Risk factors in insulin-dependent diabetes

The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). Further, a sample of 51 secondary affected siblings of IDD index cases has been compared with 265 non affected siblings (one child of each family, excluding index cases). The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. In the group of siblings HLA-identical with the index case, only two factors showed some capacity of discriminating between affected and non affected siblings: HLA-DR3 and age (less than or equal to 10 years old at onset of IDDM in the index case) (p less than 0.01). In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. If confirmed by additional family series, this scale of risk factors could be helpful in predicting risk of IDDM to siblings of diabetic children.     

Resistance to infection in murine beta-thalassemia.

Clinical evidence suggests that individuals with chronic iron overload may be at increased risk of bacterial infection. We studied this question by using a unique model in which mice homozygous for a deletion in the gene encoding for the beta-major globin develop moderate anemia, splenomegaly, and tissue iron overload, a syndrome similar to beta-thalassemia in humans. Mice heterozygous for the gene deletion were phenotypically normal. Homozygous mice were significantly more susceptible to infection with Listeria monocytogenes than were heterozygous mice (P less than 0.01). This increased susceptibility was associated with a greater number of organisms in the liver and spleen than was found in heterozygous mice (P less than 0.05). However, histologic studies demonstrated similar inflammatory responses within these organs in homozygous and heterozygous mice. The increased susceptibility of homozygous mice to infection with L. monocytogenes was not seen when homozygotes were immunized with a low dose of L. monocytogenes. Although the results were not as striking as with L. monocytogenes, homozygous mice were also found to be more susceptible to infection with Salmonella typhimurium than were heterozygous mice (P less than 0.05). Splenic mononuclear cells from homozygous mice demonstrated less responsiveness in vitro to the mitogens concanavalin A and phytohemagglutinin than did those from heterozygotes (P less than 0.05). These data suggest that there is a generalized defect in innate immunity in homozygous mice which makes them more susceptible to infection by L. monocytogenes and S. typhimurium. The site of this immunological defect is not known but is most likely in the mononuclear phagocyte and may be due to tissue iron overload.     

Dynamic alteration in splenic function during acute falciparum malaria

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.     

Oxygen radical release by adherent cell populations during the initial stages of a lethal rodent malarial infection.

A series of experiments was carried out to assess the levels of reactive oxygen intermediates (ROI) released by macrophages and monocytes during an acute malarial infection, and to consider the importance of oxidant-induced parasite killing in host protection. Adherent cell populations were removed from the peritoneum and spleen of BALB/c and B10/D2/n mice between Days 0-5 of a Plasmodium yoelii nigeriensis infection. These cell populations were quantified, characterized and their ROI-releasing capacity was measured by following ferricytochrome c reduction upon stimulation with phorbol myristate acetate (PMA). Both strains of mice displayed higher numbers of macrophages and macrophage precursors as the infection progressed; this rise was more marked and accompanied by splenomegaly in BALB/c mice. A concurrent decrease in peritoneal cell numbers was observed. Splenic adherent cell populations released much lower levels of ROI than peritoneal macrophages upon triggering. The levels of ROI released from BALB/c splenic adherent cells rose gradually until Day 3, when the parasitaemia was slightly decreased. In contrast, splenic populations from B10 mice had a decreased capacity to release ROI, particularly after Day 3, when the parasitaemia rose sharply. In further studies, electron microscopy was used to detect H2O2 release during the in vitro interaction of peritoneal macrophages and parasitized erythrocytes. Cerium chloride staining techniques demonstrated that H2O production was not dependent on phagocytosis or the presence of immune serum, although levels were increased by the presence of the latter.     

Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol

We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women, using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P less than 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Enovid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives.     

Vitamin E supplementation suppresses prostaglandin E1(2) synthesis and enhances the immune response of aged mice

The potential for vitamin E to modulate prostaglandin metabolism and alter immune response in aged mice was studied. Semi-purified diets containing 30 ppm or 500 ppm dl-alpha-tocopheryl acetate (VitE) were fed for 6 weeks to young (3 months) and old (24 months) C57BL/6J mice. Delayed hypersensitivity skin test to DNFB and the proliferative response of splenocytes to T- and B-cell mitogens were assessed. Ex-vivo synthesis of Prostaglandin E2 (PGE2) was measured in spleen homogenates and serum vitamin E was measured by HPLC. Vitamin E supplementation of aged mice enhanced percent ear swelling to DNFB as well as the mitogenic response of splenocytes to Con A and LPS (P less than 0.05). Furthermore, spleen homogenates from old mice fed 30 ppm VitE had a significantly higher PGE2 level than young mice fed 30 ppm VitE and old mice fed 500 ppm VitE (3.20 +/- 0.07 micrograms/g vs. 2.60 +/- 0.08 and 2.3 +/- 0.10, respectively). Thus, the vitamin E enhanced immune response of aged mice appears to be mediated by decreased prostaglandin synthesis.     

Climatic adaptation in thermogenesis and thermal insulation in wood mice (Apodemus argenteus)

Wood mice (Apodemus argenteus) were trapped live at three different altitudes (below 1,000, 1,900, and 2,400 m) during a 1-year period (Feb. 1984-Jan. 1985). After remaining at the trapped locations for 10-14 days, they were transferred into a climatic chamber at an altitude of 610 m. Oxygen consumption (VO2) and colonic temperature (Tco) were measured at chamber temperatures (Ta) of five steps (30, 20, 10, 0, and -10 degrees C) in freely moving conditions. In response to Ta of 0 degrees C for the mice trapped in winter when their mean local habitat temperature (Te) were lower than 0 degrees C, there was a significant inverse correlation between VO2 and Te (r = -0.70, p less than 0.001) whereas no significant correlation (r = 0.23) was observed in the mice trapped in other seasons when Te was higher than 0 degrees C. The correlation between Tco and Te was significant (r = -0.66, p less than 0.001) over the entire range of Te. The pelt weight of the mice trapped at Te higher than 0 degrees C had a significant inverse correlation with Te (r = -0.65, p less than 0.001), but not in the mice trapped at Te lower than 0 degrees C. After measurement of VO2 and Tco at Ta of 0 degrees C, the mice who had lived in colder habitats (below 0 degrees C) showed 0% mortality, whereas the mortality of the populations which had lived in warmer habitats was 13%. These results suggest that, in wood mice, adaptation to severe cold is established by an enhanced thermogenesis and by an increased insulation of the pelt in moderate cold.     

Pitted red cell counts in Nigerian children with sickle cell anemia: correlation with age and splenic size

Using direct interference phase-contrast microscopy (Normansky Optics), pit counts were performed on 32 HbSS patients, aged 3 to 17 years. The influence of age and splenic size on counts were also investigated. Nine HbSS and 15 HbAA age and sex-matched, healthy individuals served as controls. The mean +/- SD counts in the three groups were 11.1 +/- 9.1%, 1.7 +/- 1.4% and 1.8 +/- 1.7%, respectively. The older SS patients tended to have higher values, but the linear correlation with age was not impressive (r = 0.28). Seventeen (53.1%) patients had counts greater than 10%, while 8 (25%) had less than 3.5%. Five patients with gross splenomegaly had a mean count of 4.3 +/- 1.9%, significantly lower than the figure of 12.3 +/- 7.9% for the patients without splenomegaly (P less than .001), demonstrating retained reticulo-endothelial function in such patients.     

Volumetric Splenomegaly in Patients With Polycythemia Vera

BackgroundNon-palpable splenomegaly in patients with polycythemia vera (PV) has seldom been addressed. In this retrospective study, we evaluated non-palpable, volumetric splenomegaly defined based on age- and body surface area (BSA)–matched criteria in patients with PV diagnosed according to the 2016 World Health Organization diagnostic criteria.MethodsPatients with PV who underwent abdominal computed tomography (CT) and who had palpable splenomegaly at diagnosis from January 1991 to December 2020 at Chungnam National University Hospital were enrolled. The spleen volume of each patient was determined by volumetric analysis of abdominal CT and adjusted for the patient’s age and BSA. Then the degree of splenomegaly was classified as no splenomegaly, borderline volumetric splenomegaly, overt volumetric splenomegaly, or palpable splenomegaly.ResultsOf the 87 PV patients enrolled, 15 (17.2%) had no splenomegaly, whereas 17 (19.5%), 45 (51.7%), and 10 (11.5%) had borderline volumetric, overt volumetric, and palpable splenomegaly, respectively. The degree of splenomegaly did not affect the cumulative incidence of thrombotic vascular events (10-year incidence: 7.7%, 0%, 22.3%, and 50.7%, respectively, P = 0.414). By contrast, splenomegaly tended to adversely affect myelofibrotic transformation (10-year cumulative incidence: 0%, 0%, 7.1%, and 30.3%, respectively, P = 0.062). Moreover, the cumulative incidence of myelofibrotic transformation was significantly higher in patients with overt volumetric or palpable splenomegaly than those with no or borderline volumetric splenomegaly (10-year incidence: 0% vs. 10.3%, respectively; 15-year incidence: 0% vs. 26.3%, respectively, P = 0.020). Overall survival (OS) differed among patients with different degrees of splenomegaly (15-year OS: 100%, 78.6%, 71.7%, and 51.9%, respectively, P = 0.021).ConclusionThe degree of splenomegaly, including volumetric splenomegaly, based on age- and BSA-matched reference spleen volumes at diagnosis reflects disease progression in PV patients. Therefore, volumetric splenomegaly should be evaluated at the time of diagnosis and taken into consideration when predicting the prognosis of patients with PV.     

Methionine enkephalin combined with AZT therapy reduce murine retrovirus-induced disease

AZT (7.5 or 15 mg/kg/dose) and the neuropeptide methionine enkephalin (Met-ENK, 1 or 3 mg/kg/dose) were used in a combined protocol for therapy of established murine retroviral infection. In both models used, Friend virus leukemia (FV) and BM5 complex (lymphadenopathy and immune deficiency, the drug combination was able to reduce mortality and splenomegaly. While increasing mean survival time of those animals that did not survive infection by FV, when compared to infected control mice or mice treated with AZT alone, Met-ENK used alone at 1 and 3 mg/kg/mouse had no effect in reducing morbidity or mortality due to either virus. This suggested that Met-ENK had no direct antiviral effect at the concentrations used. In fact, mice treated with either single drug therapy or the combination still yielded virus in their spleen, even when splenomegaly was absent. The data suggest that Met-ENK, which has been reported to be immunostimulatory, acts in combination to improve the efficacy of AZT in reducing progression of disease in murine retrovirus models for human AIDS.     

Current clinical aspects and role of parasitic density in the manifestations of falciparum malaria

56 patients carriers of Plasmodium falciparum were observed throughout 1987: 47 males and 9 females of a mean age of 32. The following clinical aspects were observed: Falciparum malaria: 35 cases, malaria with a low parasitaemia (less than 1,000 HPM): 5 cases, tropical splenomegaly syndrome: 3 cases, isolated bi- or tricytopenia: 10 cases, cerebral malaria: 1 case, asymptomatic carriers: 2 cases. Statistically speaking, no significant correlation was observed between parasitaemia and the following clinical and biological symptoms: fever, splenomegaly, Hb level, platelet count. However, we noted a level of parasitaemia higher in the acute forms of malaria (Falciparum malaria and cerebral malaria) than in the non typical forms (chronic visceral malaria, haematological disorders). All asymptomatic carriers, who represent "malaria infection", presented a low parasitaemia (less than 1,000 HPM).     

NK activity in carrageenan-treated mice

NK activity was determined by measuring 51chromium released from Yac-1 target cells incubated with spleen cells from normal or carrageenan (Car)-treated mice. Intraperitoneal administration of a single dose of i-Car (3 mg) provoked splenomegaly in mice. This splenomegaly accompanied during the first days (2-3), a marked increase of NK activity, then a decrease of this activity at day 8-9. It was returned to normal level at day 30. The modulation of NK activity in Car-treated mice is not due to the variation of the number of NK cells, since the frequency of target-binding cells (TBC) was not modified. The increase in NK activity during the first days may be due to the presence of interferon induced by carrageenan. Concomitant injection of an anti-mouse interferon globulin with carrageenan abolished the boosting of NK activity. NK activity of spleen cells from Car-treated mice at day 8 could not be stimulated by interferon in vitro as it could with the normal spleen cells. No decrease of NK activity was observed in Car-treated mice at day 8, when indomethacin was administered. Hence the decrease of this activity in Car-8 mice might be partially due to the alteration of NK effector cells induced by prostaglandins.     

Renin release and autoregulation of blood flow in a new model of non-filtering non-transporting kidney.

1. A recently developed model of a non-filtering, non-transporting dog kidney, obtained by an in situ filling of tubules with low-viscosity oil, was applied for studies of renin release and autoregulation of renal blood flow (RBF). 2. Renal blood flow was partially autoregulated after oil blockade of tubules, as indicated by a mean autoregulation index (Semple-de Wardener (1959) of 0-5. This was comparable to autoregulation of the stop-flow kidney (index 0-6) and contrasted with abolition of autoregulation after hypertonic mannitol loading at stop-flow conditions (index 1-1). 3. The aortic construction at a suprarenal level, which decreased renal perfusion pressure of the oil-blocked kidney 35 +/- (S.E. of mean) 6 mmHg, produced an increase in arterial plasma renin activity of 1-8 +/- 0-1 ng. ml.-1 (P less than 0-02). Renin secretion rate decreased 33 to 70 ng.min-1 in three dogs in which renal perfusion pressure was reduced to 60--66 mmHg, but increased 110 +/- 41 ng.min-1 when pressure reductions were kept within the renal blood flow autoregulation range (n=8, P less than 0-025). 4. These results suggest that signals from the tubular receptor (macula densa) are not necessary for stimulation of renin release or autoregulation of renal blood flow.     

A novel animal model for motion sickness and its first application in rodents

The present work was designed to establish a novel animal model for motion sickness (MS) in rodents and to evaluate the effects of a combination of scopolamine and modafinil on MS with this novel method. It was found that the rats and mice presented several symptoms induced by rotation such as, piloerection, tremble, urinal and fecal incontinence. As the rats and mice are lack of emesis response to rotation, we used a score based on abovementioned symptoms as an index for the severity of MS in rodents. MS index was determined in 260 mice with this novel method. It was found that the distribution of MS index was normal (W=0.99; P=0.23. P>0.05 considered values' normal distribution). The effects of scopolamine on MS were studied in mice and rats. It was found that scopolamine significantly decreased MS index at the dose of 0.3 mg/kg in mice and 1.0 mg/kg in rats. Finally, the effects of a combination of scopolamine and modafinil were observed with this novel method in rats. It was found that the efficacy of the combination (5.0+5.0 mg/kg) was greater than the single drugs (10 mg/kg). Even the smallest dose of the combination (0.5+0.5 mg/kg) had a similar effect to large dose of scopolamine or modafinile when they were used alone. In conclusion, this animal model is suitable for MS study in rats and mice and the combination of scopolamine and modafinil might be a new method to treat or prevent MS.     

Deletion of purE attenuates Brucella melitensis infection in mice.

We previously showed that a purE mutant (delta purE201) of Brucella melitensis 16M is attenuated for growth in cultured human monocytes (E. S. Drazek, H. H. Houng, R. M. Crawford, T. L. Hadfield, D. L. Hoover, and R. L. Warren, Infect. Immun. 63:3297-3301, 1995). To determine if this strain is attenuated in animals, we compared the growth of the delta purE201 mutant with that of strain 16M in BALB/c mice. The number of bacteria in the spleen and spleen weight peaked for both strains between 1 and 2 weeks postinfection (p.i.), though the number of delta purE201 cells was significantly less than the number of 16M cells recovered from the spleens of infected mice. During the next 6 weeks, delta purE201 was essentially eliminated from infected mice (three of five mice sterile; < 100 CFU in two of live mice at 8 weeks p.i.), whereas bacteria persisted at a high level in the spleens of 16M-infected mice (about 106 CFU per spleen). The number of bacteria in the livers and lungs of mice infected with either strain paralleled those in the spleen. Mice infected with 16M had a strong inflammatory response, developing dramatic and prolonged splenomegaly (five to eight times normal spleen weight) and producing serum interleukin-6. In contrast, mice infected with delta purE201 developed only mild, transient splenomegaly at 1 week p.i. and produced no interleukin-6 in their serum. We further characterized the host response to infection by measuring changes in immune spleen cell populations by flow cytometry. CD4- and CD8-positive lymphocytes declined by I week in both experimental groups, while MAC-1-positive cells increased. T-cell subpopulations remained low or declined further, and MAC-1 cells increased to three times normal levels during 8 weeks of infection with 16M but returned to normal by 4 weeks after infection with delta purE201. These results document infectivity and attenuation of delta purE201 and suggest that it should be further evaluated as a potential vaccine.     

Induction of splenomegaly in mice by killed Coxiella burnetii cells

Splenomegaly induced in mice inoculated intraperitoneally (i.p.) with purified formalin-killed phase I and phase II Coxiella burnetii (C.b.) cells was dose-dependent. The phase I cells induced higher splenomegaly than phase II cells. The splenomegaly-inducing ability of phase I cells was reduced upon incubation with phase I but not with phase II antiserum, whereas the phase II cells preincubated with phase I or phase II immune sera induced higher splenomegaly than the phase II cells alone. Phase I cells caused lower splenomegaly in mice previously immunized with C.b. The splenomegaly-inducing ability of phase I cells was abolished by mild acid hydrolysis, by treatment either with phenol-chloroform-petroleum ether (PCP) or with a chloroform-methanol (CM) mixture. However, either the CM or the PCP-treated phase I cells retained their capacity to protect mice challenged with virulent phase I C.b.     

中国野生小鼠1号染色体遗传结构研究

目的 对我国25个不同地区野生小鼠遗传多样性进行检测.方法 本研究利用1号染色体上20对微卫星标记,采用多重PCR技术对我国25个不同地区野生小鼠遗传多样性进行检测,统计了野生小鼠群体等位基因数、期望杂合度、等位基因范围、G-W统计量以及群体间的遗传距离.利用MEGA软件进行系统发生分析.结果 野生小鼠群体在20个STR位点上平均等位基因数为(15.4±3.5),而实验小鼠群体在20个STR位点上平均等位基因数为(5.3±1.0).而对于两个群体之间的平均期望杂合度来说,野生小鼠群体(0.886±0.04)明显高于实验小鼠群体(0.727±0.112)(t=-6.7025,P=1.04×10-6).在野生小鼠群体中20个STR位点的G-W统计量为(0.781±0.132),明显高于实验小鼠群体的G-W统计量(0.377±0.184)(t=-8.8744,P=1.76×10-8).结论 这些指标都说明野生小鼠具有更丰富的遗传多样性.根据不同野生小鼠群体与实验小鼠群体间的聚类分析,显示野生小鼠群体与实验小鼠群体明显聚为两个类别.

Abstract：

Objective Recent studies have shown that the genetic diversity of wild mouse (Mus musculus )is far more extensive than the laboratory mice, and these diversities are useful for genetic studies of complex traits and can be important genetic resources. This sutdy is to detect the diversity of wild mice captured in 25 regions of China. Methods In this study, 20 STR loci of Chr1 were selected and analyzed, using multiplexed tandem PCR ( MT-PCR ) technology to detect the diversity of wild mice captured. The allele number, expected heterozygosity, allele range, G-W index of wild mice, and genetic distance between wild mouse populations were calculated by Alequin software. MEGA software is used for phylogenetic analysis. Results Wild mice had number of alleles of ( 15.4±3.5 ) for 20 STR loci,while the laboratory mcie had (5.3 ± 1.0 ) alleles. The wild had higher level of average expected heterozygosity (0. 886 ±0.04 ) for 20 STR loci than the laboratory derived hybrids (0. 727 ± 0. 112 ),(t= -6.7025, P=1.04 × 10-6). The G-W stat of 20 STRloci were (0.781 ± 0. 132) in wild population, significantly higher than those of laboratory mice whose G-W stat were (0.377± 0. 184 )(t= -8.8744, P=1.76×10-8). Conclusion Wild mouse (Mus musculus) has more extensive genetic diversity. According to the cluster analysis between wild mice and laboratory mice, they were clearly clustered into two categories.     

Immunoreactive erythropoietin and erythropoiesis stimulating factor(s) in plasma from hypertransfused neonatal and adult mice. Studies with a radioimmunoassay and a cell culture assay for erythropoietin

The objective was to study whether the high erythropoietic stimulatory activity found in plasma from neonatal mice during the growth period is erythropoietin (Ep) alone, or Ep in combination with other factors. Plasma from hypertransfused neonatal (20 d) and adult (13-20 weeks) mice were compared with a radioimmunoassay (RIA) and a cell culture assay for Ep. The RIA determines immunoreactive Ep (iEp) while the cell culture assay reflects erythropoiesis stimulating factor(s) (ESF). Compared to control values, hypertransfusion resulting in PCVs of 55% and higher reduced the mean iEp levels in neonatal and adult mice by 82% and 38%, respectively (P less than 0.01). There was no detectable difference between the mean iEp levels of hypertransfused neonatal and adult animals (P greater than 0.3). The parallel ESF data showed a reduction in mean plasma ESF levels by 68% in hypertransfused neonatal and 72% in hypertransfused adult animals (P less than 0.001). And notably, in contrast to the iEp data, the mean ESF level found in hypertransfused neonatal mice with PCVs of 55% and higher was significantly above that of hypertransfused adult animals (P less than 0.001). No correlation was found between PCV and iEp (r less than 0.4, P greater than 0.1) or ESF (r less than 0.2, P greater than 0.2) in hypertransfused animals. The parallel data from the two Ep assays show that plasma from hypertransfused 20-d-old mice contain one or more erythropoietic stimulatory factors not detected by the RIA. It is concluded that part of the high erythropoietic stimulatory activity found in plasma from neonatal mice is due to non-Ep factors.     

Splenic lymphoma with villous lymphocytes

Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.     

Enlarged spleens without enlarged lymph nodes in tlr3-/- pkr-/- mice.

Initial phenotypic studies in a mouse containing mutations in both toll-like receptor 3 (TLR3) and RNA-de-pendent protein kinase R (PKR) revealed comparable spleen and bone marrow cell populations in tlr3(-/)-, pkr(-/-), and tlr3(-/-)pkr(-/-) mice to wild-type controls. Splenomegaly developing between 8 and 10 weeks of age was observed in tlr3(-/-) and tlr3(-/-)pkr(-/-) mice but not in wild-type or pkr(-/-) mice. Palpably enlarged cervical, axillary, and inguinal lymph nodes accompanied by enlarged spleens were observed in 12-18-week-old tlr3(-/-) mice at a higher frequency compared with other genotypes. The enlarged spleens and lymph nodes observed in tlr3(-/-) mice were accompanied by destruction of organ architecture and lymphocyte infiltration. However, the enlargement of these organs was not the result of clonal proliferation of one lymphocyte subset. It is likely this phenotype is a result of TLR3 deficiency in combination with an additional, uncharacterized genetic defect or the presence of an infectious agent. These data also suggest that PKR may have a role in preventing progression from splenomegaly to lymphadenopathy in these mice.