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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 199 records · Page 11Linked to original sources

Clinical significance of antibodies to native or denatured 60-kd or 52-kd Ro/SS-A proteins in Sjögren's syndrome.

OBJECTIVE: To evaluate the clinical significance of antibodies to native or denatured (anti-n or anti-d) 60- or 52-kd Ro/SS-A proteins (60K or 52K) in Sjögren's syndrome (SS). METHODS: The presence of antibodies to denatured and native Ro/SS-A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy. RESULTS: The incidence of anti-d-60K without anti-d-52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti-d-52K without anti-d-60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti-Ro/SS-A had anti-n-60K. Serologic abnormalities and salivary gland dysfunction were associated with anti-n-60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti-d-60K. Anti-d-52K was not associated with any extraglandular or glandular symptoms in SS. CONCLUSION: The data indicate that anti-n-60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.

Autoantibodies↗

Effect of interleukin-2 on the biodistribution of technetium-99m-labelled anti-CEA monoclonal antibody in mice bearing human tumour xenografts.

We have evaluated whether interleukin-2 (IL-2) at low doses can enhance delivery of radionuclides to tumour sites by improving the access of the radio-labelled antibody. The effects of 1000 or 2000 units of IL-2 on the biodistribution of technetium-99m-labelled anticarcinoembryonic antigen (CEA) monoclonal antibody, ZCE025, in athymic mice bearing human CEA-positive tumour (MKN45) xenografts were investigated. Treatment with IL-2 resulted in a significantly higher tumour uptake (1.2-1.5-fold) compared with the control group. Some normal organs, such as heart, lung, liver, spleen and kidneys, showed increased 99mTc uptake following the IL-2 treatment. Pretreatment with IL-2 also induced an enhancement of the permeability index for mouse IgG in tumours and in normal organs, whereas the blood flow in both normal organs and tumours remained at control levels. The effects of IL-2 were found to be dose-dependent. The IL-2 treatment increased the plasma CEA levels but not the CEA content in tumour tissues, suggesting that IL-2 enhanced the leakage of CEA from tumour to blood. The enhancement ratios of the tumour 99mTc-ZCE025 uptake following treatment with IL-2 were 1.4 and 1.8 in mice bearing small and large tumours, respectively. Our experimental results indicated that the low dose of IL-2 enhanced the vascular permeability sufficiently to increase the amount of antibody delivered to the tumour target. Administration of IL-2 would render radioimmunotherapy more effective, especially in patients with large tumour burdens.

Animals↗

Naturally occurring antiacne agents.

Antibacterial activity of various secondary metabolites from plants against Propionibacterium acnes was tested. In addition, the study of combinations of compounds to enhance the total activity against this follicular bacterium was investigated. A series of long-chain alcohols was studied in great detail to gain new insights into the role of the hydrophobic alkyl groups in the activity.

Acne Vulgaris↗

Antimicrobial agents from Heterotheca inuloides.

By bioassay directed fractionation, four sesquiterpenoids 1-4 were isolated as antimicrobial agents from the dried flowers of Heterotheca inuloides, a Mexican medicinal plant locally known as "arnica". 7-Hydroxy-3,4-dihydrocadalin (3) and 7-hydroxycadalin (4) exhibited potent antibacterial activity against Gram-positive bacteria with minimum inhibitory concentrations (MICs) ranging from 6.25 to 12.5 micrograms/ml. Notably, 7-hydroxy-3,4-dihydrocadalin showed bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) with a minimum bactericidal concentration (MBC) of 12.5 micrograms/ml.

Anti-Bacterial Agents↗

Lung cancer containing growth hormone-releasing hormone associated with hypertrophic osteoarthropathy. Case report.

In a 49-year-old man, large-cell carcinoma of the lung was accompanied by raised serum levels of growth hormone (GH) and growth hormone-releasing hormone (GHRH) and hypertrophic osteoarthropathy. Immunohistochemically the tumour contained GHRH but not GH. The osteoarthropathy disappeared after resection of the primary tumour and did not reappear after its recurrence. The high serum GH level presumably was due to ectopic GHRH production in the tumour. The hypertrophic osteoarthropathy was not clearly attributable to these hormones.

Carcinoma, Non-Small-Cell Lung↗

[Changes in abdominal muscle strength with respect to aging].

It has been generally agreed that muscle strength decreases with advance of age in adulthood. In order to study the effect of aging in abdominal muscle strength, abdominal muscle strength, height, body weight and grip strength were measured in 144 healthy subjects aged from 20 to 88 years old. The abdominal muscle strength was measured using a grip dynamometer. Curve between aging and strength revealed that the abdominal muscle strength gradually decreased with aging during many decades, but rapidly decreased in the fifth decade and over in males and seventh decade and over in females. Among these data, significant correlations were observed between abdominal muscle strength and age (only in males; r = -0.64), abdominal muscle strength and grip strength (in males; r = 0.75, in females; r = 0.47), age and grip strength (in males; -0.72, in females; r = -0.60), and, age and height (in males; r = -0.55, in females; r = -0.46). The results suggest that decrease of abdominal muscle strength is due to aging, although the degree of the decrease is affected by the generation studied. The method to measure abdominal muscle strength originally developed by us is easy and useful to understand changes of age-related muscular strength.

Abdominal Muscles↗

[Exercise and rest myocardial scintigraphy with 201TlCl/99mTc-MIBI dual energy acquisition using triple-energy window scatter correction].

We carried out dual 201Tl/99mTc-MIBI imaging, to reduce the time required for exercise myocardial scintigraphy. We investigated 4 different protocols. In protocol (A), Tl was injected at rest followed by the injection of MIBI at peak exercise. Dual SPECT images were obtained by 201Tl/99mTc simultaneous acquisition. Protocol (B) means reverse either, in which MIBI was injected at rest followed by the administration of Tl at peak exercise. In protocol (C), exercise was performed first with MIBI-injection, and then Tl was injected at rest after one hour later. Simultaneous acquisition was also performed. In protocol (D), after the rest Tl-imaging, MIBI was injected at peak exercise, and then the MIBI-imaging was done. In protocol (A), (B) and (C), simultaneous acquisition was performed using TEW (Triple-Energy Window) scatter correction. Thanks to using dual isotopes, all procedures could be completed within 1-2 hours, which was much shorter than the conventional myocardial perfusion imaging. Scatter correction was useful for accurate diagnoses, when the simultaneous imaging is performed.

Exercise Test↗

[Quantitative evaluation of liver function with 99mTc-GSA scintigraphy using extraction index].

Extraction index (EI5) was introduced to evaluate liver function quantitatively with 99mTc-GSA (GSA) scintigraphy, and it was compared with conventional indices; receptor index (LHL15) and clearance index (HH15). EI5 is expressed as following equation: EI5 = (L5 - L3)/(H3 + H5) * PH/PL where L3, L5: counts at 3 or 5 minutes after the injection in the liver ROI, respectively, H3, H5: counts at 3 or 5 minutes in the heart ROI, respectively; PL, PH: numbers of pixels in the liver- and heart-ROI, respectively. We performed GSA scintigraphy in 40 patients with liver dysfunction and calculated values of the indices. Good correlations were observed between EI5 and liver function tests. Correlation coefficients were almost equal to or higher than those between conventional parameters and liver functional tests. EI5 was thought to be a practical index, and it could be calculated in a short time without aid of computer. Evaluation of local liver function may be possible, because EI5 was corrected with numbers of pixels in the liver- and heart-ROI; which was not considered in the conventional parameters.

Adult↗

[Phase I clinical study for 111In-DTPA-IgG].

A phase I study was performed in three health volunteers to evaluate the safety and biodistribution of 111In-DTPA-IgG, a newly developed imaging agent for inflammation/infection. No adverse effect was observed. There were no clinically significant changes in blood chemistry, hematology, and urinalysis parameters, physical examinations or vital signs. 111In-DTPA-IgG in blood exhibited a biexponential disappearance, consisting of a fast component (t1/2 alpha) ranging from 5.72 to 8.51 hours, and a slow component (t1/2 beta) ranging from 34.0 to 35.5 hours. Twelve percent of the injected dose was eliminated in the urine within 72 hours. Dosimetry estimates indicated that up to 80 MBq of 111In-DTPA-IgG can be safely administered to subjects without exceeding generally accepted absorbed dose for other scintigraphic procedures for inflammation/infection. The organs receiving the highest absorbed dose was the liver followed by the kidneys, heart, and lungs. Each of these organs received less than 40 mGy per 80 MBq administered. The safety data and dosimetry estimates indicated that it is safe to proceed with phase II studies with a 40-80 MBq dose of 111In-DTPA-IgG.

Adult↗

[Clinical evaluation of myocardial perfusion imaging with 99mTc-tetrofosmin].

Myocardial perfusion imaging with Tc-99 m-1,2-bis (bis (2-ethoxyethyl) phosphino) ethane (Tc-99 m-tetrofosmin) was performed in 26 patients with ischemic heart disease (IHD) or suspected to have IHD. The agent was administered both at rest and at peak exercise. Exercise and rest studies were performed on the same day or on different days. The injected dose ranged from 296 MBq-740 MBq. Image quality was adequate for diagnosis, and was superior to that of T1-201 scintigraphy. Results from the tetrofosmin imaging corresponded well with findings of T1 scintigraphy, with a segmental concordance of 87%. Sensitivity and specificity were 70% and 93%, respectively. Our results suggested that tetrofosmin could be a promising Tc-99m labeling agent for the evaluation of myocardial perfusion.

Evaluation Studies as Topic↗

Genomic DNA structure of a gene encoding cytosolic ascorbate peroxidase from Arabidopsis thaliana.

A genomic DNA clone encoding cytosolic ascorbate peroxidase was isolated from a genomic library of Arabidopsis thaliana, using a cDNA for the enzyme as a probe. Nucleotide sequence and primer extension analyses of this gene (APX1) revealed nine exons split by eight introns, one of which is inserted in the 5'-untranslated region. The exon/intron organization of the APX1 gene differs from that of the guaiacol peroxidase genes.

Amino Acid Sequence↗

Indium-111-labelled liposomes: dosimetry and tumour detection in patients with cancer.

Neutral phospholipid vesicles (VesCan), which had been prepared for clinical use, were loaded with 37 MBq indium-111 and administered to seven patients with malignant tumours. The median lipid dose was 2.0 mg/kg. Sequential images showed rapid blood clearance at the early stage, with homogeneous uptake of 111In-labelled VesCan (111In-labelled V-liposomes) in the liver and spleen. Dosimetric estimates for these organs were 1.2 and 1.5 mGy/MBq, respectively, with a whole-body exposure dose of 0.076 mGy/MBq. Total renal excretion of 111In was less than 10% of the injected dose, occurring mainly as 111In-EDTA in three patients. Gamma camera images 24-48 h after administration revealed increased activity in the tumours of four patients. 111In-labelled V-liposomes may enable the demonstration of the tumour site without toxicity and with radiation doses comparable to other radionuclide imaging techniques.

Aged↗

Effect of alpha-interferon on anti-alpha-fetoprotein-monoclonal-antibody targeting of hepatoma.

We studied the potential of alpha-interferon (IFN-alpha) to enhance alpha-fetoprotein (AFP) and thus alter the localization of 125I-labeled antibody to the human hepatoma xenograft in athymic mice using monoclonal antibody (MAb) 19F12, which recognized AFP on the surface of human hepatoma cells. Treatment of the human hepatoma cell NuE with IFN-alpha increased the surface expression of AFP 2.4-fold in an IFN-dose-dependent manner. The IFN-alpha treatment substantially increased (2.7-fold) the localization of 125I-labeled 19F12 to NuE xenografts in athymic mice. The increase in localization of 125I-labeled 19F12 was dependent on the circulating plasma IFN levels. Our experimental results suggested that IFN-alpha could act as a potent modulator of the cellular antigen AFP, and be used to enhance the targeting of a conjugated MAb to hepatoma cell populations.

Animals↗

Respiratory failure due to pulmonary lymphangitis carcinomatosis.

A man with primary lung cancer developed respiratory failure due to lymphangitis carcinomatosis that was diagnosed by transbronchial lung biopsy specimen. After combination chemotherapy with high-dose etoposide and cisplatin (CDDP), he was able to cease oxygen therapy and showed improvement of his lymphangitis carcinomatosis. He received a total dose of 13,400 mg/m2 of etoposide. This case suggested that respiratory failure due to lymphangitis carcinomatosis can be a treatable condition.

Adenocarcinoma↗

Stage IA non-Hodgkin's lymphoma of the Waldeyer's ring. Limited chemotherapy and radiation therapy versus radiation therapy alone.

Seventeen patients with stage IA non-Hodgkin's lymphoma of the Waldeyer's were treated with radiation therapy with or without chemotherapy. All lesions were judged as having intermediate grade malignancy in the Working Formulation. Eight patients received combined treatment with three cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and radiation therapy with 30 to 40 Gy. Another 9 patients were treated with radiation therapy 40 to 60 Gy alone. After a median follow-up of 69 months, all 8 patients, treated with combined modality were alive and relapse-free, whereas 4 of the 9 treated with irradiation alone had relapsed. All relapses occurred trans-diaphragmatically. Two of the 4 relapsing patients were saved, but the other two died of the disease. The 5-year relapse-free and cause-specific survival rates were 100% and 100% in the combined modality group, and 56% and 76% in the radiation therapy alone group (relapse-free: p = 0.04, cause-specific: p = 0.16). There were no serious complications related to the treatment, although most patients complained of mouth dryness and most patients given CHOP had paresthesia. Our opinion was that the total impact of these two side-effects on quality of life was less pronounced after combined modality than after radiation therapy alone. Limited chemotherapy and radiation therapy seemed to be more beneficial than radiation therapy alone not only in relapse-free survival but also in quality of life after treatment.

Adult↗

Relationship between autoantibodies and clinical parameters in Sjögren's syndrome.

Glandular function as estimated by salivary function scintigraphy and extraglandular manifestations were compared among 174 Sjögren's syndrome (SS) patients according to their anti-Ro/SSA, anti-La/SSB, and anti-U1RNP autoantibody status, to clarify the relationship between these autoantibodies and clinical parameters in SS. These antibodies were detected by RNA-immunoprecipitation. Anti-La/SSB or only anti-Ro/SSA antibody was common in 84 primary SS (P-SS) patients, whereas the frequency of only anti-U1RNP was high in 90 secondary SS (S-SS) patients, especially in those with systemic lupus erythematosus (SLE). Antibody-negativity was common in SS with rheumatoid arthritis and was also found in 33% of P-SS. In P-SS, salivary gland dysfunction and parotid swelling were severe in patients who had serological abnormalities with anti-Ro/SSA and with or without anti-La/SSB. They were mild in antibody-negative patients who had mild extraglandular symptoms and in patients with only anti-U1RNP antibody who had Raynaud's phenomenon, pulmonary fibrosis, and later disease onset. P-SS patients positive for both anti-Ro/SSA and anti-U1RNP had SLE-like features. SS could be classified clinically according to these autoantibodies.

Autoantibodies↗

[Gynecomastia].

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Gynecomastia↗

Compton scatter compensation using the triple-energy window method for single- and dual-isotope SPECT.

The spatial distribution of scattered photons varies depending on many factors such as object size and source distribution. We propose a triple-energy window (TEW) scatter compensation method for determining position-dependent Compton scatter. We estimated the count of primary photons at each pixel in the acquired image using the 24% main window centered at the photo peak energy and 3 keV scatter rejection windows on both sides of the main window. We conducted a physical evaluation of this method using phantoms and also applied this method to patients in a clinical trial. The TEW method performed Compton scatter compensation with good accuracy.

Gamma Cameras↗