Immunosuppressive drugs and hypertrophic cardiomyopathy.
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Adult↗
Biomedical subjects
R Nishimura
Publications and source records attributed to R Nishimura.
Expression and secretion of the beta subunit of human chorionic gonadotropin by bladder carcinoma in vivo and in vitro.
Expression and secretion of the beta subunit of human chorionic gonadotropin (hCG) by bladder carcinoma cell lines were investigated in vitro and in vivo. As an in vitro study, immunoreactive hCG beta (IR-hCG beta) secreted into the culture media of two bladder transitional cell lines (KoTCC-1 and HT-1197) was analyzed using three kinds of enzyme immunoassays which were specific for intact hCG, free hCG beta, and beta core fragment (beta-CF). Both of the cell lines were determined to secrete IR-hCG beta into the media, which consisted principally of free hCG beta, but detectable levels of intact hCG and beta-CF were not present in the media. Northern blot analysis revealed that the hCG beta gene was expressed in both KoTCC-1 and HT-1197 cells where the sizes of mRNA from these cells were smaller than those from placental and NJG choriocarcinoma cells. As an in vivo study, distribution of IR-hCG beta was analyzed in the tumor tissues, sera, and urine of the mice and the rats transplanted with KoTCC-1 cells. By the immunohistochemical study, the IR-hCG beta was clearly observed in transitional cell carcinoma cells of the transplanted tumor. High levels of IR-hCG beta were detected in both the serum and urine from the animals, but there were quantitative and qualitative differences between serum and urinary IR-hCG beta. Quantitatively, the concentrations of IR-hCG beta in the urine were consistently much higher than those in the serum. Qualitatively, free hCG beta was exclusively detected in the serum whereas high levels of beta-CF in addition to free hCG beta were found in the urine. Intact hCG could not be detected in the serum and urine. These distributions of IR-hCG beta in the animals transplanted with KoTCC-1 cells were completely analogous to those in a patient with hCG beta-producing bladder carcinoma. The present study shows that the same metabolic pathway of IR-hCG beta is operating in mice and rats as in humans, indicating that IR-hCG beta found in patients with bladder carcinoma originates from the tumor and it may be recognized as a tumor marker when beta-CF is measured in the patient's urine.
Animals↗
Ovarian strumal carcinoid with markedly high serum levels of tumor markers.
We report a 54-year-old woman with ovarian strumal carcinoid in association with dermoid cyst and mucinous cystadenoma in the same ovary and who had markedly high serum levels of CEA (202 ng/ml), CA125 (710 U/ml), and CA19-9 (11,500 U/ml). These tumor markers were not found in the thyroid tissue or carcinoid by immunohistochemical methods, but their serum levels decreased to below the cutoff levels after surgery. In our case, the change of serum levels of these tumor markers may be useful for the follow-up after surgery.
Biomarkers, Tumor↗
Combination assay of urinary beta-core fragment of human chorionic gonadotropin with serum tumor markers in gynecologic cancers.
Ectopic production of the immunoreactive beta-subunit of human chorionic gonadotropin (IR-hCG beta) by gynecologic malignancies has been well recognized, but IR-hCG beta has not yet been established as a clinically useful tumor marker, except for germ cell tumors. We measured the concentrations of IR-hCG beta-related molecules, intact hCG, free hCG beta, and beta-CF, in the sera and urine of patients with various gynecologic cancers (cervical, endometrial, and ovarian cancers) to assess their clinical usefulness as a tumor marker in comparison with serum tumor markers such as CEA, SCC, CA125, and CA19-9. The highest incidence of IR-hCG beta was obtained in the assay for beta-CF in the urine, with positive rates of 47.7% (94 of 197) for cervical, 37.8% (14 of 37) for endometrial, and 84.4% (38 of 45) for ovarian cancers with a cut-off value of 0.2 ng/mg of creatinine. In cervical cancer, there was no significant correlation between the concentrations of urinary beta-CF and serum SCC, and 57.9% (114 of 197) of the patients were detected by the combination assay of these tumor markers. Serial determination in 22 cervical cancer patients with elevated urinary beta-CF level prior to therapy showed that its level decreased after successful treatment, but 4 of 5 patients with persistent or recurrent disease had elevated levels of urinary beta-CF. All of the ovarian cancer patients examined were detected by the combination assay of urinary beta-CF and serum CA125. The levels of urinary beta-CF showed little correlation with those of the serum tumor markers, indicating the usefulness of the combination assay of urinary beta-CF with serum tumor markers for detecting cervical and ovarian cancers.
Biomarkers, Tumor↗
Establishment of a myeloid leukaemic cell line (SKNO-1) from a patient with t(8;21) who acquired monosomy 17 during disease progression.
A novel cell line SKNO-1 was established from the bone marrow cells of a 22-year-old male suffering from acute myeloblastic leukaemia (AML) M2 with t(8;21) whose disease became resistant to chemotherapy after acquisition of 17 monosomy. SKNO-1 has been maintained for more than 36 months as a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent line. Morphologically, SKNO-1 cells were myeloblasts somewhat matured. The cells grow in suspension with a doubling time of 48-72 h. The survival and growth of SKNO-1 cells was absolutely dependent on granulocyte-macrophage colony stimulating factor (GM-CSF). SKNO-1 cells possessed t(8;21) and monosomy 17 which were observed in original leukaemic cells. We confirmed that the AML1 gene, located on chromosome 21, was rearranged and the AML1-MTG8 fusion transcript was expressed in SKNO-1 cells. Over-expression and mutation of the p53 gene were also detected in SKNO-1. It is likely that alterations of AML1 or MTG8 gene and p53 gene contribute to a disease progression in this case. Since t(8;21) translocation is a common chromosome abnormality in AML, and inactivation of the p53 gene may play a crucial role in disease progression in AML, SKNO-1 would be a useful tool for analysing the molecular mechanisms in myeloid leukaemogenesis.
Adult↗
Potent thyrotropic activity of human chorionic gonadotropin variants in terms of 125I incorporation and de novo synthesized thyroid hormone release in human thyroid follicles.
Using a highly sensitive bioassay for TSH, in which human thyroid follicles incorporate 125I and release de novo synthesized thyroid hormone into the culture medium, the thyrotropic activities of various hCG preparations were studied. Under the culture conditions employed, bovine TSH (bTSH) was approximately 6- to 9-fold more active than human TSH (hTSH). Highly purified hCG prepared from urine of normal pregnant women (CR 127) had only a trivial thyrotropic activity equipotent to 0.00022 microU bTSH/U hCG or 0.0013 microU hTSH/U hCG (19.7 microU hTSH/mg hCG). Hybrid hCG (AB1ER) also elicited low thyrotropic activity (14.0 microU hTSH/mg), whereas crude hCG had moderate thyrotropic activity (0.041 hTSH microU/U hCG or 127 microU/mg protein). Deglycosylated hCG, a very weak LH/hCG receptor agonist, was the most potent agonist in thyroid follicles (588 microU hTSH/mg protein). hCGs purified from urine of patients with trophoblastic tumors had greater TSH-like activity (37-84 microU hTSH/mg protein) than purified hCG. Asialo-hCG purified from a patient with choriocarcinoma had very potent TSH-like activity (468 microU hTSH/mg). Submaximal doses of bTSH and hCG variants produced additive stimulation of thyroid function. Furthermore, the thyrotropic effect of hCG was inhibited by anti-TSH receptor antibody obtained from patients with myxedema. These in vitro findings suggest that although hCG is reported to exert potent cAMP-stimulating activity on rat thyroid-like cells (FRTL-5) and Chinese hamster ovary cells transfected with hTSH receptor complementary DNA (0.092-0.72 microU hTSH/U hCG), the thyrotropic activity induced by authentic hCG in human thyroid follicles is too weak to cause hyperthyroidism in normal pregnancy. However, hCG produced by some trophoblastic tumors, particularly asialo-hCG, has potent thyrotropic activity sufficient to cause clinically overt hyperthyroidism when produced excessively.
Animals↗
Cardiopulmonary effects of medetomidine, medetomidine-midazolam and medetomidine-midazolam-atipamezole in dogs.
Cardiopulmonary effects of medetomidine (20 micrograms/kg)-midazolam (0.3 mg) (Me-Mi) were compared with those of medetomidine alone (80 micrograms/kg) (Me80) in dogs. The intramuscular administration of this combination caused bradycardia and transient mild pressor response. Heart rate decreased soon after the administration and remained significantly below the baseline value with average values of 50-70 beats/min. Blood pressure increased to its maximum within 5 to 10 min then decreased gradually. Cardiac index decreased corresponding the decrease in heart rate. However these changes were less profound than those of Me80 indicating significantly higher values in cardiac index and lower values in systemic vascular resistance. Effects on the respiratory function were slight. The reduction of the dose of medetomidine to one-fourth in Me-Mi was effective to reduce the adverse effect of medetomidine, especially in peripheral vasoconstriction. Atipamezole effectively reversed cardiopulmonary effects induced by medetomidine-midazolam. Heart rate and cardiac index increased and systemic vascular resistance decreased significantly after administration of atipamezole. The possible use of an antagonist as a reversal agent might enhance the value and availability of medtomidine-midazolam as a chemical restraint agent in dogs.
Adrenergic alpha-Antagonists↗
Superselective intraarterial infusion of cisplatin for squamous cell carcinoma of the mouth: preliminary clinical experience.
OBJECTIVE: The purpose of this study was to assess the initial clinical response to superselective intraarterial infusion of cisplatin for treating stage III and stage IV squamous cell carcinoma of the mouth. SUBJECTS AND METHODS: Thirteen patients received intraarterial cisplatin therapy. The tumors were located in the tongue (n = 7), gingiva (n = 3), buccal mucosa (n = 1), hard palate (n = 1), and floor of the mouth (n = 1). A coaxial technique was used to place microcatheters in the lingual, facial, inferior alveolar, buccinator, and distal internal maxillary arteries, depending on tumor location. The feeding vessels were identified by staining the tumor with infusion of indigocarmine dye in the selected vessel. Relatively low-dose cisplatin (30-40 mg/m2) was injected at the rate of 50 mg/hr. Two or three injections were performed, with a 1-week interval between injections. After chemotherapy, eight patients underwent surgery, four had radiation therapy, and one had both. RESULTS: Thirty-four intraarterial infusions were done successfully without any complications. Arterial infusion of indigocarmine dye was useful for exact identification of feeding vessels, especially when the tumor was extensive, at the margin of the arterial supply, or near the midline. The overall response rate was 92% (complete response [tumor completely resolved], 38%; partial response [tumor reduction > or = 50%], 54%). Ten of 13 patients had no recurrence from 4 to 19 months (mean, 10 months) after treatment. Two patients died of metastatic diseases 6 months after surgery or radiation therapy. One patient had local recurrence 8 months after surgery and postoperative irradiation. No systemic toxicity such as renal failure, liver dysfunction, or bone marrow suppression was observed. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. Trigeminal neuralgialike symptoms and reduced mouth opening occurred in two cases and one case, respectively, probably due to direct toxicity to the peripheral trigeminal nerve and masticatory muscles, respectively. CONCLUSION: Superselective intraarterial infusion of low-dose cisplatin is feasible and safe and may have important applications in treating advanced carcinoma of the mouth.
Aged↗
Improved lipid visualization with a modified osmium tetroxide method using ultrasonic treatment and intensification with imidazole or triazole.
Formalin fixed autopsy tissue containing lipids were cut into 1-5 mm thick blocks, washed well, then postfixed in 2% OsO4 in 0.03 M veronal acetate buffer for 30, 60, 90, 120, or 180 min with or without ultrasonic treatment. Tissues exposed to ultrasound for 90 min showed superior penetration of OsO4 and well preserved histological architecture. Tissues also were immersed for 1 hr in veronal acetate buffer (pH 7.4) containing 0.5% imidazole or triazole and compared with untreated controls. Paraffin sections, 4 microns thick, were examined under a light microscope with an image analyzer. Both intensity and percentage area of osmium blackening were significantly higher in samples immersed in imidazole or triazole than in untreated controls. No difference was observed between imidazole- and triazole-immersed samples. The OsO4 method, modified by ultrasound treatment and imidazole- or triazole-immersion, can be applied to routine formalin fixed autopsy materials for improved lipid visualization.
Fatty Liver↗
Skull metastasis from hepatocellular carcinoma. CT, MR and angiographic findings.
CT, MR and angiographic findings of 6 patients with 9 skull metastases from hepatocellular carcinoma (HCC) were reviewed. In 3 of 6 patients, local pain or neurologic deficit was the initial main manifestation of the disease, although all had been treated for chronic liver disease. In the remaining 3 patients, skull metastases were detected following treatment of HCC. The metastatic lesions appeared as expansile osteolytic masses on CT and as hypervascular masses on angiography. All lesions were demonstrated on MR imaging. Compared with the brain parenchyma, the lesions were iso- or hypointense on T1-weighted and T2-weighted MR images. The lesions were moderately to markedly enhanced by Gd-DTPA. Flow voids were shown in the tumors in 5 lesions. HCC should be included in the differential diagnosis of an osteolytic hypervascular lesion of the skull, especially in Oriental patients. The relatively hypointense tumor on T2-weighted MR images associated with flow void, different from primary skull tumors or directly invasive tumors, may support the diagnosis of HCC metastasis.
Aged↗
Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer.
BACKGROUND: Some patients with lung cancer have been found to have elevated levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR-beta), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR-beta has been demonstrated to consist of at least three different molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in body fluids. In this study, the authors qualitatively analyzed IR-beta in the serum and urine of patients with lung cancer and assessed its clinical usefulness as a tumor marker. METHODS: Highly sensitive and specific enzyme immunoassays were established to measure intact hCG, free hCG beta, and beta-CF in the serum and urine of patients with lung cancer. RESULTS: Of 99 patients with lung cancer, almost half of the patients achieved positive values of IR-beta in the urine, although only 12 had elevated values of IR-beta in the serum. The greater part of the elevated urinary IR-beta was identified to be beta-CF by gel chromatography on Sephadex G-100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the authors to assess its usefulness as a tumor marker for lung cancer. Based on the cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall positive rate of urinary beta-CF for lung cancer was 48.5% (48 of 99 patients). The incidence of the marker increased with stage of disease, from 35.7% (15 of 42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma (SCC)-related antigen, measured simultaneously in the same patients. The author were encouraged that there was no significant difference in the positive rates of urinary beta-CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in which most of the positive cases had the elevated levels of serum free hCG beta (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine). CONCLUSIONS: Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF might be a potential tumor marker of lung cancer.
Adenocarcinoma↗
Restoration of oral function after maxillectomy with osseous integrated implant retained maxillary obturators.
This study assesses the success rate of osseous integrated implantation in assisting the prosthetic obturation of maxillectomy defects. Twenty-three patients received a total of 85 osseous integrated implants used for retaining maxillary obturators between 1985 and 1993. Defects include 13 radical maxillectomies, 5 premaxillary resections, 4 subtotal maxillectomies, and 1 soft-palate resection. Thirteen patients (50 implants) received a radiation dose ranging from 5,040 to 7,940 cGy. Implants can be placed at the time of ablation or subsequently. Efforts were made to spare uninvolved segments of the maxilla, especially premaxillary segments and tuberosities, at the time of ablation. Following a 6-month period of integration, implants were uncovered and utilized in prosthetic rehabilitation. Specific implant sites reveal variable success rates, with the anterior maxilla being 86% successful compared with the posterior maxilla being 57% successful. Radiation reduces the success rate from 80% to 55%, although it does not eliminate a patient from being a candidate for implantation. Prosthetic rehabilitation of large maxillary defects can be greatly facilitated with the use of osseous integrated implants in the remaining midfacial skeleton.
Alveolar Bone Loss↗
A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase.
Autophosphorylated growth factor receptors provide binding sites for the src homology 2 domains of intracellular signaling molecules. In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, leading to activation of the Ras signaling pathway. We have investigated whether the platelet-derived growth factor (PDGF) receptor binds GRB2-Sos. In contrast with the EGF receptor, the GRB2 does not bind to the PDGF receptor directly. Instead, PDGF stimulation induces the formation of a complex containing GRB2; 70-, 80-, and 110-kDa tyrosine-phosphorylated proteins; and the PDGF receptor. Moreover, GRB2 binds directly to the 70-kDa protein but not to the PDGF receptor. Using a panel of PDGF beta-receptor mutants with altered tyrosine phosphorylation sites, we identified Tyr-1009 in the PDGF receptor as required for GRB2 binding. Binding is inhibited by a phosphopeptide containing a YXNX motif. The protein tyrosine phosphatase Syp/PTP1D/SHPTP2/PTP2C is approximately 70 kDa, binds to the PDGF receptor via Tyr-1009, and contains several YXNX sequences. We found that the 70-kDa protein that binds to the PDGF receptor and to GRB2 comigrates with Syp and is recognized by anti-Syp antibodies. Furthermore, both GRB2 and Sos coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2 binds directly to tyrosine-phosphorylated Syp in vitro. These results indicate that GRB2 interacts with different growth factor receptors by different mechanisms and the cytoplasmic phosphotyrosine phosphatase Syp acts as an adapter between the PDGF receptor and the GRB2-Sos complex.
3T3 Cells↗
Antagonistic effects of antipamezole on medetomidine-midazolam induced sedation in dogs.
Antagonistic effect of atipamezole (80 micrograms/kg) on medetomidine (20 micrograms/kg)-midazolam (0.3 mg/kg) induced sedation was evaluated in dogs. Atipamezole effectively reversed sedation and significantly shortened arousal time and total recovery time without apparent side effects. Atipamezole also effectively reversed changes in heart rate, respiratory rate and body temperature produced by medetomidine-midazolam. The possible use of atipamezole as a reversal agent might enhance the value and availability of medetomidine-midazolam for a chemical restraint agent in dogs.
Adrenergic alpha-Agonists↗
Histopathological findings of the digits in dairy cows in Japan.
Two hundred and thirty-nine digits of 45 Holstein dairy cows, which were raised in typical Japanese dairy farms and received poor hoof management, were randomly obtained in the slaughterhouses and examined histopathologically. The findings were classified into 5 grades on the basis of the severity of circulatory disturbances and of keratogenesis. The lesions from Grade 1 to 5 were considered as manifestations of serial lesions indicating that subclinical laminitis advanced to other hoof lesions. The incidence of Grade 2, regarded as subclinical laminitis, reached approximately 50% of digits examined. The lesions classified as Grades 3 (23.9%) and 4 (5.4%) were mainly characterized by circulatory disturbances, which were similar to those of chronic laminitis in the previous reports. The incidence of Grade 5, characterized by sole ulcer, was 5.4%. It is suggested that a considerable number of daily cows in Japan suffered from subclinical laminitis, which may be the cause of recent high incidence of hoof diseases in dairy cows.
Animals↗
Morphological analysis of cervical vertebrae in ataxic foals.
Morphological differences between cervical vertebrae were statistically analyzed in ataxic foals to clarify abnormal structural factors in the pathogenesis of this problem. At first, multiple regression analysis and cluster analysis were performed with 28 variables in C3-C7 of 39 control foals without lameness. As a result, there were no sex differences in the growth of all cervical vertebral sites, and the most suitable categorization of the age of the foals was 3 clusters of 8 months old or younger, 9-12 months old and 13 months old or older in any sites in the cervical vertebrae. Twenty-eight ataxic and 19 control foals at the age of 13 months or older were then used for discriminant analysis with 20 variables. As a result, 1-7 variables on C3-C7 were selected for sufficient discrimination, in which the heights of the cranial and caudal orifices of the spinal canal, longitudinal length of the vertebral head and height of the vertebral fossa strongly contributed to the discrimination of all the cervical vertebrae. In addition, the widths and longitudinal diameters of the articular processes on articular surfaces strongly contributed to the discrimination of the caudal region of the neck. In conclusion, it was suggested that the lesion in the cervical spinal cord observed in ataxic foals was caused by morphological abnormalities including osteochondrosis and subsequent degenerative joint disease in the cervical vertebrae.
Animals↗
Efficacy of the new radiographic measurement method for cervical vertebral instability in wobbling foals.
Cervical myelography and survey radiography was performed on 12 light breed wobbling foals and a new radiographic measurement method was applied for more accurate diagnosis of cervical vertebral instability. Ratios of stenosis of the spinal canal on survey radiography and myelography using relative values in an individual foal were defined on radiograms of lateral flexed position of mid-cervical region, and coincidence between the ratios and histopathological lesions in the cervical spinal cord was investigated. Five of 6 foals had ratios of stenosis on myelography more than 40% at the intervertebral sites where the most severe histopathological lesions were observed. Four of 6 foals had ratios of stenosis on survey radiography more than 40% at the intervertebral sites where the most severe histopathological lesions were observed. Four of 6 foals had ratios of stenosis on survey radiography more than 40% at the intervertebral sites where the most severe histopathological lesions were observed. False-positive diagnosis of CVI was observed in 1 out of 6 foals without histopathological lesion when both ratios of stenosis on myelography and survey radiography were applied. Although the standard value of 40% should be further investigated, the new radiographic measurement method in this study is very useful in clinical diagnosis of cervical vertebral instability in wobbling foals, and the presence of lesions in the cervical spinal cord and their sites by survey radiography may be estimated more accurately.
Animals↗
Relationships between radiography of cervical vertebrae and histopathology of the cervical cord in wobbling 19 foals.
Nineteen wobbling foals (17 males and 2 females) showing lameness of hindlimbs at 6 to 21 months of age were investigated radiographically and histopathologically. Minimum sagittal diameter (MSD), minimum flexion diameter (MFD) and minimum dural sagittal diameter (MDD) were measured on plain radiograms or myelograms taken at neutral and flexed positions as indicators of narrowed vertebral canal. After necropsy, the cervical spines and the spinal cord were examined macroscopically and respectively the relationships between radiographic findings and the corresponding morphological lesions were evaluated. Radiographically, lower values than each minimum reference limits were recorded in 14 foals in MSD, 5 foals in MFD and 6 foals in MDD, respectively. According to the histopathologic examination, the disappearance of axons and myelin sheaths, vacuolated spongy degeneration and appearance of macrophages were recognized symmetrically in the white matter of the cervical cord. These lesions were centrally located at the spinal cord radiographically demonstrated as compressed sites in 12 out of 17 foals examined. Macroscopically, asymmetrical overgrowth of one side of the process, encroachment of articular processes into the intervertebral foramina and proliferation of bone around articular facets were observed in the articular processes of bone specimens in the caudal neck of 6 foals. In conclusion, the equine incoordination might mainly be caused by the cervical stenotic myelopathy resulting from cervical vertebral malformation, and therefore the cervical vertebral radiography, especially myelography, is quite very important and effective for the diagnosis of wobbling foals.
Animals↗