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Biomedical subjects

J Mao

Publications and source records attributed to J Mao.

At least 109 records · Page 6Linked to original sources

Effects of the combined oral administration of NSAIDs and dextromethorphan on behavioral symptoms indicative of arthritic pain in rats.

The effects of combined single oral treatments with non-steroidal anti-inflammatory drugs (NSAIDs) and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DM) on arthritic pain were examined in a rat model of adjuvant-induced arthritis. Although 12.5-100 mg/kg doses of DM alone produced no reliable effects, treatments with ibuprofen (IB, 50 and 100 mg/kg but not 12.5 or 25 mg/kg) produced mild analgesia in arthritic rats as determined using the Randall-Sellito test. IB showed a dose-response relationship which appeared to plateau at doses of 50 and 100 mg/kg. Adding 50 mg/kg DM to each IB dose resulted in significantly greater analgesic activity than IB alone at doses of 25, 50 and 100 mg/kg. A similar interaction between 50 mg/kg DM and 50 mg/kg IB occurred with respect to spontaneous pain behavior. Adding 25 mg/kg DM to 25 mg/kg IB likewise increased analgesia as measured by both the Randall-Sellito and spontaneous pain behavior tests (both P < 0.05). Five more NSAIDs were evaluated using the Randall-Sellito test, which included naproxen (NP), piroxicam (PIR), etodolac (ET), diclofenac (DC), and ketorolac (KE). For all six NSAIDS, the addition of 50 mg/kg DM reliably increased their analgesic potency, as indicated by reliable increases in previously effective NSAID doses (all six NSAIDs) as well as previously ineffective NSAID doses (IB, NP, DC, and PIR). These data demonstrate that DM greatly potentiates the analgesic activity of IB, DC, NP, PIR, ET, and KT and increases the peak effect over the NSAIDs alone. Similiar to DM's previously demonstrated enhancement of opioid analgesia in acute pain, the combination of DM and an NSAID may represent a novel analgesic approach to improved management of arthritic pain.

Administration, Oral↗

A molecular pathologic study on apoptosis in retinoblastoma and the mechanism of spontaneous regression in retinoblastoma.

OBJECTIVE: The present study was designed to prove the existence of apoptosis in retinoblastoma (Rb) and to determine the pathogenic mechanism of spontaneous regression of Rb as well as the relationship between them. METHODS: Qualitative morphological study on Rb was performed by means of light microscope, electron microscope and TdT mediated biotin-dUTP nick-end labeling (TUNEL). Quantitative study was performed by automatic image analysis technology (AIAT) stained with Feulgen reaction. RESULTS: The characteristic regressed area occurred in all 47 cases of Rb. Morphological changes observed within Rb closely resembled the apoptotic cell described by Kerr et al in 1972. Under electron microscope, details of apoptosis were observed in 7 cases of Rb: the morphological sequence of events occurred in and around the cell nucleus. The morphology of the TUNEL labeling Rb cell was various. TUNEL labeling showed more positive cells in regressed area, while fewer in advanced area. AIAT revealed that apoptosis index (AI) in regressed areas was higher than that in other areas of Rb, DNA average ploidy (DP) consisted with the histology grade of Rb, the degree of hyperdiploid (DH) in metastatic area was distinctly higher than that in other areas (P < 0.05). CONCLUSIONS 1. Morphologic evidence proved the existence of apoptosis, especially more in regressed area of Rb. 2. Apoptosis may participate in the spontaneous regression of Rb. Apoptosis contributed to the spontaneous regression of Rb. 3. Tumor growth parameters of Rb (AI, DP, DH) obtained by AIAT may be used as quantitative index for pathologic classification, the selection of clinical treatment and the prognostic evaluation.

Apoptosis↗

Increases in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy.

Eight days after chronic constrictive sciatic nerve injury (CCI), protein kinase C gamma (PKC gamma) immunoreactivity reliably increased in the spinal cord dorsal horn of CCI rats with demonstrable thermal hyperalgesia as compared to sham-operated controls. Such PKC gamma immunostaining was observed primarily in neuronal somata (ipsilateral > contralateral, laminae I-II > III-IV), indicating postsynaptic sites of PKC gamma increases. Both the development of thermal hyperalgesia and the increase in PKC gamma immunoreactivity in CCI rats were prevented by once daily intrathecal administration with 10 nmol MK-801 for 7 days. The present results provide further evidence for a role of PKC in N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms of thermal hyperalgesia.

Animals↗

Increases in protein kinase C gamma immunoreactivity in the spinal cord of rats associated with tolerance to the analgesic effects of morphine.

Our previous studies have indicated a critical role of protein kinase C (PKC) in intracellular mechanisms of tolerance to morphine analgesia. In the present experiments, we examined (1) the cellular distribution of a PKC isoform (PKC gamma) in the spinal cord dorsal horn of rats associated with morphine tolerance by utilizing an immunocytochemical method and (2) the effects of the N-methyl-D-aspartate receptor antagonist MK-801 on tolerance-associated PKC gamma changes. In association with the development of tolerance to morphine analgesia induced by once daily intrathecal administration of 10 micrograms morphine for eight days, PKC gamma immunoreactivity was clearly increased in the spinal cord dorsal horn of these same rats. Within the spinal cord dorsal horn of morphine tolerant rats, there were significantly more PKC gamma immunostained neurons in laminae I-II than in laminae III-IV and V-VI. Such PKC gamma immunostaining was observed primarily in neuronal somata indicating a postsynaptic site of PKC gamma increases. Moreover, both the development of morphine tolerance and the increase in PKC gamma immunoreactivity were prevented by co-administration of morphine with 10 nmol MK-801 between Day 2 and Day 7 of the eight day treatment schedule. In contrast, PKC gamma immunoreactivity was not increased in rats receiving a single i.t. administration of 10 micrograms morphine on Day 8, nor did repeated treatment with 10 nmol MK-801 alone change baseline levels of PKC gamma immunoreactivity. These results provide further evidence for the involvement of PKC in NMDA receptor-mediated mechanisms of morphine tolerance.

Animals↗

Susceptibility artifact reduction in fat suppression.

Strong fat signal in regions where a large susceptibility difference exists, for instance at the interface between air and tissue near the maxillary sinus, may not be eliminated by currently available fat suppression techniques without sacrificing the overall quality of the images. In this article, we show that this fat signal, which appears as a susceptibility artifact, can be significantly reduced by using an optimized presaturation pulse with sharp edges and a broad bandwidth, while causing minimal disturbance of the water signal. Several optimized presaturation pulses can be reproduced by the Fourier coefficients provided in the Appendix.

Adipose Tissue↗

Physical and linkage mapping of human carbamyl phosphate synthetase I (CPS1) and reassignment from 2p to 2q35.

Carbamyl Phosphate Synthetase I (CPS1) (EC 6.3.4.16) is a highly conserved mitochondrial enzyme catalyzing the first committed step of waste nitrogen metabolism in the urea cycle. Using FISH for physical mapping and CEPH families for linkage analysis, we mapped the CPS1 gene (CPS1) to 2q34-->q35, reassigning it from 2p where it was originally mapped.

Carbamoyl-Phosphate Synthase (Ammonia)↗

Diagnosis of renal artery stenosis: feasibility of combining MR angiography, MR renography, and gadopentetate-based measurements of glomerular filtration rate.

OBJECTIVE: Our aim was to evaluate the feasibility of combining in a single test (1) structural evaluation of renal arteries with MR angiography, (2) functional evaluation of global glomerular filtration rates calculated on the basis of plasma disappearance of gadopentetate dimeglumine, and (3) renographic analysis of individual kidneys based on the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine. SUBJECTS AND METHODS: We used unenhanced MR angiography to measure patency of the renal arteries in 10 healthy volunteers and in 10 patients with renal artery stenosis. Calculations of global glomerular filtration rate were based on measurements of plasma disappearance of gadopentetate dimeglumine as shown by MR relaxometry. For renography with gadopentetate dimeglumine, we generated curves that showed changes in signal intensity in both kidneys over time; intrarenal kinetics were studied by measuring the time of arrival of gadopentetate dimeglumine in the cortex and outer medulla of the kidney. Conventional angiograms, measurements of global glomerular filtration rate based on plasma disappearance of 99mTc-DTPA, and 99mTc-DTPA renograms were used as reference standards. We compared the two different methods of determining global glomerular filtration rates by computing the correlation coefficient of the linear regression of rates derived from studies with gadopentetate dimeglumine versus rates derived from studies with 99mTc-DTPA. RESULTS: In all volunteers, renal arteries were well visualized, and global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine were normal. In nine of 10 patients, correlation was good between findings on MR angiograms and findings on conventional arteriograms. Finding were discordant in one patient because the patient moved during the MR angiography. For all six patients studied, correlation was good between measurements of global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine and those based on clearance of 99mTc-DTPA (r = 98%). CONCLUSION: Our results suggest the potential of magnetic resonance for a comprehensive approach for detection of renal artery stenosis. This novel approach provides structural evaluation of renal arteries with unenhanced MR angiography. MR renography is done and global glomerular filtration rates are determined by using MR relaxometry after injection of contrast material. Corticomedullary transit times can be determined on the basis of the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine.

Adult↗

A two-year experience with laparoscopic cholecystectomy--a report of 1475 cases from Kunming, China.

Over a 2-year period, from 12 September 1991 to 11 September 1993, laparoscopic cholecystectomy was performed on 1475 patients with benign gallbladder disease in Kunming General Hospital, Yunnan, China. Of these, 28 cases (1.9%) were converted to open surgery. Various complications were documented in 27 instances including extrahepatic bile duct injury in 4 cases (0.3%), postoperative haemorrhage requiring laparotomy in 3 cases (0.2%) and bile leak from cystic duct stump in 1 case (0.07%). There was 1 (0.07%) death in the series. The junction between the gallbladder infundibulum and the cystic duct is an important landmark which laparoscopic surgeons must identify in the course of the procedure. Because the junction remains a comparatively constant landmark, in difficult laparoscopic cholecystectomy, excessive dissection of the bile duct would be unnecessary. During dissection of the hepatic hilus, blund dissection is recommended and the blind use of cautery and haemostasis should be avoided.

Bile Ducts, Extrahepatic↗

The association of neuropathic pain, morphine tolerance and dependence, and the translocation of protein kinase C.

This series of studies has investigated the involvement of the NMDA receptor and the translocation of PKC in the seemingly unrelated phenomena of neuropathic pain and tolerance and dependence to narcotic analgesic drugs. This work has demonstrated that the NMDA receptor and PKC translocation are importantly involved in neuropathic pain and morphine tolerance or dependence and that these phenomena may be importantly interrelated. Neuropathic pain following nerve injury is a major chronic pain syndrome. Utilizing a rat model of painful peripheral mononeuropathy produced by CCI of the sciatic nerve, the authors have investigated central mechanisms of postinjury neuropathic pain. Behavioral and pharmacological studies indicate that thermal hyperalgesia and spontaneous pain behaviors observed in this model are attenuated by treatment with NMDA receptor antagonists. A consequence of NMDA receptor activation is calcium influx, which in turn can result in translocation of PKC from cytosol to membrane. Inhibitors of intracellular PKC translocation and activation block thermal hyperalgesia and spontaneous pain behaviors after CCI and also reduce the elevated spinal cord neural activity in CCI rats. Furthermore, spinal cord levels of membrane-bound PKC reliably increase in CCI rats as a result of translocation of PKC revealed by the [3H]PDBu autoradiographic assay. This increase in membrane-bound PKC is associated with postinjury neuropathic pain behaviors in CCI rats and both pain-related behaviors and membrane-bound PKC are reduced potently by GM1 ganglioside.

Animals↗

Instability of frog virus 3 mRNA in productively infected cells.

Cloned DNA restriction fragments encoding representative frog virus 3 messages were used as probes to assess the stability of viral transcripts in infected fathead minnow cells. Analysis of Northern blot hybridization profiles confirmed earlier findings and revealed that in infected cells the steady-state level of representative frog virus 3 (FV3) messages increased throughout the replication cycle. However, when actinomycin D was added at 4 hr after infection to block the synthesis of new transcripts, viral messages were observed to turn over rapidly, with half-lives of approximately 2 hr. These results indicate that viral transcripts were not preferentially stabilized in FV3-infected cells and suggest that the high steady-state level of viral messages present at late times after infection was due to viral transcription outpacing message degradation. Moreover, the instability of viral messages challenges the suggestion that the terminal dyad symmetry (hairpin structure) observed in all frog virus 3 messages sequenced to date plays a role in transcript stability.

Animals↗

Isolation and characterization of a rat luteal cDNA encoding 20 alpha-hydroxysteroid dehydrogenase.

We report the isolation and characterization of a full length cDNA encoding rat 20 alpha hydroxysteroid dehydrogenase derived from rat corpus luteum RNA. The predicted amino acid sequence of the protein encoded by the 20 alpha HSD clone is composed of 323 amino acids possessing an approximate molecular weight of 37 kDa. The sequence of peptides derived from the purified protein was found in the translated sequence of the open reading frame. cDNA and amino acid sequence indicate that the rat ovarian 20 alpha HSD belongs to the aldo-keto reductase family of enzymes. Northern analysis revealed a 1.2 Kb 20 alpha HSD mRNA in corpora lutea undergoing luteolysis. Prolactin reduced markedly 20 alpha HSD mRNA expression. No signal was detected in other tissues examined, demonstrating the specific expression of this enzyme in the corpus luteum.

20-Hydroxysteroid Dehydrogenases↗

Genetic mapping of the human growth hormone-releasing factor gene (GHRF) using two intragenic polymorphisms detected by PCR amplification.

We have analyzed the human growth hormone-releasing factor (GHRF) gene by high-resolution restriction mapping of its PCR amplification products. Two intragenic PCR fragment length polymorphisms (PCRFLPs) were detected in introns A and C of the GHRF gene, whose heterozygosities are 40 and 7%, respectively. Linkage analysis using the CEPH panel showed that GHRF is linked to several markers on chromosome 20 and assigned the GHRF locus to a region near the centromere between D20S27 (assigned to 20p12.1-p11.23) and D20S16 (assigned to 20q12). These intragenic PCRFLPs and the tightly linked polymorphisms should provide useful markers for linkage studies of GHRF alleles in familial disorders of growth such as isolated growth hormone deficiency.

Base Sequence↗

Identification of a new spore coat protein gene in the cellular slime mold Dictyostelium discoideum.

Genomic DNA encoding the prespore cell-specific PL3 cDNA was cloned and sequenced, revealing that the gene consists of three exons separated by short 100-bp introns. The single long open reading frame predicts a primary translation product of 70 kDa after removal of a cleavable signal peptide, two-thirds of which consists of four kinds of amino acid repeat elements, including two found in other spore coat proteins. The 85-kDa PL3 protein synthesized in vivo accumulates specifically in regulated secretory vesicles of prespore cells (prespore vesicles), as determined microscopically using antibody against a PL3 gene fusion product expressed in Escherichia coli. The protein later accumulates extracellularly in the spore coat, which is formed during sporulation, as determined ultrastructurally and by Western blot analysis of SDS-PAGE gels. In addition to its high proportion of repeat elements, the PL3 protein has the following properties which distinguish it from other spore coat proteins: (1) it is located at the outer extent of the middle layer, beneath the outer layer, (2) its dissociation from the coat requires the presence of protein denaturants and reducing agents at elevated temperature, and (3) a large proportion of the protein is not dissociated from the coat even under these conditions, as determined by ultrastructural analysis of the extracted coat. The PL3 protein may contribute to the structure of the coat at the interface between the middle, cellulosic layer and the outer, electron-dense, proteinaceous layer.

Amino Acid Sequence↗

Germline RET mutations in MEN 2A and FMTC and their detection by simple DNA diagnostic tests.

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are two closely related cancer syndromes inherited in an autosomal dominant manner. Mutations in the RET proto-oncogene were found in MEN 2A and FMTC families. In this study we report seven different germline mutations in the RET proto-oncogene in five of five MEN 2A and five of six FMTC families. Each of the mutations involves a cysteine residue in the extracellular cysteine-rich domain of the RET receptor tyrosine kinase. We developed simple polymerase chain reaction based diagnostic tests for all seven mutations in these families.

Base Sequence↗