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Biomedical subjects

S Sekiguchi

Publications and source records attributed to S Sekiguchi.

At least 145 records · Page 8Linked to original sources

Intramuscular metastasis of carcinoma.

Four cases of intramuscular metastasis of carcinoma are reported. The preoperative clinical diagnosis of all four cases was soft-tissue sarcoma. Definitive diagnoses, made by open biopsy, were uterine carcinoma, gastric carcinoma, lung carcinoma, and hypopharyngeal carcinoma. All patients died from lung, liver, or brain metastasis several months after open biopsy despite surgery, chemotherapy, or radiation therapy. Case reports of macroscopic metastases to muscle are rare, and the authors report four such cases experienced during a 15-year period.

Adenocarcinoma↗

[A case of acute eosinophilic pneumonia with Kerley's lines (A and B) on chest X-ray].

A 18-year-old woman presented to our hospital complaining of an acute onset of progressive dyspnea with nonproductive cough and high fever. The patient was in her usual good health until the previous day, when she started to develop symptoms 8 hours after taking aspirin for a headache. The chest roentgenogram revealed Kerley's lines (A and B), perivascular cuffing and hilar haze with bilateral pleural effusions. Body temperature was 38 degrees C and PaO2 was 48 torr. Infectious diseases and extrinsic allergic alveolitis were excluded. The lymphocyte stimulating test was negative for aspirin. Acute eosinophilic pneumonia was strongly suggested by bronchoalveolar lavage showing a marked increase in eosinophils without peripheral eosinophilia. By the seventh hospital day all clinical and radiographic signs were improved without steroid therapy. Most cases of acute eosinophilic pneumonia reported previously showed diffuse infiltrative shadows on the chest roentgenogram. The present case had interesting radiographic findings which suggested interstitial pulmonary edema.

Acute Disease↗

[Laboratory tests in primary care medicine: pre-clinical, ambulatory screening test system on the basis of the patient's chief complaints in the initial diagnosis making].

We have explored the efficacious laboratory test system to be performed before the first medical contact with a physician on the basis of the patient's chief complaints and their abnormalities of the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology by analyzing 2,625 complaints from 2,175 new patients visited the outpatient unit of Comprehensive Medicine, National Defense Medical College. The patients with complaints such as general fatigue, fever of unknown origin or reno-urinary symptoms showed higher abnormalities of these diagnostic tests than those in 750 patients performed these tests irrespective of the patient's chief complaints. However, complaints originated from neurological, gastro-intestinal, cardiovascular or respiratory diseases were not associated with abnormalities of these laboratory tests in the patients as compared to those in 750 patients mentioned above. These results indicate that (1) clinical usefulness of the "essential laboratory tests" are variable depending on the patients chief complaints and these tests are recommended for the patients with complaints such as general fatigue, fever of unknown origin or reno-urinary symptoms as pre-clinical ambulatory screening tests before history taking and physical examination to enable to make accurate initial diagnosis and subsequent efficacious medical approach and (2) test items should be selected depending on the patient's chief complaints.

Adolescent↗

Effect of verapamil on the class I major histocompatibility complex antigen expression in K562 chronic myelogenous leukemia cells treated with recombinant human interferon-gamma.

The effects of various compounds which modulated the intracellular signal transduction on the induction of class I major histocompatibility complex (MHC) antigens by recombinant human interferon-gamma (rIFN-gamma) were investigated using K562, chronic myelogenous leukemia cells. Class I or class II MHC antigens were not expressed in untreated K562 cells and rIFN-gamma (600 units/ml) weakly induced class I antigens on the cells. Among the compounds tested, verapamil but not the calcium ionophore A23187 enhanced the rIFN-gamma-induced class I antigen expression at both the surface molecule and mRNA levels and enhancement by verapamil occurred in a dose-dependent manner at non-toxic concentrations examined (approximately 50 microM). Verapamil alone had no inducible effect on MHC antigen expression. Deprivation of Ca2+ in culture medium by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) could not cause an enhancement of class I antigen induction by rIFN-gamma. Simultaneous exposure of K562 cells to rIFN-gamma (600 units/ml) and recombinant human tumor necrosis factor (rTNF; 1000 units/ml) in combination with verapamil (50 microM) resulted in a further increase of class I antigens in the cells. The expressions of c-myc oncogene in K562 cells were not changed when the cells were treated with rIFN-gamma (600 units/ml) or verapamil (50 microM), either alone or in combination. These results indicate that verapamil synergistically interacts with rIFN-gamma on the class I antigen induction in K562 cells irrespective of c-myc gene expression and that class I antigen induction in this cell line may not be relevant to calcium influx triggered by IFN-gamma.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Oligo-2',5'-adenylate synthetase activity in cells persistently infected with human T-lymphotropic virus type I (HTLV-I).

Spontaneous production of interferon-gamma (IFN-gamma) was shown in several T-lymphoblastoid cell lines persistently infected with human T-lymphotropic virus (HTLV-1). However, the produced IFN-gamma was not always associated with the induction of the antivirus state. The induction of oligo-2',5'-adenylate synthetase (2-5AS) by IFN was studied in five human T-cell lines persistently infected with HTLV-I (MT-1, MT-2, SMT-1, HUT 102 and OKM-2). Four cell lines are able to produce IFN-gamma spontaneously, while the OKM-2 cell line is not. Poor induction of 2-5AS was recognized in three (MT-1, MT-2 and SMT-1) of the four cell lines producing IFN-gamma, though the poor induction was improved after long-term cultivation of cells with IFN-alpha. On the contrary, in the OKM-2 cell line, significant activity of the enzyme was induced by IFN-alpha. Induction of 2-5AS was not correlated with cell growth inhibition, but with the antivirus state. Furthermore, an inverse relationship between IFN-gamma production and 2-5AS induction was demonstrated in these cell lines with the exception of HUT 102 cells.

2',5'-Oligoadenylate Synthetase↗

Oxygen-transport and solution properties of polylipid/Hb vesicles (ARC).

Polymerized phospholipid vesicle encapsulating Hb (polylipid/Hb vesicle) was prepared from a mixture of unsaturated phospholipid, cholesterol and unsaturated fatty acid and polymerization by gamma-ray irradiation. The average radius of resulting vesicles was 203 +/- 39 nm and concentrated Hb (30 wt%) was efficiently encapsulated. gamma-Ray polymerization proceeds theoretically at low temperature (4 degrees C). P50 and oxygen transporting efficiency were adjusted to 40 mmHg and 40%, respectively. Oncotic pressure and solution viscosity can be controlled to the same values as blood.

Blood Substitutes↗

Studies on the quality control of stroma-free hemoglobin.

Analytical methods for phospholipids and blood group antigen were developed using HPLC-UV and EIA, respectively, for the quality control of SFH. These methods had sensitivities superior to those of conventional assays. In addition, the HPLC method could isolate PS, which might play an essential role in blood coagulation. The above analytical methods were applied to evaluate three representatives SFH preparation methods, 36,000xg centrifugation followed by the filtration with a 0.22 um filter, ultrafiltration with a 100 kd membrane, and filtration with the BMM-40 nm membrane. Both the BMM method and the ultrafiltration method were shown to remove more than 99.7% of phospholipids, and more than 99.99% of blood group antigen. On the other hand, the centrifugation preparation still contained much of both components. The BMM filter was originally developed as a virus removal filter. The virus removal efficiency of the BMM-40 nm was examined with a genetic technique, the PCR method. The BMM-40 nm was demonstrated to remove HB viruses with an efficiency of eight log or more. These results indicate that the BMM is a useful filter to prepare a stroma-free, virus-reduced hemoglobin solution.

Antigens↗

Development of analytical methods to evaluate SFH.

For the determination of stroma content in SFH, two analytical methods were developed, the HPLC-UV for phospholipids and the enzyme immunoassay for blood group antigen. These analytical methods were applied to evaluate three representative SFH preparations. The 36,000 x g centrifugation method was shown to contain higher amount of stroma components. On the other hand, the BMM-40 nm and the ultrafiltration method with a 100 kd membrane was shown to remove more than 99.7% of phospholipids and almost all of blood group antigen from hemoglobin solutions. These results demonstrated that these analytical methods were very useful in evaluating any highly purified hemoglobin solutions.

ABO Blood-Group System↗

[Comparable evaluation of serological diagnostic tests (ELISA, IFA and PA methods) for the detection of anti-Borrelia burgdorferi antibody].

We have evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA) and particle agglutination (PA) method as serological screening tests for Lyme-borreliosis. Serum samples obtained from two patients with Lyme-borreliosis showed marked high antibody titers for Borrelia burgdorferi when measured by these methods. Of the serum of 368 healthy members of the Self-Defense Force in north-eastern Japan screened for the antibody to B. burgdorferi, 8.4%, 3.7%, 4.6% were found positive by the ELISA, IFA, and PA method, respectively. However, Western blot analysis of these "positive" sera demonstrated no identical bands to those seen in the serum from the patients with Lyme-borreliosis. While 85% and 15% of Treponema pallidum hemagglutination test (TPHA)-positive sera (20 samples) showed a false-positive reaction by the ELISA and IFA method, respectively, no cross-reaction to the anti-B. burgdorferi antibody was observed in these sera by the PA method. The analysis of the serum of the patients with autoimmune diseases (rheumatoid arthritis; 11 cases, systemic lupus erythematosus; 46 cases) by the ELISA and PA methods resulted in a cross-reaction to some extent, which suggested that the antibodies produced by autoimmune mechanisms such as the anticardiolipin antibody can cause a cross-reaction to the anti-B. burgdorferi antibody. These findings indicate that the PA and ELISA rather than the IFA method should be recommended for rapid and conventional screening of Lyme-borreliosis and that serum "positive" for the anti-B. burgdorferi antibody determined by these tests should be confirmed by Western blot analysis to negate the cross-reactions.

Agglutination Tests↗

["Essential laboratory tests" in primary care medicine--experiences in Comprehensive Medicine, National Defense Medical College].

The "essential laboratory tests" were applied to 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College, to determine the usefulness of these tests in primary care medicine. The "essential laboratory tests" have contributed to the establishment of the initial diagnosis or confirmation of the "tentative initial diagnosis", and to the estimation of the nature or degree of seriousness of the disease. In addition, other diseases not related to the patient's chief complaint could be screened in 32% of the new patients examined with these tests. The "essential laboratory tests" were also found to be useful for the estimation of the presence of malignant tumors in 12 patients with various kinds of malignancies as well as the estimation or evaluation for such conditions as infection or inflammation, anemia, liver or renal dysfunction, and the ambulatory screening of metabolic diseases including hyperlipidemia, liver or urinary tract diseases. In conclusion, simultaneous performance of the "essential laboratory tests" with the history taking and the physical examination will provide important medical information in primary care medicine.

Clinical Laboratory Techniques↗

[Usefulness of "essential laboratory tests" for the establishment of the initial diagnosis in new outpatients].

"Essential laboratory tests" advocated by Japan Society of Clinical Pathology were simultaneously performed with the history taking of the present illness and the physical examination in 1,026 new patients visited the outpatient unit of Comprehensive Medicine, National Defense Medical College. We have analyzed the usefulness of the "essential laboratory tests" for the establishment of the initial diagnosis in evaluable 750 patients by comparing the diagnosis made only by the history taking and the physical examination (tentative initial diagnosis) with that included the results of these laboratory tests. The "essential laboratory tests" had contributed to remarkably increased incidences of metabolic and endocrine diseases, liver or biliary tract diseases, renal and urinary tract diseases and anemia after the application of these tests. The initial diagnoses of 61 patients were successfully established by the addition of the "essential laboratory tests" among 157 cases of which tentative initial diagnoses remained undetermined. These tests confirmed the tentative diagnoses in 78 patients, while 78 tentative diagnoses were negated and corrected after evaluation of the results of these tests. Furthermore, the diagnostic tests such as CRP and leukocyte count were useful for the estimation of the nature or degree of seriousness of the disease in 57 patients. In addition, other diseases not related to the patient's chief complaint could be detected in 238 patients (303 total number of diseases) by these tests. These results indicate the usefulness of the "essential laboratory tests" not only for the establishment of more accurate initial diagnosis but also for the screening of the "hidden" diseases such as hyperlipidemia and liver dysfunction.

Adolescent↗

[Laboratory tests in primary care medicine: "essential laboratory tests" (2). Usefulness of hematological, biochemical and serological tests in diagnosis of new outpatients].

We evaluated diagnostic utility of the hematological, biochemical and serological tests comprised in the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology in 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College. Of 750 evaluable patients, 52 showed anemia associated with such conditions as ulcer or cancer of digestive tract, inflammatory disease, or renal failure. Leukocytosis (greater than 9,000/microliters) was found only in 25 of 112 CRP-positive (greater than 0.3 mg/dl) patients, suggesting bacterial infection. Forty-four patients showed hypoproteinemia and/or hypoalbuminemia indicating chronic conditions including liver and inflammatory disease. Elevation of serum creatinine level was found in 4 patients subsequently diagnosed with renal failure, whereas 32 patients demonstrated elevated BUN. After application of the "essential laboratory tests", 97 patients were diagnosed with hyperlipidemia (total cholesterol greater than 230 mg/dl and/or triglyceride greater than 250 mg/dl). Determination of serum enzyme activity was useful not only for the diagnosis of liver dysfunction or biliary tract disease but also for those of hematological malignancies or myogenic disorders; however, in patients with abnormal values of LDH, gamma-GT and ALP, clinical significance was not clarified in 53%, 38% and 59%, respectively. These results indicate that the "essential laboratory tests" are useful in the following aspects of primary care medicine: for (1) estimation of the degree or nature of infection or inflammatory status; (2) classification of anemia and its relation to underlying diseases; (3) evaluation of patient general condition and protein-producible function of liver; (4) evaluation of renal function; (5) ambulatory screening for metabolic diseases such as hyperlipidemia; and (6) diagnosis of liver and biliary tract diseases.

Ambulatory Care↗

The influence of tumor cell density on cellular accumulation of doxorubicin or cisplatin in vitro.

The effect of tumor cell density on the cellular pharmacokinetics of doxorubicin (DXR) and cisplatin (CDDP) was studied using MOLT-3 human acute lymphoblastic leukemia cells. As determined by the MTT assay, the growth-inhibitory effect of DXR was approx. 40 times lower when cell density was increased from 10(6) to 10(8) cells/ml (positive inoculum effect), whereas little or no influence of cell density was observed in CDDP-induced cell-growth inhibition. As measured by high-performance liquid chromatography using a fluorescence detector, the cellular accumulation of DXR showed 6- and 18-fold decreases after 1 h incubation when the cells were concentrated from 10(6) to 10(7) and 10(8) cells/ml, respectively. Only at low cell density (10(6) cells/ml) did the amount of DXR in the cells increase with increasing exposure times of up to 6 h. The DXR concentration in the supernatant that was separated from a cell suspension showing a density of 10(8) cells/ml fell to 20% of that obtained at 10(6) cells/ml. The metabolites of DXR, including Adriamycinol and Adriamycinone, were not detectable in the cell extracts or supernatants at any cell density examined. In contrast, the cellular accumulation of CDDP calculated from the platinum concentration, which was measured with a flameless atomic absorption spectrophotometer, was essentially identical at all cell densities examined; moreover, extension of the exposure period resulted in a linear increase in the amount of CDDP in the cells. CDDP concentrations in the supernatants were equally retained, irrespective of cell densities. These observations indicate that the positive inoculum effect shown in DXR-induced cell-growth inhibition results from the decreased cellular accumulation of the drug at high cell densities. We found no influence for cell density on the cellular accumulation of CDDP that might be relevant to the therapeutic potentiation of this drug at high tumor-cell density.

Cell Count↗

A human leukemia cell line made resistant to two folate analogues, trimetrexate and N10-propargyl-5,8-dideazafolic acid (CB3717).

We established a novel human acute lymphoblastic leukemia cell line made resistant to two folate analogues, trimetrexate (TMQ) and N10-propargyl-5,8-dideazafolic acid (CB3717), by sequential exposure of the 200-fold TMQ-resistant cells (MOLT-3/TMQ200) to CB3717. A 30-fold-resistant subline to CB3717 was selected from the TMQ-resistant cells and designated as MOLT-3/TMQ200-CB371730. This double-folate-resistant cell line was 15-fold more resistant to methotrexate (MTX) than MOLT-3/TMQ200; however, TMQ resistance was decreased to 10-fold as compared to MOLT-3/TMQ200. The doubly resistant cells also showed 2-fold cross-resistance to 5-fluorouracil (5-FU). Equimolar concentrations of leucovorin almost completely reversed the inhibitory effect of MTX on the doubly resistant cells and partially that of CB3717 and TMQ; on the other hand, leucovorin enhanced the inhibitory effect of 5-FU. Thymidylate synthase activities demonstrated little or no difference among these three cell lines, being consistent with no overexpression of mRNA for this enzyme in the doubly resistant cells. MOLT-3/TMQ200 cells displayed classical multidrug resistance; sequential development of CB3717 resistance in the TMQ-resistant cells resulted in an enhancement of the multidrug-resistance phenotype and a concomitant increase of MDR1 mRNA. The development of a complex resistance pattern seen in this double-folate-resistant subline indicates intricacy in the study of drug resistance after multidrug chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗