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Biomedical subjects

M Mukai

Publications and source records attributed to M Mukai.

At least 127 records · Page 7Linked to original sources

Secretory carcinoma of the breast in a 51-year-old male.

Approximately 100 female secretory carcinoma cases have been reported. Although this tumor was initially termed juvenile carcinoma as the patients were all children and adolescent females, subsequent reports demonstrated that it occurs in females of all ages. Moreover, to date, only five males with this tumor have been reported. As with the initial female secretory carcinoma cases, all five were children or young adults. A very rare case of non-invasive secretory carcinoma of the breast arising in a 51-year-old Japanese male is described. He presented with a lump in his left breast. The surgically resected tumor was a typical secretory carcinoma histologically, except that there was no infiltration of the surrounding stroma, and was composed of tumor cells with vacuolated cytoplasm that contained secretory materials. This case, the first recorded secretory carcinoma of the breast in a middle-aged male, demonstrates that this tumor may also arise in mature males, as is the case in females. Physicians should not rule out the possibility of a secretory carcinoma of the breast regardless of patient age and gender.

Breast Neoplasms, Male↗

Small solid renal lesions: usefulness of power Doppler US.

PURPOSE: To evaluate whether the vascular pattern at power Doppler ultrasonography (US) improves diagnostic accuracy in small solid renal lesions over that at gray-scale US. MATERIALS AND METHODS: Gray-scale and power Doppler US were performed prospectively in 64 small (1.5-3.0-cm-diameter) solid renal lesions (26 renal cell carcinomas [RCCs], 34 angiomyolipomas, two oncocytomas, two pseudotumors). At gray-scale US, echogenicity and homogeneity of the lesion, an anechoic rim, intratumoral cysts, shadowing, or a central scar were sought. At power Doppler US, the vascular distribution was divided into four patterns. RESULTS: Findings at gray-scale US included an anechoic rim or intratumoral cysts in 20 of 26 RCCs (77%) and the two oncocytomas. Shadowing was seen in seven of 34 angiomyolipomas (21%). Echogenicity, homogeneity, and a central scar were not pathognomonic. At power Doppler US, pattern 3 (peripheral) or 4 (mixed penetrating and peripheral) was seen in all RCCs, seven of 34 angiomyolipomas, and the two oncocytomas. Pattern 1 (intratumoral focal) or 2 (penetrating) was seen in 27 angiomyolipomas. Pattern 1 or 2 was characteristic of angiomyolipoma. The rate of correct diagnosis was significantly increased with combined US (78%) as compared to that with gray-scale (42%) or power Doppler (45%) US alone. CONCLUSION: The vascular distribution at power Doppler US could add important information to gray-scale US findings for differential diagnosis of small solid renal lesions.

Adenoma, Oxyphilic↗

Colorectal cancer recurrence in the liver: detection by PET.

Positron emission tomography (PET) has been successfully used in the imaging of various cancers. In this retrospective study, we examined clinical utility of PET in the imaging of liver metastasis from colorectal cancer. Results of PET were compared with those of ultrasonography (US) and contrast-enhanced computer tomography (CT) in 11 liver metastases seen in eight patients with recurrent colorectal cancer. The detection rates were 73% (8 of 11 metastases) by US, 73% (8 of 11 metastases) by CT, and 82% (9 of 11 metastases) by PET. PET correctly identified US-negative and CT-negative liver metastases. However, PET was negative in one patient with minute metastases. The findings in our preliminary study were in agreement with those of previous reports. A prospective study is warranted to determine the optimum role of PET in the management of patients with colorectal liver metastasis.

Aged↗

IgA class anti-beta2-glycoprotein I in patients with systemic lupus erythematosus.

OBJECTIVE: To search for a possible relationship between the presence of IgA class anti-beta2-glycoprotein I antibody (abeta2-GPI) and clinical manifestations, including thrombotic episodes, in patients with systemic lupus erythematosus (SLE). METHODS: Serum IgA abeta2-GPI levels in 124 Japanese patients with SLE were measured using a phospholipid independent enzyme immunoassay. Relationships to clinical histories and to various laboratory data including IgG and IgM class abeta2-GPI were examined. RESULTS: Twenty-five percent of patients with SLE were positive for IgA abeta2-GPI. Patients with a history of thrombosis had significantly higher probabilities for positivity of IgA abeta2-GPI, compared to those without. The presence of IgA abeta2-GPI was correlated with presence of lupus anticoagulant and/or biological false positive result for serological syphilis test. Titer of IgA abeta2-GPI significantly correlated with values of IgG abeta2-GPI, IgM abeta2-GPI, and anti-DNA antibodies. CONCLUSION: The presence of IgA abeta2-GPI may be related to the occurrence of thrombosis in patients with SLE. Measurements of IgA abeta2-GPI may be of value for evaluating risk of thrombosis in patients with SLE.

Antibodies, Anticardiolipin↗

[Immunohistochemical staining of thymidine phosphorylase in primary colorectal carcinoma and metastases].

Thymidine phosphorylase (TdRPase) is an enzyme involved in the pyrimidine metabolism. It was reported that many cancers contained higher levels of TdRPase than normal tissues. And TdRPase has been reported to be identical with the platelet-derived endothelial cell growth factor. To clarify the distribution of TdRPase in primary and metastatic colorectal cancer, we carried out immunohistochemical staining of formalin-fixed specimens. We investigated 35 primary colorectal cancers resected surgically, 27 hepatic metastases and 8 lung metastases from colorectal carcinoma. TdRPase was highly expressed in primary colorectal cancer with lung metastases (100.0%) and surgically resected lung metastases cancer (87.5%). The staining correspondence between primary colorectal cancer and metastases was 19 cases (70.4%) in the liver metastases and 7 cases (87.5%) in the surgically resected lung metastases. The above results suggested that immunohistochemical staining for primary colorectal cancer may provide information about the sensitivity of metastases to the chemotherapy.

Adult↗

[Acute exacerbation of subacute interstitial pneumonia after thoracoscopic lung biopsy].

A 55-year-old woman was admitted to our hospital with progressive dyspnea that had begun one month before. Chest rentogenogram revealed groundglass appearance and reticular shadows bilaterally. Pulmonary function tests showed both decreased vital capacity and diffusing capacity. Bronchoalveolar lavage fluid had a high lymphocyte fraction with a low CD4+/CD8+ ratio. Thoracoscopic lung biopsy revealed thick, fibro-edematous interstitium and diffuse infiltration of lymphocytes. We also observed an intra-alveolar exudate with infiltration of histiocytes and lymphocytes. The clinical features and pathological findings were consistent with subacute interstitial pneumonia, which was the entity proposed by Kawabata and colleagues. The patient developed acute respiratory failure four days after lung biopsy and died despite steroid pulse therapy. Although subacute interstitial pneumonia has been reported to respond to steroid therapy, and to have a good prognosis, we believe that subacute interstitial pneumonia could fatally worsen when associated with lung biopsy, infection, or some other stimulus.

Acute Disease↗

[Method of preventing hepatic artery occlusion during continuous intrahepatic arterial infusion chemotherapy of 5-FU].

A randomized clinical trial of combined use of steroids, which have a vascular endothelium-protecting action, was performed to develop a method to prevent hepatic artery occlusion during continuous intrahepatic arterial infusion chemotherapy with 5-FU. The steroid used was dexamethasone palmitate (Limethason), which has a high rate of uptake by endothelial cells. The 24 patients with advanced colorectal cancer were divided into 2 groups randomly and both were treated with 5-FU 250 mg/day by continuous hepatic arterial infusion for three weeks. The weekly dose was 5-FU 7 V (1,750 mg) adjusted to 50 ml with physiological saline in Group A and 5-FU 7 V (1,750 mg) adjusted to 50 ml with Limethason 1 A (4.0 mg of dexamethasone palmitate) in Group B. The reservoir was replaced every week. No changes in the mixture (appearance, pH, granule diameter, dexamethasone palmitate content) were observed up to one week. Hepatic arterial stenosis was observed in 8 cases in Group A (67%), but was not observed in any of the cases in Group B. The above results indicated that Limethason has a preventive effect against hepatic artery occlusion.

Anti-Inflammatory Agents↗

The Role of Contrast-Enhanced High Resolution MRI in the Surgical Planning of Breast Cancer.

The role of contrast-enhanced high resolution MRI for planning surgery in breast cancer was evaluated. Of 72 patients examined, 57 patients had invasive ductal carcinoma, 2 had mucinous carcinoma, 1 had medullary carcinoma, 7 had invasive lobular carcinoma, 2 had ductal carcinoma in situ (DCIS) and 3 had Paget's disease. A 1.5 T Signa imager (GE Medical Systems, Milwaukee, WI) was used with a dedicated breast coil. The pulse sequence based on RARE(rapid acquisition with relaxation enhancement) was used with a fat suppression technique. After examining both breasts, the affected breast alone was examined with Gd enhancement. Linear and/or spotty enhancement on MRI was considered to suggest DCIS or intraductal spread in the area surrounding the invasive cancer. Of 72 patients, 50 showed linear and/or spotty enhancement on MRI and 41 of those 50 patients had DCIS or intraductal spread. In contrast, 22 of 72 patients were considered to have little or no intraductal spread on MRI and 17 of the 22 patients had no or little intraductal spread on pathological examination. The sensitivity, specificity and accuracy for detecting intraductal spread on MRI were 89%, 82% and 81%, respectively. Discrepancies in the estimated extent of intraductal spread were less than 2 cm in 90% of the patients according to pathological mapping. High resolution MRI was considered useful in detecting intraductal spread and in estimating its extent, however, larger study using precise correlation with pathology is necessary.

Journal Article↗

Cloning and characterization of a pH-sensing regulatory factor that modulates transport activity of the human H+/peptide cotransporter, PEPT1.

We have isolated a cDNA encoding a pH-sensing regulatory factor protein that modulates transport activity of the human H+/peptide cotransporter, hPEPT1, from the human duodenum cDNA library. The cDNA (1,724 bp) for the regulatory factor (hPEPT1-RF) had an open reading frame encoding a 208-amino acid. The 18-195 amino acid residues of hPEPT1-RF were completely consistent with the 8-185 amino acid residues of hPEPT1, whereas the 1-17 and 196-208 residues were unique sequences. Using a reticulocyte lysate, the in vitro synthesized hPEPT1-RF RNA translated a product of approximately 23 kDa. Northern blot analysis and reverse transcription-coupled PCR revealed that both hPEPT1 and hPEPT1-RF mRNA transcripts are expressed in Caco-2 cells. When expressed in Xenopus oocytes, hPEPT1-RF showed no transport activity of glycylsarcosine, but shifted pH profile of the dipeptide transport mediated by the coexpressed hPEPT1. The pH profile of glycylsarcosine uptake in oocytes coexpressing hPEPT1 and hPEPT1-RF was almost similar to that in the Caco-2 cells. This is the first demonstration of cDNA isolation of a regulatory factor which modulates hPEPT1 activity.

Amino Acid Sequence↗

Catalytic activities and structural properties of horseradish peroxidase distal His42 --> Glu or Gln mutant.

The distal histidine (His) is highly conserved in peroxidases and has been considered to play a major role as a general acid-base catalyst for peroxidase reaction cycle. Recently, however, the X-ray structure of chloroperoxidase from the marine fungus Caldariomyces fumago has revealed that a glutamic acid is located at the position where most of the peroxidase has a histidine residue, suggesting that the carboxyl group in the glutamic acid (Glu) can also assist cleavage of an O-O bond in peroxides [Sundaramoorthy, M., Terner, J., & Poulos, T. L. (1995) Structure 3, 1367-1377]. In order to investigate catalytic roles of the glutamic acid at the distal cavity, two horseradish peroxidase mutants were prepared, in which the distal His42 has been replaced by Glu (H42E) or Gln (H42Q). The formation rate of compound I in the H42E mutant was significantly greater than that for the H42Q mutant, indicating that the distal Glu can play a role as a general acid-base catalyst. However, the peroxidase activity of the H42E mutant was still lower, compared to that for native enzyme. On the basis of the CD, resonance Raman, and EPR spectra, it was suggested that the basicity of the distal Glu is lower than that of the distal His and the position of the distal Glu is not fixed at the optimal position as a catalytic amino acid residue, although no prominent structural changes around heme environment were detected. The less basicity and improper positioning of the distal Glu would destabilize the heme-H2O2-distal Glu ternary intermediate for the peroxidase reaction. Another characteristic feature in the mutants was the enhancement of the peroxygenase activity. Since the peroxygenase activity was remarkably enhanced in the H42E mutant, the distal Glu is also crucial to facilitate the peroxygenase activity as well as the enlarged distal cavity caused by the amino acid substitution. These observations indicate that the distal amino acid residue is essential for function of peroxidases and subtle conformational changes around the distal cavity would control the catalytic reactions in peroxidase.

Catalysis↗

Regulation of thymocyte lineage commitment by the level of classical protein kinase C activity.

Thymocyte-positive selection involves signaling through TCR and accessory molecules, and the signaling intensity appears to be critical for this event. The specific inhibitor of classical Ca2+-dependent protein kinase C (cPKC), Gö 6976, inhibited positive selection in fetal thymus organ culture, indicating that cPKC activation is essential for positive selection. The major protein kinase C isoforms in CD4+ CD8+ thymocytes are cPKC-alpha, cPKC-beta, and the novel Ca2+-independent protein kinase C, nPKC-epsilon. To analyze the effect of cPKC activation level on positive selection, we used thymocytes from TCR transgenic mice with nonselecting and RAG-2 -/- backgrounds as they were developmentally arrested at the CD4+ CD8+ stage without positive selection signals. These thymocytes survived and acquired CD4/CD8 lineage commitment in suspension culture upon transient stimulation with limited concentrations of the selective activator of cPKC-alpha and -beta, thymeleatoxin, and the calcium ionophore, ionomycin. However, neither 12-deoxyphorbol 13-phenylacetate 20-acetate, which selectively activates cPKC-beta, nor ingenol 3,20-dibenzoate, which selectively activates nPKC-epsilon, exerted such an effect. The thymeleatoxin/ionomycin concentrations corresponded to those that inhibit glucocorticoid-induced apoptosis in thymocytes and were lower than those that induce proliferation of mature T cells. The CD4 lineage commitment required a higher level of cPKC activity than the CD8 lineage commitment. CD8alpha or CD4 mRNA expression was down-regulated. Functional helper and killer T cells were induced from the CD4 and CD8 lineage-committed cells, respectively, by additional stimulation. These results suggest that thymocyte lineage commitment in positive selection is regulated by the level of cPKC-alpha activity or by the levels of cPKC-alpha and -beta activities.

Animals↗

Domain-directed polymerase chain reaction capable of distinguishing bacterial from host DNA at the single-cell level: characterization of a systematic method to investigate putative bacterial infection in idiopathic disease.

The use of a broad-range PCR to target conserved sequences in the bacterial ribosome has long been recognized as an approach to investigating idiopathic human diseases for the presence of bacteria. An important example is rheumatoid arthritis where the hypothesis of a bacterial etiology remains viable despite failure of previous methods to identify a causative organism. Practical implementation of this strategy, however, was impeded by requirements unique to the study of these diseases. Hence, an adequately characterized method for achieving this has not appeared. We now describe such a method based on the use of a broadly reactive pair of deoxyinosine-containing primers. Detailed characterization addressing these requirements provided evidence that DNA from at least 96% of potential prokaryotic pathogens would be detected. The sensitivity was shown to approximate that of a single organism per reaction. Importantly, this sensitivity was shown to be maintained among multiple targets and to be unimpaired by a large excess of human DNA. Similar results were obtained with extracts of inflamed human synovial fluid to which as little as 0.01 pg of bacterial DNA or, alternately, a single organism per reaction was added. This method was also shown correctly to detect the causative bacteria in clinically infected synovial fluids, further documenting its applicability to such specimens. Finally, it was converted to an in situ method by which bacterial sequences were histochemically localized to Michaelis-Guttman bodies in tissue sections from a patient with malakoplakia, a poorly understood infectious disease. The broad reactivity and high sensitivity achieved by this approach translate into a high likelihood of detecting an unknown bacterium if present in a clinical specimen. Conversely, if properly controlled, the failure of this method to detect such organisms can provide evidence supporting rejection of the bacterial etiology hypothesis, an important aspect unique to this approach. For those bacterial sequences that are detected, the ability to localize them in situ would help define their histologic context and hence facilitate their pathogenetic interpretation. The present method should therefore be appropriate for use in systematically studying rheumatoid arthritis as well as a number of other important idiopathic disorders where a bacterial etiology is suspect.

Bacterial Infections↗

Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat.

The inflammatory cytokines interleukin (IL) 1 and tumor necrosis factor (TNF) may play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the role of IL-1 in hepatic I-R injury, we investigated the effect of pretreatment with IL-1 receptor antagonist (IL-1ra) on the production of IL-1, TNF, histological findings in the liver, and the survival rate for 7 days. Rats were subjected to 90 min of partial liver warm ischemia by clamping the vessels of the left and middle lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before liver ischemia was induced. IL-1alpha and TNF levels were determined in blood and liver at 0, 30, 90, and 180 min after reperfusion. In a second experiment to determine the effect of IL-1ra pretreatment on survival rate, after 90 min of partial liver ischemia, the right lateral and caudate lobes were excised, leaving only the ischemic lobes. In both groups, IL-1alpha was undetectable in blood, but increased in liver tissue. TNF increased in both blood and liver tissue as reperfusion time increased. Histological evidence of tissue injury was minimal in the IL-1ra-treated group. Furthermore, in the IL-1ra-treated group, the production of TNF decreased in both blood and liver tissue compared with the nontreated group. Survival rates in the IL-1ra-treated and nontreated group were 80% and 30%, respectively. The data demonstrated that the production of IL-1 and TNF increases in hepatic I-R injury and that pretreatment with IL-1ra protects the liver from ischemic insult, indicating an important role for IL-1 in I-R injury.

Animals↗

Frozen-section-guided breast-conserving surgery: implications of diagnosis by frozen section as a guide to determining the extent of resection.

This study was conducted to analyze retrospectively the results of performing sector resection on 56 breasts in 54 patients with breast cancer. The glands were resected with a 2-cm tumor-free margin on both lateral sides and the distal side, and with more than a 3-cm tumor-free margin on the nipple side. The frequency of positive resection margins for the cancer cells was 7/56 (12.5%) on the nipple side and 12/46 (26.1%) on the lateral sides, with an overall frequency of 15/56 (26.8%). There were positive resected margins for cancer cells on both the nipple and lateral sides in 4/46 patients (9%). Assuming the equivocal margins were positive for cancer cells, an accurate diagnosis by frozen section examination was made in 51 of the 56 operations (91.1%). Additional resection of the margins was performed in all 20 cases of a positive resected margin for cancer cells according to the diagnosis by frozen section. Thereafter, the resected margins became negative in 13 cases (65%), but remained positive in 7 cases (35%). These results show that performing diagnosis by frozen section of the surgical margins is an effective guide to resecting tumors adequately.

Adult↗

Increased endothelial cell retraction and tumor cell invasion by soluble factors derived from pancreatic cancer cells.

BACKGROUND: Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood. METHODS: The activities of the endothelial cell retraction in conditioned media (CM) derived from three human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system. RESULTS: The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparin-bound and unbound fractions. CONCLUSIONS: PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.

Cell Adhesion↗