAP/VIP and GFAP/AVP, some portions of VIP-like-immunoreactive or AVP-like-immunoreactive neuronal somata and processes were found to be engulfed by GFAP-LI astroglial processes. The possible functional roles of the morphological interactions between astroglial and neuronal elements are discussed.

Animals↗

Cholinergic mechanism and blood pressure regulation in the central nervous system.

Cholinergic neurons in numerous brain regions have been implicated in blood pressure regulation. One of the most important brain regions where cholinergic neurons play a role in the pathogenesis of hypertension is the rostral ventrolateral medulla (RVL), an essential source of efferent sympathetic activity. Pharmacological and biochemical studies have revealed that acetylcholine release in the RVL is increased in experimental hypertension regardless of its etiology and that this enhanced release of acetylcholine leads to hypertension. The lateral parabrachial nucleus, another important hindbrain area involved in blood pressure regulation, is responsible for the enhanced release of acetylcholine in the RVL of hypertensive animals. Moreover, recent studies have demonstrated the involvement of the hypothalamic defence area, an area believed to be involved in the hypertension induced by chronic stress, in the release of acetylcholine in the RVL and also have demonstrated the existence of direct projections from the hypothalamic structures to the lateral parabrachial nucleus. More studies about mechanisms of the enhanced release of acetylcholine in the RVL of experimentally hypertensive animals will provide important information for central mechanisms of hypertension.

Animals↗

Pre-operative assessment of metastatic parotid tumors.

Metastatic disease to the parotid gland is rare and its diagnosing procedures are not established. We assessed several parameters, including the prior history of malignancy, fine needle aspiration cytology (FNAC) and magnetic resonance (MR) imaging and determined the most useful combinations for diagnosing metastatic parotid tumors. The primary tumors were squamous cell carcinomas of the eyelid, larynx, tonsil and of unknown origin, malignant melanoma of the auricle and small cell lung carcinoma. In three of four patients with parotid lymph node metastasis who underwent MR imaging, rim enhancement of the tumor was observed on gadolinium (Gd)-enhanced fat-suppressed T1-weighted MR images (sensitivity 75%). In the histopathologic examinations, the tumor was encapsulated and massive infiltration of normal lymphocytes was found peripheral to the capsule. These were not seen in the patients with metastasis to the parotid parenchyma via hematogeneous dissemination or with advanced-stage parotid node metastasis. The FNAC diagnosis accorded with the tumor histology in five of six patients (sensitivity 83%). Three of the six patients had a prior history of malignancy in other sites (sensitivity 50%). The triad of FNAC, prior history of malignancy and enhanced MR images was identified as the combination most useful in the diagnosis of metastatic parotid tumors (sensitivity 100%).

Aged↗

Primary thyroid lymphoma associated with metastatic thyroid tumor: discrimination with US.

We surgically treated a 75-year-old man who suffered from metastatic adenocarcinoma from the colon associated with primary thyroid lymphoma measuring 1 cm maximum in diameter. Radiologic findings were correlated with histopathology of excised specimens. Ultrasonography could discriminate between these two tumors based on the margin characteristics and the lesion echogenicity: the metastatic tumor was shown as an ill-defined hypo to iso echoic mass, while the malignant lymphoma was detected as a well-defined markedly hypoechoic mass. In addition, we could confirm that early-stage primary thyroid lymphoma even as small as 1 cm shows the same radiologic appearance as that of a bulky lymphoma.

Adenocarcinoma↗

Molecular cloning of cDNA for p10, a novel protein that increases in the regenerating legs of Periplaneta americana (American cockroach).

Previously, we purified a protein with a molecular mass of 10 kDa (p10) that increases transiently during the regeneration of legs in the nymphal American cockroach Periplaneta americana, and showed that it is localized exclusively in the cytosol and on the external side of the newly formed epidermis of the regenerating legs [Nomura, A. et al. (1992) Int. J. Dev. Biol. 36, 391-389]. We isolated p10 cDNA and analyzed the expression of the p10 gene. The results indicated that p10 is synthesized as a precursor protein with a putative prosegment including a signal sequence at its N-terminal. The deduced amino acid sequence of p10 showed 53% and 47% identities with those of A10 (a Drosophila antennal protein) and CLP-1 (a moth, Cactoblastis cactorum labial palp protein), respectively. Expression of the p10 gene was shown to be significantly enhanced in regenerating Periplaneta legs. Immunoblotting analysis revealed that p10 was expressed not only in the regenerating legs, but also in the antennae and heads of nymphal and adult cockroaches.

Amino Acid Sequence↗

Cloning of cDNA for regenectin, a humoral C-type lectin of Periplaneta americana, and expression of the regenectin gene during leg regeneration.

We isolated cDNA for regenectin, a C-type lectin of the American cockroach (Periplaneta americana), and analysed expression of the regenectin gene in the regenerating legs. Regenectin was found to be a member of the Periplaneta lectin-related protein family. We found that the regenectin gene was expressed specifically in the epidermal cells of the newly formed regenerating legs. Together with our previous results, these results suggest that regenectin is synthesized by epidermal cells, secreted into the regenerating leg saccule, and assembles around myoblasts to form leg muscle fibers in situ.

Amino Acid Sequence↗

Vitamin A deficiency reduces the responsiveness of pineal gland to light in Japanese quail (Coturnix japonica).

Synthesis of melatonin in pineal gland is under the control of light environment. The recent finding of the presence of rhodopsin-like photopigment (pinopsin) and retinal in the avian pinealocytes has led to a hypothesis that vitamin A is involved in photoresponses of the pineal gland. We have thus analyzed the effect of vitamin A deficiency on the regulatory system of melatonin synthesis in the pineal gland of Japanese quail. Depletion of vitamin A from Japanese quails was attained by feeding them with a vitamin A-free diet supplemented with retinoic acid. In the vitamin A-deficient birds, diurnal rhythm in melatonin production persisted such that the phase of the wave was similar to that seen in the control birds. However, the amplitude of the nighttime surge of pineal melatonin was damped by vitamin A deficiency. When the control birds were briefly exposed to light at night, pineal melatonin dropped to the daytime level. In contrast, only slight decrease was observed in the vitamin A-deficient quails. The light responsiveness was restored after feeding the vitamin A-deficient quails with the control diet for 1 week. These results indicate that vitamin A plays essential roles in maintaining sufficient responsiveness of the avian pineal gland to photic input.

Animals↗

Advances in cereal gene transfer.

Over the past five years, transgenic strains of various major cereals have been produced, with transformation of rice and maize being most common. A majority of the cereal transformants obtained to date has been generated by the particle bombardment technique, but Agrobacterium-mediated transformation is rapidly becoming the method of choice. Rice, the plant in which transformation-related technology is most advanced, appears to be the model monocotyledon for basic and applied studies.

Edible Grain↗

Oxygen toxicity induces apoptosis in neuronal cells.

1. A high oxygen atmosphere induced apoptosis in cultured neuronal cells including PC12 cells and rat embryonic cortical, hippocampal, and basal forebrain neurons associated with DNA fragmentation and nuclear condensation. 2. The sensitivity of CNS neurons to a high-oxygen atmosphere was the following order; cortex > basal forebrain > hippocampus. 3. Cycloheximide and actinomycin-D inhibited the apoptosis, indicating that it depends on new macromolecular synthesis. In contrast, cultured postnatal CNS neurons were resistant to oxidative stress. 4. Neurotrophic factors such as nerve growth factor (NGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) blocked the apoptosis induced by a high-oxygen atmosphere.

Animals↗

Molecular cloning of cDNA and tissue-specific expression of the gene for SII-K1, a novel transcription elongation factor SII.

BACKGROUND: Transcription elongation factor SII has been shown to promote read-through by RNA polymerase II of pausing sites within various eukaryotic genes in vitro by inducing cleavage of the 3'-end of the nascent transcript in the ternary elongation complex. Recently, we showed that various mouse tissues contain multiple SII-related proteins. Of these, 'general SII' was ubiquitously expressed, whereas the others were expressed in a tissue-specific manner. We have identified testis-specific SII (SII-T1) and shown that it was expressed exclusively in spermatocytes. RESULTS: A new SII cDNA clone (pSII-K1) was isolated from mouse kidney. This clone contained an open reading frame which encoded a protein consisting of 347 amino acid residues (SII-K1). A comparison of the amino acid sequences of SII-K1 with those of general SII and SII-T1 revealed that their amino- and carboxy-terminal regions were very similar, but that the sequence of the 95 internal residues (87/181) was unique to each. The recombinant SII-K1 produced in Escherichia coli stimulated RNA polymerase II as did general S-II. The gene for SII-K1 was found to be expressed strongly in the heart, liver, skeletal muscle and kidney, but not in other tissues examined. Contrary to the expression of the general SII gene, the SII-K1 gene was expressed only in 15- and 17-day-old embryos during mouse embryonic development. CONCLUSIONS: We identified a novel member of SII family transcription elongation factor named SII-K1. This factor was expressed exclusively in the heart, liver, kidney and skeletal muscle. During mouse embryonic development, no significant expression of the SII-K1 gene was detected before the formation of these tissues.

Amino Acid Sequence↗