Prediction of human herpesvirus 6 infection after allogeneic bone marrow transplantation.
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Adolescent↗
Biomedical subjects
H Furukawa
Publications and source records attributed to H Furukawa.
Biologically active oligodeoxyribonucleotides. 5. 5'-End-substituted d(TGGGAG) possesses anti-human immunodeficiency virus type 1 activity by forming a G-quadruplex structure.
A series of hexadeoxyribonucleotides (6-mers), d(TGGGAG), substituted with a variety of aromatic groups at the 5'-end were synthesized and tested for anti-human immunodeficiency virus type 1 (HIV-1) activity. While unmodified d(TGGGAG) (31) had no anti-HIV-1 activity, compound 23 with a 3,4-di(benzyloxy)benzyl (DBB) group at the 5'-end potently inhibited the HIV-1IIIB-induced cytopathicity of MT-4 cells in vitro (IC50 = 0.37 microM) without cytotoxicity up to 40 microM. A thermal denaturation study on the 5'-end-substituted 6-mers by means of the circular dichroism (CD) spectra demonstrated that the aromatic substituent attached at the 5'-end of the 6-mer strongly enhanced the formation of a parallel helical structure consisting of four strands (quadruplex). On the contrary, compound 36, in which one of the guanosines of 23 was replaced by a thymidine, did not form a quadruplex, thus exhibiting no anti-HIV-1 activity. Moreover, both compound 15, with a tert-butyldiphenylsilyl group solely at its 3'-end, and compound 21, with a relatively small substituent, a benzyl group, at the 5'-end, formed quadruplexes but had no anti-HIV-1 activity. These findings led us to the conclusion that both the quadruplex structure and the aromatic substituent with adequate size at the 5'-end are crucial for the interaction of the 5'-end-substituted 6-mers with the V3 loop as well as the CD4 binding site on viral gp120, resulting in anti-HIV-1 activity.
Anti-HIV Agents↗
Specificity of pyridinium inhibitors of the ubiquinone reduction sites in mitochondrial complex I.
Dual binding sites for pyridinium-type inhibitors in bovine heart mitochondrial complex I have been proposed (Gluck, M. R., Krueger, M. J., Ramsay, R. R., Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167-3174). The marked biphasic nature of the dose-response curve for inhibition of the enzyme by MP-6(N-methyl-4-[2-(p-tert-butylbenzyl)propyl]pyridinium) makes this compound the first selective inhibitor of the two sites (Miyoshi, H., Inoue, M., Okamoto, S., Ohshima, M., Sakamoto, K., and Iwamura, H. (1997) J. Biol. Chem. 272, 16176-16183). Modifications of the structure of MP-6 show that a tert-butyl group on the benzene ring, a methyl group attached to the pyridine nitrogen atom, para-substitution pattern in the pyridine ring, and the presence of a branched structure in the spacer moiety are important for the selective inhibition. On the basis of the structural specificity, we synthesized a selective inhibitor, MP-24 (N-methyl-4-[2-methyl-2-(p-tert-butylbenzyl)propyl]pyridinium), which elicits greater selectivity. Characterization of the inhibitory behavior of MP-24 provided further strong evidence for the dual binding sites model.
Animals↗
A comparative study of abnormal prion protein isoforms between Gerstmann-Sträussler-Scheinker syndrome and Creutzfeldt-Jakob disease.
Proteinase K (PK)-resistant prion protein (PrPres) isoforms were examined in three patients with Gerstmann-Sträussler-Scheinker syndrome (GSS) carrying proline-to-leucine mutation at codon 102 in prion protein gene (PRNP), and in nine patients with sporadic Creutzfeldt-Jakob disease (CJD). PrPres isoform termed 'type A', which showed a more prominent band of highly glycosylated form than both a lower glycosylated band and an unglycosylated band in immunoblotting, was exclusively found in the GSS patients examined. In eight of nine CJD patients, electrophoretic mobilities of three PrPres glycoforms were similar to type A, but the ratio of these glycoforms termed 'type B' was distinct from that of type A. On the other hand, one sporadic CJD case with wild-type PRNP had a different PrPres isoform termed type C, which showed higher molecular shift of each of the PrPres glycoforms. There was no significant relationships among genotypes, clinical features and PrPres isoforms in sporadic CJD cases. Our finding suggests that type A PrPres isoform is specifically found in the patients with GSS carrying codon 102 mutation, and there are at least two different PrPres isoforms in the patients with sporadic CJD.
Amyloid↗
Four cases of human herpesvirus 6 variant B infection after pediatric liver transplantation.
BACKGROUND: Little is known about human herpesvirus (HHV)-6 infection after liver transplantation. We present our experiences with four cases of HHV-6 infection after liver transplantation from living related donors. METHODS: Peripheral blood was collected from four donor and recipient pairs at the time of transplantation and biweekly from the recipients after transplantation. We attempted to isolate HHV-6 and measure antibody titers to HHV-6 and HHV-7. RESULTS: HHV-6 was isolated from four recipients approximately 2 weeks after transplantation. A significant rise in HHV-6 antibody titers was observed in four recipients at some point in their course, whereas HHV-7 antibody titers were increased in one recipient. Four isolates were variant B. When HHV-6 was isolated, all recipients had an unexplained fever. CONCLUSIONS: HHV-6 variant B infection after pediatric liver transplantation was confirmed. HHV-6 infection occurred approximately 2 weeks after transplantation. Moreover, there appears to be an association between HHV-6 infection and unexplained fever.
Antibodies, Viral↗
Hemophagocytic syndrome in five patients with Epstein-Barr virus negative B-cell lymphoma.
BACKGROUND: The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma. METHODS: Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens. RESULTS: Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection. CONCLUSIONS: In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS.
Aged↗
Interleukin-1, but not stress, stimulates glucocorticoid output during early postnatal life in mice.
The development of neuroendocrine functions depends not only on genetically determined mechanisms but also on phenotypic signals. Some of these signals may derive from the immune system. For example, interleukin-1 beta (IL-1 beta) stimulates glucocorticoid output during the early postnatal period, and administration of this cytokine at birth induces permanent alterations in the HPA axis in adulthood. We have extended these studies and found that the glucocorticoid response elicited in 5-day-old mice by a low dose of IL-1 beta is not desensitized by previous exposure to the cytokine. We have also compared the magnitude of the increase in corticosterone levels induced by IL-1 in 3-day-old and adult mice to that caused by acute stress. IL-1 beta and acute stress caused a comparable increase in corticosterone levels in adult mice. In newborn mice, however, IL-1 beta, but not restraint or cold stress, stimulated corticosterone output. Thus, IL-1 beta can elicit a corticosterone response during the postnatal stress-hyporesponsive period. Furthermore, when the corticosterone levels attained following IL-1 beta administration were compared to the basal levels of the hormone at a given age, the increase in plasma corticosterone levels was several fold higher in newborn than in adult animals. These data, together with the long-lasting endocrine effects of cytokine exposure at birth, suggest an important role of immune cytokines in the programming of neuroendocrine functions during ontogeny.
Aging↗
Administration of interleukin-1 at birth affects dopaminergic neurons in adult mice.
Interleukin-1 beta (IL-1 beta), a cytokine that plays a relevant role during inflammatory and immune processes, can also affect brain neurotransmitters and the activity of peripheral sympathetic nerves. Because both brain and peripheral catecholaminergic systems in mice are not fully developed at birth, we speculated that the development of these systems may be susceptible to modifications when mice are exposed to IL-1 beta early in life. Here we report that the administration to mice of a low dose of IL-1 beta during the first days of life results in a decreased dopamine content in the hypothalamus in adulthood. We also show that the dopamine content of the superior cervical sympathetic ganglia was reduced in adult mice that were treated with IL-1 beta at birth. No changes in noradrenaline content nor in its metabolite MHPG were detected in the brain and peripheral sympathetic ganglia of these animals. This indicates that central and probably also peripheral dopaminergic neurons are preferentially affected by IL-1 beta treatment at birth. Collectively, these results indicate that an increased production of IL-1 beta during infectious or inflammatory processes in the perinatal period may induce long-lasting, probably permanent, alterations in central and peripheral neurotransmitter systems.
Aging↗
Helical computed tomography in the diagnosis of portal vein invasion by pancreatic head carcinoma: usefulness for selecting surgical procedures and predicting the outcome.
OBJECTIVE: To evaluate the use of helical computed tomography (CT) in diagnosing portal vein (PV) invasion by pancreatic head carcinoma and its usefulness in predicting outcome. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Twenty-seven patients with carcinoma involving the pancreatic head were preoperatively studied with helical CT. All patients underwent resection. MAIN OUTCOME MEASURE: By quantifying the contact between the tumor and PV on helical CT, the relationship between them was classified into 1 of 4 types: type 1, visible fat layer between PV and the tumor; type 2, with the total PV circumference defined as 360 degrees, contact between the tumor and PV was considered to be 90 degrees or less; type 3, contact ranged between 91 degrees and 180 degrees; and type 4, contact greater than 180 degrees. Helical CT results were compared with intraoperative observation, histological findings of the resected specimen, and postoperative course. RESULTS: When helical CT showed type 3 or 4, the case was diagnosed as positive for PV invasion. Sensitivity, specificity, and overall accuracy were 83%, 100%, and 89% when compared with the intraoperative assessment, and 92%, 79%, and 85% with the histological assessment, respectively. One- and 2-year survival rates were 86% and 69% for type 1, 100% and 75% for type 2, and 33% and 12% for type 3, respectively. The survival rates of patients with types 1 and 2 were significantly higher than that of those with type 3 (P<.05). All 3 patients with type 4 died within 9 months. CONCLUSIONS: Helical CT facilitates detection of PV invasion by pancreatic head carcinoma. The extent of PV involvement reflected the outcome after pancreatectomy.
Adenocarcinoma↗
Small polypoid lesions of the gallbladder: differential diagnosis and surgical indications by helical computed tomography.
OBJECTIVES: To demonstrate the helical computed tomographic (CT) features of small polypoid lesions of the gallbladder and to establish a clinical strategy based on CT findings for the treatment of such lesions. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Thirty-one patients with polypoid lesions of the gallbladder (< or = 3 cm) underwent CT followed by resection. MAIN OUTCOME MEASURE: The detectability of the lesions on both unenhanced and enhanced CT and the configuration of the lesions on enhanced CT were prospectively evaluated in comparison with the histopathological findings. RESULTS: Unenhanced CT detected 14 (45%) of the 31 lesions, whereas enhanced CT detected all of the lesions. The detection rates of the neoplastic lesions (adenoma, adenocarcinoma, and metastatic tumor) and cholesterol polyps were 81% (13/16) and 7% (1/15), respectively (P<.001). Among the 20 lesions demonstrated as pedunculated, 6 (30%) were neoplastic, whereas 10 (91%) of the 11 lesions demonstrated as sessile were neoplastic (P<.001). When a lesion was demonstrated on unenhanced CT or its shape was sessile on enhanced CT, the case was diagnosed as a neoplastic lesion. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the CT diagnosis of the neoplastic lesions were 88% (14/16), 87% (13/15), 88% (14/16), 87% (13/15), and 87% (27/31), respectively. CONCLUSION: Computed tomography can differentiate neoplastic and nonneoplastic small polypoid lesions of the gallbladder and reliably identify the presence of neoplastic lesions that should be resected.
Adult↗
Chronic myeloid leukemia with minor-bcr breakpoint developed hybrid type of blast crisis.
Although a breakpoint in the minor breakpoint cluster region (m-bcr) of the BCR gene is observed in about two-thirds of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, this type of genomic rearrangement occurs very rarely in chronic myeloid leukemia (CML). We describe here the eighth case of m-bcr CML, and delineate unique clinical characteristics found in common to the 7 cases reported previously. Monocytosis with a low neutrophil/monocyte ratio resembling chronic myelomonocytic leukemia was the most striking feature of m-bcr CML. Splenomegaly and basophilia were not conspicuous in chronic phase. A high percentage of immature granulocytes and low neutrophil alkaline phosphatase score were the findings in common with classical CML. Lymphoid and myeloid blast changes have been observed at and shortly after presentation so far. We found a hybrid type of blast crisis in the course of m-bcr CML.Thus, m-bcr CML may be a definite subtype of CML, exhibiting distinct clinical characteristics. The presence of fusion product of m-bcr mRNA in an earlier myeloid cell may involve monocytic lineage in addition to myeloproliferative defects.
Blast Crisis↗
Limited surgery for early gastric cancer in cardia.
BACKGROUND: Because there are some difficulties with the diagnosis of invasion or the endoscopic resection technique, almost all gastric tumors are resected surgically. Surgeons now are performing a limited operation for early gastric cancer of the upper stomach (EGCUS) without lymph node metastasis. This paper discusses and evaluates the surgical technique and the results of the limited operation for EGCUS. PATIENTS AND METHODS: Since 1988, a total of 34 patients with EGCUS, diagnosed as intramucosal invasion, have undergone a limited operation--fundectomy--which includes a limited proximal gastrectomy, a limited lymph node dissection, and a procedure preserving the vagal nerve. The surgical risk, postoperative complications, and survival rates of the fundectomy patients (group A) were compared with those of patients undergoing a total gastrectomy for EGCUS (group B). RESULTS: Blood loss was lower in group A (300+/-193 mL) than in group B (555+/-316 mL) (P <.05). The incidence of postoperative pancreatic fistula also was lower in group A (0%) than in group B (15.0%) (P <.05). All patients in both groups (except one who died of a cerebral infarction) are alive without recurrence. CONCLUSION: Compared to the results of a total gastrectomy, performance of a limited fundectomy for EGCUS decreased surgical risk and postoperative complications without decreasing the survival rate.
Adult↗
Indications for hepatectomy for hepatocellular carcinoma - what stage of the disease is the best indication for surgery?
To determine the clinical and tumor stage of hepatocellular carcinoma (HCC) that is the best indication for surgery, the postoperative long-term outcomes of patients who underwent hepatic resection were examined retrospectively. Of 975 patients with HCC who underwent regional therapy, 384 patients (39%) received hepatic resection (HR), 534 (55%) had transcatheter arterial chemoembolization (TACE), and the remaining 57 (6%) received percutaneous ethanol injection (PEI) into the tumor. The criteria defined by liver Cancer Study Group of Japan was used for staging and liver functional reserve (i.e., clinical staging). In the 133 patients with stage I HCC, there were no significant differences among the survivals of the HR, TACE, and PEI groups. In the 314 patients with stage II HCC, the 5- and 7-year survival rates were 51% and 46% in the HR group, 23% and 10% in the TACE group, and 0% and 0% in the PEI group. The survival of the HR group was significantly better than the survivals of the TACE and PEI groups (P < 0.001). The 5- and 10-year survivals of the stage II HCC patients who had HR were 64% and 47% in the clinical stage I (i.e., good liver function) group, significantly better than the 5; and 10-year survivals (32% and 23%) in the clinical stage II (i.e., bad liver function) group (P < 0.0001). Patients with good liver function in stage II are expected to have better survival and are considered to be the most suitable for HR.
Aged↗
An alternatively spliced form of the human CD94 gene.
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Alternative Splicing↗
Transcortical sensory aphasia following left frontal infarction.
Two right-handed patients who exhibited language disability after left frontal infarction are described. The patients spoke fluently and exhibited excellent repetition ability from the onset of infarction without exhibiting any oral apraxia, but had deficits in auditory comprehension, naming, reading and writing. In both patients, brain magnetic resonance imaging (MRI) revealed infarction in the left inferior frontal gyrus, the middle frontal gyrus and the anterior part of the lower precentral gyrus. Single photon emission computed tomography (SPECT) revealed decreased blood flow in the same regions as those shown to be infarcted by MRI. The MRI and SPECT findings and the symptoms of these patients suggest that left frontal lesions that encompass Broca's area produce fluent aphasia if the posterior part of the left precentral gyrus or motor cortex remains intact and that lesions anterior to Broca's area and the middle frontal gyrus produce a deficit in auditory comprehension of single words as well as sentences.
Aphasia, Wernicke↗
Intraoperative cytodiagnosis for detecting a minute invasion of the portal vein during pancreatoduodenectomy for adenocarcinoma of the pancreatic head.
During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we frequently encountered cases in which the superior mesenteric-portal venous confluence (SMPVC) was involved with cancer. With regard to the indication of the concomitant SMPVC resection, as suggested by recent papers, a better long-term outcome would be expected if the cancer invasions were limited to the tunica adventitia or media of the SMPVC wall. Since this raised fears whether such a small SMPVC invasion was always detectable by macroscopic inspection alone, we have performed an intraoperative cytology on the touch smear of the exposed SMPVC wall for 23 patients with pancreatic head cancer. All of their SMPVCs were separated from the pancreatic head and appeared to be intact at a macroscopic level. As a result of the cytologic examination, however, 7 patients (30%) were newly diagnosed as having cancer cells on the SMPVC wall, and they received an additional resection of the SMPVC. Postoperative histology indicated that cancer invasion into the SMPVC wall was present in 6 of the 7 patients, and that the cancer invasions were limited in the tunica adventitia in 5 patients and to the tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC resection, our intraoperative cytology on the touch smear of the SMPVC is worth performing more actively on the macroscopically intact-looking SMPVC during resection of pancreatic cancer.
Adenocarcinoma↗
Should the aortic valve homograft be recryopreserved?
BACKGROUND: The number of homograft donors is limited and the once-thawed homograft may be unsuitable for the recipient and obliged to be wasted. The purpose of this study was to investigate the possibility of recryopreserving and using the once-thawed homograft for another patient. METHODS: Canine aortic valve leaflets were frozen to -80 degrees C by a programmed freezer, stored in liquid nitrogen, and thawed after 1 week. A subgroup of leaflets was left at 4 degrees C for 15 minutes, re-cryopreserved, and thawed after 1 week. Pathologic and flow cytometric evaluations were performed. RESULTS: After thawing, by pathology, alignment of the fibers was acceptably maintained but the membrane and cytoplasm of the fibroblast were damaged. These findings were not significantly aggravated even after rethawing. By flow cytometry, fibroblast viability was 90.7%+/-1.7% immediately after thawing, 87.6%+/-1.0% after thawing for 15 minutes at 4 degrees C, 63.7%+/-2.7% during refreezing at 0 degrees C, and 39.4%+/-4.3% after rethawing. CONCLUSIONS: From the standpoint of fibroblast viability, it is not possible to recryopreserve the once-cryopreserved and thawed aortic valve homograft.
Animals↗
Current status of intestinal transplantation in children.
PURPOSE: A clinical trial of intestinal transplantation (Itx) under tacrolimus and prednisone immunosuppression was initiated in June 1990 in children with irreversible intestinal failure and who were dependent on total parenteral nutrition (TPN). METHODS: Fifty-five patients (28 girls, 27 boys) with a median age of 3.2 years (range, 0.5 to 18 years) received 58 intestinal transplants that included isolated small bowel (SB) (n = 17), liver SB (LSB) (n=33), and multivisceral (MV) (n=8) allografts. Nine patients also received bone marrow infusion, and there were 20 colonic allografts. Azathioprine, cyclophosphamide, or mycophenolate mofetil were used in different phases of the series. Indications for Itx included: gastroschisis (n=14), volvulus (n=13), necrotizing enterocolitis (n=6), intestinal atresia (n=8), chronic intestinal pseudoobstruction (n=5), Hirschsprung's disease (n=4), microvillus inclusion disease (n=3), multiple polyposis (n=1), and trauma [n=1). RESULTS: Currently, 30 patients are alive (patient survival, 55%; graft survival, 52%). Twenty-nine children with functioning grafts are living at home and off TPN, with a mean follow-up of 962 (range, 75 to 2,424) days. Immunologic complications have included liver allograft rejection (n=18), intestinal allograft rejection (n=52), posttransplant lymphoproliferative disease (n=16), cytomegalovirus (n=16) and graft-versus-host disease (n=4). A combination of associated complications included intestinal perforation (n=4), biliary leak (n=3), bile duct stenosis (n=1), intestinal leak (n=6), dehiscence with evisceration (n=4), hepatic artery thrombosis (n=3), bleeding (n=9), portal vein stenosis (n=1), intraabdominal abscess (n=11), and chylous ascites (n=4). Graft loss occurred as a result of rejection (n=8), infection (n=12), technical complications (n=8), and complications of TPN after graft removal (n=3). There were four retransplants (SB, n=1; LSB n=3). CONCLUSIONS: Intestinal transplantation is a valid therapeutic option for patients with intestinal failure suffering complications of TPN. The complex clinical and immunologic course of these patients is reflected in a higher complication rate as well as patient and graft loss than seen after heart, liver, and kidney transplantation, although better than after lung transplantation.
Child, Preschool↗