Biomedical subjects
Publications and source records attributed to T Imai.
Lipoma of the diaphragm is an extremely rare entity. A case of this disease is herein reported, together with the review of the literature. The patient described was a 70-year-old male, who was admitted to our hospital with an abnormal shadow on his chest X-ray film. The primary tumor, located above the left hemidiaphragm, was successfully resected by video-assisted thoracic surgery, and the final diagnosis of lipoma originating in the diaphragm was made.
We report an immunohistochemical investigation of the striatal efferents in the striatum, globus pallidus, and substantia nigra of five patients with multiple system atrophy (MSA): olivopontocerebellar atrophy (2), striatonigral degeneration (2), and Shy-Drager syndrome (1). All patients manifested parkinsonism during the clinical course of their illness. The administration of levodopa improved the symptoms of two patients, but not of the other three. Brain tissues from five age-matched neurologically normal subjects served as controls. Immunohistochemical assays were carried with antibodies against met-enkephalin, substance P, and calbindin-D28k. Irrespective of the clinical form of multiple system atrophy, the immunoreactivity with the antibodies was reduced at the dorsolateral portion of the striatum and the ventrolateral portions of the globus pallidus and of the substantia nigra. The woolly fiber arrangement of reaction product deposits seen in both segments of the globus pallidus of normal individuals was totally absent in the ventrolateral portions of the three patients who did not have a response to levodopa. By contrast, there were positively stained woolly fibers in globus pallidum segments of the two levodopa-responsive patients, even though their number and size were decreased in comparison with controls. These results indicate that the three clinical forms of multiple system atrophy share common topographic alterations of the striatal efferent system and that the severity of the involvement correlates with the clinically observed effect of levodopa on the parkinsonism.
Two types of fragmented keratin were prepared from buffalo horn and hoof using savinase and Na2S, and their physicochemical and biopharmaceutical properties were examined in mice. The number-average molecular weight of enzymatically fragmented keratin (E-FK), chemically fragmented keratin (C-FK), and fragmented gelatin (FG) were 8000, 33,000, and 6600, respectively. The systematic acute toxicity of FKs was significantly low. Moreover, the immunogenicity of FKs was significantly lower than that of superoxide dismutase. FKs and FG were partially hydrolyzed by trypsin. FKs were digested easily by alpha-chymotrypsin, but FG underwent less hydrolysis under the same conditions. FKs were bound to plasma proteins, including albumin, and also to some proteins in liver and kidney homogenates. In plasma, E-FK was hydrolyzed slowly, but in liver and kidney homogenates it showed slightly faster hydrolysis. In contrast, FG was not hydrolyzed in any of the media used here. After intravenous administration of FKs and FG to mice, these molecules were rapidly eliminated from the plasma. E-FK and C-FK were taken up into the kidneys (CLuptake, kidney; 10,400, 11,600 microliters/h/g), and then gradually excreted in urine. FG was excreted rapidly into urine (CLurine; 6360 microliters/h). Interestingly, C-FK was also taken up into the liver (CLliver; 4820 microliters/h). These results indicated that fragmented keratins are biodegradable materials and might be used as new types of liver- and kidney-specific targeting carriers.
A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.
To determine whether angiotensin (ANG) II, a vasoconstrictor hormone, activates constitutive nitric oxide synthase (cNOS) in endothelial cells (ECs), we investigated the cellular mechanism by which ANG II induces nitric oxide (NO) formation in cultured bovine ECs. ANG II rapidly (within 1 min) and dose-dependently (10(-9)-10(-6) M) increased nitrate/nitrite (NOx) production. This effect of ANG II was abolished by a NOS inhibitor, NG-monomethyl-L-arginine. An ANG II type 1 (AT1) receptor antagonist (DuP 753), but not an ANG II type 2 (AT2) receptor antagonist (PD 123177), dose-dependently inhibited ANG II-induced NOx production. A Ca(2+)-channel blocker (barnidipine) failed to affect ANG II-induced NOx production, whereas an intracellular Ca2+ chelator (BAPTA) and a calmodulin inhibitor (W-7) abolished NOx production induced by ANG II. A protein kinase C (PKC) inhibitor (H-7) and down-regulation of endogenous PKC after pretreatment with phorbol ester decreased NOx production stimulated by ANG II. ANG II transiently stimulated inositol 1,4,5-trisphosphate (IP3) formation, and increased cytosolic free Ca2+ concentrations; these effects were blocked by DuP 753. Our data demonstrate that ANG II stimulates NO release by activation of Ca2+/calmodulin-dependent cNOS via AT1 receptors in bovine ECs.
To clarify the precise function of incidentally discovered adrenocortical adenoma, immunohistochemical and dispersed adrenal cell studies were performed. We have recently seen five patients with so-called nonfunctioning adrenocortical adenoma. Diurnal variation in plasma cortisol and suppression of plasma cortisol and urine 17-hydroxycorticosteroids in response to dexamethasone administration revealed adrenocortical function within normal limits in all cases, and no signs or symptoms of adrenal steroid hormone excess were evident. Since a high uptake of iodomethylnorcholesterol was recognized in each adrenal mass, it was supposed that these adrenal tumors produced steroid hormone to a certain extent, and each patient received unilateral adrenalectomy. P450c17, a key enzyme involved in cortisol production, was expressed in the tumor region in all cases in an immunohistochemical study. Upon in vitro steroidogenesis with dispersed adrenal cells in two cases, all steroid hormones measured except for aldosterone (progesterone, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, dehydroepiandrosterone and androstenedione) were produced in a culture medium. The results indicated that these tumors possessed the capacity for cortisol production, which was in agreement with the results of an iodomethyl-norcholesterol scintigraphy. All patients with mild hypertension or diabetes mellitus had no signs or symptoms of steroid hormone excess, but they could potentially develop a steroid excess syndrome such as Cushing's syndrome in the future.
Glucose plays an important role in fetal development and energy metabolism. Facilitative glucose transporter-1 (GLUT1) has been found in placenta. However, little is known about GLUT1 modulation in placental cells. To examine changes in mouse placental GLUT1 levels caused by 8-bromo-cAMP, we performed 2-deoxyglucose uptake experiments, Northern blot analysis and immunoblot analysis using a primary mouse placental cell culture. Immunohistochemical analysis showed that GLUT1 was localized to the ectoplacental cone and the labyrinth zone of mouse placentas on days 7 and 11 of pregnancy respectively. Treatment of mouse placental cells with 250 mumol/l 8-bromo-cAMP resulted in a significant (P < 0.01) decrease in glucose uptake on days 2-5 of culture. The inhibitory effect of 8-bromo-cAMP on glucose uptake was concentration-dependent. Glucose uptake was also inhibited by 100 micrograms/l cholera toxin and by 0.1 mmol/l forskolin. Northern blot and immunoblot analysis revealed that both GLUT1 mRNA and protein levels were also decreased by 8-bromo-cAMP. These findings suggest that 8-bromo-cAMP inhibits glucose transport activity in mouse placental cells in culture.
BACKGROUND: Bilateral renal cell cancer (RCC) is an imperative indication of nephron sparing surgery (NSS). In the present study, we examined a new modality for NSS; intraoperative ultrasonography, argon beam coagulator (ABC) and fibrin glue. PATIENTS AND METHODS: We performed NSS against 7 kidneys in 5 patients, including 3 with synchronous and 2 with asynchronous tumors. Radical nephrectomy was performed on the contralateral kidney in 2 patients including one with asynchronous and the other with synchronous RCC. RESULTS: To examine satellite lesions and exact tumor extent within the kidney, intraoperative ultrasound scan was performed for all cases. Intraoperative ultrasound scan was shown to be useful for the above mentioned purposes because of its high resolving power. After clamping of the renal artery and surface cooling, dissection of the kidney was done by knife holder or by ultrasonic aspirator. Hemostasis was made by figure eight sutures with chromic catgut or poliglecaprone 25 monofilament, followed by coagulation using ABC, and with fibrin glue. Duration of arterial clamp ranged 20 approximately 78 min under surface cooling. Major complication did not occur except urinary fistula in one case caused by inadequate placement of a double J ureteral catheter. Postoperative renal functions were well preserved and any additional therapy for daily life was not needed in each patient. CONCLUSION: For performing NSS, the use of intraoperative ultrasound scan, ultrasonic aspirator, ABC and fibrin glue seemed to be useful, encouraging us to widespread its indication.
For determining the spread of multiple bone lesions in generalized disseminated atypical mycobacteriosis a rare disease, bone scintigraphy was found useful in our two patients. They were both female, and the pathogenic microbe was M. avium intracellulare complex. The disease appeared to have been induced by defatigation. The depression of cellular immunocompetence was also suspected to be responsible. Bone scintigraphy disclosed multiple abnormal accumulations systematically. The Definitive diagnosis in these cases was established by biopsy. In differential diagnosis of this disease by bone scintigraphy, bone metastasis of a malignant tumor was considered of primary importance. Although antitubercular chemotherapy resulted in improvement of subjective symptoms and inflammation, abnormal accumulation persisted. There was necessity for taking notice that in the decision of the treatment effect of this disease, improvement of abnormal accumulations on bone scintigraphy was delayed that of inflammatory reaction.
Simultaneous transmission emission protocol (STEP), developed for the non-uniform attenuation correction of single photon emission computed tomography (SPECT) was evaluated using the cardiac phantom prepared with and without a myocardial wall defect. Emission computed tomography (ECT) of the cardiac phantom using 201Tl was acquired. Transmission data (TCT) were taken using a line source of 99mTc. Myocardial images with STEP method were superior in the homogeneity of intramyocardial radioactivity and spatial resolution to the conventional SPECT images. This is an excellent method because of the accurate matching position between TCT and ECT images and shortening the examination time by simultaneous data acquisition. It would be clinically useful for diagnosing various myocardial diseases.
Severe mitral regurgitation (MR) due to abnormal chordae tendineae as a primary cause is rare. This clinicopathologic study included four such cases which occurred among 6,500 consecutive autopsies on persons older than 60 years. This paper describes three of these cases. Case 1 was a 76-year-old woman with congestive heart failure, MR and atrial fibrillation. She died of acute myocardial infarction. The heart weighed 360 g. Mitral regurgitation was caused by a thick and long abnormal chorda originating from the posteromedial papillary muscle and protruding into the atrial surface of the middle scallop of the posterior mitral leaflet associated with prolapsed anterior mitral leaflet. Case 2 was an 81-year-old woman with MR and congestive heart failure. She died of acute myocardial infarction. The heart weighed 480 g. There were abnormal chordae tendineae with very few branches at the posterior commissure. Parts of both mitral leaflets on the sides of posterior commissure were also prolapsed. Case 3 was a 91-year-old man with MR and atrial fibrillation. He died of congestive heart failure. The heart weighed 530 g. Abnormal chordae tendineae with reticular structures originated from the anterolateral papillary muscle and protruded into the anterior mitral leaflet, which induced severe MR. These cases had abnormally protruding chordae tendineae, abnormal branching, and abnormal structures of the chordae tendineae, respectively. These abnormal chordae tendineae were considered to be congenital anomalies. Clinically all patients had a holosystolic murmur (Levine III-IV degrees), refractory congestive heart failure and atrial fibrillation. The etiology of the MR in these three patients was suspected to be ruptured chordae tendineae demonstrated on echocardiograms. These patients had heavy hearts (mean 457 g) with enlarged left atria and thickened mitral valves, which corresponded to the appearance of severe MR.
To study immunorecognition of free type and complex type prostate-specific antigen (PSA) by current commercial PSA assays, sera from 3 patients with stage D2 prostate cancer were separated by Sephacryl S-200 chromatography and determined by Delfia PSA, ACS-PSA and Eiken PA kits. Two antibodies used in the 3 kits are 2 monoclonal, 1 monoclonal and 1 polyclonal and 2 polyclonal antibodies, respectively. Following chromatography, two PSA peaks were obtained in all patients. One was about 100 kDa and the other about 30 kDa. The former was considered to be the complex type PSA (complex with alpha-1 antichymotrypsin) and the latter to be free type PSA. As to free type PSA, the ACS-PSA kit and Eiken PA kit quantitated PSA values approximately 5.1 and 2.5 times higher than the Delfia PSA kit. For complex type PSA, the quantity determined by ACS-PSA kit was approximately 1.3 times higher than that determined by the Delfia PSA kit, while the quantity determined by the Eiken PA kit was about one third of that determined by Delfia PSA kit. The ratio of complex type PSA to total PSA (free type PSA + complex type PSA) was 74.8 +/- 14.9% (mean +/- SD) when determined by Delfia PSA kit, 59.3 +/- 18.4% by ACS-PSA kit and 52.9 +/- 13.8% by Eiken PA kit. The range of this ratio determined by ACS-PSA kit was from 47.3% to 80.5% in the 3 patients. These findings suggest that there are qualitative differences in immunorecognition of free type PSA and complex type PSA among current commercial PSA assays and that there are quantitative differences in the ratio of the 2 forms of PSA in serum among prostatic cancer patients. The measurement and follow-up of both free type and complex type PSA might be important for diagnosis and monitoring of prostate cancer.
The amount of Leukotriene B4 (LTB4) released from neutrophilic leukocyte activated by calcium ionophore was measured to examine neutrophilic functions regarding the changes during normal pregnancy and differences between normal pregnant women and preeclamptic women. In addition, we examined the arachidonic acid (AA) content and fatty acid composition of neutrophilic phospholipid in normal pregnant women. In a normal pregnancy, the amount of LTB4 released decreased significantly with gestation. In preeclamptic women, the amount of LTB4 released was significantly higher than that in normal pregnant women, but there was no significant difference from non-pregnant women. Normal pregnant women showed a significantly decreased AA content with gestation. Regarding other fatty acids, as to fatty acid composition, there was increased saturated fatty acid and decreased unsaturated fatty acid with gestation. The results suggested that the LTB4 released was inhibited more in pregnant women than in non-pregnant women, and pregnant women also had decreased AA content. In addition, changes in fatty acid compositions showed signs of decreased fluidity of the cell membrane. This phenomenon is thought to be due to a mechanism to inhibiting the activation of neutrophilic leukocytes accompanied by a decrease in the amount of LTB4 released. Conversely, no similar inhibition was observed in preeclamptic women, and the failure of this mechanism seemed to contribute to the development of preeclampsia.
Titers of IgE antibody specific for the pollen of Chamaecyparis obtusa (C. obtusa) were determined by AlaSTAT and CAP-RAST in 221 patients with Japanese cedar pollinosis. IgE antibody to C. obtusa tested positive by CAP-RAST at a higher rate (80.5%) than by AlaSTAT (52.6%). The results obtained from the two assays were compared with those from intradermal skin test. CAP-RAST had a higher sensitivity than that of AlaSTAT. Because the two methods showed no differences in the determination of IgE antibody specific for Cryptomeria japonica, the above differences between AlaSTAT and CAP-RAST are surmised to be ascribable to the differences of C. obtusa antigen used in the both assays.
A 60-year-old man presented with sudden palpitations in September 1993, and was admitted to hospital with a diagnosis of atrial fibrillation and heart failure. The patient was suspected of having collagen disease, because of a positive test for antinuclear antibodies and a high sedimentation rate. He was referred to lou hospital. Chest radiographic findings were suggestive of cardiomegaly and cardiac murmurs were audible, which indicated the presence of heart disease. A chest Ct scan revealed a lesion surrounding the intramediastinal large vessels and the heart from the level of the confluence of the left brachiocephalic vein and the superior vena cava. Suspicion of a mediastinal tumor led the patient to be admitted to the respiratory department. Percutaneous needle biopsy with a Trucut needle revealed non-specific chronic inflammation. An abdominal CT scan showed that the lesion surrounding the descending aorta traversed the diaphragm, reached the renal pelvis along both renal arteries, and caused narrowing of the ureter and left hydronephrosis. Based on these findings, retroperitoneal fibrosis was diagnosed. Treatment with steroids caused the lesion to shrink.
The anticancer drug distribution in pelvic arterial infusion chemotherapy with bilateral internal iliac arterial catheter placement with coil occlusion of the superior, inferior and obturator arteries was indirectly evaluated by serially performed DSA, CTA and RI on 18 patients with pelvic malignancies. The distribution was judged to be Excellent (E), defined as uniform distribution in the entire lesion alone, in 9 of 18 patients (50%) evaluated prior to the start of the arterial infusion (AI), and as Good (G), defined as uniform distribution in the entire lesion and partly on an unaffected portion, in 9 (50%). Of the 11 patients evaluated after 7 times AI, E was found in 3 patients (27%), G in 7 (64%) and Fair (F), defined as distribution with a defect in the lesion, in one patient (9%). Of the 11 patients evaluated after 14 AI, E was found in 5 (45%), G in 4 (36%) and F in 2 (18%). Of the 7 patients evaluated after 21 AI, E was found in 2 (29%), G in 4 (57%) and F in one (14%). G was found in 2 of 2 patients (100%) evaluated after 28 AI. These results suggest that this method can maintain a favorable anticancer drug distribution even after multiple sessions of AI.
Human monoclonal antibody (hMAb) AE6F4 has been shown to be potentially useful for immunocytological detection of lung cancer cells in sputum. By recombinant DNA technology, IgM type hMAb AE6F4 was switched to lgG. The IgG mimic recombinant AE6F4 antibody expression plasmid was assembled using the antibody heavy chain gene, which ligated the gene encoding VH and CH1(mu) domains of hMAb AE6F4 heavy chain to the gene encoding CH2(gamma 1) and CH3(gamma 1) domains of human IgG heavy chain, and the antibody light chain gene of hMAb AE6F4. The recombinant antibody expressed by baby hamster kidney (BHK)-21 cells showed molecular size equivalence to IgG, and consisted of human mu-gamma hybrid heavy and kappa light chains. The immunological specificity of the recombinant antibody was the same as that of hMAb AE6F4 by immunoblotting analysis to the 14-3-3 protein, the putative antigen of hMAb AE6F4, and by immunohistochemical and immunocytological analyses using tissue sections and sputa of lung cancer patients. The transfected BHK-21 cells produced the recombinant antibody persistently and the productivity was greater than 20 times that by human-human hybridoma producing hMAb AE6F4.
The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.