Volume 111  ·   Issue 08  ·  1998

OBJECTIVE To review the background of telomerase activation and the methodology involved in its determination, and the clinico-pathological significance of telomerase activation in human cancers. METHODS An English-language literature search using MEDLINE (1966-1997) and bibliographic reviews of textbooks and review articles. RESULTS Progressive shortening of telomeres was associated with continuous cell division in normal somatic cells. Telomerase was activated in most cancer cells and immortal germ cells to maintain their telomeric lengths. The occurrence and clinical pathological significance of telomerase activation was evaluated in various types of human cancer. CONCLUSIONS Telomerase activation is a common event in human cancers and may be as a useful marker for malignant cells. Telomerase may also be a therapeutic target for cancer treatment.

Purpose To summarized the methods for establishment, characteristics of vascular lesions in brain and heart and the application of stroke-prone renovascular hypertensive rats (RHRSP). Data sources and methods Most published original articles about RHRSP in our laboratory were reviewed. RESULTS After the renal arteries were constricted bilaterally with ring-shape silver clips, the stroke-prone renovascular hypertensive rats were established. Hypertension was produced in all RHRSP (100%). The peak of blood pressure in RHRSP reached 29.1±3.0 kPa. The lesions of cerebral arteries and arterioles and the damage of cerebral capillary structure by hypertension were observed in the RHRSP. The incidence of spontaneous stroke was 56.4% within 40 weeks after the renal artery constriction. Left ventricular hypertrophy and small coronary arterial lesions in myocardium were discovered in all RHRSP. Myocardial infarction occurred spontaneously in 41.8% of RHRSP. The animal models have been used for the studies on mechanisms of stroke and myocardial infarction. CONCLUSIONS Because the vascular lesions in cerebrum and heart in RHRSP are similar to that in human beings with hypertension, RHRSP can be used in the studies on mechanisms of hypertensive arteriosclerotic stroke and cardiac lesions and on verifying the effects of different medications to complications of hypertension, and the results might be more reliable than that in animal models without hypertension.

The diagnosis of acute pancreatitis (AP) in the clinical setting of chronic renal failure (CRF) is often difficult because of infrequency of common symptoms of AP such as abdominal pain, vomiting, and inability to retain food. We recently experienced a case of severe AP in CRF and successive continuous hemodiafiltrations (CHDF) relieved her from acute phase of severe AP. Interleukin (IL)-6, inflammatory cytokine, playing an crucial role in pathogenesis of AP could be a favorable clinic marker in this patient. CHDF reducing IL-6 may be a considerable treatment for AP in CRF.

Angiotropic lymphoma is a rare, newly confirmed lymphoma which can affect multi-organs, preferentially the skin and the central nervous system. Mostly, the neoplastic cells were B-lymphocyte origin whereas rare T-lymphocyte. The authors report three rare cases of T-lymphocyte origin. The recent literature of this rare disease is reviewed.

Pulmonary lymphangioleiomyomatosis (LAM) is a very rare idiopathic disease which predominantly affects premenopausal women leading to death from respiratory failure. LAM typically presents with progressive dyspnea, cough, pneumothorax and chylothorax.

In the recent 10 years, an important step forward on the studies of prion disease is the findings of three cases in which there were concomitant Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD) (Table). Since then the concept that CJD or AD is an independent and different disease in entity has been changed. We found a patient who clinically demonstrated a slowly progressive dementia of 12-year duration and neuropathologically suffered from both AD and CJD.

OBJECTIVE To facilitate the identification of transplanted retinal pigment epithelial (RPE) cells, we sought to double-label the cells with 5-bromodeoxyuridine (BrdU) and with natural pigment. The BrdU is not lost during cell division but does require immunohistochemical methods for visualization; the pigment on the other hand, allows immediate, obvious identification, but is gradually lost with cell division. Together they provide a convenient, long-term double label. METHODS Non-confluent RPE cells at the second to the fifth passages were labelled with 5-BrdU and pigment. The double-labelled RPE cells were transplanted onto Bruch's membrane of 72 eyes of New Zealand albino rabbits. The labelled cells were localized by anti-BrdU antibody and the avidin biotin-alkaline phosphatase complex (ABC-AP) method, and by visible inclusions of pigment. RESULTS The transplanted RPE cells had distinct basal and apical morphology, and were in close contact with the photoreceptor outer segments of the host. The BrdU label was restricted to the nuclei of the RPE cells, which were stained blue. The pigment was located in the cytoplasm of the apical portion of these RPE cells. No evidence of severe rejection was seen. CONCLUSIONS Using this double-label method, transplanted RPE cells could be readily and reliably identified till one year after transplantation. The transplanted RPE cells revealed normal morphology with some function: they had distinct basal and apical morphology as seen in close contact with the outer segment of photoreceptor cells. The junctional complexes were well formed with neighboring RPE cells. The transplanted RPE cells phagocytose shed outer segments of the host. No evidence of rejection was observed, suggesting that the subretinal space of the rabbit may possess some degree of immunologic privilege. This experiment provides reliable evidence for the clinical research of allotransplantation of RPE cells.

OBJECTIVE To study the effect of the body proportion and pubertal growth spurt on the stature of children with β-thalassaemia major. METHODS The height, sitting height, upper to lower segment (U:L) ratio and pubertal development were determined in 71 Chinese children (38 girls and 33 boys) with β-thalassaemia. The growth patterns of 20 patients with complete growth data between 3 years and final height, were analyzed according to whether they underwent a pubertal growth spurt or not. RESULTS 27% of the boys and 32% of the girls had a height below the 3rd percentile. About 60% of all the children had a U:L ratio below the 10th percentile for age. Abnormal body proportion was found in patients with or without growth retardation. 34% of the 41 children over the age of 14 years underwent spontaneous puberty. In 28 patients over the age of 16 years, a growth spurt was observed in 46% of the children during spontaneous or induced puberty. The retrospective analysis showed that the height deviation from the mean in adulthood was significantly higher in patients without pubertal growth acceleration than in those with a growth spurt (x = -11.8 cm, s = 7.6 cm vs x = -4.4 cm, s = 4.4 cm; P = 0.02). CONCLUSIONS An abnormal U:L ratio was commonly observed in patients with β-thalassaemia major and may be one factor contributing to the short stature of these patients. Abnormal puberty was present in a significant proportion of children and the lack of a pubertal growth spurt was found to be detrimental to adult height.

OBJECTIVE To evaluate the diagnostic accuracy of outpatient hysteroscopy. METHODS Outpatient CO2 hysteroscopy using video-camera for monitoring was performed on 429 patients from November 1995 to December 1996. The indications included post-menopausal bleeding (32.2%), menorrhagia (25.4%), irregular bleeding (24.7%), intermenstrual spotting (10.2%) and others (7.5%). RESULTS Hysteroscopy was successfully performed on 420 (97.9%) patients. Although no anaesthetics were used, only two (0.47%) patients complained of severe pain during the procedure. Twenty-one (4.9%) patients had poor view due to submucosal fibroid or bloody view. There were no operative complications. Normal uterine cavity was found in 36.8% and atrophic endometrium in 34.7% of patients. The pathologies included submucosal fibroid (10.7%), endometrial polyp (5.8%) and fibroid polyp (2.8%). Five (1.2%) out of 429 patients were confirmed histologically to have endometrial carcinoma. No malignant lesions were missed. A total of 372 (86.7%) patients had histological confirmation of hysteroscopic findings. In 57 (13.2%) patients, the histological results did not correlate with the hysteroscopic findings. CONCLUSIONS Outpatient hysteroscopy and suction curettage is a safe, cost-effective and acceptable procedure.

OBJECTIVE To investigate the maternal-fetal transmission of human papillomavirus (HPV). METHODS Samples of exfoliated cervical cells were obtained from 73 pregnant women on their third-trimester examinations. Samples of fetal membranes, amniotic fluid and nasopharyngeal swab were obtained from the parturients and their neonates. The presence of HPV types 16, 18 and 35 deoxyribonucleic acid was detected by polymerase chain reaction (PCR) and endonuclease method. RESULTS HPV types 16, 18 and 35 deoxyribonucleic acid were found in 26 (35.6%) of 73 specimens of cervical cells obtained from the parturients, and in 31 (42.5%) of 73 specimens of fetal membranes, 6 (15.4%) of 39 specimens of amniotic fluid, and 5 (14.7%) of 34 neonatal nasopharyngeal swabs obtained from the neonates. The restriction endonuclease analysis of the amplified products showed that HPV types 16, 18 and 35 were positive in 24.7%, 9.6% and 1.4% respectively of parturients, and 11.0%, 4.1% and 0 respectively of neonates. The maternal-fetal transmission rate of HPV was 50% (7/14) for spontaneous vaginal delivery, and 33.3% (4/12) for cesarean section. CONCLUSIONS HPV can be transmitted from mothers to their babies not only through the placenta during pregnancy, but also through the genital tract during delivery.

OBJECTIVE To investigate the short-term effects of chemotherapy-surgery-chemotherapy regimen on clinically inoperable advanced ovarian cancer. METHODS Retrospective analysis was made on 16 cases of stage III and 2 cases of stage IV epithelial ovarian cancer with fixed pelvic mass. Neoadjuvant chemotherapy with CP (cisplatin + cyclophosphamide) or CAP (CP + adriamycin) regimen was given by intraarterial, intraperitoneal, or systemic routes accordingly for an average of 2.8 courses. Sixteen of the 18 cases were assessed to be operable after preoperative chemotherapy. The uterus, adnexa, omentum, pelvic lymph nodes (14/18), and implants were included in the cytoreductive surgery. Pelvic masses were found to have almost disappeared in 9, and macroscopic residuals were found in 11 (residuals <2 cm in 2, and >2 cm in 5) of the 18 cases. Postoperative chemotherapy (CP, CAP, or CEP, E = VP16) was given for an average of 5.9 courses. RESULTS Five out of 7 patients followed up for over 3 years have been surviving for 46, 44, 40, 38 and 36 months, respectively. CONCLUSIONS Chemotherapy-surgery-chemotherapy regimen has beneficial effects on clinically inoperable advanced ovarian carcinoma.

OBJECTIVE To prepare and identify monoclonal antibody (McAb) against recombinant human tissue factor pathway inhibitor (rhTFPI) and to use it for measurement of TFPI by ELISA, and to evaluate the effects of the McAb on dilute prothrombin time (PT) and activated partial thromboplastin time (APTT). METHODS After intrasplenic immunization of Balb/c mouse with TFPI, hybridoma technique was used to raise monoclonal antibody against rhTFPI. The McAb was well-characterized and labelled with horseradish peroxidase (HRP) by using assay of TFPI in ELISA. Furthermore, the McAb was added to normal and factor IX deficient plasma for observation of dilute PT and APTT. RESULTS Two hybridomas (4F4, 4F8) secreting McAb against TFPI were established. The Ig class and subclass of the McAb purified from 4F8 was IgG1. Immunoblotting results indicated that the McAb4F8 only recognized a single band of TFPI with molecular weight of 34.8 KD. The results of Sandwich enzyme-linked immunosorbent assay (ELISA) by using the HRP labelled McAb4F8 showed that the mean of TFPI in normal human plasma is 103.2±11.5 μg/L. The McAb 4F8 was also proved to shorten markedly dilute prothrombin time of factor IX deficient plasma and normal plasma. CONCLUSIONS We established two hybridomas cell lines (4F4, 4F8) and obtained the McAb4F8 against TFPI and reported the levels of TFPI in healthy adult human plasma by Sandwich ELISA with HRP labelled McAb4F8 in Chinese.

OBJECTIVE To evaluate the effect of dimethyl sulfoxide (DMSO) on the major immediate early promoter of human cytomegalovirus. METHODS THP-1 cells were transfected with plasmids pCAT760, pIE1-163, pIE1-183, pIE1-193 and pIE1-213, respectively, and exposed to dimethyl sulfoxide in the presence or absence of lipopolysaccharide. The extracts of these cells were performed by chloramphenicol acetyl transferase assay. The nuclear extracts of THP-1 cells treated with dimethyl sulfoxide in the presence or absence of lipopolysaccharide were prepared for the DNA binding reaction by electrophoretic mobility shift assay. RESULTS Dimethyl sulfoxide increases the expression of the cytomegalovirus major immediate early promoter, and also upregulated expression of the minimal major immediate early promoter containing triplicates of either the 18 base pair or 19 base pair sequences. Furthermore, gel mobility shift assays showed that dimethyl sulfoxide enhances Nuclear Factor κB and CyclicAMP response element binding protein to bind to the 18 base pair and 19 base pair repeats. CONCLUSIONS One mechanism whereby DMSO enhances human cytomegalovirus replication is through upregulating the major immediate early promoter. This effect on human cytomegalovirus gene expression is, in part, related to enhanced Nuclear Factor κB and CyclicAMP response element binding protein activity.

OBJECTIVE To clinically evaluate the protective effect of procaine blocking on nerves. METHODS Electrophysiological examination before and after procaine blocking was conducted on 32 nerves during operation, 18 of which were donor nerves and 14 were injured ones. RESULTS The latency of somatosensory evoked potentials (SEPs) was lengthened (15.30%) and the amplitude was lowered (18.47) after procaine blocking. Compared with the values before procaine blocking, the differences were significant (P<0.01 and P<0.05, respectively). SEP waves disappeared after procaine blocking in some cases (28.13%). CONCLUSIONS Latency of SEP is lengthened and amplitude is lowered after procaine blocking. In some cases, SEPs even disappear.

OBJECTIVE To compare surgery (S) alone with combined radiotherapy and surgery (R + S) in the management of patients with supraglottic laryngeal cancer. METHODS Between 1981 and 1994, patients were stratified according to stage and randomised to either surgery (S) or 4000cGy of radiotherapy and surgery. There were 102 patients in the S group and 99 in the R + S group who completed at least 3-year follow-up. RESULTS Using Kaplan-Meier survival method showed no significant difference between the two groups. When the patients were grouped according to tumour stage, a significant reduction in the regional recurrence was noted in the R + S group for stage I-III disease (Cox multivariate analysis, P<0.02). They had an increased relative risk of 1.8 (95% confidence 1.1-2.9) for neck recurrence. There was no significant difference in neck recurrence rates in the two groups for stage IV disease. When Cox proportional hazard model was used, only TNM stage (P<0.02) and histological nodal status (positive lymph nodes, P<0.01) were found to be independent risk factors for regional control. CONCLUSIONS Preoperative radiotherapy can improve regional cervical control of stage I-III supraglottic cancer as compared with surgery alone.

OBJECTIVE To explore the relationship between receptor for advanced glycosylation end products (RAGE) gene expression in the kidneys of diabetic rats and the role of aminoguanidine on it. METHODS Among four groups of rats, 2 groups received streptozotocin (STZ) to induce diabetics (DM) and were followed by either aminoguanidine (AG) treatment for 12 weeks or no therapy. Two groups of normal rats in which one received AG and the other given water served as control (Con). Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the amount of receptor of advanced glycosylation and products (RAGE) messenger RNA (mRNA) expression. RESULTS After 4 weeks of diabetes inducement, RAGE mRNA levels showed a continuous increase up to 12 weeks both in diabetic renal cortex and medulla compared with mRNA levels at the end of 2 weeks. The RAGE mRNA levels in renal cortex and medulla of control rats did not change significantly with age. AG as the prototype inhibitor of advanced glycosylation end products (AGEs) formation, when administered to diabetic rats for 4 weeks, had no visible effect on the alterations of renal RAGE mRNA in diabetes. By continuous administration up to 8 weeks, those alterations of RAGE mRNA both in diabetic renal cortex and medulla were all ameliorated [P<0.05, (diabetes without AG) versus (diabetes with AG)]. In addition, diabetic animals had a progressive increase in urinary protein excretion compared to control rats from week 4 onwards. Similarly, after 8 weeks diabetic rats had significantly higher glycated Hb (GHb) (DM without AG vs Con: 7.71±0.22% vs 2.95±0.52% P<0.001). AG treatment for 8 weeks decreased GHb by 24.78% and retarded the rate of rise in albuminuria in diabetic rats as compared with that in untreated diabetic rats (DM with AG vs DM without AG: 22.04±0.91 μg/24 h vs 70.25±13.05 μg/24 h, P<0.001). CONCLUSIONS Gene expression of RAGE in renal cortex and medulla was altered in diabetic rats and excessive gene expression of RAGE in kidney tissue may enhance the interactions between advanced glycosylation end products (AGEs) and its receptor (RAGE) which would contribute to the development of diabetic nephropathy. Cumulative AGEs play an important role in increasing RAGE gene expression in vivo. The decrease of AGEs level by AG therapy ameliorate the abnormal regulation of RAGE gene expression.

The Chinese pharmaceutical production has been developing rapidly in the past decade. It was reported that the drug expenditure of whole country reached to $ 10.8 billion in 1996. The trend of an increasing amount of money spent on drugs appears to be persistent and even accelerating.

OBJECTIVE To find an effective method for the treatment of malignant cerebral glioma by opening the blood-brain-barrier (BBB). METHODS The concentration of methotrexate (MTX) in tumor was measured in 18 patients with cerebral glioma, and 155 patients with malignant glioma were treated by intracarotid infusion of papaverine and Bis-chloronitrosourea (BCNU). RESULTS After intracarotid infusion of papaverine for reversible opening of BBB, the MTX concentration in tumor tissue was 1810±380 ng/g, higher than that in patients without papaverine infusion (997±126 ng/g). Eighty-nine patients with glioblastoma and 66 patients with anaplastic astrocytoma received intracarotid infusion of papaverine and BCNU (250 mg) for an average of 2.14 times. The mean survival time of these patients was 114.5 weeks, median survival time was 140 weeks, and five-year survival rate was 22.97%. CONCLUSIONS The combined chemotherapy with papaverine and BCNU through intra-arterial infusion is simple, safe and effective in treating malignant cerebral glioma so long as the tumor is sensitive to the drugs.