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Biomedical subjects

S Takagi

Publications and source records attributed to S Takagi.

At least 379 records · Page 21Linked to original sources

[Effective treatment of CMMoL with F-COP (epirubicine, cyclophosphamide, vincristine, prednisolone) therapy].

A 66-year-old female was admitted with high fever and loss of consciousness. For the past one year, she has experienced recurrent febrile episodes. On admission, the presence of monocytosis, thrombocytopenia of the peripheral blood and dysplastic findings of the bone marrow cells indicated chronic myelomonocytic leukemia (CMMoL). The high fever persisted in spite of treatment with antibiotics. Although she was treated by pulse therapy with methyl-prednisolone, her clinical symptoms did not improve. Pleural effusion and ascites were also noted. Treatment with F-COP (epirubicine, cyclophosphamide, vincristine, prednisolone) therapy, resulted in a dramatic improvement of her condition. The F-COP therapy was given monthly for the next 7 months. This case suggests that F-COP therapy may be effective for some patients with CMMoL.

Aged↗

[Two sibling patients with late-onset familial amyloidotic polyneuropathy and atypical clinical manifestations].

Brothers (case 1 and case 2) had familial amyloidotic polyneuropathy type 1 (FAP type 1) confirmed with sural nerve biopsy and DNA analysis. Both patients were unique in that their ages at onset were 56 and 52, and that their only manifestation was sensori-motor polyneuropathy, without clinically apparent autonomic involvements such as orthostatic hypotension, sweat dysfunction and sphincter dysfunction, or severe organ involvement such as gastrointestinal features and myocardial involvement after the onset. They are also unique in that their parents were healthy. The initial manifestation was sensori-motor polyneuropathy starting in the lower extremities. These atypical manifestations made the diagnosis of FAP type 1 difficult in the present cases. Based on reports in the literature and the present cases, there might be a tendency that in patients with late-onset FAP type 1 the clinical manifestations are generally mild and autonomic involvement and organ disturbance are absent or mild. In the etiological diagnosis of polyneuropathy, FAP type 1 should be considered especially in steadily progressive patients.

Age Factors↗

Serial changes of the serum macrophage colony-stimulating factor level after cytoreductive chemotherapy.

To investigate the physiologic role of macrophage colony-stimulating factor (M-CSF) in hematological recovery from bone marrow hypoplasia, we used an enzyme-linked immunosorbent assay to measure serial changes of the serum M-CSF level during 25 intensification chemotherapy courses given to seven patients with acute non-lymphocytic leukemia who were in complete remission. Three M-CSF peaks were observed during therapy: the first peak was during or just after chemotherapy, the second peak was around the leukocyte nadir, and the third peak coincided with a rapid increase in the monocyte count. We could find no significant correlation between the height of the second peak and the time from the initiation of therapy to hematological recovery. On the other hand, there was a significant positive correlation between the height of the second peak and the interval from the last day of chemotherapy to the peak (r = 0.62, p = 0.001), and there was a significant negative correlation between the peak height and the time from the peak until hematological recovery (defined as a neutrophil count of over 500/microliters (r = -0.63, p = 0.001) and a leukocyte count of over 1,000/microliters (r = 0.55, p = 0.008)). However, we found only a weak correlation between the peak height and monocyte recovery. These data suggest that increased M-CSF levels lead to the stimulation of granulocyte progenitors, and that we can predict the time of neutrophil recovery by monitoring the serum M-CSF level and finding its peak.

Adolescent↗

[Intra-arterial infusion chemotherapy with side-hole catheter for primary and metastatic liver, bile duct, and pancreas cancers].

Dislodgement and obstruction of catheter inserted into the artery are great hazards for the hepatic artery infusion chemotherapy. To prevent dislodgement, a new Anthron-coated catheter with a side hole was applied for the treatment of 32 patients with primary and metastatic liver cancer, bile duct cancer and pancreas cancer. The tip of the catheter was advanced deep into the gastroduodenal artery, proper or right hepatic artery, or splenic artery. Anti-cancer drugs were administered through the proximal side hole for targeting cancer. If necessary, the gastroduodenal artery was occluded with a metal coil. No dislodgement or obstruction of the catheter was noticed in the 32 patients thus treated. The new Anthron-coated catheter with a side hole proved to be useful for prevention of catheter dislodgement and accomplishment of long-term intra-arterial infusion chemotherapy.

Aged↗

[Hereditary angioneurotic edema associated with DIC and treated effectively by nafamostat mesilate].

A 36-year-old woman with disseminated intravascular coagulation syndrome (DIC) was admitted to the Third Department of Internal Medicine of the National Defense Medical College Hospital. Even after she recovered from DIC, she had a low level of C1-inactivator. Her past history, family history and family study revealed that she and her family showed hereditary angioneurotic edema (HANE). There have been no reports of HANE associated with DIC. She had two HANE attacks after discharge. We used nafamostat mesilate, a strong inhibitor of activated first complement component, to treat the attacks. She obtained subjective relief and her serological data were improved. Nafamostat mesilate was considered effective for HANE attack.

Adult↗

[Usefulness of dipstick test for determining leukocytes and bacteria in urine].

The value of a simple dipstick test (BMtestLN, Boehringer Mannheim-Shionogi) for determination of leukocytes and bacteria in urine was examined. This test consisted of detection of esterase, an enzyme present in leukocytes and the nitrate reduced by bacteria. A total of 666 clinical urine specimens were tested with both tests. The evaluation of leukocytes in urine was compared with microscopic examination, and the identification and measurement of strains was performed using a semiquantitative plate culture method as a reference. The leukocyte esterase test had a sensitivity of 85.3%, a specificity of 67.3%, positive predictive value of 54.7% and negative predictive value of 90.8%. The range of the sensitivity value of nitrate test was 25.7% for the detection of bacteriuria (bacteria greater than or equal to 10(4) CFU/ml). This test had a specificity of 99.6%, positive predictive value of 94.8% and negative value of 82.9%. We concluded that this dipstick test is not useful for determination of the slight change of pyuria, but sensitive for the determination of acute and untreated urinary tract infections.

Bacteriuria↗

[Measurement of serum type III procollagen aminopeptide with RIA-gnost PIIIP coated tube: changes in patients with various alcoholic liver diseases after abstinence].

In 55 patients with various alcoholic liver diseases, serum type III procollagen aminopeptide (PIIIP) was measured on admission, on biopsy (2-4 weeks after admission) and on discharge from hospital (3 months after admission) using RIA-gnost PIIIP Coated Tube, an assay kit recently launched by Hoechst Japan Limited. Serum PIIIP on admission showed a good correlation with the degree of hepatic fibrosis and was significantly higher in any disease group than in healthy controls, suggesting its usefulness as an indicator of hepatic fibrosis. After abstinence, however, serum PIIIP level exhibited an increasing tendency in all the disease groups except alcoholic hepatitis, and the number of laboratory tests showing a significant correlation with PIIIP decreased as compared with that on admission. The mechanism of serum PIIIP elevations seen after abstinence is yet to be elucidated in detail, considering their possible association with factors other than collagen synthesis in the liver.

Adult↗

Impairment of L-arginine metabolism in spontaneously hypertensive rats.

Plasma L-arginine concentrations were determined in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) before and after water immersion stress. There was no difference in the plasma levels of L-arginine before stress loading between SHR and WKY rats. A significant decrease in the L-arginine level was found in the adult SHR rats after the stress stimuli. However, there was no change in plasma levels of L-arginine in the adult WKY rats before and after water immersion stress. In the weanling rats, significant increases were observed in the plasma L-arginine levels after stress loading in both strains. These findings indicate that there may be an impairment of the L-arginine metabolism in the SHR rats with age and that it may involve in the genesis of hypertension in the SHR rat through the L-arginine-EDRF system.

Aging↗

A novel alternatively spliced viral mRNA transcribed in cells infected with human T cell leukemia virus type 1 is mainly responsible for expressing p21X protein.

The pX sequence of human T cell leukemia virus type 1 (HTLV-1) has been thought to be expressed as a doubly spliced mRNA that codes for p40tax, p27rex and p21X. However, we identified a novel alternatively spliced mRNA in the HTLV-1 infected cells by using reverse transcription followed by the polymerase chain reaction. This mRNA contains only the first and third exons of the doubly spliced mRNA and encodes only p21X. Our data that this mRNA is responsible for expressing p21X exists in most of HTLV-1 infected cells strongly suggests that p21X may play a crucial role for HTLV-1 replication.

Base Sequence↗

In vitro hydrolysis of oligomannose-type sugar chains by an alpha-1,2-mannosidase from microsomes of developing castor bean cotyledons.

An alpha-1,2-mannosidase involved in the processing of N-linked oligosaccharides was prepared from the microsomal fraction of developing castor bean cotyledons. The processing alpha-mannosidase was solubilized with 1.0% Triton X-100 and purified by ion-exchange chromatography followed by two gel filtration steps. The enzyme obtained could convert Man9GlcNAc2-PA to Man5GlcNAc2-PA, but this enzyme was inactive with Man5GlcNAc2-PA, Man4GlcNAc2-PA, and p-nitrophenyl-alpha-D-mannopyranoside. The enzyme was optimally active between pH 5.5-6.0. The processing mannosidase was inhibited by deoxymannojirimycin, EDTA, and Tris ions but not by swainsonine. Structural analyses of the mannose-trimming intermediates produced by the alpha-mannosidase revealed that specific intermediates were formed during conversion of Man9GlcNAc2-PA to Man5GlcNAc2-PA.

1-Deoxynojirimycin↗

Intracellular localization of tyrosine kinase substrates beneath crosslinked surface immunoglobulins in B cells.

Crosslinking of surface immunoglobulins (sIg) in B cells led to the accumulation of submembranal phosphotyrosine, which was followed morphologically with the PY20 antiphosphotyrosine monoclonal antibody. Phosphotyrosine was not detected before sIg crosslinking. After sIg crosslinking, phosphotyrosine-containing proteins were redistributed from scattered small clusters near the plasma membrane to a juxtanuclear region, where immunofluorescent staining decreased with time. Double immunofluorescent staining of individual cells showed accumulation of phosphotyrosine beneath crosslinked sIg molecules at the cell surface. The sIg molecules were subsequently internalized more rapidly than the phosphotyrosine-containing molecules were redistributed. Genistein, a protein tyrosine kinase (PTK) inhibitor, blocked intracellular tyrosine phosphorylations but not cell surface patching of crosslinked sIg. When polyacrylamide beads coated with anti-Ig antibodies were added to the cells, intracellular tyrosine phosphorylation occurred beneath the regions of contact with the beads. This study provides an independent line of evidence confirming recent biochemical experiments that show that crosslinking of the antigen receptor induces PTK activity in B cells, and that components of the newly described sIg complex are among the PTK substrates. The surprising finding that the bulk of the induced phosphotyrosine remains associated with crosslinked sIg for many minutes suggests a role for complex local protein interactions in phosphotyrosine-mediated signal transduction through the antigen receptor of B cells.

Antibodies, Monoclonal↗

Effect of genistein, a tyrosine kinase inhibitor, on latent EBV activation induced by cross-linkage of membrane IgG in Akata B cells.

The activation of phosphoprotein tyrosine kinases was studied in the regulation of EBV activation in Akata cells after cross-linking membrane IgG with anti-IgG. Protein tyrosine phosphorylation was induced in Akata cells after stimulation with anti-IgG, as determined by immunoblotting with the PY20 anti-phosphotyrosine mAb. The frequency of phosphotyrosine-activated cells was also measured by immunofluorescence with the PY20 antibody. Genistein, an inhibitor of tyrosine kinases, at non-cytotoxic doses blocked EBV activation, as measured in the induction of EBV Ag, EBV immediate early BZLF1 mRNA, and its protein product ZEBRA. Such inhibitions were reversed upon removing genistein from the cultures. Genistein inhibition of early Ag induction depended upon the time of addition of genistein after stimulation with anti-IgG. These findings indicate that activation of tyrosine kinase is required for EBV activation after cross-linking membrane IgG in Akata cells.

Antibodies, Anti-Idiotypic↗

Aggravation of subclinical diabetes insipidus during pregnancy.

BACKGROUND: Transient polyuria and polydipsia during pregnancy are rare, and their cause is not entirely clear. Possible explanations include the exacerbation of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. METHODS: We studied two women in whom overt polyuria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. RESULTS: One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in response to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopressin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per liter) before and during hypertonic-saline infusion 30 months post partum. The other patient had partial neurogenic diabetes insipidus. She had subnormal basal plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin level and a subnormal decrease in urine flow in response to the administration of vasopressin, and a normal response to desmopressin. After pregnancy, when her urine volume was normal, she had no increase in plasma vasopressin in response to hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin level and a normal renal response to vasopressin administration. CONCLUSIONS: Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.

Adult↗

A diurnal variation of vasoactive intestinal peptide (VIP) mRNA under a daily light-dark cycle in the rat suprachiasmatic nucleus.

We detected a diurnal change of vasoactive intestinal peptide (VIP) messenger RNA (mRNA) in the rat suprachiasmatic nucleus (SCN) using the in situ hybridization technique combined with computed image analysis. The amount of VIP mRNA was greatest at 02.00 h, the next largest level was seen at 20.00 h during the dark phase and smallest at 14.00 h during the light phase. We also confirmed that the onset of the fluctuation of mRNA occurred 2-6 h prior to the diurnal variation of the content of VIP-like immunoreactivity by semiquantitative immunocytochemistry. These findings suggest that light stimulus from the retina is a primarily influence on the transcription of VIP mRNA and induces a diurnal variation of VIP synthesis.

Animals↗

Haemodynamic changes during the apnoea test for diagnosis of brain death.

Haemodynamic responses to the apnoea test for the diagnosis of brain death were investigated in nine patients with severe head injury or cerebrovascular disease. To prove apnoea, the ventilator was disconnected for ten minutes and oxygen was insufflated to avoid hypoxaemia. No respiratory movement was seen in any patient. Ten minutes after disconnecting the ventilator, PaCO2 was increased to 78 +/- 3 mmHg and pH was reduced to 7.17 +/- 0.02. Adequate oxygenation was maintained in all patients. Cardiac output increased from 4.8 +/- 0.7 to 5.7 +/- 0.8 L.min-1 (P less than 0.05), and mean pulmonary artery pressure increased from 11 +/- 1 to 17 +/- 2 mmHg (P less than 0.01). However, mean arterial pressure, heart rate, pulmonary artery wedge pressure and right atrial pressure did not change. Plasma catecholamines were measured in three patients. Plasma norepinephrine concentrations increased in all three patients but the changes in plasma epinephrine were minimal. These circulatory responses to acute hypercapnia were less than those reported in awake volunteers and in patients during general anaesthesia. However, since plasma norepinephrine concentration increased during the test, some sympathoadrenal response, probably of spinal origin, was present, and may have prevented the direct depressant circulatory effects of acute hypercapnia. In conclusion, the apnoea test did not produce haemodynamic disturbances when respiratory acidosis was limited to a pH 7.17 +/- 0.02 and PaCO2 60-80 mmHg.

Adult↗

Formation of intranuclear replication compartments of Epstein-Barr virus with redistribution of BZLF1 and BMRF1 gene products.

The localizations of the Epstein-Barr virus immediate-early transcriptional activator BZLF1 protein ZEBRA, of the BMRF1 early antigen diffuse component (EA-D), and of viral DNA replication were studied in the Burkitt's lymphoma cell line Akata treated with anti-human immunoglobulin antibodies. Prompt and sequential appearance of ZEBRA, EA-D, and viral DNA was observed in about 70% of the cells. At early times after activation, ZEBRA had a diffuse intranuclear distribution, but later it was concentrated in globular regions within the nucleus. EA-D appeared first in a finely stippled pattern and then in a diffuse pattern. At late times, EA-D concentrated in globular regions similar to those with ZEBRA. Double staining for ZEBRA and EA-D revealed that ZEBRA followed the morphological changes of EA-D with a 1-2 hr delay and that both finally coalesced in the same structures, where in situ hybridization localized replicating viral DNA. The redistribution of both ZEBRA and EA-D to these compartments depended upon the replication of lytic viral DNA. These findings indicate that these globular regions are sites for viral replication and that transcription of EBV late genes may be regulated in these structures.

Animals↗

Projection of the retinal ganglion cells to the tectum differentiated from the prosencephalon.

The alar plate of the prosencephalon differentiates into a tectum-like structure when transplanted into the mesencephalon around the 10-somite stage. Here, we report on the projection pattern of the retinal ganglion cells to the transplants. Optic nerve fibers were labeled with horseradish peroxidase (HRP) and 3H-proline, and the innervation of the optic nerve fibers to the chimeric tectum was analyzed by HRP histochemistry on whole-mounted specimens, by autoradiography and by electron microscopy on embryonic day 16. In the chimeric tectum, the transplant was distinguished from the host by difference in nuclear structure between the quail and the chick cells. It was shown that the transplant had the laminar pattern of the optic tectum when the transplant was integrated into the host mesencephalon. The whole-mount HRP histochemistry showed that the optic nerve fibers extend to the transplants. Autoradiography showed that the distribution pattern of silver grains was similar in both the host and the transplant. These results may indicate that the optic nerve fibers turn to the transplant and terminate on the transplant. Electron microscopy further confirmed that optic nerve fibers ended by making synaptic contacts with the dendrites in the transplant region of the tectum. These results indicate that the transplant with the laminar pattern of the optic tectum is a true tectum receiving input from the eye.

Animals↗

Hepatotoxicity of DR-3438, tienilic acid, indacrinone and furosemide studied in vitro.

A new diuretic antihypertensive, DR-3438, and marketed diuretic drugs were evaluated for their toxicity in vitro. Hepatocytes were isolated from male rats by the collagenase perfusion method and incubated in Dulbecco's modified Eagle medium containing various doses of DR-3438, tienilic acid, indacrinone or furosemide. Tienilic acid decreased cell viability and glutathione content in hepatocytes and increased lipid peroxidation in the cells. Indacrinone also decreased cell viability, but neither cell viability nor glutathione content was affected by furosemide or DR-3438.

Animals↗