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Biomedical subjects

R Liang

Publications and source records attributed to R Liang.

At least 127 records · Page 7Linked to original sources

Incidence and pathology of primary brain lymphoma in Hong Kong Chinese patients.

Primary brain lymphoma (PBL) is an uncommon extranodal lymphoma. Its incidence is rapidly increasing in both immunocompromised and immunocompetent patients in Western countries. Eighteen cases of PBL were identified during a 16-year period among HIV negative patients in Queen Mary Hospital, Hong Kong. One case of post-transplantation lymphoproliferative disease (PTLD) was positive for Epstein Barr virus (EBV) encoded RNA (EBER) by in situ hybridization. All the remaining 17 immunocompetent cases were classified as diffuse large B-cell lymphoma, except for one case of Burkitt's lymphoma. EBER expression was negative in all 13 cases tested. Immunostaining for bcl-2 and bcl-6 was positive in 8/11 and 6/11 cases tested, with heterogeneous combination of expression and intensity. The incidence rate of PBL in immunocompetent patients was stable at 1.03 per million per year. The incidence of PBL in post transplantation (0.16%) and HIV related setting (0.29%) is also low in Chinese. PBL in Chinese patients is almost uniformly represented by EBV negative, diffuse large B-cell lymphoma, confined to the brain. However, the molecular pathogenesis may be heterogeneous.

Adult↗

CD-30 positive peripheral T-cell lymphoma of the Waldeyer's ring.

We describe a patient with peripheral T cell lymphoma of the Waldeyer's ring that ran a highly aggressive course. This is followed by a discussion on the differential diagnoses of nasal T/NK cell lymphoma and Ki-1 ALCL, based on clinical and pathological features.

Adult↗

Diagnosis and management of primary nasal lymphoma of T-cell or NK-cell origin.

The primary nasal natural killer cell (NK/T cell) lymphoma is histologically characterized by angiocentricity with invasion of blood vessels and blockage of blood vessels by lymphoma cells, resulting in marked ischemic necrosis of the normal and neoplastic tissues. The cytological appearances of the neoplastic cells are highly variable and accompanied by a mixture of inflammatory cells. On immunophenotyping, the diagnostic features are surface CD3(-), cytoplasmic CD3 epsilon(+), and CD56(+). For the majority of the cases, T-cell receptor gene rearrangement is absent, confirming an NK-cell origin of the tumor cells. Clonal proliferation of Epstein-Barr virus (EBV) is usually present in the tumor cells and is a useful diagnostic marker. Patients commonly present with nasal symptoms: mass, obstruction, or bleeding. The tumor is locally invasive and may infiltrate surrounding tissues and organs, such as the orbits, nasopharynx, oropharynx, and palate. The cranial nerves are sometimes affected. The tumor may also disseminate to skin, gastrointestinal tract, and the testis at the time of progression. Occasionally, other organ sites such as the skin are involved, sparing the nose, and it is then called the non-nasal type. A high index of suspicion is required for the diagnosis of this disease. Because of the small size of the specimen and the necrotic nature of the tumor, biopsy of the nasal tissue may not be easy to interpret. Repeated biopsies are often required. The special stain for EBV in the tumor cells may also be helpful in making the correct diagnosis. Response of primary nasal T-/NK-cell lymphoma to local treatment such as radiotherapy is often not satisfactory. Combined chemotherapy and radiotherapy has been used and appears to be more effective.

Antigens, Neoplasm↗

[Study of relativity between HBV M and HBV DNA in the cases with hepatitis B].

OBJECTIVE: Serum samples of 414 cases with hepatitis B were detected for hepatitis B markers (HBV M) and HBV DNA, in order to investigation the relationship between HBV M and HBV DNA, and its clinical significant. METHODS: HBV M and HBV DNA were detected by ELISA and blot hybridization methods respectively. RESULTS: HBV DNA positive rates in the groups of acute and chronic hepatitis B were higher than that in the group of liver cirrhosis (P <0.01); HBV DNA positive rates had no apparent difference between the HBsAg, HBeAg, anti-HBc positive group and the HBsAg, anti-HBs, anti-HBc positive group. Direct relativity was shown between the titer of HBsAg and/or HBeAg and the positive rate of HBV DNA. CONCLUSIONS: HBV DNA can be treated as a sign of HBV activity; the appearance of anti-HBs can not be taken as indicator of ceasing of HBV replication; the changes in HBsAg and HBeAg titers may be used as clinical evaluation on HBV replication and index for anti-viral therapeutic effect.

Adult↗

T-lymphocyte activation increases hypothalamic and amygdaloid expression of CRH mRNA and emotional reactivity to novelty.

Stimulation of T-cells with staphylococcal enterotoxin B (SEB) significantly elevates interleukin-2 (IL-2) and contemporaneous activation of the hypothalamic-pituitary-adrenal (HPA) axis and c-fos in the paraventricular nucleus (PVN) of BALB/cByJ mice. Such neural signaling may promote cognitive and emotional adaptation before or during infectious illness. Because corticotropin-releasing hormone (CRH) is an anxiogenic neuropeptide that may mediate the stressor-like effects of immunological stimuli, we measured neuronal CRH mRNA alterations in mice challenged with SEB. Increased CRH mRNA levels were observed in the PVN and central nucleus of the amygdala (ceA) 4-6 hr after SEB administration. This was associated with plasma ACTH increases, which could be abrogated by the systemic administration of anti-CRH antiserum. Additional experiments did not support a role for IL-2 or prostaglandin synthesis in activating the HPA axis. Behavioral experiments testing for conditioned taste aversion did not confirm that SEB challenge promotes malaise. However, consistent with the notion that central CRH alterations induced by SEB may affect emotionality (e.g., fear), SEB challenge augmented appetitive neophobia in a context-dependent manner, being marked in a novel and stressful environment. It is hypothesized that immunological stimuli generate a cascade of events that solicit integrative neural processes involved in emotional behavior. As such, these data support the contention that affective illness may be influenced by immunological processes and the production of cytokines and are consistent with other evidence demonstrating that autoimmune reactivity is associated with enhanced emotionality.

Adrenocorticotropic Hormone↗

Outcome of Chinese patients with chronic myeloid leukaemia (CML) underwent allogeneic bone-marrow transplantation (BMT).

UNLABELLED: Clinical studies have shown that patients with chronic myeloid leukaemia (CML) treated with allogeneic bone-marrow transplantation (BMT) experience not only prolonged disease-free survival but also complete cure in some. Therefore, we followed a cohort of 81 Chinese patients who received allogeneic BMT. PATIENTS AND METHODS: The donors were either relatives (65 siblings, 1 parent) or unrelated volunteers (15). BMT was performed at a median interval of 11.6 months from diagnosis of CML, and the stages of disease before BMT were: first chronic phase (60 patients), accelerated or second chronic phase in (10 patients), and blastic crisis (11 patients). Three conditioning regimens were employed: Bu-Cy, Cy-TBI, or Bu-Cy-TBI. Standard cyclosporin and short methotrexate protocol were used for acute graft-versus-host disease (GvHD) prophylaxis. RESULTS: There were five graft failures with three after related BMT. Patients after related or unrelated BMT had a comparable rate of neutrophil recovery (median = 22 days), but significant delay in platelet recovery occurred after unrelated BMT (median = 34 vs. 20 days, P < 0.05). The latter also had higher incidence of acute GvHD (73% vs. 41%, P < 0.05), although the incidence of chronic GvHD was not different between groups. At a median follow-up of 43.5 months, patients after related BMT had a significantly better rate of disease-free survival (68% vs. 37.3%, P < 0.05) and overall survival (81% vs. 38.9%, P < 0.05) at 4 years. Subgroup analysis of patients after related BMT showed the outcome was better when they were transplanted at first chronic phase. Multivariate analysis showed that advanced disease (RR = 2.01, 95% CI = 1.48-2.73) significantly worsened the outcome of BMT, whereas the presence of chronic GvHD had a protective effect against relapse and survival (RR = 0.09, 95% CI = 0.02-0.38). CONCLUSION: Allogeneic BMT is a curative form of treatment for patients with CML. Treatment outcome is best for those who undergo transplants from HLA-matched siblings during the first chronic phase.

Acute Disease↗

Advanced stage and unfavorable Hodgkin's disease in the Chinese-a 20-year experience.

We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977 to December 1997. There were 29 male and 28 female patients. The median age was 27 years old (range, 13-59). Lactate dehydrogenase levels ranged from 104 units/l to 2320 units/l (median, 433). Eighteen (31.6%), 13 (22.8%), and 26 (45.6%) patients had stage II bulky, stage III, and stage IV disease, respectively. Twenty-five (44%) patients had B symptoms. One (1.8%), 3 (5.3%), 36 (63.2%), and 17 (29.8%) had lymphocyte predominant, lymphocyte depleted, nodular sclerosis, and mixed cellularity histology, respectively. Chemotherapy regimens included mechlorethamine, vincristine, procarbazine, prednisone (MOPP) (n = 9), adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) (n = 23), MOPP alternating with ABVD (n = 13), and COPP-ABV hybrid (n = 12). Complete remission was achieved in 47 (82.4%) patients. Eleven patients (23%) relapsed after the first complete remission and four (36%) attained a second complete remission with salvage chemotherapy. Projected overall survival was 69.0% at 10 years and 20 years. Disease-free survival rates were 71% at 10 years and 20 years. Of the potential prognostic factors analyzed (age, sex, stage, lactate dehydrogenase, serum albumin level, regimen, B symptoms and bulky disease) by using the Cox regression model, only a low albumin level was found to adversely affect overall survival (P = 0.003). In conclusion, despite the relative low incidence of Hodgkin's disease in Hong Kong Chinese, the treatment outcomes in patients with advanced stage or unfavorable Hodgkin's disease is comparable to Caucasian patients.

Adolescent↗

Extra-medullary relapse of leukemia following allogeneic bone marrow transplantation.

The curative effect of allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia is attributed to the intensive conditioning chemotherapy with or without radiotherapy, as well as an immune-mediated graft versus leukemia (GVL) effect. A different pattern of relapse has been observed after allogeneic BMT for patients with leukemia. Compared with treatment using conventional chemotherapy alone, isolated extra-medullary relapse of disease appears to be seen more commonly after allogeneic BMT. While a full donor's hematopoiesis may be retained, prolonged morphological remission has been observed in the recipient's bone marrow. There appears to be a population of leukemic cells with an affinity to extra-medullary tissues. The failure of the leukemic clone to repopulate the recipient's marrow suggests the presence of a more profound GVL effect in the marrow environment. The optimal treatment for extra-medullary relapse of leukemia following allogeneic BMT remains uncertain. In the case of isolated extra-medullary relapses following BMT, the leukemia may still be responsive to further treatment with chemotherapy and/or radiotherapy. The prognosis is poor in general, but prolonged survival has been observed in some of these patients. With the preservation of donor's hematopoiesis in the recipient's marrow, the use of intensive chemotherapy followed by donor lymphocyte or stem cell re-infusion is a promising option.

Bone Marrow Transplantation↗

Qualitative and quantitative magnetic resonance imaging in haemoglobin H disease: screening for iron overload.

OBJECTIVES: To evaluate the clinical utility of magnetic resonance imaging (MRI) in screening for iron overload in non-transfusion dependent Haemoglobin (Hb) H disease. PATIENTS AND METHODS: Thirty-six non-transfusion dependent HbH patients were evaluated with axial spin echo T1 and gradient echo T2 MRI of the abdomen and heart. The ratios of signal intensities (SIR) of the liver, spleen, pancreas and heart to paraspinous muscles were calculated. SIR <1 was taken as indicative of iron overload. Qualitative grading (0-4 scale) of iron overload was also performed. The relationship between T1 and T2 SIR and serum ferritin, and that between qualitative grading and serum ferritin were examined using standard statistical methods. Comparisons were also made between qualitative grading and quantitative T1 and T2 SIR data in diagnosing iron overload. Six patients underwent liver biopsies. RESULTS: T2 SIR was more sensitive in detecting iron overload than T1 SIR. Thirty-three livers, 13 spleens, six pancreas and one heart were diagnosed as having iron overload with T2 SIR, including three patients with normal serum ferritin. A positive diagnosis by T2 SIR was more closely related to that of qualitative grading than T1 SIR. Serum ferritin was negatively correlated with hepatic SIR (T1 and T2), and with T2 SIR of the spleen and pancreas, even after adjustment for age. Liver haemosiderosis was confirmed in all six patients who underwent liver biopsies. Liver iron concentration of only one and a half times the normal was found in one patient with positive MR findings. CONCLUSION: MR is a non-invasive, effective method for early detection of iron overload particularly in the liver and spleen. Qualitative grading and quantitative T2 SIR data are equivalent in diagnosing iron overload. Routine screening of non-transfusion dependent HbH patients will identify high risk patients in whom early therapeutic intervention may prevent further complications and morbidity.

Adult↗

Donor lymphocyte infusion induced molecular remission in relapse of acute myeloid leukaemia after allogeneic bone marrow transplantation.

Donor lymphocyte infusion (DLI) has been used successfully to induce remissions in relapse of acute myeloid leukaemia (AML) after bone marrow transplantation (BMT), but molecular eradication of leukaemia has rarely been documented. A patient with AML-M4Eo relapsed after HLA-identical sibling BMT in first complete remission (CR). Cytogenetic and molecular genetic investigations confirmed inv(16) and CBFbeta/MYH11 fusion characteristic of M4Eo. A second remission was obtained with chemotherapy. Full donor chimerism was demonstrated by fluorescence in situ hybridisation. However, molecular evidence of minimal residual disease still persisted, and donor lymphocyte infusion (DLI) was administered. This resulted in molecular eradication, and the patient remained in clinical and molecular remission 16 months from DLI. Our observations showed that, for AML relapse after BMT, molecular leukaemia eradication could be achieved by DLI so that, in cases where genetic markers are available, molecular monitoring should be performed to assess the efficacy of treatment.

Adult↗

Isolated extramedullary relapse of acute lymphoblastic leukaemia after allogeneic bone marrow transplantation.

Isolated extramedullary relapse of acute lymphoblastic leukaemia (ALL) with sparing of the marrow after allogeneic bone marrow transplantation (BMT) is a rare occurrence, and the mechanisms underlying the selective involvement of extramedullary sites remain undefined. These might be due to relapse in sanctuary sites where the leukaemic cells are resistant to chemotherapy, or a stronger putative graft-versus-leukaemia (GVL) effect in the marrow as compared with peripheral tissues. We report two ALL patients with repeated episodes of extramedullary relapse after BMT in whom both mechanisms might be operating. In the first patient, the marrow was in morphologic and molecular remission before isolated leukaemic relapse in the central nervous system (CNS) occurred. Subsequent secondary infiltration of leukaemic cells into the marrow was only evident molecularly but not morphologically, implying that the relapse had arisen in a sanctuary CNS site. In the second patient, a first relapse in the marrow, which was induced into morphologic and molecular remission by chemotherapy and donor lymphocyte infusion, was followed by extramedullary relapses without any subsequent involvement of the marrow. This suggested that factors, likely to be due to a GVL effect, were stronger in the marrow than in peripheral tissues.

Adult↗

Structure and transcriptional regulation of the ovine placental lactogen gene.

Ovine placental lactogen (oPL), a member of the growth hormone/prolactin gene family, is produced by chorionic binucleate cells at the maternal-fetal interface, and is thought to modulate metabolic processes and enhance fetal growth. We have determined that the oPL gene contains five exons and four introns, and the transcriptional start site was mapped 91 bp 5' of the initiation codon (AUG). An additional 4.5 kb of 5'-flanking sequence was sequenced and used for transient transfection analysis in human (BeWo) and rat (Rcho-1) choriocarcinoma cell lines to examine trophoblast cell-specific activity. Trophoblast cell-specific transactivation of the reporter gene was conferred by the proximal 1. 1 kb of oPL gene 5'-flanking sequence. Transfection of deletion constructs derived from the 1.1 kb of 5'-flanking sequence resulted in varying profiles of transactivation between the two choriocarcinoma cell lines, but maximal activation in both cell lines resided within the proximal 383 bp of oPL gene 5'-flanking sequence. DNase I protection analysis using ovine chorionic binucleate cell nuclear protein, identified 19 footprints within the 1.1-kb sequence, six of which are located within the 383-bp region. Electrophoretic mobility-shift assays and mutational analysis identified two functional GATA (-67, -102) sequences as transactivators of the oPL gene. However, a previously undefined element (GAGGAG) residing at -338 and -283 is required for full transactivation, and mutation of either significantly reduces reporter activity. In addition, an AP-2 site (-58) and an E-box (-163) were identified and may coordinate oPL transactivation. Transcriptional regulation of human and rodent PL genes has been previously characterized, and our results indicate that tissue-specific regulation of oPL expression may result from cis-acting elements in common with human and rat genes expressed within the placenta. However, our data indicate that regulation of oPL also results from novel cis-acting elements.

Animals↗

Histological changes during clearance of chronic hepatitis B virus infection by adoptive immunity transfer.

BACKGROUND: Serological clearance of hepatitis B surface antigen (HBsAg) has been described after reception of hepatitis B surface antibody positive marrow, via allogeneic bone marrow transplantation (BMT). Histological changes during the clearance of HBsAg are unknown. METHODS AND RESULTS: We described two chronic hepatitis B carriers (both hepatitis B e antigen negative), who cleared HBsAg after allogeneic bone marrow transplantation. Both received hepatitis B surface and core antibody positive human leucocyte antigen identical donors' marrow and had serological clearance of HBsAg 15 and 7 weeks after allogeneic BMT, respectively. Both events were preceded by hepatic flare. Both patients were also treated with famciclovir for the prevention of hepatitis B reactivation after BMT. Histological examination during the flare showed only mild necroinflammatory activity with multiple foci of confluent necrosis, associated with moderate lymphocytic infiltration. The majority of these lymphocytes were cluster of differentiation (CD) 8 positive. Using immunohistochemistry, there was no detectable hepatic expression of hepatitis B core antigen. However, HBsAg was positive, mainly in the area of confluent necrosis. Using in situ hybridization, hepatitis B virus (HBV) DNA was detected in the nucleus of 5% of hepatocytes, but not in the cytoplasm. CONCLUSIONS: At their last follow up, 22 and 16 months after BMT, the serum of both patients remained HBsAg negative, hepatitis B surface antibody positive and HBV-DNA negative by branched DNA assay.

2-Aminopurine↗

Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage.

Epidemiological evidence suggests that certain paternal exposures to metals may increase the risk of cancer in the progeny. This effect may be associated with promutagenic damage to the sperm DNA. The latter is packed with protamines which might sequester carcinogenic metals and moderate the damage. Human protamine P2 has an amino acid motif at its N-terminus that can serve as a heavy metal trap, especially for Ni(II) and Cu(II). We have synthesized a pentadecapeptide modeling this motif, Arg-Thr-His-Gly-Gln-Ser-His-Tyr-Arg-Arg-Arg-His-Cys-Ser-Arg-amide (HP21-15) and described its complexes with Ni(II) and Cu(II), including their capacity to mediate oxidative DNA degradation [Bal et al. (1997) Chem. Res. Toxicol., 10, 906-914 and 915-921]. In the present study, effects of HP21-15 on Ni(II)- and Cu(II)-mediated DNA oxidation by H2O2 at pH 7.4 were investigated in more detail using the circular plasmid pUC19 DNA as a target, and the single/double-strand breaks and production of oxidized DNA bases, as end points. Ni(II) alone was found to promote oxidative DNA strand scission (mostly single strand breaks) and base damage, while Cu(II) alone produced the same effects, but to a much greater extent. Both metals were relatively more damaging to the pyrimidine bases than to purine bases. HP21-15 tended to increase the Ni(II)/H2O2-induced DNA breakage. In sharp contrast, the destruction of DNA strands by Cu(II)/H2O2 was almost completely prevented by HP21-15. The effect of HP21-15 on the oxidative DNA base damage varied from a limited enhancement (5-hydroxyhydantoin and thymine glycol) to slight suppression (5-hydroxycytosine, 5-hydroxyuracil, 8-oxoguanine, 8-oxoadenine, 2-hydroxyadenine, fapyguanine and fapyadenine) toward Ni(II)/H2O2. HP21-15 strongly suppressed the oxidative activity of Cu(II)/H2O2 in regard to all bases in DNA. Consistently with the above, the electron spin resonance/spin trap measurements revealed greater and more persistent generation of OH* and O2-*-like oxidants from H2O2 by the Ni(II)-HP21-15 complex than by the Cu(II)-HP21-15 complex (no O2-* was detected). Both complexes were also found to bind to DNA more strongly than HP21-15 alone. The results indicate that protamine P2 is capable of binding Ni(II) and Cu(II) and, in this way, attenuating the mediation of oxidative DNA damage by Cu(II), but not Ni(II). The effects found may be mechanistically involved in the reproductive toxicity and carcinogenicity of metals.

Animals↗