[The study on usefulness of direct intrafollicular insemination].
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Adult↗
Biomedical subjects
M Sagara
Publications and source records attributed to M Sagara.
Neuroectodermal tumors expressing c-, L-, and N-myc in transgenic mice that carry the E1A/E1B gene of human adenovirus type 12.
Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transformation of primary cultured rodent cells. In order to investigate in vivo action of the E1 region, we established a line of transgenic mice carrying the oncogenic E1A and E1B genes of human adenovirus type 12 under control of the human angiotensinogen promoter. Histopathological analyses indicated that transgenic mice heritably develop neuroectodermal tumors arising from the pelvic region with varying degrees of incidence. The transgene was expressed in the neuroectodermal tumors as well as in TNT-1 cells, a cell line established from the tumors, where the human angiotensinogen promoter was constitutively active. The high level expression of c-, L-, and N-myc without gene amplification was notable in the original tumors and TNT-1 cells, but not in another tissue examined. The co-expression of the three sets of myc family genes in both the original tumors and the established cell line provided the possibility that the target cells for transformation may belong to a specific cell type that expresses all these oncogenes during development.
3T3 Cells↗
Tissue-specific trans-activation of renin gene by targeted expression of adenovirus E1A in transgenic mice.
We generated two transgenic mice carrying the adenovirus type 12 E1 region genes under control of the human renin promoter, in which the E1A and E1B genes were expressed predominantly in the kidney. Interestingly, renal transcription of the gene for mouse renin was shown to be elevated at 28 and 40 folds as compared in those of control animals, but histone mRNA levels were unchanged. Although the transfected mouse renin promoter was promiscuously trans-activated by E1A in HeLa cells where the endogenous renin gene was silent, the transgenic studies suggested that a cellular factor(s), in addition to E1A, was required for the tissue-specific renin gene activation. These findings provide the in vivo evidence that E1A could trans-activate cellular gene transcription in a tissue-specific manner.
Adenovirus E1A Proteins↗
Expression of desmoglein I in squamous cell carcinoma of the esophagus.
Desmoglein I (DGI) is major component of the desmosomal membrane core that plays an important role in epithelial cell adhesion. The aim of this study was to explore the correlation between the expression of DGI and the clinicopathological findings of esophageal cancer. DGI expression was immunohistochemically examined using an anti-DGI monoclonal antibody in 139 patients with squamous cell carcinoma of the esophagus. Normal squamous epithelial cells strongly expressed DGI at their cell-cell boundaries. According to the intensity and pattern of DGI expression, the cancerous tissues were divided into three groups: DGI (++), DGI (+), and DGI (-). Of the 139 tumors, 35 (25%) were DGI (++), 65 (47%) were DGI (+), and 39 (28%) were DGI (-). A good inverse correlation between DGI expression and tumor invasion, lymph node metastasis, lymphatic invasion, and vessel invasion was observed. These results indicate that DGI expression may be a significant factor for invasion, metastasis, and prognosis of human esophageal cancer.
Adult↗
Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats.
We previously reported that the in vivo production of the tumor necrosis factor alpha (TNF) was significantly enhanced after the onset of diabetes in spontaneous type 1 and 2 diabetic animals. In this report we confirmed the enhanced production of TNF in streptozotocin (STZ)-induced diabetes and then attempted to suppress the enhanced TNF production with N-acetylcysteine (NAC), a precursor of glutathione synthesis. The lipopolysaccharide-induced serum TNF activities were significantly enhanced in STZ-induced diabetic rats (6-18 weeks of age) compared with those of nondiabetic rats throughout the 12-week experiment. A single, oral administration of NAC (200 or 1000 mg/kg body wt) significantly suppressed the enhanced TNF production in the diabetic rats compared with that in untreated rats in a dose-dependent manner. On the other hand, in the long-term (6 or 12 weeks) administrations, smaller doses of NAC (50 or 200 mg/kg/day) also significantly inhibited the enhanced production of TNF regardless of the dose of NAC. NAC administration, however, did not suppress the TNF production of nondiabetic rats. The long-term NAC administration affected neither body weight nor levels of serum glucose, fructosamine, albumin, and triglyceride. These results show that NAC administration significantly suppressed the enhanced TNF production in diabetic rats and indicate that NAC might be useful in preventing TNF-mediated pathological conditions in diabetes.
Acetylcysteine↗
[Drug distribution and antitumor effect of bleomycin incorporated in poly DL-lactic acid in rats].
Two bleomycin (BLM)-containing agents (BLM-PLA, BLM-SOL) were prepared, and the drug distribution and antitumor effect were studied. BLM-PLA is an agent in which BLM is incorporated into biodegradable low-molecular-weight polylactic acid, and BLM-SOL is an aqueous solution of BLM. BLM-PLA or BLM-SOL was subcutaneously administered in the back of rats. When BLM-PLA was implanted, high BLM activity of the connective tissues near the implants was maintained for 2 weeks. On the other hand, BLM activity was very low when BLM-SOL was administered. The effects of BLM-PLA, BLM-SOL and nontreatment on tumor growth and survival time were compared using subcutaneous tumor of Yoshida sarcoma in 21 rats each. The survivors and mean survival time in BLM-PLA group, BLM-SOL group and nontreatment group was 14 and 44.6 days, 5 and 23.7 days, and 0 and 11.3 days, respectively. BLM-PLA was superior to BLM-SOL in both drug distribution and antitumor effect, and consequently BLM-PLA could be a useful tool in loco-regional chemotherapy.
Animals↗
Prevention of type I diabetes with lymphotoxin in BB rats.
We previously reported that nonspecific immunomodulations with a streptococcal preparation (OK-432), an inducer of tumor necrosis factor (TNF), or with recombinant TNF prevented development of insulin-dependent diabetes mellitus (IDDM) in animal models (NOD mice and BB rats). Recently we have further reported that lymphotoxin (LT), a cytokine with functional and structural characteristics similar to those of TNF, also protected NOD mice from diabetes. In this study, we have extended our observation on the LT to BB rats. Male and female BB/Wor rats were treated intraperitoneally with recombinant human LT three times a week from 4 to 11 weeks of age. The cumulative incidence of diabetes by 14 weeks of age was 24/30 (80.0%) in nontreated control rats, whereas it was 10/26 (38.5% vs control, P < 0.01) and 4/29 (13.8% vs control, P < 0.0001) in the rats treated with 1 x 10(3) and 1 x 10(4) of LT, respectively. There was no significant difference in nonfasting blood glucose levels and body weights between nontreated control and LT-treated rats, which were nondiabetic. In the LT-treated rats, intensity of insulitis was significantly reduced in comparison with the nontreated rats. Concanavalin A-stimulated TNF/LT productivity of spleen cells was significantly lower in BB/Wor and BB/Sendai rats than in Wistar rats or other normal rat strains. On the other hand, there was no difference between BB/Sendai and Wistar rats in the in vivo TNF/LT productivity induced with LPS or with IFN-gamma plus LPS, and the TNF/LT productivity of these rats was lower on stimulation with LPS alone, but higher with IFN-gamma plus LPS than the other normal rats. These results indicate that treatment with LT, as well as TNF, modulated autoimmunity and prevented development of IDDM in BB/Wor rats which may be low producers of TNF/LT.
Animals↗
The effects of early occlusal loading on one-stage titanium alloy implants in beagle dogs: a pilot study.
The initial stages of bone healing with titanium alloy implants were compared clinically and histologically in three groups of beagle dogs: unloaded one-stage (group 1), loaded one-stage (group 2), and unloaded two-stage (group 3). No implant mobility was reported in any of the three groups. For the most part direct bone contact was achieved, but there was a significant difference in the histologic results of the interface among the animals in all three groups. Significant crestal bone loss was evident in group 2, which showed poor bone apposition to the bottom of the threads in the upper portion of the implant. New bone growth to these same areas of the threads was seen in the animals in groups 1 and 3, with the ratio of direct bone contact significantly higher for those in group 3. These differences could be attributed to the effect of early occlusal loading on the implant during initial bone healing.
Alveolar Bone Loss↗
Biochemical characteristics of human renin expressed in transgenic mice.
1. Biochemical properties of human renin expressed in transgenic mice (hRN8-12 mice) carrying the human renin gene (Fukamizu et al. Biochem Biophys Res Commun 1989; 165: 826-32) were examined. The optimum pH of the enzymic activity against human angiotensinogen was 5.5 for both plasma and renal human renin in the hRN8-12 mice. Plasma concentrations of human active and inactive renin in the plasma of hRN8-12 mice were 16.7 +/- 2.8 and 79.9 +/- 14.0 pmol of angiotensin Ih-1 ml-1, respectively, thereby indicating that the predominant form of plasma human renin is the inactive form, as is the case in humans. 2. The molecular masses of plasma human active and inactive renin and renal human active renin in the hRN8-12 mice were estimated to be 46 kDa, 48 kDa and 44 kDa, respectively, as determined by h.p.l.c. on G3,000SW. 3. Human renin in the hRN8-12 mouse kidney was bound to a concanavalin A-Sepharose column, and was eluted with alpha-methyl-D-mannoside, showing that this renin is glycosylated, as is native human renin. 4. Low sodium treatment of the hRN8-12 mice for 2 weeks increased plasma human active renin, renal human renin and renal human renin mRNA levels by 2.6-, 3.8- and 2.8-fold, respectively. Thus, the biosynthesis and secretion of renal human renin in these transgenic mice are obviously stimulated by sodium depletion.
Animals↗
Prevention of autoimmune diabetes with lymphotoxin in NOD mice.
We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats. In this study, we examined the effect of LT, which is structurally and functionally related to TNF, on NOD mice with diabetes. The cumulative incidence of diabetes at 30 wk of age was 22 of 40 (55%) in nontreated female NOD mice and was 4 of 8 (50%; NS), 3 of 29 (10%; P < 0.001), and 0 of 8 (0%; P < 0.001) in female mice treated three times a week from 4 to 30 wk of age with 5, 50, or 500 U of recombinant hLT, respectively. Intensity of insulitis was slightly reduced in the long-term LT-treated mice. LT productivity by ConA-stimulated spleen cells was examined in vitro. Although no significant difference was found between NOD mice and the other mouse strains, female NOD mice were slightly but significantly (P < 0.01) lower producers of LT immunoreactivity than male NOD mice, the diabetes incidence of which is lower than that of females. The SMLR as a marker of normal immune response, which was reported to be impaired in autoimmune animals including NOD mice, was significantly lower in female than male NOD mice. However, the low SMLR in female NOD mice was significantly increased by the administration of LT, and the increase was mediated by the responder cells of the LT-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[A basic study on usefulness of bleomycin incorporated in poly DL-lactic acid].
Poly DL-lactic acid (PLA) is one of the biodegradable polymers. Bleomycin (BLM) incorporated into small cylinders of PLA blends was prepared as a new dosage (BLM-PLA). When BLM-PLA was preserved in saline, the dissolution rate of BLM from BLM-PLA was 49.2% after 7 days, 85.2% after 14 days and 99.7% after 21 days, respectively. BLM-PLA was implanted subcutaneously into the back of 36 rats. On days 3, 7, 14, 21, 28 and 35, the connective tissues near the implants, lymph node, lung, liver and kidney were removed and BLM activity was measured. The BLM concentration was maintained at a high level in the connective tissues until 14 days, and in the lymph node between 21 and 28 days. On the other hand, the BLM level was low in the lung, liver and kidney. Consequently, it was suggested that PLA is useful as a carrier for drug delivery system and that administration of BLM-PLA is an effective anti-cancer modality, especially in local chemotherapy.
Animals↗
[Hypercapnea during facial surgery under local anesthesia].
We examined the ventilation of patients whose faces were draped during facial surgery under local anesthesia. Ten patients who underwent eye surgery received hydroxyzine 25 mg and pentazocine 15 mg i.m. before local anesthesia. Arterial blood samples and end-tidal respiratory gases from nasal cannulae were collected at the following selected times: before draping their faces, 10 min, 30 min, 60 min after draping, and after the drapes were removed. Both arterial carbon dioxide tension (42 +/- 1 mmHg before draping and 46 +/- 1 mmHg at 10 min) and end-tidal carbon dioxide tension (33 +/- 2 mmHg before draping and 36 +/- 1 mmHg at 10 min) were elevated significantly after their faces were draped. Hypercapnea was completely eliminated by suctioning the expired gases. It is concluded that hypercapnea is inevitable during face or neck surgery under local anesthesia, and that the expired gases should be monitored and removed.
Adult↗
Increased in vivo production of tumor necrosis factor after development of diabetes in nontreated, long-term diabetic BB rats.
We have recently reported that chronic and systemic administration of tumor necrosis factor alpha (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM). During these experiments, we unexpectedly found that in vivo production of TNF stimulated by a single injection of lipopolysaccharide was enhanced approximately 10 times in the long-term diabetic BB rats (P less than 0.0001), whose mean duration of diabetes with more than 16.8 mM (300 mg/dl) of nonfasting blood glucose level was 26.2 +/- 2.1 days, as compared to that in the rats of nondiabetes and in the rats at the onset of diabetes, whose mean duration of diabetes was 1.4 +/- 0.6 days. The long-term diabetic, but not short-term-diabetic, rats were also associated with increased levels of serum fructosamine/albumin (P less than 0.01) and triglyceride (P less than 0.01) and with a decreased level of serum albumin (P less than 0.01). The in vivo TNF productivity in the diabetic rats, including the short-term- and long-term-diabetic rats, was correlated positively with the level of fructosamine/albumin (P less than 0.05) and negatively with the level of serum albumin (P less than 0.05), but not with levels of blood glucose. None of these correlations were observed in nondiabetic rats. The increased LPS-induced serum TNF activity in the long-term diabetic state was observed not only in BB rats but also in NOD mice and GK rats, a model of non-IDDM, irrespective of sexes and ages, indicating that the enhancement of in vivo TNF production was a result of long-term diabetes. These findings indicate that some factor(s) associated with the long-term-diabetic state may prime macrophages in vivo to produce TNF. Further study is needed to reveal a mechanism of the enhanced TNF production and its possible relevance to various abnormalities associated with the chronic hyperglycemic state.
Age Factors↗
Structure and expression of the mouse angiotensinogen gene.
Angiotensinogen is a precursor of the multifunctional octapeptide hormone, angiotensin II. We have isolated the overlapping clones containing angiotensinogen gene locus from C57BL/6 mouse genomic DNA library and analyzed them by restriction enzyme mapping. The gene exhibited a structural organization similar to those of the human, rat and balb/c mouse angiotensinogen genes. Using a genomic DNA fragment of the mouse angiotensinogen gene as a probe, we have investigated the tissue distribution of angiotensinogen messenger RNA (mRNA) in C57BL/6 mouse. The angiotensinogen mRNA was highest in the liver and detectable in such tissues as brain, kidney, submandibular gland, ovary and heart. However, it was undetectable in lung and spleen under the condition used. Optimal alignments of the 5'-flanking regions among the human, rat and mouse angiotensinogen genes disclosed several deletions in the mouse sequence. To assay the promoter activity, the 5'-flanking region of the mouse angiotensinogen gene was ligated to the bacterial chloramphenicol acetyltransferase (CAT) gene, then transfected into different cultured cells. The angiotensinogen gene sequences elicited preferential expression of CAT activity when introduced into HepG2 cells derived from liver and 293 cells from kidney but not in HeLa cells from uterus, suggesting the presence of a cell type-specific promoter within the sequences. These findings on the structure and expression of the mouse angiotensinogen gene should prove useful in studying the function and control of the angiotensin.
Angiotensinogen↗
Regulation of human renin and angiotensinogen genes.
We have constructed pUCSV0cat with low background of chloramphenicol acetyltransferase (CAT) activity and pUCSV3cat (positive control), both containing a SV40 polyadenylation signal 5' to the CAT-coding gene and to the SV40 promoter, respectively. Using this modified pUCSV0cat, we found that human embryonic 293 cells have the ability to activate the promoter of the human renin gene. In addition, we identified the cis-acting sequences responsible for cell-specific expression of the human angiotensinogen gene in its 5'-flanking region.
Angiotensinogen↗
Specificity of antibodies to type II collagen in rheumatoid arthritis.
To reassess the role of autoantibodies to type II collagen in the pathogenesis of diseases, we studied antibodies from patients with rheumatoid arthritis (RA) and from patients with relapsing polychondritis for species specificity and collagen type specificity, using an improved enzyme-linked immunosorbent assay. Antibodies were found in the sera of 15% of the RA patients and 50% of the relapsing polychondritis patients, as well as in the cartilage of 69% of the RA patients examined. Reaction with both homologous and heterologous type II collagens was common. Analysis of 19 selected RA sera revealed that autoantibodies were generally associated with specific antibodies to some species of heterologous type II collagen. In contrast, antibodies found in 4% of the non-RA controls were specific for either bovine or chick type II collagen. These findings indicate that autoantibody formation in RA and relapsing polychondritis may occur as a result of an immune response to heterologous type II collagen. However, since RA and relapsing polychondritis patient sera differed in their reactivity with the cyanogen bromide-digested peptides, it is possible that the clinical manifestation of collagen autoimmunity might be influenced by the epitope specificity of the antibodies.
Adult↗
Clinical value of magnetic resonance imaging for cervical myelopathy.
The magnetic resonance imaging (MRI) findings in 115 cases of cervical myelopathy, 121 cases of cervical radiculopathy, and 64 cases of neck pain with no neurologic deficit were prospectively studied to investigate the clinical value of MRI for cervical myelopathy. The MRI findings in the T1-weighted sagittal projection were classified into four groups according to the degree of the compressed deformities of the cervical cord. The degree of compression of the cervical cord on MRI findings showed a significant correlation with the severity of myelopathy, the anteroposterior diameter of the spinal column, and the degree of compression of the dural tube in the myelograms (P less than 0.01). Fifty-one patients of cervical myelopathy had undergone both preoperative and postoperative MRI. Of these, the spinal canal of 47 patients that was well decompressed was recognized according to plain computed tomography (CT). However, 24 (51%) of these 47 patients showed on MRI a deformity in the spinal cord amounting to cord atrophy. The correlation between the clinical function of the spinal cord and the recovery of the cord deformity on MRI at the operative levels was accurately investigated in 34 patients who had no cord deformities in the adjacent intervertebral levels. Twenty patients with cord atrophy had slightly poor clinical results, although no significant difference was found between these 20 and 14 patients with recovery in the cord deformities. From these results, it was evident that T1-weighted MRI is useful in the accurate diagnosis of compression myelopathy, in accurately deciding the level of the disease focus, and in the accurate assessment of the surgical results.
Cervical Vertebrae↗
[A study on mandibular incisal point movement of TM disorder patients].
In order to establish diagnostic and treatment system for temporomandibular (TM) disorder patients, data were collected on mandibular border and tapping movements at incisive point and compared with those from the subjects without any TM disorders. Significant differences on the ratio of left and right sides of maximum lateral deviation, maximum opening amount and length of pathway of lateral border movement were clearly obtained, the values of maximum speed and acceleration of closing phase in tapping movement obtained from TM disorder patients were also different significantly from those in the control subjects. These findings suggests that those measured indices in this study would be useful for diagnosis of TM disorders.
Dental Occlusion↗