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Biomedical subjects

J H Tian

Publications and source records attributed to J H Tian.

At least 19 recordsLinked to original sources
PubMed1999

Nocistatin reverses the effect of orphanin FQ/nociceptin in antagonizing morphine analgesia.

Nocistatin is a recently characterized neuropeptide derived from the preprohormone containing nociceptin (Orphanin FQ, OFQ). Nocistatin was reported to antagonize OFQ induced allodynia, hyperalgesia and prostaglandin E2-elicited pain responses. The aim of the present study was to determine whether nocistatin, injected intracerebroventricularly (i.c.v.), would reverse the anti-morphine effect of OFQ in rats using the tail-flick latency (TFL) as the nociceptive index. I.c.v. injection of nocistatin at doses of 0.005, 0.05, 0.5, 5, 50, and 500 ng produced no significant changes in the basal TFL, nor did it affect morphine analgesia. However, it significantly reversed the antagonistic effect of OFQ on morphine analgesia when co-injected i.c.v. at doses of 0.05, 0.5, 5, 50 and 500 ng per rat with OFQ. The dose-response curve was bell-shaped and the most effective dose was 0.5 ng. The results suggest that nocistatin can reverse the anti-morphine effect of OFQ in rat brain.

Analgesia↗
PubMed1999

Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China.

A multicentre trial was organized in China as part of an international coordinated research project to study the efficacy and toxicity of single-dose samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative treatment for painful skeletal metastases. One hundred and five patients with painful bone metastases from various primaries were treated with 153Sm-EDTMP at a dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated according to change in daily analgesic consumption, pain score, sum of effect product (SEP), Physician's Global Assessment (PGA), blood counts, and organ function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in group I and 30 of 35 in group II had a positive response, with SEPs of 22.29+/-14. 47 and 20.13+/-13.90 respectively. Of 72 patients who had been receiving analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score (KS) increased from 58.54+/-25.90 to 71.67+/-26. 53, indicating improved general condition, but the difference was not significant. Among subgroups of patients, only those with breast cancer showed a significant change in the Karnofsky score after treatment. Inter-group differences were found for net change in KS between patients with lung and patients with breast cancer, and between patients with lung and patients with oesophageal cancer. Seventeen patients showed no response. No serious side-effects were noted, except for falls in the white blood cell (nadir 1.5x10(9)/l) and platelet (nadir 6.0x10(10)/l) counts in 44/105 and 34/105 cases, respectively. Ten patients had an abnormal liver function test. Response and side-effects were both independent of dose. In conclusion, 153Sm-EDTMP provided effective palliation in 83.8% of patients with painful bone metastases; the major toxicity was temporary myelosuppression. Further studies are needed to identify better ways of determining the appropriate dose in the individual case and the efficacy of treatment.

Analgesics, Non-Narcotic↗
PubMed1998

Endogenous orphanin FQ: evidence for a role in the modulation of electroacupuncture analgesia and the development of tolerance to analgesia produced by morphine and electroacupuncture.

1. Our previous work has demonstrated that exogenously administered orphanin FQ (OFQ) antagonizes morphine analgesia and electroacupuncture analgesia (EAA) in the brain and potentiates morphine analgesia and EAA in the spinal cord of the rat. In the present study we evaluated the role of endogenously released OFQ in the development of tolerance to morphine and electroacupuncture (EA) and the analgesia produced by electroacupuncture, by use of the IgG fraction of an anti-OFQ antibody (OFQ-Ab) microinjected into the rat central nervous system (CNS). 2. EAA was produced by stimulating rats at a frequency of 100 Hz. Rats were classified as either high responders (HR) or low responders (LR) based on the analgesic effects of EA. LRs could be converted into HRs by the intracerebroventricular (i.c.v.) microinjection of OFQ-Ab at both 1:1 and 1:10 dilutions but not 1:100. HRs could be changed into LRs by the intrathecal (i.t.) injection of OFQ-Ab at both 1:1 and 1:10 dilutions, but not 1:100. 3. Acute morphine tolerance was induced in rats by repeated subcutaneous (s.c.) injections of morphine (5 mg kg, every 2 h) for 16 h. When injected i.c.v. the OFQ-Ab (1:1 dilution) had no effect on the development of acute morphine tolerance. 4. Chronic morphine tolerance was produced in rats by repeated injection of morphine (5-60 mg kg, s.c., 3 x a day) for 6 days. I.c.v. injection of OFQ-Ab (1:1 dilution) reversed this type of morphine tolerance in rats by 50% (P < 0.01). 5. Acute tolerance to the analgesia produced by EA developed after 6 h of continuous (100 Hz, 3 mA) stimulation. This tolerance was almost completely reversed by the i.c.v. injection of OFQ-Ab (1:1 dilution) (P < 0.05). 6. Chronic tolerance to the analgesic effect of EA was produced by repeatedly administering increasing current (1, 2 and 3 mA, each lasting for 10 min, for a total of 30 min) at a frequency of 100 Hz once a day for 6 days. I.c.v. injection of OFQ-Ab (1:1 dilution) reversed this kind of tolerance by 50% (P < 0.01). 7. Together these results suggest that 100 Hz EA may enhance the release of endogenous OFQ in the CNS of the rat, which in turn may act to antagonize EA-produced analgesia in the brain but potentiate EA produced analgesia in the spinal cord. Therefore, OFQ appears to play an important role in the development of tolerance to the analgesic effects produced by EA. 8. The mechanisms underlying the development of acute morphine tolerance and chronic morphine tolerance appear to be different. Central OFQ may play an important role in the development of tolerance after chronic morphine administration.

Adaptation, Physiological↗
PubMed1998

Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in immunity to malaria.

MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1(19)-specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1(19) and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1(19), but not defined epitopes, was able to induce protection; and (2) long term MSP1(19)-specific CD4+ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1(19) after either challenge with MSP1(19) or parasite. Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia.

Adoptive Transfer↗
PubMed1997

Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein-1 (MSP1[19]) of Plasmodium yoelii expressed in Saccharomyces cerevisiae: correlation of protection with antigen-specific antibody titer, but not with effector CD4+ T cells.

The 19-kDa carboxyl-terminal fragment of the merozoite surface protein-1 (MSP1) is a leading malaria vaccine candidate but is unable to induce immunity in all monkeys or all strains of mice. The mechanism of immunity is unclear, although data show that cell-mediated immunity plays a critical role following immunization with the larger mature MSP1 protein. We optimized a vaccine protocol using the MSP1(19) fragment of Plasmodium yoelii expressed in Saccharomyces cerevisiae, such that following exposure of mice to parasites, they remained undetectable in peripheral blood, whereas control animals all died at very high parasitemia within 10 days. We then depleted the vaccinated mice of >99% of CD4+ T cells by anti-CD4 mAb treatment and could show that infections in most animals remained subpatent following challenge. Furthermore, mice in which the gene for the mu-chain of Ig had been disrupted could not be immunized with MSP1(19). Immunity in normal mice did not depend on the presence of an intact spleen nor production of nitric oxide, persisting unabated when >70% of splenic macrophages were depleted. Thus, while effector CD4+ T cells may contribute to immunity, neither they nor factors associated with a Th1-type cell mediated immune response appeared to play the major role in MSP1(19)-induced protection in normal mice. Furthermore, T cells were not sufficient for immunity in mice lacking B cells. In normal mice, protection correlated with a very high titer of MSP1(19)-specific Abs (>6,400,000), predominantly G1 and G2b, which may function by merozoite neutralization.

Animals↗
PubMed1997

Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia.

Recent studies suggest that the novel opioid peptide orphanin FQ (OFQ) is involved in pain modulation. We found that intracerebroventricular (i.c.v.) administration of OFQ in the rat produced a dose-dependent antagonism of the analgesia induced by 100 Hz electroacupuncture (EA) stimulation as measured in the radiant heat tail-flick assay. Antisense oligonucleotides injected i.c.v. potentiated EA analgesia, presumably by interfering with the expression of the OFQ receptor in brain. These results suggest that endogenous OFQ exerts a tonic antagonistic effect on EA-induced analgesia. No such antagonism was observed when OFQ was injected intrathecally (i.t.). Rather, it appears that spinal OFQ produced a marked analgesic effect and enhanced EA-induced analgesia. These findings are consistent with the experimental results obtained in rats where morphine-induced analgesia is antagonized by i.c.v. OFQ and potentiated by i.t. OFQ.

Analgesia↗
PubMed1997

Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat.

1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ)-the endogenous ligand for the orphan opioid receptor (called, e.g., ORL, and LC132)-on pain modulation in the rat. We used the tail-flick assay as a nociceptive index. 2. When injected into a cerebral ventricle, OFQ (4 fmol-10 nmol) has no effect on basal tail-flick latency by itself at any dose, but dose-dependently antagonizes systemic morphine analgesia (400 fmol 50 nmol). 3. Injected intrathecally, OFQ (3 and 10 nmol) displayed an analgesic effect without producing motor dysfunction, and potentiated morphine analgesia (1 and 10 nmol). 4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL, receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms. However, no such precipitation was observed by OFQ in morphine-dependent rats.

Analgesia↗
PubMed1997

Comparison of protection induced by immunization with recombinant proteins from different regions of merozoite surface protein 1 of Plasmodium yoelii.

Vaccination with native full-length merozoite surface protein 1 (MSP1) or with recombinant C-terminal peptides protects mice against lethal challenge with virulent malaria parasites. To determine whether other regions of MSP1 can also induce protection, Plasmodium yoelii MSP1 was divided into four separate regions. Each was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The N-terminal fragment began after the cleavage site for the signal sequence and ended in the region comparable to the cleavage site for the C terminus of the 82-kDa peptide of Plasmodium falciparum. This expressed protein was 30 kDa smaller than the predicted peptide. One peptide from the middle region was produced, and the C terminus consisted of a 42-kDa fragment corresponding to the analogous peptide of P. falciparum and a 19-kDa fragment that extended 37 amino acids in the amino-terminal direction beyond the probable cleavage site. To test protection of mice against lethal P. yoelii challenge, three mouse strains (CAF1, BALB/c, and A/J) were vaccinated with each of the four recombinant proteins of MSP1. Mice vaccinated with the C-terminal 19-kDa protein were highly protected (described previously), as were those vaccinated with the 42-kDa protein that contained the 19-kDa fragment. The N-terminally expressed fragment of P. yoelii was not full length because of proteolytic cleavage in E. coli. The GST-82-kDa partial fragments induced some immunity, but the surviving mice still had high parasitemias. Vaccination with the peptide from the middle region of MSP1 gave minimal to no protection. Therefore, in addition to the C-terminal 19- and 42-kDa proteins, the only other fragment to give protection was the 82-kDa protein. The protection induced by the truncated 82-kDa protein was minimal compared with that of the C-terminal fragments.

Animals↗
PubMed1997

[Antagonistic effect of orphanin FQ on morphine analgesia in rat brain].

The discovery of a novel receptor-opioid receptor-like (ORL) receptor (1994) and its endogenous ligand-Orphanin FQ (OFQ) (1995) represented a new approach in the study of opioids and anti-opioids in CNS. Based on the high homology of ORL receptor and OFQ with their opioid family counterparts, as well as the high expression of ORL receptor mRNA and protein in the brain areas associated with nociception, the effect of OFQ on morphine induced analgesia in the rat brain was further investigated. The results showed that: (1) Intracerebroventricular (i.c.v.) injection of OFQ reversed the stress analgesia induced by i.c.v. injection of normal saline, which seems to be mediated by endogenous opioid peptides. (2) I.c.v. injection of OFQ dose-dependently antagonized morphine-induced analgesia dose-dependently. (3) I.c.v. injection of antisense oligodeoxynucleotide for the gene encoding ORL receptor to block the expression of ORL receptor in the CNS potentiated the analgesia induced by cumulative injection of morphine. The results suggest that OFQ seems to play a role of anti-opioid peptide in the rat brain.

Analgesics, Opioid↗
PubMed1997

[2 Hz and 100 Hz electroacupuncture accelerate the expression of genes encoding three opioid peptides in the rat brain].

Previous findings from this laboratory have shown that low (2 Hz) and high (100 Hz)-frequency electroacupuncture (EA) accelerated the release of different kinds of opioid peptides in the CNS. In the present study, we tried to elucidate whether EA of different frequencies would affect the transcription of genes encoding different opioid peptides. Digoxin-labeled antisense cRNA probes were used for in situ hybridization to detect the mRNA encoding preproenkephalin (PPE), preprodynorphin (PPD) and proopiomelanocortin (POMC) in the rat brain. The results showed that: (1) Neither 2 Hz nor 100 Hz EA altered the POMC mRNA level in the rat brain. (2) EA of the two frequencies induced a similar degree of increase of PPE mRNA in rostromedial reticular formation (gigantocellular, paragigantocellular and lateral reticular nucleus); whereas in supraoptic nucleus, suprachiasmatic nucleus, arcuate nucleus, paraventricular hypothalamic nucleus, ventromedial nucleus and the nucleus of lateral lemniscus, 2 Hz EA induced a higher PPE mRNA expression than 100 Hz EA. (3) 100 Hz EA markedly increased the PPD mRNA levels in supraoptic nucleus, paraventricular hypothalamic nucleus, ventromedial nucleus and parabrachial nucleus, while 2 Hz was without effect. Since de novo peptide synthesis is regarded as a natural outcome following accelerated peptide release, the present results substantiate our previous observation that EA of different frequencies exert different acceleratory effects on the release and synthesis of different opioid peptides in the central nervous system.

Acupuncture Analgesia↗
PubMed1996

Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine.

The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.

Animals↗
PubMed1996

Ultrasound-guided internal radiotherapy using yttrium-90-glass microspheres for liver malignancies.

UNLABELLED: Treatment of liver malignancies, in particular hepatocellular carcinoma, remains a serious problem because of the difficulty of delivering adequate therapeutic agents to the lesions while sparing the surrounding normal tissue. In an attempt to overcome this obstacle, intratumoral injection of 90Y, a beta-emitter, was performed. METHODS: Twenty-seven hepatocellular carcinomas and six liver metastases were studied, most of which had failed other therapeutic modalities. Guided by ultrasound, 90Y-glass microspheres (GMS) were carefully injected into predetermined tumor sites. The procedure was repeated at 3--4-wk intervals where indicated. Echographic, clinical and laboratory follow-up was conducted at regular intervals. RESULTS: Twelve to 32 mo after treatment, 27 patients were still alive, with dramatic improvement of their clinical condition: 90.6% of the tumor foci became smaller, with echogenic or blood flow changes on liver sonograms. Serum titers of alpha-FP in 10 of 13 patients returned to normal levels. Repeat biopsy in nine patients showed complete tumor destruction in eight. Six patients died of either end-stage disease or wide dispersion of the tumor. CONCLUSION: The intratumoral administration of 90Y-GMS under ultrasound guidance yielded a higher cure rate for liver malignancy with no severe side effects. The higher radiation dosage delivered by injected 90Y to the periphery of the lesions (up to 28,215-75,720 cGy) was thought to account for the successful outcome. These results show that intratumoral radionuclide injection is feasible for treatment of malignant lesions inside the body.

Adult↗
PubMed1996

[Transcriptional regulation by CREB and proteins of CREB family].

CREB (cAMP-responsive element binding protein), which can be activated after phosphorylation by protein kinase A, plays an important role in cAMP-induced gene expression. Several recent studies have suggested that a co-activator designated as CREB binding protein (CBP) is crucial in mediating the transcriptional activity of CREB. In nervous system, in addition to playing a role in neurotransmitter-induced gene transcription, CREB may take part in mediating neurotrophin signals that ultimately lead to such cellular responses as proliferation, differentiation and survival.

Activating Transcription Factor 1↗
PubMed1995

Immunogenicity and in vivo efficacy of recombinant Plasmodium falciparum merozoite surface protein-1 in Aotus monkeys.

BACKGROUND: The carboxy-terminus of the merozoite surface protein-1 (MSP1) of Plasmodium falciparum has been implicated as a target of protective immunity. MATERIALS AND METHODS: Two recombinant proteins from the carboxy-terminus of MSP1, the 42 kD fused to GST (bMSP1(42)) and the 19 kD (yMSP1(19)), were expressed in Escherichia coli and secreted from Saccharomyces cerevisiae, respectively. To determine if vaccination with these recombinant proteins induces protective immunity, we conducted a randomized, blinded vaccine trial in two species of Aotus monkeys, A. nancymai and A. vociferans. After three injections using Freund's adjuvant, the monkeys were challenged with the virulent Vietnam Oak Knoll (FVO) strain of P. falciparum. RESULTS: All three control monkeys required treatment by Day 19. Two of three monkeys vaccinated with bMSP1(42) required treatment by Day 17, whereas the third monkey controlled parasitemia for 28 days before requiring treatment. In contrast, both of the A. nancymai vaccinated with yMSP1(19) self-resolved an otherwise lethal infection. One of the two yMSP1(19)-vaccinated A. vociferans had a prolonged prepatent period of > 28 days before requiring treatment. No evidence of mutations were evident in the parasites recovered after the prolonged prepatent period. Sera from the two A. nancymai that self-cured had no detectable effect on in vitro invasion. CONCLUSIONS: Vaccination of A. nancymai with yMSP1(19) induced protective immune responses. The course of recrudescing parasitemias in protected monkeys suggested that immunity is not mediated by antibodies that block invasion. Our data indicate that vaccine trials with the highly adapted FVO strain of P. falciparum can be tested in A. nancymai and that MSP1(19) is a promising anti-blood-stage vaccine for human trials.

Amino Acid Sequence↗
PubMed1994

[A study on the pulmonary amine imaging in asthmatic patients and guinea pig asthma models].

Scintigraphic technique (SPECT) with intravenous injection of 131I-HIPDM was used to study pulmonary amine imaging in asthmatic patients and Guinea pig animal models. The results showed that the patients and animals had similar characteristic changes of amine imaging: the amine scanning pictures were not well-distributed, pulmonary amine uptake was significantly decreased but the clearance speed significantly increased as compared with those in healthy controls (P < 0.05-0.01). The only difference between the patients and the animals was that the amine imaging parameters in animals during remission recovered practically to normal, while that in patients during remission did not. The mechanism and clinical significance of the above changes were discussed.

Adolescent↗
PubMed1994

Clinical application of 131I-HIPDM in the patients with chronic obstructive pulmonary disease.

N,N,N'-trimethyl-N'-2 hydroxy-3-methyl-5-iodobenzyl-1,3-propanediamine iodine-131 (HIPDM) as a lung imaging and metabolic tracer in patients with chronic obstructive pulmonary disease (COPD) were used. 0.4 mCi 131I-HIPDM was rapidly injected into the antecubital vein. The imaging of 131I-HIPDM in the lung was different in various groups. 131I-HIPDM of the clearance by the lungs was a biphasic curve (rapid phase and slow phase). It was displayed that rapid phase of the clearance curve of 131I-HIPDM in the lungs in subjects with chronic obstructive pulmonary emphysema, especially those of smokers were very slow. The rapid phase of the 131I-HIPDM of the right lung clearance was significantly correlated with Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Functional Residual Capacity (FRC), Residual Volume (RV), Total Lung Capacity (TLC) p < 0.01; Peak Expiratory Flow Rate (PEFR), Vital Capacity (VC), Maximum Ventilatory Volume (MVV), Arterial oxygen tension (PaO2) p < 0.05. Smoking influence on clearance of 131I-HIPDM of the lung including normal smokers with normal lung function. It was considered that the analysis of the lung release of 131I-HIPDM forms a new lung dysfunction index and it was useful that found early lung damage.

Adult↗
PubMed1994

Prolonged lung retention of 131I-HIPDM in smokers.

Thirty-five subjects were divided into 4 groups; the first group was composed of 8 healthy nonsmoking subjects; the second group included 8 healthy smokers; the third group included 12 nonsmoking patients suffering from chronic obstructive pulmonary emphysema; the fourth group was composed of 7 smokers with chronic obstructive pulmonary emphysema. N,N,N'-trimethyl-N'2-Hydroxy-3-Methyl-5-iodobenzyl-1,3-propanediamine iodine-131(HIPDM) was rapidly injected into the antecubital vein. The influence of 131I-HIPDM by lung clearance was analysed thought imaging of lung and ratio of prolongation of 131I-HIPDM in the lung. Prolongation of 131I-HIPDM in the lung was shown in the smokers with chronic obstructive pulmonary emphysema in 60 minutes, and the healthy smokers, smokers with chronic obstructive pulmonary emphysema in the 24 hours after the injection of 131I-HIPDM. Smoking is an important factor of disturbance of lung clearance.

Adult↗