Cellular factors as alternative targets for inhibition of HIV-1.
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Animals↗
Biomedical subjects
M Baba
Publications and source records attributed to M Baba.
Donor-specific cytotoxic lymphocyte activity from bronchoalveolar lavage during acute canine lung allograft rejection.
OBJECTIVE: We investigated the relationship between acute lung rejection and donor-specific cytotoxic activity (DSCA) in recipient's lymphocytes obtained from bronchoalveolar lavage (BAL). METHODS: A total of 26 mongrel dogs underwent left lung allotransplantation. Dogs received either no immunosuppressive treatment (group I), cyclosporine (group II), or cyclosporine and methylprednisolone for evidence of acute rejection (group III). DSCA was measured by a 51Cr release assay, using lymphocytes from BAL samples as effector cells and 51Cr-labeled donor skin fibroblasts as target cells. The pathologic findings of the transplanted lungs were classified according to the working formulation for classification and grading of pulmonary rejection. In addition, the degree of cellular infiltration in the perivascular, peribronchial, interstitial, and intraalveolar areas was determined based on an infiltration score. RESULTS: DSCA in BAL samples was elevated during mild, moderate and severe acute rejection. The accuracy of the diagnosis of mild or moderate rejection was 92.3% at effector:target (E:T) ratios of 100:1 and 50:1. The DSCA in the BAL fluid and the total infiltration score were correlated closely with correlation coefficients of 0.859 and 0.828 at E:T ratios of 100:1 in group I and group II dogs, respectively. Lung aeration improved and DSCA decreased with methylprednisolone therapy in three of four dogs with grade 2 rejection. CONCLUSION: There is a direct relationship between the DSCA in BAL fluid and the degree of tissue damage caused by acute rejection. The DSCA can be detected by a 51Cr release assay which may hold promise for future clinical applications.
Animals↗
Inhibition by ginsenoside Rg3 of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.
The effects of concomitant use of bombesin and ginsenoside Rg3 on the incidence of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 20, s.c. injections of ginsenoside Rg3 (2.5 or 5.0 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of a higher dose of ginsenoside Rg3 with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth pattern, labeling and apoptotic indices and tumor vascularity of intestinal cancers, it significantly decreased the incidence of cancer metastasis. These findings indicate that ginsenoside Rg3 inhibits cancer metastasis through activities that do not affect the growth or vascularity of intestinal cancers.
Adenocarcinoma↗
Extranodal connective tissue invasion and the expression of desmosomal glycoprotein 1 in squamous cell carcinoma of the oesophagus.
We investigated extranodal connective tissue involvement (ECTI) in 39 patients with oesophageal carcinoma. Both the primary tumour and ECTI were immunohistochemically examined using the monoclonal antibody 32-2B for desmosomal glycoprotein 1 (DG1). Connective tissue carcinoma deposits were identified as cells within small lymph nodes, as lymphatic or venous vessel invasion or as widespread invasion beyond the capsule of metastatic lymph nodes. These histological findings were present in at least one area in 20 of 39 patients (51.3%). DG1 immunostaining intensity by tumour was graded as DG1 (++), DG1 (+) or DG1 (-). DG1 (+) or DG1 (-) primary tumours demonstrated lymph node metastases and ECTI more frequently than DG1(++) tumours (P<0.05). Among 17 patients in whom DG1 immunohistochemistry was performed on ECTI, there were three DG1(++), five DG1(+) and nine DG1(-) patients. The DG1 expression of ECTI was equal to or less intense than the primary tumour. These results indicate that reduction or loss of DG1 expression may promote ECTI and lymph node metastases. One should be aware of the potential for ECTI in oesophageal carcinomas. In the future, adjuvant therapy may be advisable for some oesophageal carcinomas based on the phenotype of individual cancer cells, including expression of DG1.
Aged↗
A cryopreservation method of human peripheral blood mononuclear cells for efficient production of dendritic cells.
The establishment of a cryopreservation method for unstimulated fresh peripheral blood mononuclear cells (PBMC) with nearly 100% viability would greatly contribute to the conduct of various immunological experiments. The cells most sensitive to freezing and thawing procedure seem to be dendritic cells (DC) and their precursors, which are of the most potent antigen-presenting cells. The authors investigated and established a method of cryopreserving fresh PBMC from which DC were recovered and differentiated efficiently by using recombinant (r) GM-CSF and rIL-4. PBMC frozen in the presence of 12% dimethylsulfoxide and 25-30% fetal calf serum recovered DC as efficiently as freshly obtained PBMC. Established DC could also be cryopreserved in the presence of 12% DMSO with their viability maintained at more than 90%. The 12% DMSO freezing solutions were superior to both the 10% DMSO solution and the previously reported DC freezing medium (2 M or 15.4% DMSO). The DC obtained from the cryopreserved PBMC expressed HLA-DR, HLA-DQ, CD80 and CD86 antigens, and stimulated allogenic PBMC to an extent almost identical to that obtained from fresh PBMC. These findings indicate that the conditioned medium utilized here enables safe cryopreservation of DC and DC precursors in PBMC.
Cell Division↗
Inhibition of interleukin-6-induced human immunodeficiency virus type 1 expression by anti-gp130 monoclonal antibody.
Interleukin 6 (IL-6) has been reported to upregulate the expression of human immunodeficiency virus type 1 (HIV-1) in infected monocyte/macrophages. Since IL-6 signal is transduced through the membrane glycoprotein gp130, we investigated the inhibitory effect of anti-gp130 monoclonal antibody (mAb) on IL-6-induced viral expression in monocytic cell lines latently infected with HIV-1. IL-6 significantly induced the expression of HIV-1 in U1 cells, whereas it had no effect in OM-10.1 cells. Flow cytometric analysis revealed that U1 but not OM-10.1 cells expressed gp130 on their surface. The anti-gp130 mAb could inhibit IL-6-induced HIV-1 expression in U1 cells in a dose dependent fashion. These results suggest that blocking the gp130 signal transduction may have therapeutic potential for the treatment of HIV-1 infection.
Antibodies, Monoclonal↗
Synchronous and metachronous carcinomas of the esophagus and head and neck.
We retrospectively analyzed the clinicopathologic findings, treatment and outcome of 22 patients with synchronous or metachronous carcinomas of the esophagus and head and neck. The patients with metachronous cancers in whom esophageal cancer occurred first had either an early-stage esophageal carcinoma or only one positive lymph node. Similarly, five of 10 patients with metachronous cancers in whom head and neck cancer was the first tumor had early-stage esophageal carcinomas. The esophageal lesion was mucosal carcinoma in four patients which was found by endoscopy with the iodine dye method. In the patients with synchronous cancers either one or both carcinomas were advanced, and the prognosis of these patients was poor compared with those of patients with metachronous carcinomas. Accordingly, endoscopic surveillance for early detection of metachronous lesions are encouraged.
Adult↗
Mouse germinal center B cells with the xid mutation retain responsiveness to antimouse CD40 antibodies but diminish IL-5 responsiveness.
The germinal center (GC) develops in secondary lymphoid tissues in response to thymus-dependent (TD) antigens. To investigate the molecular mechanism of B cell differentiation in GC, we enriched GC B cells from spleen of TD antigen-immunized wild-type and X-linked immunodeficient (XID) mice, and examined the differentiation of GC B cells into antigen-specific IgG1 antibody-forming cells (AFC) in response to anti-CD40 mAb and cytokines. A significant proportion of freshly purified GC B cells expressed receptors for IL-4 and IL-5. Anti-CD40 mAb sustained the viability of GC B cells and IL-4 co-operated with anti-CD40 mAb for further enhancement of the cell viability. Anti-CD40 mAb and IL-4 were essential for inducing differentiation of GC B cells into antigen-specific IgG1-AFC and IL-5 efficiently enhanced their differentiation. GC B cells with the xid mutation responded for proliferation to CD40 ligation to a lesser extent and for the IgG1-AFC response to anti-CD40 mAb together with IL-4, but they showed impaired responsiveness to IL-5, regardless of enhanced expression of IL-5R in response to anti-CD40 mAb and IL-4. These results suggest that anti-CD40 mAb, IL-4 and IL-5 play a critical role in the differentiation of mouse GC B cells. The GC B cells from XID mice show a functional defect with respect to IL-5-mediated differentiation.
Animals↗
Thiadiazole derivatives: highly potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replications in vitro.
We have recently reported that thiadiazole (TDA) derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication. These compounds belong to the family of nonnucleoside reverse transcriptase inhibitors (NNRTIs). In an attempt to develop more effective and pharmacologically favorable compounds, novel TDA derivatives have been synthesized and examined for their anti-HIV-1 activity in vitro. Among them, RD4-2217 was found to be the most potent inhibitor of HIV-1 replication. It inhibited replication of the HTLV-IIIB strain in MT-4 cells at a concentration of 6 nM. RD4-2217 was also inhibitory to clinical isolates and zidovudine-resistant mutants of HIV-1. The combination of RD4-2217 with zidovudine or the protease inhibitor A-75925 synergistically inhibited HIV-1 replication. Studies on the emergence of drug-resistant mutants revealed that, although much higher concentrations (1-10 microM) were required, RD4-2217 completely suppressed the breakthrough of HIV-1 in the supernatants during long-term culturing of infected cells. Furthermore, RD4-2217 at low concentrations (10 or 100 nM), in combination with zidovudine, also completely inhibited viral breakthrough. In addition, RD4-2217 had lower lipophilicity and improved protein binding as compared to its congener RD4-2024 and loviride. These results suggest that RD4-2217, one of the TDA derivatives, is worth pursuing as a candidate drug for the treatment of HIV-1 infections.
Anti-HIV Agents↗
Sho-saiko-to, a traditional Kampo medicine, enhances the anti-HIV-1 activity of lamivudine (3TC) in vitro.
Sho-saiko-to (SST), a traditional Kampo medicine, has been examined for its inhibitory effect on human immunodeficiency virus type 1 (HIV-1) replication in peripheral blood mononuclear cells (PBMCs). SST alone moderately inhibited HIV-1 replication at a concentration of 25 microg/ml. When SST was combined with zidovudine (AZT), lamivudine (3TC) or AZT plus 3TC, SST enhanced the anti-HIV-1 activity of 3TC. In contrast, SST slightly enhanced the anti-HIV-1 activity of AZT plus 3TC but did not enhance the activity of AZT alone. These results suggest that the combination of SST and 3TC has potential as a chemotherapeutic modality of HIV-1 infection.
Acquired Immunodeficiency Syndrome↗
Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives.
We have found novel piperazinyloxoquinoline derivatives to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in both acutely and chronically infected cells. 8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-didehydro-7-[4-(2-met hoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12), the most potent congener of the series, completely inhibited HIV-1 replication in acutely infected MOLT-4 cells at a concentration of 0.16 to 0.8 microM without showing any cytotoxicity. The compound completely suppressed tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 expression in latently infected cells (OM-10.1) and constitutive viral production in chronically infected cells (MOLT-4/III(B)) at a concentration of 0.8 microM. K-12 could also inhibit HIV-1 antigen expression in OM-10.1 and MOLT-4/III(B) cells at this concentration. Northern blot analysis revealed that K-12 selectively prevented the accumulation of HIV-1 mRNA in MOLT-4/III(B) and TNF-alpha-treated OM-10.1 cells in a dose-dependent fashion. It was not inhibitory to HIV-1 Tat or the cellular transcription factors NF-kappaB and Sp1, suggesting that the piperazinyloxoquinoline derivatives are a group of HIV-1 transcription inhibitors with a unique mechanism of action.
Anti-HIV Agents↗
p53 overexpression and proliferative activity do not correlate with lymph node metastasis in early gastric cancer.
We investigated p53 overexpression and the proliferative activity of the primary lesion as well as the clinicopathological features of 75 patients with gastric cancer invading the submucosa (sm cancer), of whom 14 (18.7%) had lymph node metastasis. Among the clinicopathologic features studied, only lymphatic invasion by the primary tumor was related to lymph node metastasis. There was no relationship between immunohistochemical staining for p53 protein or Ki-67 and lymph node metastasis. The p53-positive rate was 35.7 and 57.1% in patients with and without metastasis, respectively, while the mean Ki-67 labeling index was 38.9 and 38.1%, respectively. Our results suggest that p53 mutation or the proliferative activity of sm cancer do not influence lymph node metastasis, even though p53 mutation may enhance the proliferative activity and metastatic potential of advanced gastric cancer.
Adenocarcinoma↗
Measurement of pancreatic blood flow to prevent pancreatic juice leakage after pancreas-preserving total gastrectomy for gastric cancer.
In patients with gastric cancer, distal pancreatectomy was frequently performed for complete removal of the lymph nodes along the splenic artery, but this procedure sometimes induced pancreatic juice leakage, subphrenic abscess, and postoperative diabetes. To avoid these complications, pancreas-preserving total gastrectomy (PP) was developed by Maruyama et al. [World J Surg 1995; 19:552-536], with which the spleen, splenic artery, and fatty connective tissue including lymph nodes could be removed completely without distal pancreatectomy. From 1988 to 1995, 36 patients underwent PP in our department. Although there were no operative deaths and no patient developed postoperative diabetes, pancreatic juice leakage was observed in 4 patients (11.1%). We assumed that ischemia of the distal pancreas may have caused this pancreatic juice leakage and investigated the relationship between pancreatic blood flow (PBF) and this complication in 12 recent patients. A significant negative correlation between PBF in the pancreatic tail and the peak amylase level (PAL) in the drain fluid was demonstrated. Two patients with PBF values of 4.5 and 5.2 ml/min/100 g tissue, respectively, and a PAL of more than 2 x 10(5) U/l developed pancreatic juice leakage, whereas the 10 patients without this complication had PBF values above 6 ml/min/100 g tissue and a PAL of less than 2 x 10(4) U/l. These results suggest that measurement of PBF may be useful to predict the leakage of pancreatic juice after PP and that distal pancreatectomy may be preferable when PBF is extremely low.
Adult↗
Relation between smoking status of physicians and their enthusiasm to offer smoking cessation advice.
Are nonsmoking physicians more likely to give smoking cessation advice to their patients? To determine this, we sent a questionnaire individually to physicians in Tokyo. The average age of the 323 respondents was 59.8 +/- 12.9 (mean +/- SD); 84.8% of them were male and 21.1% were smokers. Among the respondents, 88.8% asked their patients about their smoking status, 79.9% advised smoking patients to stop, and 93.5% believed smoking cessation interventions to be necessary. Nonsmoking physicians were more likely to advise patients to stop smoking (85.6%) than smoking physicians (70.1%); the smoking physicians who themselves wished to reduce cigarette consumption or stop smoking were more likely to do so (85.0%) than those who did not wish to reduce or stop (43.5%). Moreover, more nonsmoking physicians seriously felt that smoking cessation interventions are necessary (31.2%) than did smoking physicians (6.5%). In conclusion, the smoking status and attitude towards smoking of physicians influences their enthusiasm to give advice to their patients against smoking.
Attitude of Health Personnel↗
Changes in motor nerve terminals following proximal constriction by a ligature.
To elucidate the effect of proximal constriction on motor nerve terminals, silk ligations were placed around the tibial nerve in the thigh of rabbits. The ligatures were tight enough to cause Wallerian degeneration in most of the large myelinated fibers; we studied those which remained unaffected. A week after operation, 9 animals showed a fall in amplitude of medial plantar muscle action potential to less than 30% of the pre-operative value on tibial nerve stimulation at the ankle. They were killed after keeping the constriction from 10 to 100 days, and the medial plantar muscles were removed for histological studies on the motor terminals of the medial plantar nerve. AChE-silver staining showed many nerve endings without terminal axons, and "junctional" terminals showing preservation of the continuity proximal to complete degeneration from 10 days to the 40 days after ligation. A few terminal and nodal sproutings were found 10 days after ligation. Transverse sections of the intramuscular portion of the medial plantar nerve showed a decrease in number of the large myelinated fibers. While the ratio of axonal caliber/external diameter of large myelinated fibers (g-ratio) was reduced, g-ratio of small myelinated fibers were varied but as high as that in normal controls from 40 days after ligation. These results indicate distal axonal degeneration (dying back) of the terminal fibers besides the Wallerian degeneration at the level of the ligature and inhibited distal sproutings, which are probably caused by a local disturbance of axonal transport resulting from proximal constriction.
Action Potentials↗
Fatty liver in a case with heterozygous familial hypobetalipoproteinemia.
We herein present a case of fatty liver in a patient with heterozygous familial hypobetalipoproteinemia. A 34-yr-old male presented with abnormally elevated levels of transaminases and a fatty liver. He was asymptomatic, and the physical examination showed nothing remarkable. The serum total cholesterol, triglyceride, LDL-cholesterol, and apolipoprotein B levels all ranged from low normal to one-half normal. His other laboratory data were all in the normal range. The patient's body mass index measured was 25.7 kg/m2, and he did not demonstrate obesity. He had no history of alcohol consumption. It was thus thought that the fatty liver in this case might be associated with heterozygous hypobetalipoproteinemia. Heterozygous hypobetalipoproteinemia with a bright liver by ultrasound was also found in several of the patient's family members. Based on these rare findings, heterozygous hypobetalipoproteinemia should thus be considered as a possible cause in patients presenting with an unexplained fatty liver.
Adult↗
Oxygen delivery as a factor in the development of fatal postoperative complications after oesophagectomy.
BACKGROUND: This study was designed to assess the impact of oxygen transport variables on outcome in 115 patients undergoing elective surgery for oesophageal carcinoma. METHODS: Haemodynamic parameters were determined using a Swan-Ganz catheter in all patients on the day before operation, 6 h after operation, and daily for the first 4 days after operation. RESULTS: Oxygen delivery and consumption at 6 h were significantly higher in survivors than in non-survivors. However, oxygen delivery and consumption in both groups did not differ significantly after postoperative day 1. Of 17 patients with oxygen delivery levels lower than 445 ml min-1 m-2 at 6 h, eight died in hospital. Oxygen delivery in patients who developed either an anastomotic leak or severe pneumonia was significantly lower 6 h after surgery. Lower levels of oxygen delivery preceded postoperative complications. CONCLUSION: Oxygen delivery 6 h after oesophagectomy correlates with postoperative complications and may be a determinant of hospital mortality.
Aged↗
[Motor nerve conduction study].
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Amyotrophic Lateral Sclerosis↗