Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Current Understanding and Future Perspectives.

PURPOSE: To review current knowledge of elevated lipoprotein(a) [Lp(a)] levels in relation to atherosclerotic cardiovascular disease (ASCVD) and discuss their potential use as biomarkers and therapeutic approaches in clinical practice. METHODS: We summarized the current understanding and recent advances in the structure, metabolism, atherogenic mechanisms, standardized laboratory measurement, recommended screening populations, and prognostic value of Lp(a), with a special focus on the current potential treatment approaches for hyperlipoprotein(a)emia in patients with ASCVD. RESULTS: Lp(a) is composed of LDL-like particle and characteristic apolipoprotein(a) [apo(a)] connected by a disulfide bond. Substantial evidence shows that elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for ASCVD through its proatherogenic, proinflammatory, and potentially prothrombotic properties. Current guidelines recommend Lp(a) measurement for patients with an intermediate-high risk of ASCVD, familial hypercholesterolemia, a family history of early ASCVD or elevated Lp(a), and progressive ASCVD despite receiving optimal therapy. Traditional Lp(a)-lowering approaches such as niacin, PCSK9 inhibitors, mipomersen, lomitapide, and lipoprotein apheresis were associated with a non-specific and limited reduction of Lp(a), intolerable side effects, invasive procedure, and high expense. The phase 2 randomized controlled trial of antisense oligonucleotide against the apo(a) encoding gene LPA mRNA showed that IONIS-APO(a)-LRX could specifically reduce the level of Lp(a) by 90% with good tolerance, which may become a promising candidate for the prevention and treatment of ASCVD in the future. CONCLUSIONS: It is reasonable to measure Lp(a) levels to reclassify ASCVD risk and manage individuals with elevated Lp(a) to further reduce the residual risk of ASCVD, especially with IONIS-APO(a)-LRX.

Hsa-miR-203 inhibits fracture healing via targeting PBOV1.

OBJECTIVE: To explore the role of hsa-miR-203 in fracture healing and its underlying mechanism. PATIENTS AND METHODS: Expression levels of hsa-miR-203 and PBOV1 in patients with hand fractures and intra-articular fractures after treatment were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). Viability and apoptosis of osteoblast cell line hFOB1.19 after hsa-miR-203 overexpression or knockdown were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The target gene of hsa-miR-203 was predicted by bioinformatics and verified by dual-luciferase reporter gene assay. Rescue experiments were conducted to further verify whether hsa-miR-203 could participate in fracture healing via PBOV1. RESULTS: No significant hsa-miR-203 expression was found in patients with hand fractures and intra-articular fractures after treatment for 7 days, which was remarkably upregulated on the 14th day. PBOV1 expression was gradually downregulated as treatment time prolongation. Overexpression of hsa-miR-203 decreased cell viability, but induced apoptosis of hFOB1.19 cells. Bioinformatics predicted that PBOV1 might be the target gene of hsa-miR-203, which was further verified by dual-luciferase reporter gene assay. The effect of hsa-miR-203 on viability and apoptosis of hFOB1.19 cells was reversed after the PBOV1 knockdown. CONCLUSIONS: Hsa-miR-203 inhibits fracture healing by regulating osteoblast viability and apoptosis via targeting PBOV1.

miR-485-5p promotes osteoporosis via targeting Osterix.

OBJECTIVE: To investigate the effect and related mechanisms of miR-485-5p on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). PATIENTS AND METHODS: The expression level of miR-485-5p was detected in clinical cases and during the osteogenic differentiation. Three group were established to study the potential function between miR-485-5p and osteogenic differentiation: miR-NC group (negative control), miR-485-5p mimics (BMSCs transfected by miR-485-5p mimics), and mimics + si-Osx (BMSCs transfected by miR-485-5p mimics and si-Osx), after the induction of osteogenic differentiation, the cell viability of BMSCs and osteogenic markers were determined. RESULTS: In our work, miR-485-5p was found up-regulated in patients with osteoporosis by comparing with health cases. Besides, during osteogenic differentiation, miR-485-5p was suppressed. These results suggest miR-485-5p has a negative regulating effect. To research potential target of miR-485-5p, we checked it in three publicly available algorithms, TargetScan, miRDB and microRNA. We found that Osterix (Osx) is a direct target of miR-485-5p, and Luciferase assays confirmed our hypothesis, the subsequent experiments showed that decreased expression of Osx resulting from the up-regulation of miR-485-5p could restrain the cell viability and the expression level of osteogenic markers CONCLUSIONS: Our research revealed the promote function of miR-485-5p on osteoporosis, indicating that miR-485-5p could be a potential therapeutic strategy for the treatment of osteoporosis.

Hepatitis B virus infection in Taiwan: The role of NTCP rs2296651 variant in relation to sex.

Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV) infection. NTCP rs2296651 is believed to be an Asian-specific variant responsible for HBV susceptibility. We investigated the relationship between rs2296651 and HBV infection in Taiwan based on stratification by gender and menopausal status. We recruited 10 017 Taiwan Biobank participants aged 30-70 years with complete genetic data and sociodemographic information. Gender-stratified multivariate logistic regression models were used to determine the relationship between NTCP variant and HBV infection. Among individuals with HBV infection, the genotype frequencies of GG, AG and AA in women were 0.85, 0.15 and 0 while those in men were 0.82, 0.18 and 0, respectively. The multivariate-adjusted odds ratios (OR) of HBV infection were 0.77 (95% CI 0.59-0.99) in women and 0.98 (95% CI 0.79-1.20) in men. The adjusted OR was 0.87 (CI 0.63-1.19) in premenopausal and 0.59 (0.36-0.97) in postmenopausal women. We found that genetic variation in the HBV receptor gene (NTCP) was significantly associated with a decreased risk of HBV infection in Taiwanese women.

[Amniotic Membrane Suspension and Autologous Serum - Are they Important for Wound Healing?] / Amnionmembransuspension und autologes Serum ­ spielt der Inhalt eine Rolle für die Wundheilung?

Autologous serum (AS) and amniotic membrane transplantation (AMT) are used in the treatment of several ocular surface diseases. AMT is associated with a surgical intervention. Surgery could be avoided by using eye drops prepared from an amniotic membrane homogenate (AMH) or amniotic membrane suspension (AMS). EGF, bFGF, IL-6 and IL-8 were detected in AMS. However, EGF and bFGF concentrations in AMS were about 1.7-17× lower than in AMH, and IL-6 and IL-8 could not be detected in AMH. 100 % AMS, 15 and 30 % AMH significantly decreased proliferation of human corneal epithelial cells (HCECs) compared to controls (p = <0.002 for all), but 15 and 30 % AMS did not affect proliferation. Migration increased significantly compared to controls with 15 and 30 % AMS (p < 0.001), but did not change significantly with 15 or 30 % AMH (p = 0.153 and p = 0.083). Proliferation of HCECs was significantly greater with 15 % AS than with 30 % AS (p < 0.001). HCEC migration was significantly greater with 30 % AS than with 5 % AS (p < 0.01). In summary, 15 and 30 % AMS and 15 and 30 % AS exhibit the best supportive effect on human corneal epithelial cells. Nevertheless, we always have to keep in mind that individual growth factor concentrations exhibit high inter-individual fluctuations in AS or AMS eye drops.

The TGF-ß/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia.

Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-ß (TGF-ß)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By maintenance therapy, these phenotypic and functional abnormalities partially normalized; however, cytotoxicity against autologous blasts remained impaired. We identified ALL-derived TGF-ß1 to be an important mediator of leukemia-induced NK cell dysfunction. The TGF-ß/SMAD signaling pathway was constitutively activated in ALL-NK cells at diagnosis and end induction when compared with healthy controls and patients during maintenance therapy. Culture of ALL blasts with healthy NK cells induced NK dysfunction and an inhibitory phenotype, mediated by activation of the TGF-ß/SMAD signaling pathway, and abrogated by blocking TGF-ß. These data indicate that by regulating the TGF-ß/SMAD pathway, ALL blasts induce changes in NK cells to evade innate immune surveillance, thus highlighting the importance of developing novel therapies to target this inhibitory pathway and restore antileukemic cytotoxicity.

Airway pH monitoring in patients with suspected obstructive sleep apnoea using the Dx-pH oropharyngeal probe: preliminary report of a prospective cohort study.

OBJECTIVES: To investigate the laryngopharyngeal reflux (LPR) episodes and pH values in patients with suspected obstructive sleep apnoea (OSA) using the Dx-pH oropharyngeal probe. DESIGN: Prospective cohort study. SETTING: Tertiary medical centre. PARTICIPANTS: Forty patients with complaint of snoring or suspected OSA were prospectively enrolled to receive full nocturnal polysomnography (PSG). The patients were divided into 2 groups: a simple snorers group if the Respiratory Disturbance Index (RDI) was < 5 and an OSA group if the RDI was ≥ 5. MAIN OUTCOME MEASURES: The patients simultaneously received Dx-pH oropharyngeal probe monitoring for 12 h from about 6 pm to 6 am of the next day. The number of LPR events was recorded if the nadir of rapid pH drops was below pH 5.0 and 5.5. The difference of LPR events between the two groups and the difference of LPR events between awake and sleep periods in each group were analysed, respectively. RESULTS: There were 18 (45%) patients diagnosed as OSA with a mean RDI of 28.7, and 22 patients (55%) diagnosed as simple snorers. Between 2 groups, there were no significant differences in the LPR events and pH values during the awake period, sleep period or overall recording period. Comparison of the LPR events and minimum pH values between the awake period and the sleep period revealed there were no significant differences in either group. CONCLUSION: Using the new sensitive Dx-pH oropharyngeal probe with PSG, we found that OSA does not correlate with a higher incidence of LPR episodes.

Pediatric Hodgkin lymphoma: are we over-scanning our patients?

Despite the favorable outcome of most pediatric patients with Hodgkin lymphoma (HL), there is rising concern about risks of carcinogenesis from both diagnostic and therapeutic radiation exposure for patients treated on study protocols. Although previous studies have investigated radiation exposure during treatment, radiation from post-treatment surveillance imaging may also increase the likelihood of secondary malignancies. All diagnostic imaging examinations involving ionizing radiation exposure performed for surveillance following completion of therapy were recorded for 99 consecutive pediatric patients diagnosed with HL from 2000 to 2010. Cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. In the first 2 years following completion of therapy, patients in remission received a median of 11 examinations (range 0-26). Only 13 of 99 patients relapsed, 11 within 5 months of treatment completion. No relapse was detected by 1- or 2-view chest radiographs (n = 38 and 296, respectively), abdomen/pelvis computed tomography (CT) scans (n = 211), or positron emission tomography (PET) scans alone (n = 11). However, 10/391 (2.6%) of chest CT scans, 4/364 (1.1%) of neck CT scans, and 3/47 (6.4%) of PET/CT scans detected relapsed disease. Thus, only 17 scans (1.3%) detected relapse in a total of 1358 scans. Mean radiation dosages were 31.97 mSv for Stage 1, 37.76 mSv for Stage 2, 48.08 mSv for Stage 3, and 51.35 mSv for Stage 4 HL. Approximately 1% of surveillance imaging examinations identified relapsed disease. Given the very low rate of relapse detection by surveillance imaging stipulated by current protocols for pediatric HL patients, the financial burden of the tests themselves, the high cure rate, and risks of second malignancy from ionizing radiation exposure, modification of the surveillance strategy is recommended.

DNA repair signature is associated with anthracycline response in triple negative breast cancer patients.

We hypothesized that a subset of sporadic triple negative (TN) breast cancer patients whose tumors have defective DNA repair similar to BRCA1-associated tumors are more likely to exhibit up-regulation of DNA repair-related genes, anthracycline-sensitivity, and taxane-resistance. We derived a defective DNA repair gene expression signature of 334 genes by applying a previously published BRCA1-associated expression pattern to three datasets of sporadic TN breast cancers. We confirmed a subset of 69 of the most differentially expressed genes by quantitative RT-PCR, using a low density custom array (LDA). Next, we tested the association of this DNA repair microarray signature expression with pathologic response in neoadjuvant anthracycline trials of FEC (n = 50) and AC (n = 16), or taxane-based TET chemotherapy (n = 39). Finally, we collected paraffin-fixed, formalin-embedded biopsies from TN patients who had received neoadjuvant AC (n = 28), and tested the utility of the LDA to discriminate response. Correlation between RNA expression measured by the microarrays and 69-gene LDA was ascertained. This defective DNA repair microarray gene expression pattern was significantly associated with anthracycline response and taxane resistance, with the area under the ordinary receiver operating characteristic curve (AUC) of 0.61 (95% CI = 0.45-0.77), and 0.65 (95% CI = 0.46-0.85), respectively. From the FFPE samples, the 69-gene LDA could discriminate AC responders, with AUC of 0.79 (95% CI = 0.59-0.98). In conclusion, a promising defective DNA repair gene expression signature appears to differentiate TN breast cancers that are sensitive to anthracyclines and resistant to taxane-based chemotherapy, and should be tested in clinical trials with other DNA-damaging agents and PARP-1 inhibitors.

Outcome of hematopoietic stem cell transplant as salvage therapy for Hodgkin's lymphoma in adolescents and young adults at a single institution.

For patients with relapsed Hodgkin's lymphoma (HL), high dose chemotherapy with stem cell rescue (HDCT-SCT) may improve survival over chemotherapy alone. We assessed the outcomes of HDCT-SCT in 37 consecutive adolescent and young adult patients with relapsed HL whose malignancy was categorized based on sensitivity to chemotherapy. We determined whether current outcomes supported the use of HDCT-SCT in all of our patients or just those patients with lower-risk characteristics such as chemosensitivity. With a median follow-up of 6.5 years, the 2-year overall survival (OS) was 89% (95% CI: 62-97%) for the chemosensitive patients (n = 21), whereas for patients with resistant disease (n = 16), OS was 53% (95% CI: 25-74%). Both autologous and allogeneic transplants were well tolerated, with 100-day treatment-related mortality under 10%. Our data show encouraging outcomes for patients with chemosensitive relapsed HL who receive hematopoietic stem cell transplant (HSCT) and support the value of the procedure even when the disease is chemoresistant.

An acute injection of Porphyromonas gingivalis lipopolysaccharide modulates the OPG/RANKL system and interleukin-6 in an ovariectomized mouse model.

BACKGROUND/AIMS: In the present study, we attempted to develop a simulated model to explore the causal effects of periodontal pathogens on skeletal homeostasis in postmenopausal osteoporosis. METHODS: Fifty-three female adult ICR mice were randomly assigned to an experimental group (ovariectomized) or a control group. A single injection of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS, ATCC 33277) or Escherichia coli lipopolysaccharide (E. coli-LPS) was administered intraperitoneally 4 weeks after an ovariectomy. Concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and the receptor activator of nuclear factor-kappaB ligand (RANKL) in serum were subsequently analyzed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Under stimulation with P. gingivalis-LPS or E. coli-LPS, the concentration of OPG rose in both groups. The serum level of RANKL showed a decreasing trend 24 h after the injection in both groups. After injection of P. gingivalis-LPS in both the experimental and control animals, the OPG : RANKL ratio increased 24 h after the booster (22.26-620.99, P < 0.05). The serum level of IL-6 in the experimental group significantly increased 1-6 h after administration of E. coli-LPS and 1-3 h after administration of P. gingivalis-LPS (P < 0.05). CONCLUSIONS: A single booster injection of P. gingivalis-LPS induced short-term changes in OPG, RANKL, and IL-6 serum levels in this ovariectomized mouse model.

Reconstitution of adenovirus-specific cell-mediated immunity in pediatric patients after hematopoietic stem cell transplantation.

Adenovirus (adv) is a significant cause of morbidity and mortality in pediatric hematopoietic stem cell transplant recipients, and control of infection seems to require antigen-specific T cells. We evaluated the recovery of adv-specific cellular immunity in this patient population related to degree of T-cell immunosuppressive therapy and compared this to adv cellular immunity of normal donors. Over 12 months, we monitored for adv DNA in stool and blood of patients and in the blood of a normal donor group. Twenty-two pediatric hematopoietic stem cell transplant (HSCT) patients (14 months-20 years) who received matched-related (MRD n=6), mismatched related (Haplo n=6) or matched unrelated donor (MUD n=10) grafts, were followed and results compared to healthy controls (n=8). Adv was detected by polymerase chain reaction in blood and/or stool from 81.8% of patients on at least one occasion post-HSCT, but only 68% of patients developed symptomatic adv infections. Recovery of adv-specific T cells was significantly delayed in the MUD and Haplo recipients, whereas recovery in the MRD group was similar to levels detected in healthy donors within 30 days post-transplant. In conclusion, recipients of alternative donor transplants at our institution have significantly delayed adv-specific cellular immune recovery, which correlates to an increased risk of adv-associated morbidity and mortality.

An open, multi-centre, phase II clinical trial to evaluate the efficacy and safety of paclitaxel, UFT, and leucovorin in patients with advanced gastric cancer.

The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.

Effects of cobalt-60 exposure on health of Taiwan residents suggest new approach needed in radiation protection.

The conventional approach for radiation protection is based on the ICRP's linear, no threshold (LNT) model of radiation carcinogenesis, which implies that ionizing radiation is always harmful, no matter how small the dose. But a different approach can be derived from the observed health effects of the serendipitous contamination of 1700 apartments in Taiwan with cobalt-60 (T(1/2) = 5.3 y). This experience indicates that chronic exposure of the whole body to low-dose-rate radiation, even accumulated to a high annual dose, may be beneficial to human health. Approximately 10,000 people occupied these buildings and received an average radiation dose of 0.4 Sv, unknowingly, during a 9-20 year period. They did not suffer a higher incidence of cancer mortality, as the LNT theory would predict. On the contrary, the incidence of cancer deaths in this population was greatly reduced-to about 3 per cent of the incidence of spontaneous cancer death in the general Taiwan public. In addition, the incidence of congenital malformations was also reduced--to about 7 per cent of the incidence in the general public. These observations appear to be compatible with the radiation hormesis model. Information about this Taiwan experience should be communicated to the public worldwide to help allay its fear of radiation and create a positive impression about important radiation applications. Expenditures of many billions of dollars in nuclear reactor operation could be saved and expansion of nuclear electricity generation could be facilitated. In addition, this knowledge would encourage further investigation and implementation of very important applications of total-body, low-dose irradiation to treat and cure many illnesses, including cancer. The findings of this study are such a departure from expectations, based on ICRP criteria, that we believe that they ought to be carefully reviewed by other, independent organizations and that population data not available to the authors be provided, so that a fully qualified epidemiologically-valid analysis can be made. Many of the confounding factors that limit other studies used to date, such as the A-bomb survivors, the Mayak workers and the Chernobyl evacuees, are not present in this population exposure. It should be one of the most important events on which to base radiation protection standards.

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer.

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement.

Hypocretins (orexins) are recently discovered hypothalamic neuropeptides that have been implicated in the etiology of narcolepsy. The normal behavioral functions of these peptides are unclear, although a role in feeding has been suggested. We measured hypocretin-1 (Hcrt-1) in the cerebrospinal fluid of dogs during a variety of behaviors. We found that 48 h without food (24 h beyond normal 24-h fasting period) produced no significant change in Hcrt-1 levels nor did feeding after the deprivation. In contrast, 24 h of sleep deprivation produced on average a 70% increase in Hcrt-1 level compared with baseline levels. The amount of increase was correlated with the level of motor activity during the sleep-deprivation procedure. A 2-h period of exercise in the same dogs produced a 57% increase in Hcrt-1 levels relative to quiet waking levels, with the magnitude of the increase being highly correlated with the level of motor activity. The strong correlation between motor activity and Hcrt-1 release may explain some of the previously reported behavioral, physiological, and pathological phenomena ascribed to the Hcrt system.

Congenital multiple plaque-like glomangiomyoma in trunk--a case report.

Congenital glomus tumor is a rare variant of glomus tumor, and glomangiomyoma is the least frequent histological type of glomus tumor. We present a case of congenital multiple plaque-like glomangiomyoma in an 11-year-old child with multiple diffuse plaques on his right lateral trunk. Histopathologic study showed a picture of typical glomus cell undergoing transition to smooth muscle cell. After literature review, this might be the first case report of congenital multiple plaque-like glomus tumor in trunk with histological appearance of a glomangiomyoma.

A model of chronic lymphocytic leukemia with Ritcher's transformation in severe combined immunodeficiency mice.

OBJECTIVE: The major aim of the study was to establish a murine model of chronic lymphocytic leukemia with B-1 cells derived from a New Zealand white mouse. MATERIAL AND METHODS: Malignant B-1 cells (named CLL-RT cells) derived from a New Zealand white mouse were injected into the peritoneal cavity of severe combined immunodeficiency mice. Upon follow-up of recipient mice, the lymphomas showed characteristics similar to chronic lymphocytic leukemia (CLL) with Ritcher's transformation. RESULTS: Blood samples from the recipient mice showed that CLL-RT cells increased rapidly in peripheral blood after 5 weeks. Serum interleukin-10 also increased significantly in recipient mice, as in human chronic lymphocytic leukemia patients. These CLL-RT cells showed a high nucleus-to-cytoplasm ratio. These cells could metastasize via circulation in the recipients and form diffuse lymphomas in various tissues. These aggressive and diffuse lymphomas were similar to Ritcher's transformation of human CLL. The cell surface antigens of the spleen and peritoneal resident cells were analyzed by flow cytometry. The CLL-RT cells constantly expressed surface immunoglobulins M and G, and CD5, CD19, B220, and CD40 molecules. They did not express any CD11b, CD3, MAC-3, CD23, NK1.1, or H-2K(d) molecules. CONCLUSIONS: The characteristics of our animal model are very similar to human CLL. This animal system could be an ideal model for the human disease. We believe the animal model would be valuable in therapeutic studies and aid in the identification of the specific genetic alleles associated with the disease.

Cutaneous B cell lymphoma in a Mongolian gerbil (Meriones unguiculatus).

A mass was noticed on the right mandible of an aged male Mongolian gerbil. Because of rapid enlargement of the mass, the animal was euthanized and submitted for pathology. The mass was firm, pink in color, 15 mm in diameter, and tightly adherent to adjacent tissues. Staining with hematoxylin and eosin revealed that the mass was a lymphoid tumor. Neoplastic cells had a large, round, dense nuclei and little cytoplasm. The tumor contained numerous mitotic figures. Immunohistochemical stains showed that the neoplastic cells expressed CD19 and IgM but lacked CD3 and CD5. Flow cytometric analysis showed that the neoplastic cells were positive for B220, IgG, and CD40. We concluded that the tumor was a primary cutaneous B cell lymphoma. In addition, the antibodies we used for the present diagnosis were anti-mouse reagents; therefore, they also were useful for subtyping gerbil lymphoid cells.