Biomedical subjects

Z Jiang

Publications and source records attributed to Z Jiang.

At least 199 records · Page 11Linked to original sources

PubMed1998

[The importance of the canine model in medical genetics].

Dog domestication dates back to as early as 100,000 years ago, or 10,000 years depending upon the data used, and nowadays more than 350 breeds are duly registered in the different kennel clubs around the world. Due to intensive selection in the course of breeding, dog presently comes in any shape, size, color one can imagine, in addition to displaying a wide panel of characters, capacities and behaviours. As a consequence of excessive breeding, numerous breeds are plagued by a large variety of genetic diseases, many of them resembling those observed in human. All this makes dog an attractive model to track down genes and alleles responsible for those phenotypic behavioural or pathological traits, provided a genome map with polymorphic markers, and genes is available.

Animals↗

PubMed1998

Expression of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of the lung with observations on the expression of these adhesion molecules in non-neoplastic lung tissue.

Intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and the lymphocyte function-associated antigen (LFA-1) are cell adhesion molecules thought to play an important role in the complex process of airway inflammation and tumor cell growth. The aim of this study was to examine the distribution of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of lung and in major cellular compartments of non-neoplastic lung tissue. We examined cellular compartments in tissue from five bronchoalveolar carcinomas, three acinar adenocarcinomas, and one colon cancer metastatic to the lung. The compartments in neoplasms included the tumor cells proper, endothelial cells within the tumor vasculature, tumor stromal cells, and tumor-infiltrating lymphocytes. The compartments in non-neoplastic lung tissue included lung endothelial cells, pulmonary lymphocytes, interstitial fibroblasts, Type II alveolar pneumocytes, and bronchial epithelial cells. ICAM-1 was expressed in tumor cells from all of the nine adenocarcinomas. In contrast, VCAM-1 expression was not identified in tumor cells from any of the nine adenocarcinomas. ICAM-1 was expressed in all cellular compartments of the non-neoplastic lung tissue, whereas VCAM-1 was expressed only in pulmonary lymphocytes and interstitial fibroblastic cells. LFA-1 was uniformly expressed in tumor-infiltrating lymphocytes from each of the nine tumors and all of the lymphocytes in non-neoplastic lung tissue. This study showed major differences in the expression of ICAM-1 and VCAM-1 in tumor cells from pulmonary adenocarcinoma and also provided evidence for a wider distribution of ICAM-1, compared with VCAM-1, in non-neoplastic cellular compartments of the lung. ICAM-1 expression was particularly noticeable in bronchial and alveolar epithelial cells. Upregulation of ICAM-1 in pulmonary adenocarcinoma might foster binding by LFA-1-bearing lymphocytes, with a possible impact on the vulnerability of tumor cells to host defense mechanisms.

Adenocarcinoma↗

PubMed1997

Synergistic inhibition of human cancer cell growth by cytotoxic drugs and mixed backbone antisense oligonucleotide targeting protein kinase A.

Protein kinase A type I plays a key role in neoplastic transformation, conveying mitogenic signals of different growth factors and oncogenes. Inhibition of protein kinase A type I by antisense oligonucleotides targeting its RIalpha regulatory subunit results in cancer cell growth inhibition in vitro and in vivo. A novel mixed backbone oligonucleotide HYB 190 and its mismatched control HYB 239 were tested on soft agar growth of several human cancer cell types. HYB 190 demonstrated a dose-dependent inhibition of colony formation in all cell lines whereas the HYB 239 at the same doses caused a modest or no growth inhibition. A noninhibitory dose of each mixed backbone oligonucleotide was used in OVCAR-3 ovarian and GEO colon cancer cells to study whether any cooperative effect may occur between the antisense and a series of cytotoxic drugs acting by different mechanisms. Treatment with HYB 190 resulted in an additive growth inhibitory effect with several cytotoxic drugs when measured by soft agar colony formation. A synergistic growth inhibition, which correlated with increased apoptosis, was observed when HYB 190 was added to cancer cells treated with taxanes, platinum-based compounds, and topoisomerase II selective drugs. This synergistic effect was also observed in breast cancer cells and was obtained with other related drugs such as docetaxel and carboplatin. Combination of HYB 190 and paclitaxel resulted in an accumulation of cells in late S-G2 phases of cell cycle and marked induction of apoptosis. A cooperative effect of HYB 190 and paclitaxel was also obtained in vivo in nude mice bearing human GEO colon cancer xenografts. These results are the first report of a cooperative growth inhibitory effect obtained in a variety of human cancer cell lines by antisense mixed backbone oligonucleotide targeting protein kinase A type I-mediated mitogenic signals and specific cytotoxic drugs.

Animals↗

PubMed1997

Adenovirus-mediated transfer of the smooth muscle cell calponin gene inhibits proliferation of smooth muscle cells and fibroblasts.

Smooth muscle cell calponin (h1 or basic isoform) is an actin-binding protein that inhibits actomyosin MgATPase activity and is abundantly expressed in differentiated smooth muscle. Western blots showed bovine tracheal (BT) smooth muscle cells in culture expressed only 2 +/- 1% (n = 8) of the amount of calponin in tissues, while NIH-3T3 fibroblasts expressed none. We tested the hypothesis that introduction of calponin to cultured BT and 3T3 cells would inhibit cytoskeletal activities associated with cell proliferation. To achieve high-efficiency expression, an adenovirus encoding the CMV-calponin construct (Adv-CaP) was generated by homologous recombination in 293 cells. With greater than 90% of BT and 3T3 cells infected with Adv-CaP, calponin expression (32 and 11 microg/mg total protein, respectively) was similar to that in smooth muscle tissues (51 microg/mg). Cells were infected with Adv-CaP for 48 h, replated at low density and proliferation rates were assessed by cell density and [3H]thymidine incorporation. Cell growth and DNA synthesis by Adv-CaP-infected cells were inhibited to one-third control values for both BT and 3T3 cells. Expressed calponin was localized primarily on stress fibers in both cell types. Calponin may act at the cytoskeletal level to retard signaling pathways that normally lead to tight coupling between cell shape and DNA synthesis.

3T3 Cells↗

PubMed1997

Effects of synthetic oligonucleotides on human complement and coagulation.

Oligodeoxynucleotide phosphorothioates (PS-oligos) are being studied as novel therapeutic agents based on their ability to inhibit gene expression. Preclinical studies produced unanticipated complement and coagulation effects in monkeys receiving high-dose PS-oligo. In the present in vitro studies, PS-oligo inhibited normal human blood clotting as well as subsequent assays for prothrombin fragment PF(1+2) and hemolytic complement. PS-oligo treatment of normal donor plasma produced concentration-dependent prolongations of clotting times, with the activated partial thromboplastin time more sensitive than prothrombin time or thrombin clotting time. PS-oligo treatment of normal donor serum similarly reduced hemolytic complement activity in a concentration-dependent manner. Reduced hemolysis correlated with increased levels of complement fragment C4d. The anti-heparin drug protamine sulfate inhibited in vitro effects of PS-oligo in both complement and coagulation assays, suggesting that charged residues in internucleotide linkages of PS-oligo mediated the observed activities. Therefore, oligonucleotides with varying internucleotide linkages, nucleotide sequence, or secondary structure were compared. Both complement and coagulation effects appeared to be independent of nucleotide sequence but were strongly related to the nature of internucleotide linkages. Several of these modified oligonucleotides have been shown previously to retain potent antisense activity and thus may represent viable alternatives for antisense therapeutics.

Blood↗

PubMed1997

The retinoblastoma gene family is differentially expressed during embryogenesis.

We report differential expression of the RB1 tumor suppressor gene and the homologous genes p107 and p130 during embryogenesis. Abundant RB1 transcripts were detected during neurogenesis, hematopoiesis, myogenesis, lens development and in the ganglion cell layer of the embryonic retina, prior to and during differentiation. The expression pattern of RB1 mirrored the defects in RB1 mutant mice (RB-/-). In the heart, lung, kidney and intestine, p107, but not RB1, was expressed. In the liver and the central nervous system p107 and RB1 were co-expressed, consistent with the accelerated cell death observed in RB-/-; p107-/- double knock-out mice. In the central nervous system, p107 expression was restricted to proliferating cells surrounding the ventricles, while RB1 was expressed in areas of both proliferating and differentiating cells. In contrast to RB1 and p107, expression of p130 was low throughout embryogenesis. In situ hybridization and Western blot analyses showed that the expression of p107 and p130 was not markedly altered in RB-/- embryos compared to control littermates. Our results suggest that members of RB1 gene family have distinct, but overlapping roles in embryogenesis, with p107 and RB1 possibly having redundant functions in the central nervous system and liver.

Animals↗

PubMed1997

Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies.

Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) that contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs.

Animals↗

PubMed1997

Reduced coronary flow reserve during exercise in cardiac transplant recipients.

BACKGROUND: Coronary flow reserve (CFR) is reduced in a majority of patients after heart transplantation (HTx). Pharmacological interventions, however, provide only limited information on CFR under physiological conditions. Thus, CFR during exercise was evaluated in the present study. METHODS AND RESULTS: Coronary angiography was performed at rest and during supine bicycle exercise in 35 patients early (2 to 3 months; n = 10) or late (1 to 6 years; mean, 2.5 years; n = 25) after HTx and in 8 controls (C). CFR was determined by parametric imaging after administration of 10 mg intracoronary papaverine, during exercise, and after 1.6 mg sublingual nitroglycerin. Epicardial coronary artery size was measured by quantitative coronary angiography. CFR after papaverine was normal early (3.6 +/- 0.5 versus C, 3.6 +/- 0.7; P = NS) and late (3.8 +/- 1.3 P = NS) after HTx. During exercise, CFR was normal early (3.1 +/- 0.6 versus C, 3.9 +/- 0.9; P = NS) but decreased late (2.3 +/- 0.6; P < .01) after HTx. The increase in coronary cross-sectional area during exercise was also diminished late after HTx (14 +/- 10% versus C, 22 +/- 10%; P < .05). Both exercise-induced CFR (r = -.39, P < .05) and coronary vasodilation (r = -.44, P < .01) were inversely correlated with time after HTx. CONCLUSIONS: CFR during exercise is normal early but reduced late after HTx, whereas CFR after papaverine administration is maintained. This difference between physiological and pharmacological vasodilation suggests progressive endothelial dysfunction after HTx.

Adult↗

PubMed1997

Three-dimensional magnetic resonance angiography in the planning of aneurysm surgery.

Standard planning for intracranial aneurysm surgery relies on the surgeon's intellectual reconstruction of the three-dimensional (3D) surgical field on the basis of a two-dimensional (2D) imaging modality, biplanar cerebral angiography. This method is relatively imprecise, and it relies on previous experience for optimal results. We describe a stereotactic magnetic resonance angiographic (MRA)-guided method based on computer segmentation techniques for the planning of aneurysm surgery that has the potential of bringing a 3D perspective to the lesion. The method has been evaluated retrospectively on 20 surgical patients in whom the aneurysm orientation and relationship to parent vessels were shown to match presurgical 3D stereotactic display. When it is adapted to frameless interactive surgical navigation, this method may become a useful adjunct in the surgical obliteration of these life-threatening lesions.

Adult↗

PubMed1997

Application accuracy study of a semipermanent fiducial system for frameless stereotaxis.

The accuracy of a semipermanent fiducial marker system developed at Wayne State University in collaboration with Fisher-Leibinger (Freiburg, Germany) was compared with reference to a standard stereotactic frame (Zamorano-Dujovny Localizing Unit; Fisher-Leibinger). For each patient in our study, 10 semipermanent markers were placed on the skull through a small incision and a pilot hole drilled for the marker; five markers were used for registration, and five were used for comparison. Gadolinium-enhanced magnetic resonance imaging was performed, and, upon registration using both ring and fiducial markers, 184 random points were collected by infrared digitization. All three-dimensional measurements (x, y, z) were converted into distance values correlating each value to the origin by the formula dij = SQRT (xij2 + yij2 + zij2). The mean difference of fiducial coordinates vs. absolute image coordinates was 1.72 +/- 0.42 mm (P = .0001), implying no significant difference. The mean difference in dij of the stereotactic ring coordinates vs. the absolute image coordinates was 3.35 +/- 0.59 mm (P = .00011). The mean difference in the fiducial markers vs. the stereotactic ring coordinates was 2.95 +/- 0.45 mm (P = .0001). All tests were declared significant at alpha = .016. The combination of interactive guidance with semipermanent fiducial markers allows for accurate localization of intracranial targets (as accurate or even more accurate than the stereotactic frame). Semipermanent fiducial markers facilitate the procedure logistically, allow for staged procedures (i.e., at the skull base or in epilepsy), and provide access for combined supra- and infratentorial approaches. We believe that the semipermanent fiducial markers system might represent an important development leading toward widespread use of interactive image guidance in conventional neurosurgery.

Cerebellum↗

PubMed1997

Dynamic 13C NMR analysis of pyruvate and lactate oxidation in the in vivo canine myocardium: evidence of reduced utilization with increased work.

In this work, substrate selection was monitored in the left ventricle of the canine myocardium by following pyruvate and lactate oxidation under in vivo conditions at basal and elevated workloads. These studies were conducted in the open chest model using dynamic 13C NMR techniques in the presence and absence of dichloroacetic acid (DCA), a well-known activator of pyruvate dehydrogenase (PDH). Following the infusion of (3-(13)C) pyruvate or (3-(13)C) lactate into the left anterior descending artery, highly variable 13C enrichments of glutamate, alanine, aspartate, and citrate were noted under low (RPP < 14,500 mmHg/min), intermediate (RPP = 15,000-25,000 mmHg/min), and high (RPP > 25,500 mmHg/min) rate pressure products (RPP). At low workloads, the myocardium typically oxidized the infused (3-(13)C) pyruvate or (3-(13)C) lactate and incorporated the labeled carbon into the glutamate pool as expected. However, in a few notable instances (n = 3), 13C-enriched pyruvate and lactate were unable to label the glutamate pool under in vivo conditions even at the lowest RPPs, indicating a lack of selection for these substrates by the tricarboxylic acid (TCA) cycle. Nonetheless, the levels of glutamate C4 enrichment observed at low workloads could usually be enhanced by infusion of DCA. Importantly, 13C NMR extract analysis revealed that (3-(13)C) pyruvate or (3-(13)C) lactate labeling of the glutamate pool was reduced (< 20%) at high workloads in spite of increased DCA concentrations.

Animals↗

PubMed1997

Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases.

To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis (AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.

Adult↗

PubMed1997

Expression of constitutive cyclo-oxygenase (COX-1) in rats with streptozotocin-induced diabetes; effects of treatment with evening primrose oil or an aldose reductase inhibitor on COX-1 mRNA levels.

Altered prostanoid metabolism participates in the pathogenesis of diabetic complications. The rate-limiting enzyme in the control of prostanoid metabolism is constitutive cyclo-oxygenase (COX-1). This study examined the possibility that altered prostanoid metabolism derives from altered COX-1 expression in those tissues from diabetic rats, with characteristic changes in prostanoid production and related haemodynamics. This account also describes a procedure for estimation of minute amounts of COX-1 mRNA by reverse transcription and competitive polymerase chain reaction (RT-cPCR) amplification. In streptozotocin-diabetic rats (STZ-D, 55 mg/kg body weight), compared with age-matched controls, the level of COX-1 mRNA (in attomoles/micrograms tRNA +/- 1SD) was significantly decreased in sciatic nerve (0.50 +/- 0.26 versus 0.89 +/- 0.32 in controls; P < 0.05) and thoracic aorta (3.99 +/- 1.67 versus 8.80 +/- 2.37 in controls; P < 0.05). There were no differences in COX-1 mRNA in diabetic and control rat kidney and retina, though there was a trend towards increased expression with diabetes in the latter. Evening primrose oil (EPO) treatment increased COX-1 mRNA in nerve and retina to levels in diabetic rats that were higher than those of non-diabetic controls (1.21 +/- 0.28 for nerve and 0.065 +/- 0.017 for retina, where control retinae gave 0.031 +/- 0.020-see above for nerve). Treatment of diabetic rats with an aldose reductase inhibitor was without effect on COX-1 mRNA levels in the tissues examined. This study demonstrates that the changes in COX-1 mRNA levels in diabetic rats are organ specific and suggests that altered prostanoid metabolism can, in part, be explained by altered COX-1 expression. Apart from providing arachidonate as substrate for COX, EPO stimulates COX-1 expression in some tissues.

Aldehyde Reductase↗

PubMed1997

Environmental and occupational determinants of blood pressure in rural communities in China.

PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community-based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self-reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population.

Adolescent↗

PubMed1997

Use of an open stereotactic ring for neurosurgical procedures.

We describe an open ring as a new design to the Zamorano-Dujovny (Z-D) stereotactic unit. The titanium base ring has an opening of 45 degrees that can be located in any chosen position. Imaging studies such as computed tomography, X-ray, positron emission tomography, digital angiography, and digital substraction angiography can be performed with the open stereotactic ring for multimodality image localization. Preoperatively and intraoperatively, this open design provides the anesthesiologist with an unobstructed pathway for airway management. During the surgical procedure, it facilitates approach to any intracranial lesion, including orbitozygomatic, combined supra-infratentorial, and others. During awake craniotomies it not only allows for easy airway management, but also provides good access to the patient's face for intraoperative evaluation of speech and visual functions. Accuracy and reliability of this unit were similar to results obtained with the original circular ring. This system can be used in conventional stereotaxis with the Z-D arc, as well as a reference for intraoperative registration with any digitizer system. The open stereotactic unit is a relatively inexpensive, reliable, and easy-to-use solution for resections using conventional stereotaxis or interactive image guidance in any intracranial site.

Aged↗

PubMed1997

Interactive image guidance in skull base surgery using an opto-electronic device.

The applicability of an image guidance frameless system based on an opto-electronic sensor device in skull base surgery was explored in this study. Five embalmed heads with external fiducial markers placed in noncoplanar points were scanned (CT scan) and different skull base approaches were reproduced in these specimens. The opto-electronic system is comprised of an infrared camera, a local rigid body, and a 24-light-emitting diode probe attached to different surgical instruments. DOS-based calibration and transformation software and Unix-based surgical planning software were also used. The anatomic landmarks identified during the dissection were matched with the corresponding points derived from computed tomographic (CT) scans. This information allowed the surgeon to develop a three-dimensional representation of the surgical field and to anticipate the next anatomic structure encountered during the dissection. This infrared device operated in real time, is not affected by external factors with regard to its accuracy, and does not interfere with standard neurosurgical techniques. This frameless system is helpful in minimizing the risk of morbidity and provides an accurate guide during the approach, as well as unobstructed access to the surgical field.

Journal Article↗

PubMed1997

[15O]-water PET and intraoperative brain mapping: a comparison in the localization of eloquent cortex.

[15O]-water PET was performed on 12 patients with structural lesions for localization of the motor (n = 5), language (receptive and expressive; n = 6), and visual cortex (n = 1). All these patients underwent interactive image-guided surgery using an infrared digitizer and intraoperative electrical stimulation mapping for motor, sensory, language, and visual cortex location. MRI-PET coregistration was performed using a surface matching approach that integrated functional information with interactive image guidance during the surgical procedure. An awake craniotomy with motor and sensory intraoperative stimulation was performed using a registered bipolar electrode that was tracked on real-time during the surgical procedure. Intraoperative functional findings were displayed and saved on the registered MRI images. The sites of functional PET activation during the performance of motor, visual and language tasks were then compared to the results of intraoperative cortical stimulation in 11 patients and visual evoked potentials in one. The results of the PET activation studies were concordant with the findings of intraoperative stimulation in all cases. During resection of the structural lesions, intraoperative stimulation was continued in the subcortical pathways, and five patients had positive responses on areas not identified by the functional PET. Furthermore, 3 patients showed transitory changes in function (speech arrest 1, naming difficulty 1, and motor weakness 1) that were reversible after changing the dissection technique or a brain retractor. [15O]-water PET was reliable in identifying the motor, visual, and language cortex. Language-related rCBF increases were highly distributive, although only part of these activations were subjected to intraoperative stimulation. We conclude that [15O]-water PET can be used for preoperative noninvasive identification of functional cortex and may be useful in neurosurgical preplanning. Intraoperative mapping still remains the main means to avoid neurological damage as it can be performed during the entire surgical procedure to avoid damage to cortex, pathways, and damage secondary to ischemia or edema (brain retraction).

Adolescent↗

PubMed1997

Toxicologic effects of an oligodeoxynucleotide phosphorothioate and its analogs following intravenous administration in rats.

The aim of the present study is to evaluate the in vivo toxicologic effects of a phosphorothioate oligodeoxynucleotide (PS oligo) and three of its analogs [PS oligo containing four methylphosphonate linkages at the 3' and 5'-ends (MBO 1), PS oligo containing four 2'-O-methylribonucleosides at both the 3'- and 5'-ends (MBO 2), and PS oligo containing an 8 bp loop region at the 3'-end (self-stabilized oligo)]. Oligodeoxynucleotides were administrated intravenously to male and female rats at doses of 3, 10, and 30 mg/kg/day for 14 days. Rats were killed on day 15, blood samples were collected for hematology and clinical chemistry determinations, and tissues, including lymph nodes, spleens, livers, and kidneys, were subjected to pathologic examinations. The toxicity profiles of the four oligodeoxynucleotides were very similar, but differed in magnitude. In terms of the severity of the abnormalities caused by the oligodeoxynucleotides, the order was MBO 2 > PS oligo > self-stabilized oligo > MBO 1. Alterations in hematology parameters included thrombocytopenia, anemia, and neutropenia. Abnormalities in clinical chemistry parameters observed with PS oligo or MBO 2 were dose-dependent elevation of liver transaminases and reduction of the levels of alkaline phosphatase, albumin, and total protein. In addition, MBO 2 caused elevation of the total bilirubin level in male rats at the 30 mg/kg dose. No major alterations in hematology or clinical chemistry were observed in rats receiving MBO 1 or self-stabilized oligo. Dose-dependent enlargements of spleen, liver, and kidney were observed, especially in rats receiving PS oligo and MBO 2. Pathologic studies showed a generalized hyperplasia of the reticuloendothelial (RE) system in the tissues examined. Alterations in the spleen were mainly RE cell hyperplasia and hematopoietic cell proliferation. In addition to RE cell hyperplasia, lymph nodes showed necrosis, hepatocytes showed cytologic alterations and necrosis, and kidneys showed renal tubule regeneration. The severity of pathologic changes observed was oligodeoxynucleotide dependent, in the order of MBO 2 > PS oligo > self-stabilized oligo > MBO 1.

Animals↗