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Biomedical subjects

K Suga

Publications and source records attributed to K Suga.

At least 109 records · Page 6Linked to original sources
PubMed1997

Abnormal FHIT transcripts in human breast carcinomas: a clinicopathological and epidemiological analysis of 61 Japanese cases.

Deletions in the short arm of chromosome 3 have been found in various human cancers, including breast cancer. Recently, the FHIT (fragile histidine triad) gene was identified at 3p14.2 as a candidate tumor suppressor gene. We examined the abnormal transcripts of the FHIT gene in 61 Japanese primary breast cancer specimens and found that 23 (38%) of them exhibited abnormalities, about half of which were categorized into two types of aberrant transcripts. Sequence analysis of these aberrant transcripts revealed the absence of exons 5-7 (type I) and exons 5-8 (type II). Clinicopathological and epidemiological analysis of patients showed that the abnormal FHIT transcripts were not associated with age, tumor-node-metastasis classification, tumor size, estrogen receptor and progesterone receptor status, local metastasis, family history of breast cancer, or lifestyle factors of patients, including cigarette smoking and alcohol consumption. On the other hand, we found that the abnormal transcripts of type I and type II were associated with the incidence of bilateral breast cancer and that decreased frequency of childbirth was also associated with FHIT abnormalities.

Adult↗
PubMed1997

Mediastinal parathyroid adenoma detected by 99mTc-methoxyisobutylisonitrile: report of a case.

We report herein the case of a 30-year-old man in whom ectopic mediastinal parathyroid adenoma was detected by 99mTc-methoxyisobutylisonitrile scintigraphy (99mTc-MIBI). The patient presented with a history of recurrent renal stones and was diagnosed as having primary hyperparathyroidism due to elevated serum levels of calcium and intact parathyroid hormone (i-PTH) levels. On admission, his serum calcium value was 12.1 mg/dl and the i-PTH level was 137 pg/ml. Ultrasonography, computed tomography (CT), and 201TlCl-99mTcO4- subtraction scintigraphy (Tl-Tc) were performed but none of these imaging techniques was able to detect an enlarged parathyroid gland. Selective venous sampling revealed that the serum i-PTH level was highest at 422 pg/ml in the left brachiocephalic vein. Exploration of the neck also proved unsuccessful. Finally, we performed 99mTc-MIBI which revealed and delineated an enlarged parathyroid gland in the upper mediastinum. Tumor extirpation was subsequently performed through a left thoracotomy. Pathologically, the tumor was confirmed to be a parathyroid adenoma and the serum calcium and i-PTH levels returned to within the normal ranges postoperatively.

Adenoma↗
PubMed1997

Fluorescence polarization study of a salt bridge between a single-chain Fv and its antigen ribonuclease A.

The interaction between a single-chain Fv (sFv) of the monoclonal antibody 3A21 and its antigen, bovine pancreatic ribonuclease A (RNase A), was studied by site-directed mutagenesis of the hypervariable regions and fluorescence polarization analysis. The affinity constants of wild-type sFv and a mutant sFv D31A (Asp31 of heavy chain was replaced by Ala) for RNase A were found to be 2.7 x 10(7) and 4.7 x 10(6) M-1 in PBS at pH 7.2 and 37 degrees C, respectively. While the affinity constant of D31A is not affected by NaCl concentration, that of wild-type sFv is almost the same as that of D31A in the presence of more than 1 M NaCl. These results demonstrate that Asp31 of the heavy chain interacts electrostatically with a positively charged amino acid residue of RNase A.

Alanine↗
PubMed1997

Two promoters in expression of estrogen receptor messenger RNA in human breast cancer.

The human estrogen receptor (ER) gene has recently been shown to transcribe two types of mRNA originating from two distinct promoters in mammary tumor cell lines, which encode the same protein. However, use of the two promoters has not been addressed in human breast cancer, which reveals a heterogeneity in terms of ER expression status and clinical characteristics. In this report, we investigated which promoter is responsible for the expression of ER in human mammary tumors by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis for discriminatory detection of the two transcripts in mammary tissues obtained from patients with breast cancer. First, the use of distinct promoters was confirmed in several mammary tumor cell lines by the present RT-PCR method. Secondly, expression levels of total ER mRNA and two types of mRNAs from the different promoters were analysed in tumor, surrounding tissue and normal tissue obtained from 12 patients with breast cancer, which showed various levels of ER protein. In tumors, levels of total ER mRNA and the mRNA transcribed from a distal promoter showed remarkable correlation to the ER protein levels with correlation coefficients 0.946 (P < 0.001) and 0.746 (P < 0.005), respectively. In contrast, mRNA from a proximal promoter showed no correlation to the ER protein levels. Our results indicate that the enhancement of the ER mRNA expression from the distal promoter plays an essential role in the mechanisms of overexpressing ER protein in human mammary tumors, implying that a tumor-specific regulation of ER expression involved use of the distal promoter.

Adult↗
PubMed1997

Structure and function of the recombinant fifth domain of human beta 2-glycoprotein I: effects of specific cleavage between Lys77 and Thr78.

In order to elucidate the mechanism of binding of beta 2-glycoprotein I (beta 2-GPI) to cardiolipin (CL), we constructed a high-level expression system for the C-terminal domain (Domain V) of beta 2-GPI using Pichia pastoris and studied its conformation and liposome-binding activity. Purified Domain V was found to have the native disulfide bonds. It had a compactly folded conformation, judging from the circular dichroism spectrum, and exhibited a cooperative unfolding transition induced by pH or urea. Also, it bound liposomes containing CL. Commercially available human beta 2-GPI is known to be selectively cleaved between Lys 317 and Thr 318. We found that bovine factor Xa weakly but specifically cleaves the corresponding site of recombinant Domain V, i.e., the peptide bond between Lys 77 and Thr 78. The conformation of the "nicked" Domain V, which was cleaved at this site, was examined by circular dichroism and fluorescence measurements, and concluded to be similar to that of the intact protein. The stability of the nicked Domain V to urea was slightly lower than that of the intact protein. Although both Domains V bound to liposomes containing CL, the affinity of the nicked Domain V was greatly reduced in comparison with the intact protein, indicating that the cleavage of the peptide bond between Lys 77 and Thr 78 controls the binding to CL. In addition, analysis of the fluorescence spectra in the presence and absence of CL liposomes indicated that Trp 76 is involved in the binding site. These results suggest that the region including Trp 76, Lys 77, and Thr 78 has a critical role in binding to CL.

Amino Acid Sequence↗
PubMed1997

SPECT with In-111 autologous platelets to detect residual splenic tissue in two patients with relapsed thrombocytopenia.

In two patients with relapsed thrombocytopenia, the authors used SPECT with In-111 labeled autologous platelets to identify residual splenic tissue after splenectomy. One case involved a previously splenectomized patient with idiopathic portal hypertension, while the other had relapsed chronic idiopathic thrombocytopenic purpura (ITP). In both patients, SPECT showed a higher In-111 uptake in the splenic tissues compared with planar images. In the patient with ITP, a small accessory spleen had been overlooked on abdominal CT because of post-operative changes, but it was identified by superimposition of SPECT/CT images. These cases indicate that In-111 platelet SPECT is useful in detecting and localizing residual accessory splenic tissue associated with relapsed thrombocytopenia.

Adult↗
PubMed1997

Radionuclide angiography and ventilation/perfusion studies in two patients with systemic arterial supply to the basal segment of the left lung.

The findings of radionuclide studies in two adult men with systemic arterial supply to the basal segment of the left lung without sequestration are reported. Radionuclide angiography with Tc-99m human serum albumin-diethylenetriamine showed that the lung was perfused by the systemic circulation rather than by the pulmonary artery. Ventilation and perfusion scans with Xe-133 and Tc-99m MAA showed a V/Q mismatch in this area, suggesting the presence of normal bronchial communication without a pulmonary arterial supply. These results also suggest the presence of a left-to-left shunt in the well-ventilated lung in this area. MRI and conventional angiography showed an aberrant artery arising from the descending thoracic aorta, supplying the basal segment of the left lung without a pulmonary artery. In both patients, left lower lobectomy showed normal alveobronchial structures without sequestration. Radionuclide angiography and ventilation/perfusion imaging appear to be reliable noninvasive methods for diagnosing this rare anomaly with a left-to-left shunt.

Adult↗
PubMed1997

Radionuclide imaging in emphysema after lung volume reduction surgery.

Three dimensional (3D) surface displays of dynamic Xe-133 and Tc-99m MAA SPECT were performed to evaluate regional lung function in two patients with pulmonary emphysema before and after thoracoscopic lung volume reduction surgery. The 3D displays were reconstructed using a color-illuminated, surface-rendering technique. For the Xe-133 studies, a fusion display of 3D equilibrium (EQ) and 3-minute washout (WO) images was used to show the distribution of Xe-133 retention, which were transparently seen within the entire lung contours delineated by the EQ image. In both patients, these 3D displays allowed an overview of the localized poorly functioning lungs with Xe-133 retention or reduced perfusion with geometric realism. The location and extent were more easily comprehended on the displays compared to the slice-by-slice presentations of tomograms. Postoperatively, the displays efficiently revealed restored function in the remaining lungs. The 3D surface displays of the two SPECT procedures providing topographic information of regional lung function appears to contribute to the treatment strategy of this surgery.

Aged↗
PubMed1997

Characterization of hepatic adenoma with atypical appearance on CT and MRI by radionuclide imaging.

The appearance of hepatic adenomas on CT and MRI are highly variable because of their varied histopathology, and images of adenomas are at times indistinguishable from those of other hepatic tumors. The authors present two patients with hepatic adenomas with extremely atypical CT and MRI manifestations demonstrating a "nodule-in-nodule" appearance. Radionuclide imaging in both patients showed decreased Ga-67 uptake in the adenomas compared to normal liver, negative colloid (Tc-99m phytate) uptake in the adenomas, and early uptake and subsequent retention of Tc-99m PMT. This correctly characterized the unique histopathologic features of the resected tumors. Radionuclide imaging using a combination of radiotracers may play an important role in aiding the diagnosis of this rare benign tumor, despite variable CT and MRI appearances.

Adenoma, Liver Cell↗
PubMed1997

Three-dimensional surface displays of perfusion SPET in the evaluation of patients with pulmonary emphysema for thoracoscopic lung volume reduction surgery.

A modified, three-dimensional display was applied to 99Tcm-macroaggregated albumin (99Tcm-MAA) SPET to help assess the effect of thoracoscopic lung volume reduction surgery (LVRS) on regional lung perfusion. Surface-rendered three-dimensional images for 99Tcm-MAA and xenon-133 (133Xe) equilibrium (EQ) SPET were obtained in 11 patients with pulmonary emphysema before and after LVRS. A single three-dimensional fusion display of both images was then reconstructed, and the perfused lungs were transparently visible through the lung contours delineated by the three-dimensional 133Xe EQ image. The extent of preserved perfusion in the lung (the perfusion index) was estimated using the ratio (%) of the total pixel numbers of the segmented perfusion data to those of the 133Xe lung volume data. The three-dimensional fusion display provided an overview of the distribution of hypoperfusion in the lungs with geometric realism and enhanced the perception of anatomic size and configuration compared with multiple tomograms and three-dimensional perfusion images without superimposition of three-dimensional 133Xe image. Post-operatively, it displayed restored perfusion in the remaining lungs, and changes in the perfusion index correlated with %FEV1 (r = 0.731, P = 0.0001) more closely than the perfusion data alone (r = 0.593, P < 0.01). This method is useful for directing LVRS and assessing its effectiveness, as it provides precise tomographic information on regional perfusion.

Aged↗
PubMed1997

Ventilation abnormalities in obstructive airways disorder: detection with pulmonary dynamic densitometry by means of spiral CT versus dynamic Xe-133 SPECT.

PURPOSE: To evaluate pulmonary dynamic densitometry (PDD) by means of spiral computed tomography (CT) for detection of ventilation abnormalities in obstructive airways disorders compared with dynamic xenon-133 single photon emission CT. MATERIALS AND METHODS: Eight-second spiral CT was performed during two to three respiratory cycles in six healthy volunteers, 19 patients with airways disorder, and six patients with restrictive lung disease. The data sets were reconstructed as 36 1-second temporally overlapping images at 0.2-second intervals, and regional PDD curves were displayed. Regional ventilation was assessed by means of Xe-133 clearance time. RESULTS: Normal lungs showed smooth, sinusoidal PDD curves with maximal amplitude in lung attenuation change (MALAC) of 54.9 HU +/- 24.5, whereas lungs with obstructive airways disorders with prolonged Xe-133 clearance showed significantly diminished MALAC (31.6 HU +/- 20.1, P < .0001), accompanied by irregularity, asynchronous phase, and deterioration of normal ventral-to-dorsal gradients in MALAC and lung attenuation. Lungs with restrictive diseases without prolonged Xe-133 clearance did not show statistically significant reduction in MALAC. In a total of 251 lung regions, regional MALAC correlated inversely with Xe-133 clearance time (r = -.842). CONCLUSION: PDD by means of spiral CT is acceptable for the detection of ventilation abnormalities in obstructive airways disorder.

Adult↗
PubMed1997

Effect of vitamin B12-deficiency on testicular tissue in rats fed by pair-feeding.

The effect of vitamin B12 (B12)-deficiency on testicular tissue was investigated through morphological observations of the rats which had been fed on a B12-deficient soybean protein diet by pair-feeding for 100 days. Testicular B12 content was depressed distinctly by the deficiency. Testes weight and their relative weight (weight per 100 g body weight) as well, decreased significantly as compared with those of pair-feeding control rats. Although the decrease in the testicular B12 content due to B12-deficiency was compensated by the administration of cyanocobalamin (CN-B12), alleviation of the decrease in testes weight and relative testes weight was not observed under the condition of the short-term CN-B12 administration. Morphological observations of the testicular tissue in B12-deficient rats revealed atrophy of the seminiferous tubules and aplasia of sperms and spermatids, while testicular findings in both ad libitum-feeding control rats and pair-feeding control rats were normal. There was a tendency for the decrease in seminiferous tubules showing spermatogenesis to be alleviated by administration of CN-B12. The above results indicate that the morphological changes in the testicular tissue are ascribable to B12-deficiency.

Animals↗
PubMed1997

[Usefulness of 3-D dynamic pulmonary xenon-133 SPECT for thoracoscopic lung volume reduction surgery in patients with pulmonary emphysema].

Six patients with pulmonary emphysema scheduled to undergo thoracoscopic lung volume reduction surgery (TLVRS) were evaluated by three-dimensional (3-D) dynamic pulmonary xenon-133 SPECT. Serial 30-second dynamic SPECT data for equilibrium and washout (for 5 min) were acquired using a continuous repetitive rotating acquisition mode with a triple-detector SPECT system. SPECT data were reconstructed to 3-D images with a color, surface-rendering technique, and a 3-D fusion image of the 3-min washout image over the equilibrium image was obtained. Regional ventilation was visually assessed on the fusion 3-D images and quantified by xenon-133 half-washout time (T1/2) and mean transit time (MTT). The 3-D fusion image localized and lateralized the worst diseased sites with xenon-133 retention. Xenon-133 retention, T1/2 and MTT were reduced on these images in five patients with improved pulmonary function tests following TLVRS. However, xenon-133 retention was greater in one with asynchronous diaphragm movement after TLVRS. This modality will assist TLVRS in determining the lung resection target and in evaluating the treatment effect.

Endoscopy↗
PubMed1996

Relationship between thallium-201 uptake and tumour proliferative ability in thyroid nodules.

To evaluate whether thallium-201 scan can reflect tumour proliferative activity in thyroid nodules. We compared the degree of 201Tl uptake with the tumour proliferative ability as assessed immunohistochmically by the labelling index of proliferating cell nuclear antigen (PCNA) in malignant and benign thyroid nodules. The case material comprised ten benign and 31 malignant surgically resected nodules from a total of 41 patients. 201Tl scan was performed 5 min (early scan) and 2h (delayed scan) after intravenous injection of 74 MBq of 201Tl. The degree of 201Tl uptake was visually divided into three grades [from (-) to (++)], as compared with its uptake in normal adjacent thyroid tissue. Immunohistochemical staining of PCNA was performed using a monoclonal antibody for PC10 on paraffin-embedded specimens. On both the early and the delayed scans, the mean PCNA index in the nodules with an intense 201Tl, i.e. (++), was significantly higher than that in nodules with a lower or with negative 201Tl uptake. The correlation was higher on the delayed 201Tl scan (P=0.009) than on the early scan (P=0.019). Our results indicate that 201Tl uptake may reflect the tumour proliferative activity of thyroid nodules, and this is especially true with regard to the uptake on delayed scans.

Biomarkers↗
PubMed1996

Increased production of interferon gamma but not interleukin 4 in human T-lymphotropic virus type I carriers.

We investigated the production of interferon gamma (IFN-gamma), interleukin 4 (IL-4), IL-1 alpha, and tumor necrosis factor alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMCs) from human T-lymphotropic virus type I(HTLV-I) carriers during short-term in vitro culture, in comparison with that by those from HTLV-I seronegative controls. PBMCs isolated from eight carriers and eight controls were cultured, and cytokine levels were measured in 1- and 3-day culture supernatants. Enhanced production of IFN-gamma was observed in all HTLV-I carriers but none of the controls. IL-4 production was not increased in the carriers except for one with a past history of toxoplasma lymphadenitis. IL-1 alpha and TNF-alpha levels were higher in the carriers. CD4+ cells were responsible for the enhanced IFN-gamma production, while monocytes were responsible for the increased IL-1 alpha and TNF-alpha production. The present study showed that the PBMCs from HTLV-I carriers consistently produced large amounts of some cytokines (IFN-gamma, IL-1 alpha, TNF-alpha) but not of other cytokines (IL-4). This imbalance in cytokine production in HTLV-I carriers may be related to the development of opportunistic infections and/or HTLV-I associated diseases including adult T-cell leukemia/lymphoma.

Adult↗
PubMed1996

Superimposition of In-111 platelet SPECT and CT/MR imaging in intracardiac thrombus.

An initial attempt to superimpose in-111-labeled platelet SPECT over CT/MRI in two patients with intracardiac thrombus is presented. One patient was a 65-year-old woman with a history of mitral and tricuspid valve replacement. This patient had a large thrombus measuring 74 x 43 x 34 mm in the right atrium. Fusion imaging with CT showed increased in-111 activity on the surface of the thrombus, which was visualized as circular activity on a planar image. The other patient was a 72-year-old woman who had a thrombus measuring 17 x 14 x 12 mm at the cardiac apex. Planar imaging showed two discrete areas of abnormal in-111 activity. Superimposition of the SPECT image over MR revealed that one of these areas corresponded to the small thrombus, whereas the other related to a previous subendomyocardial biopsy. In both patients, the activity ratio of the abnormal in-111 accumulation versus the cardiac chamber on SPECT was greater than that on planar images. The correlation of in-111 platelet SPECT and CT/MRI was useful in accurately localizing the intracardiac thrombus.

Aged↗
PubMed1996

Effect of intracellular free calcium mobilization on aggregation of umbilical cord blood platelets.

Aggregation activity of platelets in umbilical blood is lower than that in adult blood, but the reason for this is not well understood. It has recently been clarified that calcium plays a role as a second messenger of platelet aggregation, and that glycoproteins of platelet surface membrane such as glycoprotein I b and IIb/IIIa are receptors for agonists inducing aggregation. We examined the concentrations of intracellular calcium and the membrane glycoproteins of platelets in umbilical and adult blood. The increase of intracellular calcium in umbilical platelets was lower than that in adult platelets when the aggregation was induced by ADP, collagen, thrombin and epinephrine. Only calcium ionophore A23187 induced aggregation of both umbilical and adult platelets. On the other hand, there were no qualitative differences between glycoproteins I b and IIb/IIIa of these two groups. Therefore, the low aggregation activity of umbilical platelets seems to be due to low responsiveness of the intracellular calcium system, not to the disorder of functional surface membrane glycoprotein.

Adult↗