Biomedical subjects
Publications and source records attributed to N Nakajima.
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We developed a method to measure the oxidation of glucose using the primed constant infusion of [U-13C] glucose in critically ill patients fed by total parenteral nutrition. The results obtained from the isotopic method were compared to those from indirect calorimetry in the critically ill patients. A patient with esophageal carcinoma was used for the preliminary study. The study was performed on the third postoperative day, assuming severely stressed state. Priming doses of NaH13CO3 at a dosage of 0.32 mg/kg and D-[U-13C] glucose at a dosage of 0.32 mg/kg were injected. D-[U-13C] glucose was then infused at an infusion rate of 0.004 mg/kg/min. It was revealed that the time required for an isotopic plateau was approximately 45 min in plasma glucose and 120 min in an expired air in highly stressed state. Isotopic measurement and indirect calorimetry were performed simultaneously pre- and postoperatively on three patients who underwent surgery for esophageal carcinoma. Increased fat oxidation was obtained by the isotopic method, whereas indirect calorimetry indicated nonprotein RQ above 1.0. Isotopic measurement offered a useful information that cannot be obtained from indirect calorimetry concerning the energy metabolism in the critical illness. Thus our method for the measurement of glucose oxidation is both simple and useful in investigating the energy metabolism in critically ill patients.
Three pyrimidinylpropanamide antibiotics sparsomycin (1), sparoxomycins A1, A2 (2, 3), and also six analogues (4-9) have been synthesized by employing asymmetric sulfide oxidation conditions as a key step. Sparsomycin (1) and its alkyl analogues (5-7) showed higher morphological reversion activities on srctsNRK cells than 2 and 3.
Buerger's disease was originally described by Leo Buerger in 1908 as thromboangitis obliterance and has been considered as one of the most intractable vasculitis syndromes in our country. This lesion is popularly seen in male young generation with a background history of heavy smoking. Buerger's disease in Japan has been frequently seen in our practice; however, it is noted that there have been certain definitive changes in relation to number of patients, clinical manifestation as well as course of treatment in particular in surgical treatment. Firstly, the number of patients who visited at outpatient clinic as well as to admit hospital has been sharply declined. Secondly, the number of surgical treatments of Buerger's disease have also decreased. The sympathectomy, mainly lumbal sympathectomy, which was maintained at about 15 to 20% of the number of patients admitted, was virtually abolished from the practice and mainly converted to the medical and pharmacological treatment by prostaglandin. The reliability of pharmacological sympathectomy is one of the other reasons which contributed to the shift of treatment. It is also our impression that the severity of the disease itself has been changed, in other words, we do not frequently see very severely ill patients. As far as surgery is concerned the important modality in the treatment for the advanced lesion of Buerger's disease is mainly confined in small arteries with multisegmental occlusion. As a consequence, the surgical reconstructive procedures are technically difficult and long term patency rate is considered to be low. As far as our experience is concerned, it is noted that the number of bypass surgery was most frequently seen at below trifurcation segment of knee joint; in other words, peripheral, distal type bypass was the most popular, followed by above knee segment. The reconstructive surgery at femoral region was least frequently seen. On the other hand, the patency rate of bypass graft was higher in the proximal segment in comparison to the distal segment. Although the number of arterial reconstructive procedures has been definitively declined, as was seen in sympathectomy surgery. It is difficult to predict accurately what kind of factors are affecting or contributing to the change in concept in Buerger's disease as well as the course of treatment, it is suggested that the environmental factors may playing a major role for the modification of disease process.
delta Tth DNA polymerase catalyzed polymerization of dATP and dTTP into a high-molecular-weight d(A-T) copolymer using oligo-d(A-T) as the template/primer (Hanaki et al., Biochem. Biophys. Res. Commun. 244, 210-219). Taking advantage of this reaction, we developed a highly sensitive method for strand-specific detection of DNA or RNA. The probe consisted of a 40- to 50-base-long complementary sequence on the 5' side and 10 repeats of AT on the 3' side. After hybridization using the 5' side, the 3' side AT repeat region was elongated by delta Tth DNA polymerase in the presence of the dATP, dTTP, and digoxigenin (dig)-11-dUTP. The elongation condition was 52-62 degrees C for 3 h. The method named HybrAT (hybridization-AT-tailing) was at least 100-fold more sensitive than the conventional hybridization with 5' end dig-11-dUTP labeled probe.
In the present study, we demonstrate that NLT (novel liver-specific transport protein) is a multispecific organic anion transporter of the liver. The amino acid sequence of NLT shows 42% identity to that of the renal multispecific organic anion transporter, OAT1. When expressed in Xenopus laevis oocytes, NLT mediated uptake of organic anions, such as salicylate, acetylsalicylate, PGE2, dicarboxylates and p-aminohippurate. [14C]Salicylate uptake via NLT was saturable (Km = 88.8 +/- 23.4 microM) and sodium-independent. Expression of the mRNA of NLT was detected in the liver and kidney (liver >> kidney). We propose that NLT be renamed OAT2.
BACKGROUND: Positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG) can provide quantitative information about tumor glucose metabolism. The prognostic value of this technique was evaluated for breast carcinoma patients. METHODS: FDG PET was performed on 70 patients with primary breast carcinoma, and the differential absorption ratio (DAR) was calculated as an index of FDG uptake. Overall and relapse free survival curves were created by the Kaplan-Meier method, and differences between the curves were analyzed with the log rank test. For multivariate analysis, the Cox proportional hazards regression model was used. RESULTS: The mean DAR was 2.61+/-1.61 standard deviation (range, 0.65-9.39). According to the grade of DAR, patients were then classified into high DAR (> or =3.0) and low DAR (<3.0) groups. The high DAR group had significantly worse prognoses for both overall and relapse free survival (P < 0.0005 and P < 0.0001, respectively). In multivariate analysis, DAR was an independent predictor of the relapse free survival of breast carcinoma patients (P=0.0377). CONCLUSIONS: DAR, as determined by FDG PET, may be useful as a prognostic indicator for patients with primary breast carcinoma.
The diversity in the lengths and the amino acid sequences of the third complementarity determining region of the antibody heavy chain (CDR-H3) has made it difficult to establish a relationship between the sequences and the tertiary structures, in contrast to the other CDRs, which are classified by their canonical structures. Enhanced conformational sampling of two different CDR-H3s was performed by multicanonical molecular dynamics (multicanonical MD) simulation while restricting the base structures, with and without the other surrounding CDR segments. The results showed that the multicanonical MD sampled a much larger conformational space than the conventional MD, independent of the initial conformations of the simulations. When the other CDRs surrounding the CDR-H3 segments were included in the calculations, the predominant conformations at 300 K corresponded to the X-ray crystal structures. When only the single CDR-H3 loops were considered with the restricted base structures, a greater number of different conformations were sampled as putative loops, but only a small number of stable conformations appeared at 300 K. Analyses of the resultant conformations revealed a structural role for the glycine, when it is located at position three residues before the last residue of CDR-H3 (Gly-X-X-last residue), coincident with the statistical tendencies of many antibody crystal structures. This reflects the general consistency between the energetically stable conformations and the empirically observed conformations. The current method is expected to be applicable to the structural modeling and the design of antibodies, especially for the inherently flexible loops.
An economical and easily movable molecular-beam epitaxy (MBE) apparatus which prepares magnetic ultrathin films and superlattices with atomically well controlled interfaces has been designed and constructed. Cleaning and characterization of substrates, sample deposition in a layer-by-layer fashion, and characterization of samples both during and after growth can be carried out in a single ultrahigh vacuum (UHV) chamber. This MBE apparatus is combined with UHV high-field magneto-optical instruments for in situ soft X-ray magnetic circular dichroism experiments on two-dimensional magnetic systems.
BACKGROUND: The current study was undertaken to evaluate the quantitative estimation of cytologic features on aspirated smears for the preoperative differential diagnosis of follicular lesions of the thyroid. METHODS: The subjects were 60 patients with follicular lesions of the thyroid (including 20 follicular carcinomas, 15 follicular adenomas, and 25 adenomatous goiters) whose histopathologic explorations were conducted fully postoperatively. Using a microscope connected to a computerized video system, the mean nuclear area, the mean nuclear perimeter, the circular rate, the largest to the smallest dimension ratio (LS ratio) of the nuclei, and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: Among the quantitative morphometric parameters of nuclei, the circular rate was significantly higher in the group with adenomatous goiters than those with follicular carcinomas (P < 0.00001) and adenomas (P < 0.005). The group with follicular carcinomas had a higher LS ratio than the group with adenomatous goiters (P < 0.0005). The NACV value increased as the malignant potential of the lesion increased and showed significant differences between the groups. When a NACV of 21.5% was chosen as the cutoff point, the incidence of malignancy was significantly higher in patients with high NACV values than in those with low NACV values (P < 0.00001). Using this borderline value, it was possible to distinguish malignant from benign diseases with a sensitivity of 85.0%, a specificity of 82.5%, and an accuracy of 83.3%. CONCLUSIONS: Preoperative quantitative estimations of cytologic nuclear features are useful for the preoperative differential diagnosis of follicular lesions of the thyroid.
Taq and Tth DNA polymerases catalyzed polymerization of dATP and dTTP into poly d(A-T) without requiring added primer/template (Hanaki et al., Biochem. Biophys. Res. Commun. 238, 113-118), while the Stoffel fragment of Taq DNA polymerase and delta Tth DNA polymerase with respective deletions of ca. 290 and 250 N-terminal amino acids did not. The primer/template-independent polymerization appeared to proceed via two reactions, the slow process of formation of 16-19 nt long oligo d(A-T) without primer/template and the rapid process of elongation of the oligo d(A-T) by self-priming. As the former step was more sensitive to N-ethylmaleimide than the elongation reaction, probably the formation of the oligonucleotide preceded the elongation. But when the substrates were depleted, Taq DNA polymerase degraded the high molecular weigh d(A-T) polymer to the oligomers which were resistant to the further digestion by the 5'-->3' exonuclease activity of Taq DNA polymerase. Probably, the elongation and the degradation reactions proceeded simultaneously, the former process being faster than the latter in the presence of enough dATP and dTTP.
BACKGROUND: Surgical resection of hepatic or pulmonary metastases has been accepted as appropriate therapy. However, whether aggressive surgery of both hepatic and pulmonary metastases from colorectal carcinoma is of value has not been verified in detail. METHODS: The authors identified 156 patients who had undergone hepatic resection for colorectal carcinoma metastases. This study reviewed six of these patients who underwent resection of both hepatic and pulmonary metastases from colorectal carcinoma. RESULTS: Five of the patients included four who underwent pulmonary resection for pulmonary metastases after initial hepatic resection for hepatic metastases and one patient who underwent hepatic metastasis resection after initial pulmonary metastasis resection. One additional patient underwent a simultaneous resection of hepatic and pulmonary metastases. The median interval between the 2 resections was 23 months. The median follow-up was 32 months after the second resection. At the time of last follow-up, 4 patients were alive and free of recurrent disease at 6, 7, 38, and 64 months, respectively, after their second resection. The remaining 2 patients died of disease at 17 and 32 months, respectively, after the second surgery. CONCLUSIONS: The results of the current study suggest that hepatic and pulmonary resection can result in long term survival in select patients with hepatic and pulmonary metastases from colorectal carcinoma because surgery remains the only potentially curative treatment.
BACKGROUND AND OBJECTIVES: Migration into subendothelial tissue in remote organ by cancer cells are crucial events for organ-specific metastasis, including liver metastasis. This study aims to investigate the chemoattractive ingredients in liver extract, which induce migration of liver metastatic cancer cells. METHODS: Cell migrations of SU.86.86 cells, human pancreatic cancer cells raised from liver metastasis, toward the bovine liver extract were studied by chemotaxis or haptotaxis assay. Bovine liver extract was partially purified by chromatographic or gel elutriation method. RESULTS: The soluble fraction of the liver extract did not induce chemotactic migration of SU.86.86 cells. However, the insoluble fraction induced a remarkable haptotactic migratory response. C18 column unbound insoluble fractions eluted from SDS-PAGE induced chemotactic migration of SU.86.86 cells. CONCLUSION: Such bioactive components in liver extract may play an important role in the development of liver metastasis.
This study was designed to evaluate the use of hepatic venous hemoglobin oxygen saturation (ShVO2) as an indicator of hepatic oxygen supply-demand relation and also regenerative status of the liver after partial hepatectomy in rats. We assessed the ShVO2 levels for 7 days, as well as hepatic hemodynamics, oxygen consumption, DNA synthesis and energy charge of the remnant liver for 3 days after 50% hepatectomy or sham operation. Total hepatic oxygen consumption (HVO2) per liver weight, hepatic oxygen extraction ratio (HO2ER), and DNA synthesis were significantly elevated at days 1 and 3 after hepatectomy, compared with the preoperative levels. Meanwhile, significantly decreased ShVO2 levels were observed at days 1 and 3, and the ShVO2 levels were significantly correlated with the HVO2. Furthermore, the decreased ShVO2 levels were synchronized with the increased DNA synthesis in the remnant liver. Energy charge levels were also significantly decreased at day 1 after hepatectomy. These results suggest that the regenerating liver demands an increased amount of oxygen for mitochondrial oxidative phosphorylation to restore hepatic energy charge. In conclusion, the ShVO2 after hepatectomy may reflect oxygen metabolic status in the remnant liver and could be useful for estimating liver regeneration.
The bacterial endotoxin lipopolysaccharide (LPS) contributes to the cardiovascular collapse and death observed in patients with sepsis. Because LPS has such profound effects on cardiac performance, we speculate that direct effects of LPS could be demonstrated on cardiomyocytes in culture, and that these direct effects are mediated by the LPS receptor, CD14. Accordingly, in this study, we provide evidence for CD14-dependent cardiotoxic effects of LPS including the LPS-stimulated secretion of tumor necrosis factor alpha (TNF-alpha) from cardiomyocytes. TNF-alpha is an inflammatory cytokine which is known for its negative inotropic effects on cardiac performance, but has not until recently been shown to be produced by cardiac cells. In this study, LPS was found to stimulate strongly in a dose-dependent manner the secretion of TNF-alpha from cultured adult rat cardiomyocytes. Further, LPS-induced TNF-alpha secretion was blocked by an inhibitor of TNF-alpha processing, metallomatrix protease inhibitor (TAPI). Molecular and immunological evidence demonstrated the presence of LPS receptors (CD14) on cardiomyocytes. Attenuated TNF-alpha secretion following PI-PLC treatment confirmed the functional importance of CD14 for LPS-mediated myocardial effects. Importantly, LPS also triggered apoptosis in cultured cardiomyocytes as quantified by single-cell gel electrophoresis of nuclei exhibiting DNA fragmentation patterns characteristic of apoptosis (i.e. cardiac comets). Apoptotic cell death was blocked by pre-incubation with the soluble TNF-alpha receptor fragment (TNFRII:Fc), suggesting that LPS-induced apoptosis was TNF-alpha-dependent and probably involved an autocrine function for the TNF-alpha whose secretion was under LPS control. The results of this study suggest that the cardiodepressant effects of LPS are dependent on CD14 signaling and may not only be due to acute negative inotropic effects of TNF-alpha but also may be complicated by TNF-alpha-induced apoptotic cell death which effectively reduces the number of working myocardial cells.
A retrospective study was conducted for the surgical treatment on acute aortic dissection among the cardiovascular services of 5 affiliated hospital of medical school. The total of 74 cases were operated for the last 5 years period from Jan., 1991 to Dec., 1995, in which 64 cases were classified as Type A and 10 for Type B. The average age for Type A was 58.4 years old and 10% of patients were consisted of Marfan syndrome. The most frequent complications associated with dissection was aortic regurgitation (37.5%), followed by cardiac tamponade (23.4%). The surgeries were undertaken in less than 24 hours from the onset of symptom in 45.3% of patients. The localization of initial tear as was proved by intraoperative finding was at ascending aorta in 64.0%, whereas it was found at aortic arch in 21.8% of patients. The most frequent application of operative procedure was simultaneous graft replacement of ascending aorta and aortic arch (68.7%) with the use of profound hypothermia and antegrade selective cerebral perfusion (85.4%). The overall mortality rate was 25.0%, however when compared as ascending only vs ascending + arch replacement, the later group demonstrated higher mortality rate (16.6% vs 28.9%). The majority of surgical indication for Type B was hemorrhage from the dissection and 20.0% of mortality was recorded in this group of patients.
A case is reported of a brain abscess and an intracranial mycotic aneurysm associated with infective endocarditis caused by streptococcus intermedius. A 60-year-old man with a history of fever presented aphasia and right hemiparesis. A computed tomographic scan of the head revealed a low-density area with ring enhancement in the left parietal lobe consistent with a brain abscess. An angiography demonstrated an aneurysm on the distal branch of the middle cerebral artery compatible with a mycotic aneurysm. Doppler echo cardiography showed severe mitral regurgitation by chordal ruptures. The brain abscess and intracranial mycotic aneurysm were resolved under appropriate antibiotic therapy for eight weeks. Then, the mitral valve was reconstructed by replacement of the chordae tendineae with expanded polytetrafloroethylene suture and annuloplasty. The patient had no neurologic deficit except for paresthesia in the right hand, and had no mitral regurgitation at discharge.
The 78-year-old male underwent coronary angiography because of angina pectoris. He was revealed to have essential thrombocythemia with a platelet count of over 1,000,000/mm3. Essential thrombocythemia belongs to the group of chronic myeloproliferative disorders. It displays both thrombogenic and bleeding tendency due to the increased platelet count, as well as to dysfunction. CABG was performed using the left internal thoracic artery and the right gastroepiploic artery. Hydroxycarbamide was taken to regulate the platelet count before surgery. There was no difficulty with hemostasis during surgery. Warfarin and hydroxycarbamide were used as anticoagulant therapies after surgery. Postoperative CAG demonstrated both grafts to be patients. The patient remained in good condition until he died suddenly on the 159th postoperative day. The cause of death was not clear because no autopsy was carried out. The death may have been associated with a thromboembolism, acute graft thrombosis or cerebral infarction, or pulmonary embolism. This patient did not take antiplatelet drugs because the platelet count and prothrombin time was well controlled. Nonetheless, an antiplatelet agent might reduce the risk of thromboembolism in such patients. It is suggested that meticulous anticoagulation therapy must be important for a patient with essential thrombocythemia, especially in the postoperative period.