[Gene expression controlled by neural activity].
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Biomedical subjects
Publications and source records attributed to K Sano.
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Human herpesvirus 6 (HHV-6) has been proposed as one of the co-factors responsible for the development of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV) carriers. We analyzed the interaction between HHV-6 and HIV-1 in superinfected cells. Cell-free HIV-1 could superinfect human T cell lines, MT-4 and Molt-4, which had been previously infected with HHV-6. Both HHV-1 and HHV-6 replicated in the same cells. We observed two types of morphologically distinguished cells as early as 4 days after superinfection. One type (D) was degenerate cells with intracellular and extracellular HHV-6 and with less HIV-1 virions. The other type (I) was relatively intact cells with both HIV-1 and HHV-6 virions. Replication of HIV-1 was more active in the type I as compared with type D cells. The level of HIV-1 reverse transcriptase (RT) activity in the culture supernatants of cells superinfected on day 0 declined after day 7, while that in the supernatants of cell cultures infected with HIV-1 alone remained high between days 12 and 40. These results suggest that the superinfection of the HHV-6-infected cells with HIV-1 may induce a degenerative process in these cells.
Neuroblastoma is a tumour derived from the sympathoadrenal progenitors of the neural crest. It is one of the most malignant solid tumours in childhood with an annual incidence of 9.4 per 10(6) children under 15 years of age. Recent studies suggest that immunocytological detection of neuroblastoma cells in bone marrow and circulating neuroblasts during treatment may predict clinical outcome and correlate with tumour relapse. The present methods of diagnosing metastasis in neuroblastoma include histological, biochemical and immunohistological analysis. Morphological distinction between tumour cells and primitive lymphoblasts in bone marrow is often difficult, and these methods may also not always be sensitive enough for early detection of the residual and minimally circulating tumor cells. A sensitive assay for detection of such residual cells using two tissue-specific markers, NFM and SYN, by reverse transcriptase-polymerase chain reaction (RT-PCR) is reported here. Analysis of the specificity of this assay in three neuroblastoma cell lines, namely IMR 32, SK-N-SH and SY5Y showed positive expression while control peripheral blood mononuclear cells (HL 60) were negative. In reconstituted cell spiking tests, this method has the ability to detect 1-10(3) neuroblastoma cell in 10(7) normal peripheral blood mononuclear cells (PBMC), as shown by serial dilution and limiting dilution. The NFM marker was found to be a more sensitive marker. The specificity and sensitivity of this technique makes it suitable for future application in detection of minimally disseminated tumour cells in neuroblastoma patients.
Although stimulation of N-methyl-D-aspartate receptors or voltage-dependent calcium channels induces both the activation of c-fos and brain-derived neurotrophic factor (BDNF) genes, it is not certain how the activation of these genes is related. Using primary cultures of rat hippocampal neurons, we found that exposing the cells to cycloheximide allowed subsequent activation of BDNF mRNA expression, although activation of AP-1 DNA-binding activity resulting from the c-fos induction was abolished. Super-induction of BDNF gene was also caused by cycloheximide. The estimated half-life of BDNF mRNA was approximately 2.5 hrs, which was almost identical to that of c-fos mRNA. These results indicate that nascent AP-1 is not required for the activation of BDNF gene, leading to the notion that the BDNF gene can be activated by Ca2+ signals as an immediate early gene.
Using a solid-phase non-radioisotopic (non-RI) reverse transcriptase (RT) assay, antibodies inhibiting human immunodeficiency virus type 1 (HIV-1) RT activity (RTI antibody) were investigated for their ability to inhibit binding of RT to a template-primer and DNA polymerization. The RTI antibody inhibited the binding of RT to the template-primer (BI antibody), and directly reacted with the RT-template-primer complex and inhibited enzymatic activity (PI antibody). The RTI antibody interfered with formation of the RT-template-primer complex suggesting that it recognized the antigenic site involved in template-primer binding of RT molecules. Since deoxynucleotide triphosphates (dNTPs) blocked inhibition of the RT activity by the PI antibody, the antigenic site recognized by the PI antibody may be closely related to the dNTP binding site. The seropositivities of the BI and PI antibodies were 84.6% and 91.2%, respectively, in HIV-1-infected individuals; healthy individuals, HTLV-I-positive individuals, autoimmune disease patients and leukemia patients were all seronegative. No significant correlation of residual RT activities was observed when BI and PI antibodies were compared (r = 0.688). It is possible that the epitopes recognized by the BI antibody differs from those recognized by the PI antibody. The assays described are able to detect BI and PI antibodies in the sera of HIV-1-infected individuals.
Pulmonary artery (PA) end-diastolic pressure is used as an estimate of PA wedge pressure. We evaluated contrast enhanced pulmonary regurgitant signals in the assessment of PA end-diastolic pressure in 24 patients in a critical care unit. Right atrial pressure was estimated by the percent decrease of the inferior vena caval diameter with inspiration. Weak or absent pulmonary regurgitant signals were enhanced by sonicated albumin (Albunex) in 23 patients (96%). The Doppler-determined PA end-diastolic pressure (the sum of the pulmonary regurgitant pressure gradient at end-diastole and the right atrial pressure) was significantly correlated with the catheter-determined PA end-diastolic pressure (y = 0.85x + 1.72, r = 0.93). Compared with invasive hemodynamic monitoring, the contrast-enhanced Doppler technique using Albunex is effective for measuring PA end-diastolic pressure, even in critically ill patients.
Hepatocytes were isolated from rats fed a diet with or without 0.25% clofibrate, and NAD+ synthesis by the hepatocytes was determined using either [carboxyl-14C]nicotinic acid or [5-3H]tryptophan. NAD+ and total pyridine nucleotides synthesized from [14C]nicotinic acid by the clofibrate-treated cells were not significantly different from those synthesized by the control cells when expressed on the basis of nanomoles per hour per milligram of DNA. On the contrary, NAD+ synthesized from [3H]tryptophan was significantly higher in the clofibrate-treated cells (158% of the control cells) on the basis of nanomoles per hour per milligram of DNA. Clofibrate was inhibitory to tryptophan metabolism as a whole, affecting the glutarate pathway more (decreased to 37% of control) than the kynureninase flux (decreased to 64% of control). As a result, the quinolinate-NAD flux, estimated as the difference in the amounts of tryptophan metabolized by the two metabolic pathways, increased in the clofibrate-treated hepatocytes. The increase in quinolinate during the incubation was 8 times more in the clofibrate-treated cells than in the control cells, which confirmed alteration in the metabolic fluxes of tryptophan in the clofibrate-treated cells. Hepatic quinolinate phosphoribosyltransferase (EC 2.4.2.19) activity increased with dietary clofibrate and returned to the control level 1 week after removing clofibrate from the diet. Nicotinate phosphoribosyltransferase (EC 2.4.2.11) and NAD+ glycohydrolase (EC 3.2.2.5) activities remained unchanged with dietary clofibrate.
The sensitivities of two reverse transcriptase (RT) assays, an enzyme-linked oligonucleotide sorbent assay (ELOSA)-RT assay and a non-radioisotopic (non-RI) RT assay were compared. For measuring recombinant HIV-1 RT, the ELOSA-RT assay was 8 times less sensitive in dilution endpoint and 16 times less sensitive in measurement of RT from pelleted HIV-1 than the non-RI RT assay. Higher level of interference by an RNA-DNA hybrid observed in the former assay may indicate that the reduction in sensitivity was due to the presence of viral RNA in the sample of pelleted virus. The ELOSA-RT assay was interfered with to a great extent than the non-RI RT assay by fetal bovine serum and thus may be unsuitable for measuring RT from HIV-1 in a culture supernatant.
We report a case of superior vena cava (SVC) syndrome that was assessed by intravascular ultrasound (IVUS). A highly echogenic eccentric lesion was demonstrated by IVUS. The use of IVUS also confirmed in vivo that SVC syndrome following pacemaker insertion occurs as a result of intimal thickening of the venous wall.
BACKGROUND: Platelet activation and coagulation abnormality have been observed during coronary spasm. It is crucial whether platelet activation occurs even during a nonischemic period. HYPOTHESIS: This study was designed to determine whether platelets might be activated across the coronary bed during a nonischemic interval in patients with vasospastic angina. METHODS: Plasma levels of serotonin, 6-keto-prostaglandin F1 alpha, and catecholamines in the aorta and the coronary sinus were simultaneously measured in 16 patients with vasospastic angina and 13 control patients with nonischemic heart disease. RESULTS: None of these patients showed myocardial ischemia during sampling. The difference in transcardiac plasma levels of serotonin in patients with vasospastic angina was significantly higher than that in controls (1.48 +/- 1.08 ng/ml vs. 0.07 +/- 0.12 ng/ml, respectively, p < 0.001). Coronary sinus plasma norepinephrine levels in these two groups were almost the same (204.8 +/- 110.8 pg/ml vs. 190.4 +/- 131.6 pg/ml, respectively). The ratio of 6-keto-prostaglandin F1 alpha in the coronary sinus and the aorta was not different between the two groups (1.17 +/- 0.96 in patients with vasospastic angina vs. 1.15 +/- 0.68 in controls). CONCLUSIONS: These data suggest that platelet activation across the coronary bed should be ascribed to endothelial dysfunction. Lack of compensatory enhancement of prostacyclin production might be concerned with dysfunction of coronary endothelial cells in these patients.
BACKGROUND AND HYPOTHESIS: Mechanisms of heart failure in elderly hypertensive patients with hypertrophy have not been studied sufficiently. We hypothesized that impaired increment of coronary blood flow in response to increases in heart rate could be responsible for the occurrence or aggravation of heart failure. METHODS: To test this hypothesis, we measured coronary hemodynamics and lactate balance during basal conditions and atrial pacing in 21 elderly patients aged > or = 65 years (mean 74 +/- 6 years) without coronary arterial disease: 7 normotensive control patients (Group 1), 7 hypertensive hypertrophic patients without a history of congestive heart failure (Group 2), and 7 patients with such history (Group 3). Coronary sinus blood flow (CSBF) was measured in coronary sinus using a thermodilution catheter. RESULTS: During basal conditions, heart rate did not differ among the three groups (67 +/- 3 in Group 1, 65 +/- 11 in Group 2, and 63 +/- 6 beats/ in Group 3). CSBF was significantly higher in the two hypertrophic groups than in the control group, but CSBF normalized by left ventricular mass was significantly lower in both hypertrophic groups. External mechanical efficiency (EME) obtained as left ventricular work divided by myocardial oxygen consumption did not differ among groups during basal conditions (36 +/- 9% in Group 1, 35 +/- 8% in Group 2, and 29 +/- 9% in Group 3, NS). During atrial pacing to increase heart rate by 25 +/- 5% (lower) and 54 +/- 6% (higher), the increases in CSBF were markedly limited in both hypertrophic groups, and the response in Group 3 was more depressed than that in Group 2. EME did not change in the control group or in Group 2, but did decrease to 21 +/- 5% in Group 3 during the higher pacing rate (p < 0.01 vs. basal conditions). In this group, the relationship between EME and heart rate showed a significant negative correlation (r = -0.56, p = 0.02). Lactate balance in coronary sinus blood showed a tendency to production in Group 3 during the higher pacing rate, suggesting myocardial ischemia. CONCLUSION: These findings suggest that in hypertensive hypertrophic patients with a history of heart failure, the coronary circulation system is vulnerable to increasing heart rate. In medical treatment of elderly hypertensive patients, control of heart rate in addition to blood pressure control should be considered to minimize the occurrence or aggravation of heart failure.
We report the case of a 41-year-old man with a pericardial cyst treated by percutaneous aspiration and ethanol injection. He was referred to our hospital because of electrocardiographic abnormality. On admission, chest x-ray revealed a large pericardial cyst in the right cardiophrenic angle. The cyst was examined by echocardiography, computed tomography, and cytological analysis of aspiration fluid from the cyst. Ethanol sclerosis was applied for treatment of the cyst, which had continued to increase in size. There was no recurrence of the cyst 6 months after the treatment. Percutaneous ethanol sclerosis can be the first choice of treatment for pericardial cyst.
In rodents an intravenous administration of viable Cryptococcus (C.) neoformans cells frequently resulted in attachment of intravascular cryptococcal granulomas to inner walls of the large to medium-sized veins of various organs, including the lungs, liver and spleen. In order to elucidate the pathogenesis of granulomatous changes, the cells composing the intravascular granulomas were observed by electron microscopic peroxidase (PO) cytochemistry. The granuloma composing cells could be divided into the following four types according to the pattern of endogenous peroxidase activity: exudate macrophage (M phi, type I), PO-negative M phi (type II), resident M phi (type III) and other inflammatory cells (type IV). In the intravenous granulomas of the lung, the percentages of composed cells were 39.0% for type I, 57.9% for type II, 0% for type III and 3.1% for type IV. By contrast, in the interstitial granulomas in the lung, type III M phi s, possibly derived from alveolar M phi s, played a significant role in granuloma formation. This may indicate that the intravascular granuloma is almost composed of macrophages derived from monocytes rather than alveolar macrophages. The expression of ICAM-1 on endothelia of the pulmonary veins was examined by immunoelectron microscopy. An immunogold labeling index was significantly augmented on the surface of endothelia in response to intravenous challenge of C. neoformans. The intravascular granuloma demonstrates that the monocytes develop into the granuloma-composing macrophages and suppress the cryptococcal activities even in the peripheral blood resulting in an assistance of endothelial functions.
A case of ameloblastic fibro-odontoma in a 10-year-old Japanese male patient is presented. Bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were applied to investigate the cell kinetics of this lesion. The tumour proliferation activity was individually evaluated through the labelling index (LI) at the epithelial and mesenchymal components. The LI of BrdU was 0.9% in the epithelial and 2.1% in the mesenchymal component, while the LI of PCNA was 2.2% in the epithelial and 7.7% in the mesenchymal component. These immunohistochemical investigations suggest that the mesenchymal component was more proliferative than the epithelial component. Such an immunohistochemical investigation may be useful in evaluating the proliferative potential of odontogenic tumours.
PURPOSE: This study investigates the cytotoxic effect of photodynamic therapy using high-power laser irradiation on cancer cells. MATERIALS AND METHODS: High- or low-power irradiation from a pulsed Nd:YAG dye laser with or without a photosensitizer was administered to an NR-S1 carcinoma in the mouse dorsum. RESULTS: Photodynamic therapy with high-power laser irradiation yielded better results than conventional photodynamic therapy or hyperthermia with high-power laser irradiation. CONCLUSION: Photodynamic therapy with high-power laser irradiation is more effective because it generates both a hyperthermic and a photodynamic effect.
We report successful radical systematic surgery for an undifferentiated gallbladder carcinoma with metastasis to the mesocolonic lymph nodes. The patient, a 70-year-old woman, was admitted with abdominal fullness and appetite loss. Imaging modalities revealed a 10-cm tumor originating from the gallbladder and infiltrating both the liver and transverse colon. As multiple mesocolonic lymph node metastasis was confirmed on laparotomy, right hemicolectomy with systematic lymph node dissection (D3 resection) was performed, in addition to extended cholecystectomy with partial resection of segments 4, 5 and 6 of the liver and distal gastrectomy. Histologically, the tumor was diagnosed as an undifferentiated carcinoma, and metastases were indentified in the mesocolonic lymph nodes (17/50 nodes) but not in the peri-gallbladder lymph nodes (0/16 nodes). The patient has been recurrence-free for 4 years after the operation. This case illustrates that even if gallbladder cancer infiltrates into adjacent organs with regional lymph node metastasis, it is of value to perform radical surgery with systematic lymph node dissection for the involved organs.
A 48-year-old man with neurofibromatosis type 1 presented with chest pain, paroxysmal hypertension, tachycardia, and progressive respiratory insufficiency. Clinical investigation displayed calcified tumors in the anterior mediastinum and pararenal region. Histological examination at autopsy revealed composite tumors consisting of pheochromocytoma and malignant peripheral nerve sheath tumor (MPNST) at two sites: the left adrenal gland and the region surrounding the inferior vena cava, probably corresponding to the right adrenal gland. The MPNST component showed a varied histological appearance, including hyalinized bands with polygonal cells, a cartilaginous and myxoid stroma, a hemangiopericytomatous architecture, and a fibrosarcomatous structure, which suggested osteosarcoma, chondrosarcoma, angiosarcoma, and fibrosarcoma, respectively. In addition, based on the ultrastructural findings, the gastrointestinal tract was involved with mesenchymal tumors showing neurogenic differentiation. These lesions suggest the divergent cellular differentiation of neural crest-derived cells to mesenchymal elements as well as neuroectodermal neoplasms.
OBJECTIVE: A prospective study was performed to analyze whether the Glasgow Coma Scale (GCS) was useful in predicting the outcome after early surgical intervention for aneurysmal subarachnoid hemorrhage (SAH). METHODS: In a consecutive series of 765 patients who underwent surgery for aneurysms within 7 days after SAH, the level of consciousness was assessed by the GCS just before surgery and the outcome was graded by the Glasgow Outcome Scale 6 months after surgery. RESULTS: The patient distribution in accordance with the GCS sum scores in descending order from 15 to 3 was as follows: 334, 140, 58, 27, 20, 26, 27, 19, 26, 17, 20, 27, and 24 patients, respectively. In general, the higher the preoperative GCS score was, the better the surgical outcome was. The overall surgical result was significantly correlated with the preoperative GCS score (rs = 0.615, P < 0.001). With respect to the levels that distinguish the outcome along the GCS axis, a significant difference in the outcome was observed only between the GCS scores of 15 and 14 (P < 0.001, Wilcoxon test). CONCLUSION: The GCS proved useful in the preoperative evaluation of patients with SAH, in terms of outcome prediction. It is suggested that the SAH scale proposed by the World Federation of Neurosurgical Societies be reexamined, because differences in outcomes were not clear between the GCS scores of 13 and 12 or between those of 7 and 6, in which Grades III and IV and Grades IV and V are differentiated in the scale, respectively.