The significance of PrPSc detection for the diagnosis of insidious scrapie.
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Animals↗
Biomedical subjects
M Horiuchi
Publications and source records attributed to M Horiuchi.
Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system.
We investigated the reabsorptional system for carnitine in the kidney to elucidate the mechanism of carnitine deficiency in juvenile visceral steatosis (jvs) mice. Jvs mice had a higher rate of carnitine excretion at 10 days after birth than the controls, in spite of having no pathological acylcarnitine excretion in the urine. In an experiment to assay the uptake of carnitine using kidney slices, homozygous mutants showed significantly lower rates of Na-dependent carnitine uptake than controls. Heterozygous mice showed values of transport activity intermediate between homozygous mutants and homozygous controls. Scatchard plots (transport activity versus transport activity/carnitine concentration) revealed that the homozygous mutants had a defect in the high affinity site (Km = 58 microM) in the Na-dependent carnitine transport system in the kidney. These results indicate that the primary defect of jvs mice is most probably related to the system for reabsorption of carnitine in the kidney.
Absorption↗
Detection of PrPSc in sheep at the preclinical stage of scrapie and its significance for diagnosis of insidious infection.
A field sheep insidiously infected with natural scrapie was diagnosed at the preclinical stage through detection of the core fragment of PrpSc (PrPcore) in peripheral lymph nodes by the biopsy method. Three out of 32 euthanized healthy sheep were found positive for PrPcore in the spleen and lymph nodes. Mice that were inoculated with spleen homogenate of one of these sheep showed clinical signs of scrapie and were positive for PrPcore in their brain samples. These results suggest that the detection of PrPcore is significant for diagnosis in the preclinical phase of scrapie.
Animals↗
Mapping of determinants of the host range for canine cells in the genome of canine parvovirus using canine parvovirus/mink enteritis virus chimeric viruses.
Feline panleukopenia virus (FPLV), mink enteritis virus (MEV) and canine parvovirus (CPV) are more than 98% similar in DNA and predicted amino acid sequences, but they show different host-cell specificities; CPV is able to replicate in canine cells in culture, whereas FPLV and MEV cannot or replicate only to a low titre. To map the genomic region responsible for the host range of CPV in vitro, CPV/MEV chimeric viruses were generated by transfecting infectious CPV/MEV chimeric plasmids into a cultured feline kidney cell line, and their host cell ranges were analysed. The 60 to 91 map units (m.u.) region of the CPV genome, which contains a part of the capsid protein (VP) gene encoding from amino acid 91 (in the VP2 sequence) to the carboxy terminus of VP protein, was required to impart the ability to replicate in canine cells to MEV, although the chimeric virus containing the 60 to 91 m.u. region of the CPV genome in the MEV background did not replicate in canine cells as efficiently as did CPV derived from the infectious plasmid of CPV. Not only the VP gene, but also a part of the NS gene of CPV were considered to participate in the full expression of the ability to replicate in canine cells. Within the 60 to 91 m.u. region, five of nine amino acid changes between MEV-Abashiri and CPV-Y1 were thought to be phylogenetically CPV-common; however, a recombinant virus containing all five amino acid changes of CPV in the MEV background replicated minimally in canine cells.
Animals↗
Survey of natural scrapie in Japan: analysis of RFLP types of the PrP gene and detection of PrPSc mainly in Suffolk sheep.
We examined the brains, spleens and/or lymph nodes of 197 mainly suffolk sheep collected from Hokkaido, and the Tohoku, Kanto and Chubu districts to detect PrPSc and thus to estimate scrapie contamination in Japan. Sixteen sheep in Hokkaido and 2 sheep in other districts that were introduced from Hokkaido were positive for PrPSc. By comparison of the frequencies of the restriction fragment length polymorphism (RFLP) types of these 18 scrapie sheep with 128 healthy sheep, we confirmed the association of specific RFLP types of the PrP gene with natural scrapie. The frequency of RFLP type I in scrapie sheep was significantly higher than that in healthy sheep and those of other types in scrapie sheep. In contrast, the frequencies of type II and VI in healthy sheep were higher than those in scrapie sheep. Therefore, type I sheep seemed to be susceptible but type II and VI sheep seemed to be resistant to natural scrapie in Suffolk sheep in Japan. Furthermore, we investigated the distribution of the RFLP types of the PrP gene in 161 sheep in Japan to learn about the genetic background of the susceptibility to scrapie. There were variations in the distribution of the RFLP types in each district.
Animals↗
Characterization of monoclonal antibodies against sporadic bovine leukosis cell lines.
We report here distributions of antigens expressed on sporadic bovine leukosis (SBL) cells by a total of 38 monoclonal antibodies (mAbs) directed against three different types of SBL-cell lines, BLT2 (thymic type), BTL-PC3 (calf type) and BLS1 (skin type). Most mAbs had high reactivities with some bovine lymphoma cell lines and less reactivity with normal lymphocytes except for some peripheral blood mononuclear cells (PBM) in cattle and certain other species. They were more reactive with cultured T-cell line BTL-PC3 and B-cell lines, BL312 and KU-1, than naturally occurring lymphoid tumor cells. Among the 38 mAbs, 27 was determined the molecular weights of their recognized antigens in Western blot analyses. A mAb C419 had high reactivity with lymphoma cell lines but no reactivity with normal lymphocytes, indicating that it recognizes tumor-associated antigens of SBL.
Animals↗
Monoclonal antibody S37 induces apoptosis in bovine T lymphoma cells.
Influences of 38 monoclonal antibodies (mAbs) on the growth of bovine T lymphoma cells (BTL-27) were examined. One of them, S37, inhibited the cell growth strikingly when it was added to the cultures. S37-treated cells showed DNA fragmentation containing approximately 200-base pair multiple patterns and chromatin condensation. This evidence suggested that mAb S37 induced apoptosis in BTL-27 cells.
Animals↗
Effect of an angiotensin II receptor antagonist, TCV-116, on rat carotid artery neointimal formation after balloon injury.
Arterial injury by a balloon catheter produces marked smooth muscle cell proliferation and the participation of angiotensin II in this response has been suggested. In this study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on neointimal formation after rat carotid artery balloon injury. Oral administration of TCV-116 at doses of 1, 5 or 10 mg/kg/day significantly reduced the cross-sectional intimal area by 30%, 46% and 54%, respectively, and reduced the ratio of the intimal to medial cross-sectional areas by 23%, 41% and 50%. An angiotensin-converting enzyme inhibitor, lisinopril, had an effect similar to that of TCV-116. The effect of both drugs was significantly correlated with the reduction of both blood pressure and cardiac hypertrophy. We conclude that TCV-116 can prevent neointimal formation after balloon injury as well as reducing blood pressure and preventing cardiac hypertrophy.
Angiotensin Receptor Antagonists↗
[Current status of clinical trials on pre- and postoperative chemotherapy for head and neck cancer].
The purpose of this paper is to discuss the current status and issues of clinical trials in pre- and post-operative chemotherapy for head and neck cancer, focusing on 1) neo-adjuvant chemotherapy, 2) concurrent radiotherapy and chemotherapy, and 3) adjuvant chemotherapy. Although neo-adjuvant chemotherapy did not increase survival, it produced a higher rate of organ preservation in some sites such as the larynx and maxilla. Concurrent radiotherapy and chemotherapy is the most promising primary chemotherapy approach to prolong survival of patients with locally advanced resectable and unresectable disease. It is the only systemic approach consistently shown to improve local-regional control and survival in randomized trials. No survival benefit is evident in trials of adjuvant chemotherapy, the third major treatment category, but some randomized trials produced a significant reduction in distant relapse rate. Based on the results obtained so far, future clinical trials should be continued to search for more effective programs in the systemic control of advanced head and neck cancer.
Antineoplastic Combined Chemotherapy Protocols↗
[A prospective randomized trial of adjuvant chemotherapy with UFT for head and neck carcinoma. Head and Neck UFT Study Group].
A prospective randomized trial was performed in 67 institutions for the purpose to evaluate the efficacy of adjuvant chemotherapy after radical treatment of head and neck carcinoma. A comparison was made between the following two groups; one-year oral administration of UFT, 300 mg/day, after radical treatment (UFT group); and a non-treatment group. Patients were classified under the following three categories; 1) stage II-IV, receiving radical surgery; 2) stage II, receiving radical radiotherapy; and 3) nasopharyngeal cancer. The numbers of cases were 424, 111 and 25, respectively, and they were randomized into two groups. The numbers of eligible cases were 398, 105 and 25, respectively. Statistical analysis was performed in the cases receiving radical surgery and in those receiving radical radiotherapy. As the results, in cases receiving radical surgery no significant difference was observed in 3-year survival rates (77.9% for UFT group vs 72.9% for non-treatment group) or 3-year relapse-free rates (73.4% for UFT group vs 66.2% for non-treatment group) between the two groups. However, the distant relapse rate was significantly lower in the UFT group than in the non-treatment group (7.9% vs 14.6%; p = 0.034). In the cases receiving radical radiotherapy, no significant differences was observed in either 3-year survival rates or 3-year relapse-free rates. Thus it was suggested that UFT maintenance therapy might suppress the distant metastasis after radical surgery. We considered a further confirmative trial for patients at high risk of distant metastasis after radical surgery to be advisable.
Administration, Oral↗
[Role of neoadjuvant chemotherapy for management of resectable head and neck cancer].
This review covers the clinical significance of neoadjuvant chemotherapy as initial treatment for squamous cell carcinoma of the head and neck, especially focusing on advanced but resectable disease. The rates of complete response (CR) after chemotherapy depended on the regimens and varied from 15% to 35%. Combined use with DDP/5-FU was considered as a most effective regimen. In addition of leucovorin to DDP/5-FU regimen, CR rate increased more than 50%. A randomized clinical trial has not shown any advantage for survival in advanced head and neck cancer. Recent reports have shown that distant metastases diminished in patients treated with neoadjuvant chemotherapy. When primary lesions disappeared completely after neoadjuvant chemotherapy, sequential use of radiotherapy can make the long term relapse-free in those lesions. This effort may lead to a modality of cancer treatment without surgery, so organ preservation will be possible.
Antineoplastic Combined Chemotherapy Protocols↗
Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2 receptor.
A cDNA clone encoding the mouse angiotensin receptor subtype 2 (AT2 receptor) was isolated from a mouse fetal cDNA library. Mouse AT2 receptor full-length cDNA contains a 1089-base-pair open reading frame which encodes a protein of 363 amino acid residues. Hydropathy analysis reveals seven putative transmembrane domains. Specific binding of [125I]CGP42112A was demonstrated in membranes of COS-7 cells transfected with the cDNA. Scatchard analysis and ligand displacement profile were typical of the AT2 receptor. Northern blot and reverse transcription-polymerase chain reaction analyses demonstrated that AT2 receptor mRNA was expressed abundantly in fetus and in a lesser amount in adult brain. Analysis of the mouse AT2 receptor gene reveals that the mouse AT2 receptor locus exists as a single copy in the genome, and that the gene does not contain introns in the coding region.
Angiotensin II↗
Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors.
Angiotensin II acts on at least two distinct receptor subtypes (AT1 and AT2). Most known effects of angiotensin II in adult tissues are attributable to the AT1 receptor. The function of AT2 receptor is undefined, but its abundant expressions in fetal tissues, immature brain, skin wound, and atretic ovarian follicles suggest a role in growth and development. Previous studies suggested that AT2 receptor may not be G protein-coupled. Here, from a rat fetus expression library, we cloned a cDNA encoding a unique 363-amino acid protein with pharmacological specificity, tissue distribution, and developmental pattern of the AT2 receptor. It is 34% identical in sequence to the AT1 receptor, sharing a seven-transmembrane domain topology. A review of prior data on other receptors suggests that this receptor may belong to a unique class of seven-transmembrane receptors (including somatostatin SSTR1, dopamine D3, and frizzled protein Fz) for which G protein coupling has not been demonstrated. All members of this class exhibit fetal and developmental and/or neuronal-specific expression. A conserved motif in the third intracellular loop, distinguishing this class from "classical" G protein-coupled receptors, may mediate novel intracellular effects.
Amino Acid Sequence↗
Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency.
We have reported the clinical and biochemical findings in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency. This paper is the first report about cardiomyopathy in jvs mice. Adult jvs mice (at the age of 2-3 months) show cardiac hypertrophy which is caused by enlargement of the cardiac muscle cell associated with increases of non-collagen protein and DNA content. Carnitine administration (2 mg/head, twice a day, from 1 month of age) significantly suppresses the cardiac hypertrophy, showing that carnitine deficiency plays an important role in the development of the cardiac hypertrophy. The discovery of cardiac hypertrophy in carnitine-deficient jvs mice will lead to clarification of the pathophysiology of cardiomyopathy in systemic carnitine deficiency in human beings.
Animals↗
Carbamoylphosphate synthetase deficiency in an adult: deterioration due to administration of valproic acid.
A 24-year-old patient had symptoms of lethargy, convulsions and hyperammonaemia during valproic acid therapy. Cessation of valproic acid treatment brought about an improvement both of the symptoms and of the hyperammonaemia. However, enzymatic analysis after the cessation of valproic acid therapy revealed a complete absence of carbamoylphosphate synthetase (CPS) activity in liver biopsy. A unique polypeptide band, corresponding to the control CPS protein in molecular weight ('CPS-like' protein), was found in normal amounts in the patient's liver on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. This CPS-like protein seemed to be more labile than the control, because the polypeptide band became faint after freeze-thawing. Intravenous administration of L-alanine resulted in a significant increase of serum urea and a transient increase of blood ammonia concentrations. These results strongly suggest that the patient has a labile CPS protein with no activity in vitro but some activity in vivo. We consider that valproic acid may have disrupted some metabolic adaptation by reducing N-acetylglutamate in the liver, which in combination with CPS deficiency induced severe hyperammonaemia.
Adult↗
Construction of an infectious DNA clone of the Y1 strain of canine parvovirus and characterization of the virus derived from the clone.
We have cloned genome fragments of canine parvovirus strain Y1 from replicative-form DNA and double-stranded DNA synthesized from virion DNA in vitro, and constructed a recombinant plasmid containing a full-length Y1 genome (pCPVY 1). When this recombinant plasmid was transfected into cell cultures, an infectious virus could be recovered. To characterize this pCPVY 1-derived virus, its biological properties were compared with those of the parental strain. No difference was observed between them in antigen expression, viral DNA replication, hemagglutination ability, and virus multiplication, indicating that the virus derived from the infectious plasmid inherited the biological properties of the authentic Y1 strain. Therefore, this recombinant plasmid appears to be useful for reverse genetics of canine parvovirus.
Animals↗
Physical dependence on morphine induced in dogs via the use of miniosmotic pumps.
The difference between the development of physical dependence on morphine administered via Alzet miniosmotic pumps as well as syringe injection (twice a day) at fixed times was examined in conscious dogs. Physical dependence was quantified by polygraphically measuring naloxone-precipitated withdrawal signs on the day 8 after the subcutaneous implantation of miniosmotic pumps which supplied morphine at 1-5 mg/kg/day. Morphine plasma levels were maintained at 19-25 and 41-47 ng/mL during infusions of morphine at doses of 2.5 and 5 mg/kg/day, respectively. Morphine withdrawal was characterized by hyperactivity, biting, digging, tremors, nausea, hyperthermia, and increased wakefulness, and by electroencephalographic (EEG) activation in the amygdala and hippocampus, followed by dissociation of the EEG in the cortex (fast wave) from that in the limbic (slow wave) system, increased heart rates, and raised blood pressure. These morphine withdrawal signs seemed to be more severe than those exhibited in animals that had received syringe injections of morphine at the same doses. These results suggest that the use of miniosmotic pumps in dogs may be a very convenient and useful method for both evaluating drug dependence and studying its mechanisms.
Animals↗
Characterization of renal aldosterone receptors in genetically hypertensive rats.
To investigate the aldosterone responsiveness of genetically hypertensive rats, we compared characteristics of renal cytosolic aldosterone receptors from the M strain of stroke-prone, spontaneously hypertensive rats (M-SHRSP) with normotensive Wistar-Kyoto rats (WKY). In M-SHRSP, blood pressure was elevated significantly at 6 wk of age, when their plasma aldosterone concentrations were similar to those in WKY. Decreases in urine volume and sodium excretion were also observed in M-SHRSP. At 10 wk of age, M-SHRSP plasma aldosterone concentrations became significantly higher than those in WKY. On the other hand, the concentration of renal cytosolic aldosterone receptors (type I, aldosterone specific) had already increased at 6 wk of age in M-SHRSP, with no difference in affinity, and levels remained increased thereafter. There were no significant differences in molecular weights or ionic charges of either "activated" or "non-activated" aldosterone-receptor complexes between M-SHRSP and WKY, indicating that the molecular properties were similar in both groups. These results suggest that the increased concentration of aldosterone receptors in the kidneys of M-SHRSP might increase their aldosterone responsiveness and contribute to the development of high blood pressure in these animals.
Animals↗