The suppression of heart and liver allograft rejection by liver suppressor factor one (LSF-1) and its possible human homologue.
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Biomedical subjects
Publications and source records attributed to T Goto.
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Mutations of p53 tumor suppressor gene occur in a subset of aggressive prostatic carcinomas and are detectable by immunohistochemistry. However, it is uncertain whether p53 overexpression really reflects p53 gene mutation or loss of p53 function. p21WAF1, an inhibitor of cyclin-dependent kinases, is activated by wild-type p53 protein, not by mutant type. Therefore, it is possible that combined analysis of p21WAF1 and p53 proteins aids in determining the functional status of p53 immunostaining. Routinely processed prostatic tissues from 60 patients with prostatic adenocarcinomas were examined by immunohistochemistry for p21WAF1 and p53 expression. As for tissue distribution, p21WAF1 protein was expressed mostly in the luminal layers, in contrast, p53 protein was restricted to the basal layers of benign prostatic glands. In prostatic adenocarcinomas, p21WAF1 protein was more likely to be expressed in well-differentiated areas; in contrast, p53 protein was more likely in poorly differentiated areas in the tumors. The percentage of positive nuclear areas for p21WAF1 and p53 proteins in prostatic adenocarcinomas, assessed by CAS200 computerized image analyzer, were 8.6+/-10% and 16+/-14% (mean+/-SE), respectively. The survival study showed that the p53+/ p21- phenotype showed poorer prognosis than p53+/p21+. Multivariate analysis showed that p21WAF1 expression, clinical stage, and Gleason score were independent prognosticators. In conclusion, p21WAF1 immunohistochemistry is a useful method for interpretation of p53 immunohistochemical results. Combined analysis by p21WAF1 and p53 immunostaining would predict the patient survival more accurately than p53 immunostaining alone.
A simple contrast-enhancement method is described for electron microscopic imaging of the human immunodeficiency virus (HIV) from a sample embedded in Lowicryl K4M resin, by immuneelectron microscopy. Ultrathin sections were treated with a mixture of ruthenium red dye (RR) and osmium tetroxide (OSO4). This treatment provided good contrast enhancement of the entire ultrastructural image of virus particles without the loss of immunolabelling. RR/OsO4 solution is simple to prepare and provides a better contrast than that which is achieved during conventional post-embedding immunoelectron microscopy. Treatment of ultrathin sections from low temperature-embedded samples with RR/OsO4 solution is recommended.
In this study we investigate the gene regulatory functions of Drosophila Fish-hook (Fish), a high mobility group (HMG) Sox protein that is essential for embryonic segmentation. We show that the Fish HMG domain binds to the vertebrate Sox protein consensus DNA binding sites, AACAAT and AACAAAG, and that this binding induces an 85 degrees DNA bend. In addition, we use a heterologous yeast system to show that the NH2-terminal portion of Fish protein can function as a transcriptional activator. Fish directly regulates the expression of the pair rule gene, even-skipped (eve), by binding to multiple sites located in downstream regulatory regions that direct formation of eve stripes 1, 4, 5, and 6. Fish may function along with the Drosophila POU domain proteins Pdm-1 and Pdm-2 to regulate eve transcription, as genetic interactions were detected between fish and pdm mutants. Finally, we determined that Fish protein is expressed in a dynamic pattern throughout embryogenesis, and is present in nuclear and cytoplasmic compartments.
STUDY OBJECTIVES: To compare acceleromyography (AMG) and electromyography (EMG) with xenon or sevoflurane anesthesia during vecuronium-induced neuromuscular blockade. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENTS: 28 ASA physical status I and II adult patients presenting for elective surgery. INTERVENTIONS: Patients received vecuronium for neuromuscular blockade and either xenon (n = 11) or sevoflurane (n = 17) anesthesia. MEASUREMENTS AND MAIN RESULTS: The first twitch depression, which was expressed as a ratio of the first twitch to that obtained before the blocking drug was administered (T1/Tc), was measured simultaneously by AMG and EMG. T1/Tc as measured by AMG consistently demonstrated greater depression than that by EMG during recovery. The limits of agreement were unacceptably wide, suggesting that T1/Tc obtained by AMG is a poor predictor of T1/Tc as measured by EMG. Such relations were not affected by the anesthetic (xenon or sevoflurane) used. CONCLUSION: AMG and EMG-cannot be used interchangeably with either xenon or sevoflurane anesthesia.
The localization of cathepsin K protein in mouse osteoclasts was examined by immunolight and immunoelectron microscopy using the avidin-biotin-peroxidase complex method with anti-cathepsin K (mouse) antibody. With light microscopy, a strong immunoreaction for cathepsin K was found extracellularly along the bone and cartilage resorption lacunae and detected intracellularly in vesicles, granules, and vacuoles throughout the cytoplasm of multinuclear osteoclasts and chondroclasts attached to the surface of the bone or cartilage. Mononuclear cells, probably preosteoclasts, some distance from the bone also contained a few cathepsin K-positive vesicles and granules. Cathepsin K was sometimes found in the cisternal spaces of the rough endoplasmic reticulum and vesicles of the Golgi apparatus with electron microscopy of the basolateral region of the osteoclasts. Cathepsin K-positive vesicles and granules as lysosomal compartments were present in various stages of fusion with vacuoles as endosomal compartments that contained fragmented cathepsin K-negative fibril-like structures. Some of the vacuoles (endolysosomes), which seemed to be formed by this process of fusion, contained cathepsin K-positive vesicles and fibril-like structures that did not show the regular cross striation of type I collagen fibrils. In the apical region of the osteoclasts, cathepsin K-positive vesicles and pits had already fused with or were in the process of fusing with the ampullar extracellular spaces. There were large deposits of cathepsin K on fragmented fibril-like structures without regular cross striation in the extracellular spaces, as well as on and between the cytoplasmic processes of the ruffled border. There were also extensive deposits of cathepsin K on the type I collagen fibrils with cross striation in the bone resorption lacunae. Osteoblasts and osteocytes were negative for cathepsin K. In the immunocytochemical controls, no immunoreaction was found in the osteoclasts or preosteoclasts, or on the collagen fibrils in the resorption lacunae. The results indicate that cathepsin K is produced in mature osteoclasts attached to the bone and secreted into the bone resorption lacunae. The findings suggest that cathepsin K participates in the extracellular degradation of collagen fibrils in the resorption lacunae and in the subsequent degradation of the fragmented fibrils in the endolysosomes. It is also suggested that cathepsin K degrades the organic cartilage matrix.
Free light chains (FLC) are a natural product of B lymphocytes and, as such, represent a quantifiable biomarker of cellular proliferation. Accurate measurement of the concentrations of these components in serum and urine provides a unique means of ascertaining B cell immunoglobulin synthesis during physiologic and, especially, pathologic states, where such information has important diagnostic and therapeutic implications. Previously, use of such quantitative assays has been limited due to the lack of potent serologic reagents specific for these components. We have immunized mice with kappa- and lambda-type monoclonal human light chains (Bence Jones proteins (BJP)) and have obtained monoclonal antibodies (MoAbs) that differentiate between unbound and bound light chains. These highly specific MoAbs were used to measure by ELISA the concentrations of FLC in the serum of 22 normal individuals and in urine from 16 of these subjects. The mean serum kappa and lambda FLC concentrations were found to be 16.6+/-6.1 microg/ml and 33.8+/-14.8 microg/ml, respectively. In contrast, the values for urinary kappa and lambda FLC were 2.96+/-1.84 microg/ml and 1.07+/-0.69 microg/ml, respectively. In each case studied, the serum kappa:lambda ratio was consistently less than that of urine (mean values, serum approximately 1:2; urine approximately 3:1). That the rate of synthesis of lambda-type FLC exceeded that of kappa was evidenced in assays of culture fluid supernatants of unstimulated normal peripheral blood mononuclear cells (PBMC), where the mean kappa:lambda ratio was determined to be 1:1.4. Metabolic studies in which mice were injected with pools of kappa- and lambda-type BJP prepared in ratios of 1:1, 1:2 and 1:4 demonstrated that, regardless of the proportion, kappa FLC were preferentially excreted. Our studies provide the first evidence that lambda FLC are secreted by normal PBMC at a greater rate than are kappa FLC, as evidenced in biosynthetic studies and by measurement of their serum concentrations. Further, we posit that quaternary structural differences between the two light-chain isotypes may account for the predominance of kappa versus lambda components in urine.
This article is an attempt by Japanese physicians to introduce the practice patterns and moral justification of Japanese critical care to the world. Japanese health care is characterized by the fact that the fee schedule does not reward high technology medicine, such as surgery and critical care. In spite of the low reimbursement, our critical care practice pattern is characterized by continuing futile treatment for terminal patients in the intensive care unit (ICU). This apparently wasteful practice can be explained by fundamental Japanese cultural values, social factors in Japan, the availability of extensive insurance coverage, physicians' psychological factors, lack of cost-benefit considerations and the pragmatic approach the Japanese take to situations. We attempt to make some brief suggestions regarding the improvement of our critical care practices. Although we can not fully present quantitative data to support our argument, this article represents our real-world approaches to the ethical issues in the ICU in Japan.
Full-thickness articular cartilage defects are a major clinical problem; however, presently there is no treatment available to regeneratively repair these lesions. The current therapeutic approach is to drill the base of the defect to expose the subchondral bone with its cells and growth factors. This usually results in a repair tissue of fibrocartilage that functions poorly in the loaded joint environment. The use of phenotypically appropriate chondrocytes embedded in a collagen gel delivery vehicle may provide a method that could be used to repair full-thickness articular cartilage defects with functionally satisfactory hyaline cartilage. Allograft articular chondrocytes embedded in a type I collagen gel were transplanted into large (6 x 3 x 3 mm), full-thickness articular cartilage defects in condylar and patellar weight-bearing surfaces to develop clinically applicable methods to repair articular cartilage defects. Chondrocytes were isolated from the articular cartilage of 4-week-old New Zealand rabbits and embedded in type I collagen gels. This composite was transplanted into a full-thickness defect on the medial femoral condyle and patellar groove of adolescent host rabbits. The repair cartilage was assessed histologically by a semiquantitative scoring system and biomechanically with a microindentation technique of specimens 4-48 weeks after chondrocyte transplantation. Defects in both locations were repaired with histologically apparent hyaline cartilage observed from as early as 4 weeks until 48 weeks after transplantation. The repair cartilage in the medial femoral condyle was more irregular than in the patellar groove, but in all other respects was similar. The grafted tissue did not remodel and differentiate into the morphological zones seen in normal articular cartilage. No tidemark or subchondral bony plate formed even 48 weeks after transplantation. Biomechanically, the repaired cartilage demonstrated indentation values similar to normal articular cartilage 12 weeks after transplantation and remained the same 48 weeks after transplantation. By contrast, the control (i.e., empty) defects healed with tissue that exhibited very poor metachromatic staining and exhibited very high indentation values. Incomplete bonding of the repair tissue to the normal cartilage was seen, and the surface was significantly irregular with major discontinuities. These observations provide the basis for considering the use of allograft articular chondrocytes to repair articular cartilage defects in the weight-bearing regions of the knee.
Twitch response using accelerometry and plasma concentrations, of vecuronium and its metabolite were studied in 27 surgical patients during xenon or sevoflurance anaesthesia after administration of vecuronium 0.05 mg kg-1. Anaesthesia was maintained using oxygen-xenon (MAC = 71%) or oxygen-sevoflurane (MAC = 2%) at an end-tidal concentration equal to 0.8 MAC (i.e. 57% xenon and 1.6% sevoflurane). Mean time from administration of vecuronium to 25% recovery of the first twitch of the train-of-four response was significantly shorter in the xenon group than in the sevoflurane group (12.9 (SD 2.5) min vs 19.4 (6.0) min, respectively). Plasma concentrations of vecuronium at 25% recovery were significantly higher during xenon than during sevoflurane anaesthesia (187 (49) ng ml-1 vs 136 (40) ng ml-1, respectively), while those of 3-desacetylvecuronium were similar in both groups.
We have compared the differences between end-tidal PE'CO2 and arterial PaCO2 carbon dioxide partial pressures during general anaesthesia using either a cuffed oropharyngeal airway (COPA) or a tracheal tube (TT) in spontaneously breathing adult patients. After induction of anaesthesia, a COPA was inserted in 20 patients who were allowed to breathe spontaneously. When steady state was reached, PE'CO2 and PaCO2 were recorded. The COPA was removed, the trachea intubated with a TT and spontaneous ventilation allowed to resume. After a stable PE'CO2 was reestablished, PaCO2 was measured again and PE'CO2 recorded. Mean difference between PaCO2 and PE'CO2 with the COPA was 0.72 (SD 0.45) kPa and with the TT 0.64 (0.40) kPa (ns; paired t test). Our results suggest that Pe'CO2 is a clinically acceptable indicator of PaCO2 in adults breathing spontaneously via a COPA.
The blood-gas partition coefficients of xenon, reported more than 25 yr ago in the literature, vary considerably from 0.13 to 0.20. Consequently, we have determined this variable by directly injecting xenon-saturated blood into a gas chromatograph-mass spectrometer. This technique yielded a blood-gas partition coefficient for xenon of 0.115 (95% confidence interval 0.107-0.123). The solubility in water measured identically was 0.096, consistent with the reported value of 0.085. These data and a detailed review of the literature strongly suggest that the blood-gas partition coefficient of xenon may be lower than the generally accepted value of 0.14.
A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.
UNLABELLED: We sought to determine the anesthetic duration of sevoflurane required to achieve good conditions for placement of a cuffed oropharyngeal airway (COPA) or a laryngeal mask airway (LMA). Forty adult ASA physical status I or II patients presenting for elective surgery received single-breath vital capacity inhaled induction with 5% sevoflurane via face mask; thereafter, ventilation was manually assisted. The patients were randomized to receive either a COPA or LMA placement. The time of anesthetic exposure was varied for consecutive patients using the staircase method. The mean (95% confidence interval) anesthetic time required for acceptable COPA placement (100 [55-145] s) was significantly shorter than that for LMA (160 [101-219] s). The 50% and 95% effective doses (from logistic analyses) for acceptable conditions associated with COPA or LMA placement were 90 s and 145 s or 164 s and 261 s, respectively. These findings suggest that COPA insertion is less stimulating than the LMA. IMPLICATIONS: The cuffed oropharyngeal airway is a new airway device that is similar to a laryngeal mask airway in many ways. However, it requires shorter anesthetic duration for successful placement, which suggests that it can be placed with less stimulation. It may be an alternative to a laryngeal mask airway.
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BACKGROUND: Although inhibition of nitric oxide synthase (NOS) has been reported to be antinociceptive and to reduce the threshold of general anesthesia, the mechanism of action is largely unknown. Specifically, the relation between the minimum alveolar concentration (MAC)-reducing effects of NOS inhibition and cyclic guanosine monophosphate (cGMP) concentrations in the brain has not been defined. To further characterize the effects of NOS inhibition, the authors studied the relation between the MAC of sevoflurane and the cGMP concentration of the brain after acute and chronic treatment with a neuronally selective NOS inhibitor, 7-nitroindazole (7-NI). METHODS: Sevoflurane MAC and cerebellar cGMP concentrations were determined in mice after acute intraperitoneal administration or after 1, 2, 3, and 4 days of gavage feeding of 7-NI. After acute or chronic treatment with 7-NI, the mice were separated into two groups. Sevoflurane MAC was measured by a tail-clamp method in the first group, and cerebellar cGMP concentrations were measured by enzyme-linked immunosorbent assay in the second group of the mice. RESULTS: In mice, acute intraperitoneal administration of 7-NI dose dependently decreased sevoflurane MAC and cerebellar cGMP; and 4-day-long gavage feeding with 7-NI (500 mg/ kg, every 8 h) time dependently decreased cerebellar cGMP, but sevoflurane MAC was reduced only for the first 2 days and returned to its baseline after 3 days of 7-NI feeding. CONCLUSIONS: Although an acute selective inhibition of neuronal NOS decreases sevoflurane MAC and cerebellar cGMP concentrations in mice, there was a dissociation between the two parameters during long-term neuronal NOS inhibition. There may be cGMP-independent compensatory mechanisms that mediate nociception when NOS is chronically inhibited.
PURPOSE: We report our experiences treating 5 patients who had filarial chyluria using an endoscopic approach. MATERIALS AND METHODS: Two men and 3 women 47 to 83 years old with chyluria were treated with endoscopic coagulation using guide tube methods. Intrarenal pelvic instillation of silver nitrate was not effective in 4 patients and catheterization was impossible in 1. RESULTS: The responsible lesion was successfully coagulated in all 5 patients. Because the lesion was in the ruptured portion of the caliceal fornix, we thought that chyluria had arisen in the fragile portion of the fornix (fistulization). After endoscopic treatment there was no recurrence in any patient. CONCLUSIONS: Endoscopy is effective and minimally invasive therapy for filarial chyluria.
A 46-year-old woman presented with a hypogastric mass. The preoperative diagnosis was a malignant ovarian tumor involving multiple organs, including the urinary bladder. Surgical exploration was performed with wide resection of the right ovary and uterus, including the affected ileum, sigmoid colon, and omentum. An intraoperative histopathological examination of the paravesical tissue revealed abdominal actinomycosis. Consequently, bladder resection was not done. The cause of abdominal actinomycosis in this patient was probably due to implantation of an intrauterine device 3 years previously.