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Biomedical subjects

E Tani

Publications and source records attributed to E Tani.

At least 19 recordsLinked to original sources

Measurement of interferon sensitivity in tumour cells from fine-needle aspirations.

Previous studies have shown significant correlations between interferon (IFN) induced enhancement of the enzyme 2',5'-oligoadenylate (2',5'-A) synthetase in vitro and response to IFN therapy. A limitation of this and other predictive tests is the availability of malignant cells for culture. Malignant cells can be obtained from most palpable solid tumours by fine-needle aspiration. We investigated whether malignant cells from such aspirations can be used in a 2',5'-A synthetase assay. In 23/27 (85%) of the cases sufficient amounts of viable cells were obtained, containing a high proportion (greater than or equal to 90%) of tumour cells. In 13/23 tumour samples (57%) IFN-alpha significantly enhanced the 2',5'-A synthetase levels. The use of cells from the fine-needle aspirations for prediction of IFN sensitivity, makes the 2',5'-A synthetase test applicable in a wide range of tumours at a variety of disease stages.

2',5'-Oligoadenylate Synthetase

Fine needle aspiration cytology of high grade T-cell lymphomas in human T-lymphotropic virus type 1 carriers.

We studied the fine needle aspiration (FNA) cytology of high grade peripheral T-cell lymphomas from eight human T-lymphotropic virus-1 (HTLV-1) positive patients. FNA smears from seven lymphomas showed a distinctive cytologic pattern with a dominance of rounded cells with irregular nuclei and a moderately basophilic cytoplasm. Irregular cells with a pale abundant cytoplasm were present in varying amounts. Some smears contained a few giant cells with cerebriform nuclei. In addition, plasma cells and eosinophils were found. Epithelioid cells were an inconstant finding. On histology these seven lymphomas were assigned to the pleomorphic medium-large cell subtype and all but one were of T-helper phenotype with rearrangements of the T-cell receptor. FNA smears from a lymph node in a patient with a previous histological diagnosis of lymphomatoid papulosis of the gingiva showed a monotonous pattern of large immunoblastic cells with some binucleated variants consistent with a diagnosis of high grade immunoblastic lymphoma, which was confirmed histologically. Our results show that peripheral T-cell lymphomas from HTLV-1 positive patients have cytological patterns which are distinctive enough to allow a conclusive diagnosis of high grade T-cell lymphoma. However, we do not think that the cytology of HTLV-1 positive lymphomas can be differentiated from that of virus-unrelated high grade T-cell lymphomas.

Adult

Endothelin-1 of canine basilar artery in vasospasm.

Cerebral vasospasm was induced in adult mongrel dogs by a two-hemorrhage method. The basilar arteries were quickly frozen after careful removal of surrounding blood clot and their level of immunoreactive endothelin-1, a strong vasoconstrictor produced by the endothelial and vascular smooth-muscle cells, was measured by sandwich-enzyme immunoassay. The levels of immunoreactive endothelin-1 (mean +/- standard deviation) were 112.9 +/- 7.0 pg/mg protein prior to vasospasm, 180.4 +/- 24.7 pg/mg protein on Day 2 after vasospasm, and 115.0 +/- 24.0 pg/mg protein on Day 7, showing a significant increase (p less than 0.01) in immunoreactive endothelin-1 only on Day 2. In addition, vasospasm was moderately reversed by the topical application of monoclonal antibody against endothelin-1 on Day 2 but rather resistant to topical monoclonal antibody on Day 7. It is suggested that endothelin-1 could act as a trigger in the early stages of cerebral vasospasm, but that the maintenance of cerebral vasospasm at later stages might be independent of endothelin-1.

Animals

Effects of inhibitors of protein kinase C and calpain in experimental delayed cerebral vasospasm.

Vasospasm was produced in adult mongrel dogs by a two-hemorrhage method, and the spastic basilar arteries were exposed via the transclival route on Day 7. Tonic contraction was produced in the normal canine basilar arteries by a local application of KCl or serotonin after transclival exposure. The exposed spastic and tonic basilar arteries then received a topical application of the following: 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7), a potent inhibitor of protein kinase C acting at the catalytic domain; calphostin C, a specific inhibitor of protein kinase C acting at the regulatory domain; or calpeptin, a selective inhibitor of calpain. Both spastic and tonic basilar arteries were effectively dilated by H-7. Calphostin C caused only slight dilation of spastic basilar arteries but moderate dilation of tonic basilar arteries. Dilation in response to calpeptin was remarkable in the spastic basilar arteries but slight in the tonic basilar arteries. The doses of calphostin C and calpeptin required to obtain maximum effect were markedly lower in the tonic model than in the spastic model. The spastic and tonic models had a similar dose-dependent response to H-7 but quite a different response to calphostin C or calpeptin, suggesting a difference in the function of protein kinase C and calpain in the two models. Furthermore, the effect of calphostin C on the reversal of vasospasm was increased significantly after topical treatment with calpeptin. It is suggested that the majority of the catalytic domain of protein kinase C is dissociated from the regulatory domain, probably by a limited proteolysis with calpain, and is markedly activated in vasospasm.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

[A case of aneurysm of the peripheral middle cerebral artery presenting putaminal hemorrhage--pitfall in diagnosis].

A case mimicking hypertensive putaminal hemorrhage which was first treated by CT-guided stereotactic aspiration and eventually diagnosed as a sequence of the ruptured aneurysm of the left peripheral middle cerebral artery on postoperative angiography is presented. This 41 old, right-handed, hypertensive female suffered sudden onset of headache and right hemiparesis. Next day hematoma was evacuated by the CT-guided stereotactic aspiration because of progressive deterioration of the consciousness and patient recovered well. Fourteen days after the evacuation when she presented mild right hand weakness and motor aphasia, angiography revealed a saccular aneurysm with broad neck derived from left posterior parietal artery. A neck clipping necessitated an additional anastomosis between superficial temporal artery and distal middle cerebral artery because of parent artery stenosis. Postoperatively she is doing well with slight motor aphasia. Among the typical hypertensive putaminal hemorrhage diagnosed on CT scan, it is stressed that there may be a possibility of ruptured aneurysm situated on the peripheral middle cerebral artery.

Adult

Interspecies comparison of c-myc gene in human and rat glioma cell lines.

Interspecies difference in expression of the c-myc gene between two human and three rat glioma cell lines was studied with use of a human c-myc probe. The c-myc deoxyribonucleic acid (DNA) fragments detected at higher stringency in Southern blotting, showed a difference in size and gene copy number between human and rat glioma cells. The c-myc transcript was detected at both higher and lower stringencies in Northern blotting in human glioma cells, whereas it was demonstrated only at lower stringency in rat glioma cells, and the c-myc transcript was seen in cytoplasms of both glioma cells by in situ hybridization. The c-myc protein, if examined with anti-human c-myc protein monoclonal antibody, was observed as two separate components in Western blotting and localized immunocytochemically in nuclei in human glioma cells, whereas it was detected as three separate forms in Western blotting and shown in both nuclei and cytoplasm in rat glioma cells. The above discrepancy in manifestation of c-myc DNA fragments, transcript and protein could be due to the difference in nucleotide sequence of c-myc gene between human and rat glioma cells.

Animals

Immunohistochemistry of leukotriene C4 in experimental cerebral vasospasm.

Experimental cerebral vasospasm was produced in a "two-hemorrhage" canine model and examined by immunohistochemistry for leukotriene C4 (LTC4). The immunostain for LTC4 showed a strong positivity in intima and adventitia and a scattered reaction in media of normal basilar artery. The immunoreactivity after subarachnoid hemorrhage (SAH) was little changed in intima and media. Inflammatory cells which were characterized histochemically as neutrophils and macrophages, were shown to infiltrate from the adventitia of basilar artery to the periphery of blood clot after SAH and were markedly immunoreactive for LTC4. Also the neutrophils increased in number with the lapse of time after SAH. Thus, it would be reasonable to conclude that the LTC4 responsible for the development of vasospasm would most likely be produced from the infiltrating neutrophils and macrophages. In addition, neurons in hypothalamus, median eminence, and pons, as well as ependymal and arachnoid cells were immunoreactive for LTC4 both in the control and after SAH, whereas astrocytes and oligodendrocytes were not immunoreactive for LTC4 in either case.

Animals

Effects of subarachnoid hemorrhage and a thromboxane A2 synthetase inhibitor on intracranial prostaglandins.

The effects of subarachnoid hemorrhage (SAH) on intracranial prostaglandins (PGs) were studied in canines. Subarachnoid hemorrhage was produced by the "two hemorrhage" method. Basilar artery caliber and regional cerebral blood flow (rCBF) in the occipital cortex were reduced by 42% and 43% during delayed vasospasm, respectively. Once delayed vasospasm had developed, intravenous infusion of OKY-046, a selective inhibitor of thromboxane (TX) A2 synthetase, induced no significant change in angiographic vasospasm but caused a significant increase in rCBF. In delayed vasospasm, cortical levels of PGF2 alpha were significantly decreased, whereas plasma levels of PGF2 alpha and TXB2 in the transverse sinus were significantly increased. The intravenous infusion of OKY-046 in delayed vasospasm induced a significant increase in cortical PGF2 alpha and PGE in the occipital cortex, and caused a significant increase in plasma 6-keto-PGF1 alpha and a significant decrease in plasma TXB2 in the transverse sinus. In delayed vasospasm, decreased cortical levels of PGF2 alpha may reflect a decrease in rCBF and increased plasma PGF2 alpha and TXB2 levels may reflect enhancement of intravascular coagulation. These PGs have very strong and various biological activities. The results suggest that SAH induces complicated changes of intracranial PGs and OKY-046 can improve these pathological changes.

Animals

Fine needle aspiration cytology and immunocytochemistry of metastatic melanoma.

The cytological and immunological findings of 81 metastatic melanomas are described. Fine needle aspiration was performed from secondary deposits in lymph nodes (38), subcutaneous and soft tissue (36), abdomen (5), lung (1) from 67 patients with histologically verified malignant melanoma. One patient had disease which had spread into the cerebrospinal fluid. Cytomorphologically the cases were classified as classical (47%), carcinoma-like (22%), spindle cell type (14%), lymphoma like (6%), undifferentiated (6%), myxoid type (3%), and clear cell type (2%). All cases were immunologically characterized using antibodies to S-100, vimentin and cytokeratin. All cases were S-100 positive and the majority (96%) reacted with antibodies to vimentin. A weak heterogenous reactivity to cytokeratin antibody was detected in only eight cases. The HMB45 antibody was applied to 20 cases and 16 (80%) of these tumours were positive. In summary, we found that an immunological characterization was necessary to conclusively diagnose over 50% of metastatic melanomas which presented with an equivocal cytological picture.

Biopsy, Needle

Modification of lipid peroxidation by some known substituted imidazole derivatives. An attempt to correlate their antioxidant activity with lipophilicity.

The antioxidant activity of two antiallergic agents, oxatomide, astemizole and two neuroleptic drugs, penfluridol, pimozide, structurally related, was tested, using heat-inactivated rat hepatic microsomal fraction and linoleic acid. Lipid peroxidation was induced by Fe2+/ascorbic acid and Fe2+, respectively, and evaluated spectrophotometrically as 2-thiobarbituric acid reactive material. It was found that these compounds inhibited significantly the peroxidation of microsomal membranes in a concentration-dependent manner, as well as the peroxidation of linoleic acid. The lipophilicity of the tested compounds, expressed as RM values derived from reversed phase thin layer chromatography (RPTLC), was determined and the relationship between antioxidant activity and lipophilicity was discussed.

Animals

Histamine acts directly on calcitonin gene-related peptide- and substance P-containing trigeminal ganglion neurons as assessed by calcium influx and immunocytochemistry.

Primary cultures of rat trigeminal ganglion cells were exposed to histamine, and the intracellular free-calcium concentration, [Ca2+]i, was measured by the calcium-sensitive dye fura-2. Histamine increased the [Ca2+]i of the neurons. Pretreatment of the cells with histamine H1-receptor blocker, or removal of extracellular calcium, abolished the response, however, the response was not altered by pretreatment with H2-blocker. Immunocytochemical analysis showed that these cultured cells that responded to histamine identically showed substance P- or calcitonin gene-related peptide-like immunoreactivity.

Animals

Histamine application to the nasal mucosa induces release of calcitonin gene-related peptide and substance P from peripheral terminals of trigeminal ganglion: a morphological study in the guinea pig.

Short-term effects of application of histamine to the nasal mucosa on trigeminal ganglion neurons containing calcitonin gene-related peptide (CGRP) and substance P (SP) were examined in guinea pig. Immunoreactivities to CGRP and SP in these neurons were decreased 30 min after the histamine application. The decreases were most marked at 1-3 h after application, after which the immunoreactivities began to increase, reaching the base line by 6 h after the application. The immunoreactivities to CGRP and SP in the nerve endings of nasal mucosa were not decreased. The expression of mRNAs for both peptides in the soma of trigeminal neurons was unchanged. The histamine application to the nasal mucosa may cause release of CGRP and SP from terminals of peripheral processes of trigeminal ganglion neurons, and enhance axonal transport of these peptides, but does not affect their biosynthesis in the soma of trigeminal ganglion neurons.

Animals

Neuroendocrine (Merkel-cell) carcinoma of the skin: immunocytochemical and cytomorphologic analysis on fine-needle aspirates.

Cytomorphologic and immunocytochemical characteristics of tumor cells from fine-needle aspirates of four neuroendocrine (Merkel-cell) carcinomas of the skin are described. All aspirates were cellular with dispersed small to medium sized tumor cells with scanty cytoplasm. Many mitoses were observed. Careful scrutiny revealed a tendency of the tumor cells to form microacinar and pseudorosette formations as well as small clusters of molding cells. Immunocytochemical analysis of cytospin preparations showed a peculiar dot-like cytokeratin positivity, while neuron-specific enolase staining was more diffuse. A weak S-100 positivity was observed. This staining pattern is highly suggestive of Merkel-cell tumor. It can thus be concluded that immunocytochemical analysis in conjunction with cytomorphology on fine-needle aspirates will allow the identification of neuroendocrine carcinoma of the skin and its differentiation from other small-cell neoplasias of the skin.

Aged

Immunocytochemical analysis of receptors for estrogen and progesterone in fine-needle aspirates from human breast carcinomas.

Monoclonal antibodies were used for a preoperative analysis of estrogen receptors (ERs) and progesterone receptors (PgRs) in fine-needle aspirates from 44 primary human breast carcinomas. The semiquantitative receptor values obtained in cytologic specimens correlated well with those from enzyme immunoassay analysis on surgically removed tumor tissue (r = 0.74 for PgR; r = 0.75 for ER). Cytologic smears showed a heterogenous tumor cell distribution of ER and PgR in 29 and 23 cases, respectively. The results suggest that measurement of the ER and PgR in cytologic smears is an accurate and reliable technique that can be performed on a minimum amount of tissue.

Aged

Histamine acts directly on calcitonin gene-related peptide- and substance P-containing trigeminal ganglion neurons as assessed by calcium influx and immunocytochemistry.

Primary cultures of rat trigeminal ganglion cells were exposed to histamine, and the intracellular free-calcium concentrations, [Ca2+]i, were measured by the calcium-sensitive dye fura-2. Histamine (10(-6)-10(-2) M) increased the [Ca2+]i of the neurons. Pretreatment of the cells with histamine H1-receptor blocker pyrilamine (10(-4) M), or chelation of extracellular calcium, abolished the response; however, the response was not altered by pretreatment with H2-blocker cimetidine (10(-2) M). Thus, the increase in [Ca2+]i was due to the influx of extracellular calcium mediated by H1-receptor. Immunocytochemical analysis showed that these cultured cells that respond to histamine were identically calcitonin gene-related peptide (CGRP)- or substance P (SP)-like immunoreactive. The findings suggested that histamine released from mast cells directly affected CGRP- and SP-containing sensory neurons via H1-receptor, which convey nociceptive information.

Animals

Amplification and expression of a multidrug resistance gene in human glioma cell lines.

Two human glioma cell lines were examined for multidrug resistance (MDR). A vincristine (VCR)-resistant glioma cell line showed a cross resistance to Adriamycin (doxorubicin, ADR) and etoposide (VP-16) to varying extents, suggesting the presence of MDR; the resistance to VCR was considerably decreased by calcium entry blockers. On the other hand, another VCR-sensitive glioma cell line exhibited no cross resistance to ADR or VP-16. Double minute chromosomes and homogeneously staining regions as well as clonal aberrations of chromosome 7 were not observed in cytogenetic studies of multidrug-resistant and multidrug-sensitive glioma cell lines. In Northern and Southern blot analyses, MDR gene 1 (MDR1) messenger ribonucleic acid (mRNA) was shown to be overexpressed without any amplification of the MDR1 gene in multidrug-resistant glioma cell lines as compared to multidrug-sensitive glioma cell lines. It would be reasonable to suggest that amplification of the MDR1 gene may not be a sine qua non for acquisition of MDR and that the MDR1 mRNA level may be correlated with the extent of MDR.

Antineoplastic Combined Chemotherapy Protocols