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Biomedical subjects

S Yoneda

Publications and source records attributed to S Yoneda.

At least 19 recordsLinked to original sources

Enriched stable isotopes of elements used as tracers: methods of presenting high-performance liquid chromatographic-inductively coupled argon plasma mass spectrometric data.

High-performance liquid chromatography (HPLC) of biological fluids and tissue cytosolic preparations was employed in conjunction with argon-induced inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of stable isotopes as tracers. The common way of presenting the data from the ICP-MS is by plotting the count rates versus the retention time of HPLC fractions. Additional information can be derived, e.g., the composite peaks can be further resolved, and the level of enrichment in various biological components can be expressed by alternative ways of presenting these data. The two additional approaches described here involve presenting the ratios of enriched tracer with a suitable naturally abundant mass number of the same element, and by expressing the extent of enrichment by the tracer isotope in a given fraction to that of the same mass number in the fraction derived from an untreated source. Each method of presentation has different merits and drawbacks. The data therefore may be best presented in more than one way to emphasize the conclusions from a given experiment. Observations are presented after simultaneously injecting stable isotopes of three essential elements, copper, selenium and zinc, into mice. Plasma and liver cytosolic fractions were analysed and data represented in different ways as indicated above.

Animals

Demonstration of Epstein-Barr virus genomes, using polymerase chain reaction in situ hybridization in paraffin-embedded lymphoid tissues.

We used the polymerase chain reaction (PCR) in situ hybridization (ISH) (PCR-ISH) on sections of malignant lymphoma and nonspecific lymphadenitis to detect small amounts of Epstein-Barr virus (EBV), a DNA virus of the herpes virus family. We first surveyed the EBV DNA by Southern blot analysis and PCR, and then compared results of the two PCR/ISH methodologies with the results of simplified/sensitive ISH for the positive cases. The target of the simplified in situ (DNA-ISH) was a few copies of EBV DNA per cell, and the target of the sensitive in situ (RNA-ISH) was as many as 10(7) copies of EBV RNA per cell. When EBV DNA was detected by Southern blot, DNA-ISH, RNA-ISH and PCR-ISH all revealed EBV genomes. When PCR revealed only amplified EBV DNA, DNA-ISH showed no EBV genomes, but PCR-ISH and RNA-ISH showed EBV genomes in a few cells. When PCR showed no detectable amplified EBV DNA, all of DNA-ISH, RNA-ISH and PCR-ISH showed no genomes. These findings indicate that PCR-ISH consistently detected a few copies of the EBV virions. The PCR-ISH was as sensitive as RNA-ISH. The RNA-ISH could not detect virus if RNA was not expressed, but the PCR-ISH could detect virus without such expression. The ability to detect a single copy of a specific gene in situ has many advantages and multiple applications in molecular biology, pathology, and cell biology.

Base Sequence

Simultaneous occurrence of aneurysmal subarachnoid hemorrhage and remote intracerebral hemorrhage--case report.

A 77-year-old female presented with a rare aneurysmal subarachnoid hemorrhage accompanied by a remote hypertensive intracerebral hemorrhage. With a past history of hypertension, she suddenly developed right hemiparesis followed by delayed loss of consciousness. Left carotid angiography demonstrated a left internal carotid-posterior communicating artery aneurysm. The intracerebral hematoma was located in the posterior limb of the internal capsule ipsilateral to the ruptured aneurysm. The aneurysm was clipped with a fenestrated clip 3 weeks after the onset. The rise in blood pressure at the onset of intracerebral hemorrhage probably caused the rupture of the internal carotid-posterior communicating artery aneurysm.

Aged

Study on vomiting related to the vestibulo-autonomic reflex.

The purpose of this study was to investigate the neural pathway from the vestibular labyrinth to the medullary vomiting center in the cat, using electrophysiological techniques. During electrical stimulation of the canal nerve, we found conflicting results: the pressure in the stomach sometimes increased, and sometimes decreased. There might be several neural structures between the semicircular canal nerve and the vomiting center in the dorsolateral portion of the reticular formation of medulla oblongata. Retching or vomiting-like behavior during both respiration and movement of the stomach was recorded during stimulation at several sites in the lateral medullary reticular formation. However, the evoked unit activities were not always induced by stimulation of the canal nerve.

Animals

[Development of quality of life (QOL) questionnaire for use of lung cancer patients in palliative therapy--study of validity and reliability. No.1].

We investigated the validity and reliability of QOL questionnaire for lung cancer patients in palliative therapy. The questionnaire covered twelve items: appetite, feelings, sleep, mental and physical fatigue, pain, anxiety, daily activity, abdominal and respiratory conditions, linear and face scales. The data were collected from 65 patients and analyzed with principal component analysis and correlation analysis. 1) The percentage of complete answers was 81.5%. 2) Appetite, feelings, sleep, mental fatigue, anxiety and mental scale, pain, respiratory condition, abdominal condition, physical fatigue and physical scale, and satisfied internal consistency. 3) The test-retest reliability was satisfied 4) The inquiry items were grouped into physical, mental and activity scales, and these scales belonged to different dimension. 5) There were correlations between a linear scale, face scale, total score and items. 6) In concurrent validity, there were correlations between performance status and the activity scale, SDS, STAI and the mental scale. 7) In sensitivity, the total score and face score were worst within one week after chemotherapy, and then recovered. This questionnaire was indeed valid and reliable for use as a QOL questionnaire for lung cancer patients in palliative therapy.

Adult

[Development of quality of life (QOL) questionnaire for use of lung cancer patients in palliative therapy--study of validity and reliability no. 2, the effects of chemotherapeutics in QOL].

The effects of cisplatin and carboplatin in QOL were studied using a QOL questionnaire seeking to conform their validity and reliability in lung cancer patients. The questionnaire was composed of eleven items; appetite, feeling, sleep, mental fatigue, pain, anxiety, daily activity, abdominal and respiratory conditions, linear analog and face scale as global scale. The data were collected from 21 patients treated with cisplatin (Cis group) and 9 patients administered carboplatin (Carbo group). Chronological changes of QOL were measured by AUC (area under the curve) method. 1) The total score of 9 items, linear analog and face scales rose immediately to the highest levels (worse) after treatment and maintained this level for 1 week in the Cis group. The Carbo group levels rose from 3 days and returned to the control level at 9 days after treatment. 2) AUC of the total score, linear analog and face scales in the Cis group increased significantly when compared with those of the Carbo group. 3) When compared with the Cis and Carbo groups the physiological and active scales were not different, but the psychological scale showed a significant difference between the two groups. 4) The total score of the psychological scale correlated the abdominal score in the Cis group, but not in the Carbo group. 5) Sleep and mental fatigue were related to the aggravation of QOL at 5-6 days after Carboplatin treatment. These results suggested that this QOL questionnaire had sufficient sensitivity to reflect any chemotherapeutic side-effects. 6) AUC is useful method in chronological evaluation of QOL.

Adult

[The clinical phase I study of TNP-351. The TNP-351 Research Committee].

The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which should be repeated every 3 weeks.

Adult

Genetic changes in atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia in the same patients.

The transition between atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia (AILD) was studied in serial lymph node biopsy specimens from five patients using DNA analysis with Southern blot analysis, polymerase chain reaction, chromosomal analysis, and immunophenotyping. The chromosomal analysis showed additional abnormalities as the disease progressed to those present initially, and immunological staining showed a corresponding increase in the numbers of CD4- and Ki67-positive cells. In the first biopsy from each patient a diagnosis of atypical hyperplasia with AILD was made and lymphoma excluding by the finding of only a few atypical lymphoid cells and the preservation of follicles with germinal centres. DNA analysis of lymph nodes at this stage showed either germ lines or oligoclonal rearrangements of the T-cell receptor (TCR) and immunoglobulin heavy chain genes. In the final biopsy, when a diagnosis of lymphoma with AILD was made, either a monoclonal rearrangement of the TCR was observed or one of the rearranged bands had increased in density. These results suggest selective proliferation of a clone of abnormal cells may account for the progression of atypical hyperplasia to lymphoma with AILD.

Base Sequence

Expression of human T-cell leukaemia virus type I and associated antigens, and interleukin-2 and receptor in lymph nodes of adult T-cell leukaemia/lymphoma.

To examine the relationship between the expression of human T-cell leukaemia virus type (HTLV-I) mRNA and associated antigens and clinicopathological features, we studied 31 lymph nodes of patients with adult T-cell leukaemia/lymphoma (ATLL) and related diseases, using in situ hybridization and immunohistochemistry. We classified the patients into four types on the basis of their clinicopathological features (HTLV-I associated lymphadenitis, incipient ATLL, ATLL with complete HTLV-I provirus, and ATLL with defective HTLV-I provirus. The expression of HTLV-I mRNA was detected in all 3 patients with incipient ATLL, in 5 of 10 patients with defective-provirus ATLL, in 5 of 11 patients with complete-provirus ATLL, and 3 of 7 with HTLV-I associated lymphadenitis, but the amounts were very small; approximately 1 in 10000-200000 lymph node cells express the viral genomes. This suggests that expression of viral genomes may not be important for immortalization, but it is important that to note the capacity for HTLV-I infection is preserved in each group of non-neoplastic and neoplastic states. HTLV-I mRNA was detected only in lymphocytes and/or lymphoma cells, but the HTLV-I associated antigens (env, gag and pX) were found in histiocytes and endothelial cells, as well as in lymphocytes and/or lymphoma cells. Anti-interleukin 2 receptor (IL-2R) antibody reacted with the giant cells of incipient ATLL and with the transformed lymphocytes and immunoblast-like cells of the HTLV-I-associated lymphadenitis but not with the lymphocytes in the background. Of the typical ATLL, IL-2R was found in both lymphoma cells and giant cells. IL-2 was rarely detected.

Adult

Heterogeneity of Epstein-Barr virus infection in angioimmunoblastic lymphadenopathy type T-cell lymphoma.

To investigate the relationship of Epstein-Barr virus (EBV) and angioimmunoblastic lymphadenopathy with dysproteinemia, we performed DNA analysis using the polymerase chain reaction (PCR), Southern blot, in situ hybridization, and immunohistochemical analysis of lymph nodes in five patients who were followed up and biopsied more than once. In the course of the disease, nodal architecture diminished, cellular atypia worsened, and clear cells increased in number. In the DNA analysis of the receptor genes, the clonal population increased in number. EBV nucleic acid sequences were found by either PCR or in situ hybridization in all examined nodes. The number of EBV-positive cells varied widely among the cases and throughout the course of the disease in the same patients. The analysis of EBV terminal repeats or lymphocyte-determined membrane antigen genes showed polyclonal populations of EB-infected cells. EBV-positive cells possessed intermediate- to large-sized nuclei, and the cells with large nuclei, especially, expressed latent membrane protein of EBV. These large cells varied among the cases. Double-labelling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed B-cell antigen (CD20). The presence of EBV seems to be associated with the selective defects of the immune system, rather than with the direct pathogenesis of angioimmunoblastic lymphadenopathy.

Base Sequence

Clonal analysis of Hodgkin's disease shows absence of TCR/Ig gene rearrangement, compared with T-cell-rich B-cell lymphoma and incipient adult T-cell leukemia/lymphoma.

To better characterize the clonality and pathogenesis of Hodgkin's disease (HD), we used polymerase chain reaction (PCR) and Southern blot to analyze the rearrangement of immunoglobulin (Ig) and T-cell receptor (TCR) genes, the bcl-2 oncogene, and the Epstein-Barr virus (EBV) genotype. In situ hybridization studies of EBV were also done. Twenty-six cases of HD were compared with 15 cases of non-specific lymphadenitis, 7 with incipient adult T-cell leukemia/lymphoma (ATLL), and 4 T-cell rich B-cell lymphomas (TRBL), all of which histologically resembled HD. EBV genes were detected in 20 of 26 HD patients (77%) and in 7 of 15 patients with non-specific lymphadenitis (47%), 5 of 7 with incipient ATLL (71%), and 1 of 4 with TRBL (25%). In contrast to specimens of non-specific lymphadenitis, TRBL, and incipient ATLL, only one EBV genotype was evident in the specimens of HD. EBV latent membrane protein (LMP) was detected immunologically in 16 of 26 HD patients (62%), one of four TRBL (25%) and one of seven incipient ATLL (14%), but it was not evident in non-specific lymphadenitis. The LMP positive cases showed amplified EBV genomes. Only one of the 26 cases of HD had a bcl-2 gene rearrangement by PCR, but this was not seen in any other disease. The bcl-2 protein was detected immunologically in seven of the 26 HD patients (27%) and in one of the seven incipient ATLL cases (14%). EBV has been reported to upregulate bcl-2 expression, but in this study the presence of bcl-2 protein did not correlate with the presence of the t(14;18) translocation or EBV-LMP. All TRBLs showed rearrangement of the immunoglobulin genes by PCR and/or Southern blot, and the giant cells were of B-cell type. All incipient ATLLs displayed rearrangement of the TCR genes, and the giant cells were of T-cell origin. In seven of 26 HD cases, the giant cells were weakly stained with T-cell antibodies, in another seven positive with B-cell antibodies and in 18 instances polyclonally positive for both kappa and lambda. However, PCR and Southern blot displayed only two cases of TCR gene rearrangement, while two others had very weak rearrangements of immunoglobulin gene positive only by PCR. Thus the T and B-cell genotype did not correlate with the T and B-cell phenotype recorded in these cases. The absence of Ig and TCR gene rearrangements seems to be common in HD, compared with in TRBL and incipient ATLL.

Base Sequence

Three-dimensional model of the human PAF receptor.

The amino acid sequence analysis of the human platelet-activating factor (PAF) receptor showed that residues thought to be important structurally and functionally were well conserved. This suggested similarities of the three-dimensional structure (3D structure) between the human PAF receptor and other receptors that couple to guanine nucleotide binding (G) proteins. Thus, a three-dimensional model of this receptor was constructed using the 3D structure of bacteriorhodopsin as the reference protein, by means of the BIOCES[E] computer-modeling system. This model has seven alpha-helical transmembrane segments which form a central core and an S-S bond between the second and third extracellular loops. The distance of the S-S bond is about 2 A, which is thought to be reasonable. In the transmembrane domain, the side chains of Asp-63, Asn-285 and Asp-289 became oriented toward the central core and form a negatively charged site. This receptor model suggests that the positively charged choline moiety of PAF is attracted to this negatively charged site by electrostatic forces and that PAF may induce conformational changes in the receptor, leading to G-protein activation.

Amino Acid Sequence

Immunohistological study of skin involvement in Kikuchi's disease.

Five patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease) with erythematous or popular skin lesions were studied. All patients healed naturally within a few months like the patients with no skin involvement. Histological findings for the skin lesions mimicked cutaneous malignant lymphoma. The infiltrated mononuclear cells usually demonstrated positive reactions for Ki-M1p (20-63%), lysozymes (13-54%), MT-1 (18-64%), UCHL-1 (22-39%) and LN2 (17-36%). OPD-4 and L26 positive cells were few in number. These results suggest that the infiltrated cells in a Kikuchi's disease skin lesion are composed of the same components as the affected lesion in the lymph node.

Adolescent

Effects of prostacyclin infusion on blood pressure and plasma renin activity in patients with essential hypertension.

The effects of prostacyclin infusion (6.7 +/- 2.7 ng/kg/min, 3 to 10 ng/kg/min) on blood pressure, plasma renin activity (PRA), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in 7 patients with essential hypertension (4 men and 3 women) with a mean age of fifty-eight +/- eleven years (forty-six to seventy-four years). The baseline value of 6-keto-PGF1 alpha for patients with essential hypertension was not lower than in healthy subjects. Blood pressure immediately dropped following prostacyclin infusion. Systolic blood pressure returned to the baseline value after prostacyclin infusion was discontinued. However, diastolic blood pressure and mean arterial blood pressure were still significantly decreased thirty minutes after termination of infusion. Heart rate did not change during prostacyclin infusion but decreased significantly when infusion was terminated. PRA was not significantly affected by prostacyclin infusion. The 6-keto-PGF1 alpha level was about 8 times higher than the baseline value thirty minutes after initiation of prostacyclin infusion and approximately twice as high as the baseline value thirty minutes after termination of infusion. The decrease in mean arterial blood pressure coincided with the increase in 6-keto-PGF1 alpha. There was no correlation between mean arterial blood pressure and PRA, nor between PRA and 6-keto-PGF1 alpha. These results demonstrate that production of prostacyclin is not reduced in patients with essential hypertension, and heart rate and PRA are not changed by prostacyclin infusion, although prostacyclin decreases blood pressure.

6-Ketoprostaglandin F1 alpha

Therapeutic trial of cerebral vasospasm with the serine protease inhibitor, FUT-175, administered in the acute stage after subarachnoid hemorrhage.

The therapeutic effect of the synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. Twenty-three patients with severe SAH who were admitted between February and July 1990 and who underwent surgery within 48 hours of the initial aneurysmal rupture were treated with an intravenous administration of FUT-175 soon after the operation. The patients were divided randomly into three groups, each receiving a different dose of FUT-175 (Group A, 20 mg every 12 hours for 4 days; Group B, 20 mg every 6 hours for 4 days, Group C, 40 mg every 6 hours for 4 days). The results were compared with another group of twenty-two patients with severe SAH who were admitted before February 1990 and received equivalent treatment, except they were not treated with FUT-175. In 64% of all the patients treated with FUT-175 (Groups A, B, C), and in 85% of those treated with higher doses of FUT-175 (Groups B and C), there was no spasm or only mild vasospasm on the angiogram. The incidence of a delayed ischemic neurological deficit significantly decreased from 55% in the control group to 13% in all patients treated with FUT-175 and to 7% in the patients treated with higher doses (P less than 0.05). The incidence of cerebral infarction resulting from vasospasm significantly decreased from 43% in the control group to 9% in patients treated with FUT-175. In the patients treated with higher doses of FUT-175 (Groups B and C), none developed cerebral infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[Clinical significance of serum carcinoembryonic antigen in small cell lung cancer patients].

In this study, the clinical significance of serum carcinoembryonic antigen (CEA) level in small cell lung cancer patients was investigated. The relationship between serum CEA level before treatment and the effect of chemotherapy was analyzed. In 97 evaluable patients with small cell lung cancer, the 26 who had elevated CEA values of 10.0 ng/ml or greater at diagnosis tended to be resistant to intravenous systemic chemotherapy. In patients with limited disease (LD), survival time of 13 patients whose CEA levels were 10.0 ng/ml or greater was shorter than that of the other LD patients. These findings suggest that small cell lung cancer patients with high serum CEA levels are less responsive to standard chemotherapy, and serum CEA level may be able to identify biologically different tumors from common small cell cancer.

Adult

[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for primary lung cancer].

A phase II clinical study of 254-S, a new anticancer platinum complex, for primary lung cancer was conducted by the 254-S Lung Cancer Study Group consisting of 15 institutions nation-wide. Considering the results of the phase I clinical study, 254-S was administered at 100 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals. Of 75 patients registered, 61 patients consisting of 22 with small cell lung cancer (SCLC) and 39 with non-small cell lung cancer (NSCLC) were evaluable for complete tumor response. Partial response (PR) was obtained in 17 patients, for a 27.9% response rate. The response rate for SCLC was 40.9% (9 PR in 22 patients) and that for NSCLC was 20.5% (8 PR in 39 patients). In SCLC patients with no prior chemotherapy, a 50.0% (5 PR in 10 patients) response rate was obtained. In those with prior chemotherapy, the response rate was 33.3% (4 PR in 12 patients). In NSCLC patients with no prior chemotherapy, a 22.6% (7 PR in 31 patients) response rate was obtained. In hose with prior chemotherapy, the response rate was 12.5% (1 PR in 8 patients). Major toxic effects observed were hematotoxicity such as thrombocytopenia and leukopenia, and gastrointestinal toxicity such as nausea, vomiting and anorexia. Nephrotoxicity observed was mild and infrequent in spite of the low-volume hydration performed. Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of primary lung cancer.

Adult

Effect of nifedipine on oxygen delivery in patients with angina pectoris: relation between blood viscosity and hematocrit.

The effect of nifedipine on blood viscosity and hematocrit was investigated. Blood was sampled from eight patients with angina pectoris (mean age: 59 +/- 8 yr) treated with nifedipine (20-30 mg/day) for 5 months. Using a cone-plate type viscometer, blood viscosity was determined at the shear rates of 37.5 and 375 sec-1 at 37 degrees C. Hematocrit was also measured at the same time. Since the ratio of hematocrit to blood viscosity at a shear rate of 375 sec-1 can be considered to reflect oxygen delivery, this ratio (oxygen delivery index) was also calculated. Blood viscosity at a shear rate of 37.5 sec-1 was significantly (P less than .05) decreased by nifedipine treatment, but hematocrit and the blood viscosity at a shear rate of 375 sec-1 were not changed. The oxygen delivery index, however, was significantly (P less than .01) increased after the administration of nifedipine. These results suggest that oxygen delivery increased by the treatment with nifedipine and inhibited erythrocyte aggregation by decreasing blood viscosity at low shear rate.

Aged