Volume 111 · Issue 08 · 1998

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.

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.

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.

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.

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.

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.

OBJECTIVE To study the current status of autotransplantation in the People's Republic of China and facilitate national and international exchange of relevant experiences. METHODS On the basis of the materials collected from the member units around our country, various statistical methods, such as Kaplan-Meier and chi 2 tests, were used to estimate the probabilities of leukemia free survival (LFS). RESULTS Up to July 31, 1996, a total of 1213 cases of stem cell transplantation (SCT) were performed in 61 medical units in the People's Republic of China, and 22 of the units are able to perform both allogeneic SCT (Allo-SCT) and autologous-SCT (ASCT). The remaining 41 units had the capacity only to perform autologous-SCT. There were 772 cases of autologous SCT performed. The three year probabilities of leukemia free survival for acute mylogeneous leukemia complete remission (AML-CR1) and acute lymphocyte leukemia complete remission (ALL-CR1) recipients were 56% and 42.8%, respectively. The three year probabilities of relapse were 44.8% and 47%, respectively. Among the patients with acute leukemia who attained CR1 within 40 days of diagnosis and who subsequently underwent autotransplantation within three to six months, the three year probabilities of LFS for acute mylogenous leukemia (AML) and acute lymphocyte leukemia (ALL) were 72% and 50%, respectively. CONCLUSIONS Patients who attained complete remission (CR1) within 40 days after diagnosis and underwent subsequent autologous-SCT within three to six months of CR1 enjoyed a significantly increased LFS.

OBJECTIVE To explore the anti-apoptotic mechanism and the effective apoptosis-inducing method in chronic myelogenous leukemia (CML) cells. METHODS K562 cell line was used to observe the effect of combination of herbimycin A (HMA), a tyrosine kinase inhibitor, and chemotherapeutic agents on the induction of apoptosis. RESULTS HMA or chemotherapeutic agents could inhibit the proliferation but not significantly induce apoptosis of K562 cells. However, HMA significantly enhanced apoptosis when combined with chemotherapeutic agents. Addition of sulfhydryl compound to the cultures to conjugate HMA completely abrogated this enhancing effect on K562 cells. CONCLUSIONS HMA increases the sensitivity of CML cells to chemotherapeutic agents by inactivating tyrosine kinase activity. It is promising that combination of HMA with conventional chemotherapeutic drugs may be a new strategy in the treatment of CML.

OBJECTIVE To study the suppressing genes of apoptosis, namely Bcl-2, its family genes Bax, Bcl-Xl, and the inducing gene of apoptosis Fas/Apo-1. METHODS The techniques of cytoimmuno-histiochemical stains, Western blotting and Northern blotting were used. RESULTS It was found that the antigens of Bcl-2 in acute myelogenous leukemia (AML) and acute lymphocytic (ALL) was higher than that in the normal (P<0.01). At same time, Bcl-2 was obviously lower expression in complete remission (CR) group than that in non-remission (NR) one by retrospective analysis (P<0.01). Though Bcl-2 was low expression in CR with Western blotting, there was no statistical significance (P>0.05). In CR group the expression of Bcl-2 mRNA was obviously lower than that of NR one (P<0.01). Even though leukemia expression of Bax with cytoimmuno-histiochemical stain was also lower than that in the normal people, there was no difference between CR and NR with cytoimmuno-histiochemical, Western blotting and Northern blotting (P>0.05). There was difference of Bcl-Xl mRNA in two groups (P<0.01). The expression Fas/Apo-1 in leukemia was lower than that in normal people (P<0.01). But in CR and NR, there was no difference with cytoimmuno-histiochemical stain and Western blotting. CONCLUSIONS The Changes of genes and their proteins are significant theoretically and clinically. The antigen expression of Bcl-2 and the expression of Bcl-2 mRNA may be considered as a prognostic index for AML.

OBJECTIVE To study Sma Ⅰ, Hha Ⅰ, Msp Ⅰ and Rsa Ⅰ restriction fragment length polymorphisms in vWF gene of Chinese population. METHODS The vWF gene from 52 unrelated individuals of Han Nationality, 44 of Yi tribe, 42 of Dai tribe was analyzed by polymerase chain reaction and digestion of the endonucleases of Sma Ⅰ, Hha Ⅰ, Msp Ⅰ and Rsa Ⅰ. RESULTS The allele frequencies were 0.38:0.62 for Sma Ⅰ+:Sma Ⅰ- and 0.38:0.62 for Hha Ⅰ+:Hha Ⅰ-; 0.20:0.80 for Msp Ⅰ+:Msp Ⅰ-; 0.93:0.07 for Rsa Ⅰ+:Rsa Ⅰ- in Chinese Han population. The theoretical heterozygous rates were 0.46, 0.46, 0.36 and 0.13 of these polymorphisms, respectively. The allele frequencies were 0.43:0.57 for Sma Ⅰ+:Sma Ⅰ- and 0.43:0.57 for Hha Ⅰ+:Hha Ⅰ-, 0.26:0.74 for Msp Ⅰ+:Msp- in Yi tribe and 0.36:0.64 for Sma Ⅰ+:Sma Ⅰ- and Hha Ⅰ+:Hha Ⅰ-, 0.17:0.83 for Msp Ⅰ+:Msp Ⅰ- in Dai tribe. The theoretical rates were 0.49 for Sma Ⅰ and Hha Ⅰ and 0.38 for Msp Ⅰ in Yi tribe; and 0.45 for Sma Ⅰ and Hha Ⅰ, 0.28 for Msp Ⅰ in Dai tribe, respectively. CONCLUSIONS The allele frequencies and theoretical rates of these polymorphisms in vWF gene are different between Chinese populations and Caucasians. They should be useful for the carrier detection and prenatal diagnosis in vWD families of Chinese.

OBJECTIVE To evaluate whether hypermethylation of calcitonin (CT) gene could serve as a transforming signal of myelodysplastic syndrome (MDS) to leukemia. METHODS Bone marrow aspirates from 35 MDS patients, including 25 refractory anemia (RA), 10 refractory anemia with excess of blasts (RAEB) or refractory anemia with excess of blasts in transformation (RAEBt) and 7 cases of acute myeloid leukemia (AML) transformed from MDS, were studied on methylation rate in 5' end of CT gene by polymerase chain reaction (PCR) technique using methylation-sensitive endonuclease Hpa Ⅱ with external references of undigested DNA and Msp I digested DNA and internal reference of 112 bp fragment containing codon 61 of N-ras oncogene. The RESULTS were expressed as calcitonin gene methylation rate (CTMR) calculated from the densitometer-analyzed integral calculus of PCR products of 566 bp CT(a1), 112 bp N-ras(b1) by using Hpa Ⅱ-digested DNA and PCR products of 566 bp CT (a0), 112 bp N-ras(b0) by using undigested DNA according to the formula, CTMR = (a1/b1)/(a0/b0) x 100%. RESULTS The CTMRs in total 35 MDS, 25 RA, 10 RAEBt and 7 cases of AML transformed from MDS were 36.87%±25.10%, 28.12%±24.01%, 58.74%±16.49%, and 54.03%±7.06% respectively, significantly higher than that in control group (P<0.001, P<0.05, P<0.001 and P<0.001, respectively). CONCLUSIONS The results suggest that hypermethylation of CT gene occurs in early stage of leukemic transformation and CTMR might be a useful marker in predicting the transformation of MDS to AML.

OBJECTIVE To investigate the association of the absence or presence of aspartic acid at position 57 of the HLA-DQ β chain (NA or A) with susceptibility or resistance to insulin-dependent diabetes mellitus (IDDM) in a Southern Chinese population. METHODS Sixty-nine IDDM patients and 47 healthy controls in a Southern Chinese population were HLA-DQB1 genotyped by one-step sequence specific polymerase chain reaction (ssPCR). RESULTS The frequencies of NA and A were 64.5% and 35.5% in the IDDM patients, and 40.4% and 59.6% in the control subjects respectively (RR for NA was 2.68, P<0.01). The frequencies of NA/NA, NA/A and A/A phenotypes were 47.8%, 33.3% and 18.8% in the IDDM patients, and 31.9%, 17.0% and 51.1% in the controls respectively (P<0.01). The frequency of A/A phenotype was significantly lower in the IDDM patients than in the control subjects (RR = 0.22, P<0.01). DQB1* 0302 and DQB1* 0201 were more frequent in IDDM patients than in control subjects. The younger the age of IDDM onset, the higher the allele frequencies of DQB1* 0201 and DQB1* 0302. CONCLUSIONS The present study suggests that the NA confers the susceptibility to IDDM, while the A confers the protection against IDDM in patients of Southern Chinese origin. These associations are more clearcut in childhood-onset IDDM patients.

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.

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 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 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 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.

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.