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Biomedical subjects

N Nakashima

Publications and source records attributed to N Nakashima.

At least 73 records · Page 4Linked to original sources
PubMed1998

The second subunit of DNA polymerase III (delta) is encoded by the HYS2 gene in Saccharomyces cerevisiae.

DNA polymerase III (delta) of Saccharomyces cerevisiae is purified as a complex of at least two polypeptides with molecular masses of 125 and 55 kDa as judged by SDS-PAGE. In this paper we determine partial amino acid sequences of the 125 and 55 kDa polypeptides and find that they match parts of the amino acid sequences predicted from the nucleotide sequence of the CDC2 and HYS2 genes respectively. We also show by Western blotting that Hys2 protein co-purifies with DNA polymerase III activity as well as Cdc2 polypeptide. The complex form of DNA polymerase III activity could not be detected in thermosensitive hys2 mutant cell extracts, although another form of DNA polymerase III was found. This form of DNA polymerase III, which could also be detected in wild-type extracts, was not associated with Hys2 protein and was not stimulated by addition of proliferating cell nuclear antigen (PCNA), replication factor A (RF-A) or replication factor C (RF-C). The temperature-sensitive growth phenotype of hys2-1 and hys2-2 mutations could be suppressed by the CDC2 gene on a multicopy plasmid. These data suggest that the 55 kDa polypeptide encoded by the HYS2 gene is one of the subunits of DNA polymerase III complex in S.cerevisiae and is required for highly processive DNA synthesis catalyzed by DNA polymerase III in the presence of PCNA, RF-A and RF-C.

Amino Acid Sequence↗
PubMed1998

Association of a polymorphism of the endothelial constitutive nitric oxide synthase gene with myocardial infarction in the Japanese population.

We investigated the association between variations in the endothelial constitutive nitric oxide synthase (ecNOS) gene and the presence of myocardial infarction. The results indicate that the mutant allele (ecNOS'4a) is an independent risk factor for myocardial infarction in the Japanese population, especially in those lacking other conventional risk factors.

Aged↗
PubMed1998

Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative pancreatoscopy with the ultrathin pancreatoscope for the main pancreatic lesions of mucin-producing tumors of the pancreas (MPT). DESIGN: Prospective diagnostic test study with a criterion standard of pathologic examination and masked comparison. SETTING: A university hospital. PATIENTS: Twenty-four consecutive patients with MPT referred for surgery in whom endoscopic retrograde pancreatography, endoscopic ultrasonography, and computed tomography had been performed as a diagnostic examination. All patients underwent surgery and the diagnosis was confirmed by pathologic examination. INTERVENTION: Intraoperative pancreatoscopy was performed with the ultrathin pancreatoscope. MAIN OUTCOME MEASURES: Findings of intraoperative pancreatoscopy, endoscopic retrograde pancreatography, and endoscopic ultrasonography were confirmed by pathologic examination of resected specimens. The diagnostic accuracy of these 3 modalities in detection of MPT lesions in the main pancreatic duct was compared. RESULTS: The diagnostic criterion of MPT lesions in the main pancreatic duct by intraoperative pancreatoscopy was a granular and papillary mural nodule. An MPT lesion in the main pancreatic duct was found in 17 of 24 cases. Intraoperative pancreatoscopy detected 10 cases of intraductal MPT lesions that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. Five of 10 cases were intraductal multicentric lesions. In 3 of these 5, additional pancreatic resection was performed. For diagnosis of MPT lesions, the sensitivity, specificity, and overall accuracy of intraoperative pancreatoscopy were all 100%; respective values were 43.8%, 100%, and 60.9% for endoscopic retrograde pancreatography and 47%, 100%, and 62.5% for endoscopic ultrasonography. CONCLUSIONS: Intraoperative pancreatoscopy is safe and effective in diagnosing the intrapancreatic duct extension and multicentric lesions of MPT. It provides important information for operative strategy and contributes to successful pancreatic surgery.

Adult↗
PubMed1998

Twenty-four-hour ambulatory oxygen desaturation and electrocardiographic recording in obstructive sleep apnea syndrome.

BACKGROUND: Although nocturnal pulseoximetry is routinely performed in obstructive sleep apnea syndrome (OSAS), pulseoximetry over a 24-h period has not been studied. HYPOTHESIS: The purpose of the study was to determine whether simultaneous 24-h oxygen desaturation and electrocardiographic (ECG) recording might be used to screen for daytime sleep sequelae in patients with OSAS. METHODS: Simultaneous recording of arterial oxygen saturation (SpO2) and ECG was conducted over a 24-h period in 18 male patients with OSAS (mean age 51.3 years) who were diagnosed by standard polysomnography (PSG), and in 15 age-matched healthy subjects (mean age 52.7 years) as controls to evaluate circadian variation of these parameters. The measures of heart rate variability (HRV) were calculated from 24-h ambulatory ECGs. Seventeen patients with OSAS showed excessive daytime sleepiness (EDS). We calculated the duration in which SpO2 decreased to < 90% (duration of SpO2 < 90%). The number of apnea/hypopneas per hour (AHI) during sleep was investigated with Apnomonitors (Chest MI, Co., Tokyo) on the same day as the SpO2 recordings. RESULTS: Controls showed no episodes of oxygen desaturation. In patients with OSAS, driving (33.3% of patients with OSAS) was the most common activity in which SpO2 decreased to < 90%, followed by daytime napping (27.8%) and resting after meals (22.2%). The duration of SpO2 < 90% over a 24-h period correlated significantly with the duration levels recorded during sleep (r = 0.99, p < 0.05) and in the afternoon (r = 0.62, p < 0.05), and with the AHI (r = 0.55, p < 0.05), but not with the duration of SpO2 < 90% in the morning. The number of ventricular premature beats correlated significantly with the duration of SpO2 < 90% for a 24-h period, but not with measures of HRV. Ventricular tachycardia was found in two (11.1%) and ST-T depression in three patients (16.6%) with underlying cardiac diseases. CONCLUSION: Our results suggest that daytime sleep attacks accompanied by oxygen desaturation in patients with moderate to severe OSAS may contribute to the occurrence of traffic or cardiovascular accidents. We conclude that 24-h ambulatory recordings of SpO2 and ECG are useful for screening for daytime sleep sequelae associated with the potential risk of this pathology in OSAS during social activities.

Adult↗
PubMed1998

Properties of a new picorna-like virus of the brown-winged green bug, plautia stali

A picorna-like virus was isolated from the brown-winged green bug, Plautia stali. The virus was named Plautia stali intestine virus (PSIV) based on the multiplication site of the virus in the infected insects. PSIV is a spherical particle with a diameter of 30 nm. Particles of PSIV were found to contain a 9.1-kb single-stranded RNA. Polyacrylamide gel electrophoresis of purified PSIV particles revealed three major (33, 30, 26 kDa), one medium (35 kDa), and one minor (4.5 kDa) structural proteins. The molar ratios of the proteins suggested that the 35-, 33-, 30-, 26-, and 4.5-kDa proteins corresponded to VP0, VP1, VP2, VP3, and VP4 of vertebrate picornaviruses. Immunological assays indicated that PSIV and Nezara viridula virus-1, which is a picorna-like virus of the green stinkbug in South Africa, were serologically distinct. PSIV was detected in the intestine with enzyme-linked immunosorbent assay but not in the salivary glands, fat bodies, Malpighian tubules, and reproductive organs of viruliferous P. stali. The virus was also detected on the surface of the eggs and in the feces of infected insects. These results suggest that excrement of infected insects are the primary inoculum of the virus in a colony of P. stali. The nonviruliferous adults of P. stali usually survive a few months in laboratory, while the average of adulthood lifetime in viruliferous P. stali was about 13 days. PSIV also infected two other stinkbugs, Nezara viridula and Halyomorpha halys. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Air bubbles in the subclavian or internal jugular veins: a common finding on contrast-enhanced CT.

We investigated the frequency of air bubbles in the subclavian (SCV) or internal jugular (IJV) vein in 200 patients who underwent contrast-enhanced CT of the head and neck. Half the patients were reviewed retrospectively (group 1), while the other half were investigated prospectively after the radiologists who administered the contrast medium were instructed to be careful not to inject even a single air bubble during the procedure (group 2). Air bubbles were observed in the SCV or IJV in 15 of the 100 patients in group 1, while in group 2, there were 4 such patients. Air injection, a common "complication", can be reduced by care during the procedure.

Air↗
PubMed1998

Pathological significance of elevated soluble CD14 production in rheumatoid arthritis: in the presence of soluble CD14, lipopolysaccharides at low concentrations activate RA synovial fibroblasts.

In order to establish what contributes to elevated levels of soluble CD14 (sCD14) in rheumatoid arthritis (RA) plasma, levels of sCD14 were compared in RA-paired plasma and synovial fluids and, further, in the culture supernatants of monocyte-rich fractions from patients with RA and healthy donors, and macrophage-rich fractions from RA synovial tissues. The results showed elevated sCD14 in RA synovial fluid in 9 of 16 paired samples and in RA macrophage-rich fractions, suggesting that elevated sCD14 in RA plasma might be due to the sCD14 production by RA synovial macrophages. From the molecular analysis of elevated sCD14, the proteolytic cleavage of membranous CD14 (mCD14) was important in accelerated sCD14 production. Lipopolysaccharides (LPS) at low concentrations and sCD14 increased the ICAM-1 expression on RA synovial fibroblasts. This result implies that in vivo RA synovial fibroblasts may be sensitive to LPS in the presence of sCD14 and LPS-binding protein (LBP).

Adult↗
PubMed1998

Sarcomatous transformation of pituitary adenoma after bromocriptine therapy.

We reported a case of sarcomatous transformation of pituitary adenoma occurring in a 21-year-old woman. She had previously undergone surgery for pituitary adenoma (prolactinoma) 5 years earlier. Since then, she had received only bromocriptine medication therapy. The operation was repeated because of a relapse of the tumors. Histologically, the tumors were composed of adenomatous epithelial nests and fibrosarcomatous spindle cell components intermingled with each other. lmmunohistochemically, adenomatous epithelial cells were stained positively with cytokeratin and prolactin. Fibrosarcomatous spindle cells were stained only with vimentin. The proliferation activity (Ki-67 expression) was much higher in the sarcomatous components than in common pituitary adenoma. p53 immunostaining was also positive in sarcomatous components. This was thought to be the first reported case of sarcomatous transformation of pituitary adenoma not associated with radiation therapy.

Adenoma↗
PubMed1998

Complete nucleotide sequence of spheroidin gene of Anomala cuprea entomopoxvirus.

The complete nucleotide sequence of the spheroidin gene of Anomala cuprea entomopoxvirus (AcEPV) was determined. The sequence was compared with those of spheroidin genes of EPVs such as Melolontha melolontha EPV (MmEPV, Genus A), Choristoneura fumiferana EPV (CfEPV, Genus B) and Amsacta moorei EPV (AmEPV, Genus B). The gene harbored an open reading frame (ORF) of 2826 nt, with the same size as that of MmEPV belonging to the same genus, capable of coding for a polypeptide of 109.0 kDa. The predicted amino acid (aa) sequence showed a greater or moderate similarity to the corresponding sequence of the other EPVs, showing a 94, 40 and 41% aa identity with MmEPV, CfEPV and AmEPV, respectively; the identity was 89, 53 and 54% at the nucleotide level. The hydropathy plots also showed a greater similarity in organization to MmEPV and moderate similarity to the viruses of Genus B. In the polypeptide, 44 cysteine residues, which are likely to be involved in paracrystal formation and seven potential N-glycosylation sites were detected. The number of cysteine residues and N-glycosylation sites also depended on the difference in genera (A or B). Thus, the spheroidin gene of EPVs was well conserved within the same genus.

Amino Acid Sequence↗
PubMed1998

DNA polymerase epsilon encoded by cdc20+ is required for chromosomal DNA replication in the fission yeast Schizosaccharomyces pombe.

BACKGROUND: DNA polymerase II (PolII), the homologue of mammalian DNA polymerase epsilon, is essential for chromosomal DNA replication in the budding yeast Saccharomyces cerevisiae and also participates in S-phase checkpoint control. An important issue is whether chromosomal DNA replication in other eukaryotes, including the fission yeast Schizosaccharomyces pombe--in which the characteristics of replication origins are poorly defined--also requires DNA polymerase epsilon. It has been shown that DNA polymerase epsilon is not required for the in vitro replication of SV40 DNA by human cell extracts. RESULTS: We have cloned and sequenced S. pombe pol2+, which is identical to the cell-cycle gene cdc20+, encoding the catalytic polypeptide of DNA polymerase epsilon (Pol epsilon). The predicted amino acid sequence of Pol epsilon is highly homologous to that of S. cerevisiae PolII and human Pol epsilon. Consistent with this, the Pol epsilon polypeptide was recognized by polyclonal antibodies against S. cerevisiae PolII holoenzyme (PolII*). The terminal morphology of cells containing the disrupted pol2 gene was similar to that of DNA replication mutant cells and cdc20 mutant cells. Furthermore, the Pol epsilon activity from temperature-sensitive S. pombe cdc20 mutant cells was temperature-sensitive, and chromosomal DNA replication in the mutant cells was inhibited at the restrictive temperatures. CONCLUSION: These data strongly suggest that Pol epsilon is required for normal chromosomal DNA replication in S. pombe, as is PolII in S. cerevisiae. Thus, eukaryotic chromosomal DNA is replicated differently from that of viral SV40 DNA.

Amino Acid Sequence↗
PubMed1998

Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3.

Saccharomyces cerevisiae Dis3p, which interacts with Ran/Gsp1p, complements Schizosaccharomyces pombe dis3-54. Consistent with the functional conservation of Dis3p in S. cerevisiae and S. pombe, the human ORF (accession number: R27667) was found to be highly homologous to yeast Dis3p. Based on its nucleotide sequence, we cloned a full-sized human DIS3 cDNA. The cloned human cDNA partly but significantly restored the temperature-sensitivity of S. cerevisiae dis3. Thus, Dis3p was found to be structurally and functionally conserved from yeast to mammals. Consistent with the report that S. cerevisiae Dis3p is identical to Rrp44p, which comprises the exosome involved in ribosomal RNA processing, S. cerevisiae Dis3p was found to be localized in the nucleolus. Similar to S. cerevisiae Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran.

Amino Acid Sequence↗
PubMed1998

Diagnostic value of the Amplicor PCR assay for initial diagnosis and assessment of treatment response for pulmonary tuberculosis.

We evaluated the Amplicor PCR assay as an initial diagnostic tool on the basis of clinical diagnosis, and assessed this assay as a follow-up test for patients with pulmonary tuberculosis during chemotherapy. Of the 208 specimens from 155 patients who were bacteriologically and/or clinically diagnosed with active tuberculosis before chemotherapy, 144 were Amplicor PCR-positive (sensitivity, 69.2%), which was equal to the results of culturing. Among 89 specimens which showed positive results by smear and culturing, the Amplicor PCR assay detected 87 (97.8%), whereas among 55 specimens which showed smear-negative but culture-positive results, the Amplicor PCR assay detected 46 (83.6 %)(P= 0.003). No false positive results were found in the two systems (specificity, 100%, 120/120). The Amplicor PCR assay was also evaluated as a follow-up test using 926 specimens from 207 patients receiving active tuberculosis chemotherapy. Among 433 specimens which showed Amplicor-PCR positive, 222 (51.3%) were culture-negative. On the other hand, among 233 culture-positive specimens, only 12 (5.2%) were Amplicor PCR-negative. Therefore, this assay is useful for the rapid diagnosis of tuberculosis. The duration of Amplicor PCR-positive after culture-negative conversion was significantly associated with the presence of cavitary lesion, smear-positive specimens before treatment, and smear-positive specimens with negative cultures during chemotherapy.

Antitubercular Agents↗
PubMed1998

Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome.

The long-term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle-aged (40-64 years), and aged (> or = 65 years) using a questionnaire survey. One hundred and forty-eight patients with OSAS aged 17-78 years (136 men, 12 women, mean 52.0+/-12.3 years), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval: 55.6-87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (87.6%). In the young group, only one death (a 19-year-old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO2) fell below 90% (time of SaO2 <90%) of 205 min. The survival rate in middle-aged patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO2 <90% was significantly longer in the middle-aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle-aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle-aged group (57.9 vs 90.4%). Cox proportional-hazard regression model including age, hypertension, BMI, AHI, lowest SaO2, and time of SaO2 <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle-aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle-aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.

Adolescent↗
PubMed1998

Evaluation of a membrane filter assay system, Ortho HCV Ab Quick Pack, for detection of anti-hepatitis C virus antibody.

A simple membrane immunoassay assay system, Quik Pack, for the detection of hepatitis C virus antibody was compared with two enzyme-linked immunosorbent assays (ELISAs) in a study of 600 serum samples. Quik Pack exhibited excellent sensitivity and specificity: 96.0 and 99.7%, respectively, versus the ELISA-2 and 99.7 and 99.4%, respectively, versus the ELISA-3.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Effects of general receptor for phosphoinositides 1 on insulin and insulin-like growth factor I-induced cytoskeletal rearrangement, glucose transporter-4 translocation, and deoxyribonucleic acid synthesis.

We investigated the effects of general receptor for phosphoinositides-1 (GRP1), a recently cloned protein that binds 3,4,5-phosphatidylinositol [PtdIns(3,4,5)P3] with high affinity, but not PtdIns(3,4)P2 nor PtdIns(3)P, on insulin and insulin-like growth factor I (IGF-I)-induced cytoskeletal rearrangement, glucose transporter-4 (GLUT4) translocation, and DNA synthesis. GRP1 consists of an NH2-terminally located coiled coil domain followed by a Sec7 domain and a COOH-terminal pleckstrin homology (PH) domain that is required for PtdIns binding. We used microinjection of glutathione-S-transferase fusion proteins containing residues 239-399 (PH domain), residues 52-260 (Sec7 domain), residues 5-71 (N-terminal domain), full-length GRP1, and an antibody (AB) raised against full-length GRP1 coupled with immunofluorescent detection of actin filament rearrangement, GLUT4 translocation, and 3'-bromo-5'-deoxyuridine incorporation. Microinjection of these constructs and the AB had no effect on insulin-induced GLUT4 translocation or DNA synthesis. However, microinjection of the GRP1-PH and the GRP1-Sec7 domain as well as the alpha-GRP1-AB significantly inhibited insulin- and IGF-I-stimulated actin rearrangement in an insulin receptor-overexpressing cell line (HIRcB) compared with that in control experiments. Coinjection of GRP1-Sec7 along with constitutively active Rac (Q67L) did not inhibit Rac-induced actin rearrangement. Furthermore, GRP1 is not able to bind and act as a nucleotide exchange factor for the small GTP-binding proteins of the Rho family. As GRP1 acts as a guanine nucleotide exchange factor for ARF6 proteins, we propose a signaling pathway distinct from the small GTP-binding protein Rac, connecting PtdIns(3,4,5)P3 via GRP1 to ARF6, leading to insulin- and IGF-I-induced actin rearrangement.

3T3 Cells↗
PubMed1998

RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway.

Human RagA and RagB is reported to be 52% identical to a putative GTPase of Saccharomyces cerevisiae, Gtr1p. According to the reported nucleotide sequence, we amplified human RagA and RagBs cDNAs from the human B cell cDNA library with PCR. Both cDNAs rescued a cold sensitivity of S. cerevisiae, gtr1-11. Furthermore, we introduced into the cloned human RagA cDNA, the mutation 'T21L' corresponding to the gtr1-11 mutation which has been reported to suppress not only all of rcc1-, temperature-sensitive mutants of Ran/Gsp1p GTPase GDP/GTP-exchanging factor, but also rna1-1, a temperature-sensitive mutant of Ran/Gsp1p GTPase-activating protein. The resulting RagAgtr1-11 cDNA partially, but significantly, suppressed both rcc1- and rna1-1 mutations. These results indicated that RagA and RagBs are functional homologues of S. cervisiae Gtr1p. Interestingly, while wild-type human RagA and RagBs were localized within the cytoplasm, similar to S. cerevisiae Gtr1p, the mutated human RagAgtr1-11 corresponding to a dominant negative form of RagA was distributed in discrete speckles in the nucleus, being localized side by side with SC-35, a non-snRNP of the splicing complex. In contrast, a dominant positive form of RagA, Q66L was localized in the cytoplasm. Thus, RagA was suggested to shuttle between the cytoplasm and the nucleus, depending on the bound nucleotide state.

Amino Acid Sequence↗
PubMed1998

Differential effects of intrathecally administered delta and mu opioid receptor agonists on formalin-evoked nociception and on the expression of Fos-like immunoreactivity in the spinal cord of the rat.

This study examined the effects of intrathecally (i.t.) administered mu and delta opioid receptor agonists on the flinching behavior and the expression of Fos-like immunoreactivity (Fos-LI) in the spinal cord elicited by s.c. injection of 5% formalin in one hindpaw of the rat. Intrathecal pretreatment with either the delta-1 opioid receptor agonist [D-Pen2,5]enkephalin (DPDPE) or the delta-2 opioid receptor agonist [D-Ala2,Glu4]deltorphin (DELT) produced a dose-dependent inhibition of flinching behavior in phase 1 and phase 2 that was antagonized by coadministration of the delta-1 opioid receptor antagonist 7-benzylidinenaltrexone or the delta-2 opioid receptor antagonist Naltriben, respectively. Although i.t. pretreatment with 60 micrograms of DPDPE produced a small decrease in the numbers of Fos-LI neurons in laminae I, IIi and IIo, as well as laminae V and VI and laminae VII-X, i.t. pretreatment with 30 micrograms of DELT did not decrease the number of Fos-LI neurons in any region of the spinal cord. In contrast, i.t. pretreatment with an equieffective dose of the mu opioid receptor agonist [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) not only significantly decreased the number of flinches in phase 1 and phase 2, but also nearly completely prevented the expression of Fos-LI in all regions of the spinal cord. These effects were antagonized by pretreatment with the mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Phe-Thr-NH2. The efficacy of i.t. administered DAMGO suggests that a direct spinal action contributes to the inhibition of noxious stimulus-evoked Fos-LI in the spinal cord produced by systemically administered mu opioid receptor agonists such as morphine. The relative lack of effect of DPDPE or DELT suggests that delta opioid receptors do not modulate the early-immediate gene c-fos. Alternatively, because delta opioid receptor agonists inhibit synaptic transmission in the spinal cord by predominantly presynaptic mechanisms and do not hyperpolarize dorsal horn neurons, the excitatory inputs that persist in the presence of these agonists may be sufficient to activate the c-fos gene. Taken together, these results provide new evidence, at the level of a "third messenger," that the antinociception produced by i.t. administration of delta and mu opioid receptor agonists is mediated by different mechanisms.

Analgesics, Opioid↗