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PubMed1995

Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

Animals↗
PubMed1996

Twenty-four-hour rhythms in immune responses in rat submaxillary lymph nodes and spleen: effect of cyclosporine.

Twenty-four-hour variations in cellularity, lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation, and natural killer (NK) activity were examined in submaxillary lymph nodes and spleen of rats injected with Freund's complete adjuvant or its vehicle and kept under light from 08:00 to 20:00 h daily. A significant daily variation in cellularity was detected, exhibiting maxima at 09:00 h in submaxillary lymph nodes (nonimmunized and immunized rats) and at 13:00 h in spleen (immunized rats only). Submaxillary lymph node LPS- and Con A-mitogenic effect displayed maximal activity during daytime (peak at 13:00-17:00 h). In spleen, the maxima for 24-h rhythm in LPS-induced cell proliferation and NK activity occurred at midnight and at early morning (09:00 h), respectively. Con A-induced spleen cell proliferation peaked at midday in nonimmunized rats only. Injection of the immunosuppressive drug cyclosporine decreased Freund's adjuvant-induced augmentation of LPS and Con A mitogenic effect in both tissues and diminished spleen cell number. Cyclosporine blunted circadian rhythms in submaxillary lymph node Con A response and cell number, while it shifted the maximum in LPS effect to peak at 01:00 h. Cyclosporine also suppressed the circadian changes in LPS- and Con A-induced spleen cell proliferation, but not those found in NK activity. The results indicate the existence of 24-h rhythms in immune responses of rat submaxillary lymph nodes and spleen with maxima at different times of the day and that were significantly affected by cyclosporine injection.

Animals↗
PubMed1985

Effects of the removal of adherent and phagocytic cells on the spleen cell lymphoproliferative response of tumor-bearing mice.

Cell-mediated immunity was investigated in two BALB/c mouse tumor systems using the lymphoblastogenesis test with phytohemagglutinin as the mitogen. This lymphoproliferative response was quantitated using the Stimulation Index (SI). There was little evidence for suppressor cell activity in cell mixing experiments in which spleen cells from #51 cell-injected mice were mixed with spleen cells from normal mice. Following macrophage removal by Sephadex G-10 columns and carbonyl iron ingestion, there were no significant changes in the SI values for spleen cells from the #51 cell-injected mice. In contrast, spleen cells from mice injected with H238 cells, a herpes virus-transformed cell line, had a significantly lower SI value than that of normal mice. Suppressor cell activity was demonstrated in cell mixing experiments in which spleen cells from H238 cell-injected mice were mixed with normal spleen cells. Removal of adherent cells from spleen cells from H238 cell-injected mice by Sephadex G-10 columns restored the SI value to that of normal mice. An increased SI value was also seen after removal of phagocytic cells by carbonyl iron. These results suggested that cells with the functional properties of macrophages played an important part in the immunosuppression observed in the H238 tumor system. Comparison of the two macrophage depletion methods suggested that another cell population was also involved in the suppressive effect. Results of immunofluorescent techniques with anti-Lyt-1 and anti-Lyt-2 monoclonal antibodies show these cells to be Ly 1-, Ly 2,3+ phenotypes of T-lymphocytes.

Animals↗
PubMed1991

Distribution of laminin and types IV and III collagen in fetal, infant and adult human spleens.

The immunohistochemical distribution of the basement membrane (BM) proteins, laminin and type IV collagen, and interstitial type III collagen was investigated in 12 fetal spleens at the 15th-38th gestational weeks (g.w.) and in spleens of 8 infants from term to 4 years. The results were compared with the distribution of the same proteins in adult human spleen. BM proteins were found to be abundantly present in the red pulp of all spleens during the whole of development. The content of type III collagen gradually decreased with advancing age and, in adult spleen, there were only occasional positively staining fibers in Billroth's cords. This finding indicates that the composition of reticular fibers in the red pulp of spleen is different from the reticular fibers elsewhere in lymphoreticular tissue. Early signs of ring fiber formation in the walls of venous sinuses were detectable at the 15th-19th g.w., although their more complete development occurred relatively late from the 36th g.w. onwards. Ring fibers contained both laminin and type IV collagen in all the investigated spleens. They never stained for type III collagen. The developing white pulp was positive for BM proteins, but showed no staining for type III collagen at the 15th g.w. At later ages, the white pulp stained similarly for both BM proteins and type III collagen.

Adult↗
PubMed1980

Erythrocyte uptake by the dog's spleen during splenic venous pressure elevation.

The spleens of chloralose-urethane anaesthetized dogs were isolated, placed in a plethysmograph and perfused at constant arterial pressure from a cannulated femoral artery. Splenic venous pressure (PV) was elevated by between 2.5 and 20 cm H2O: it caused pressure-dependent increases in spleen volume of up to 98 +/- 12 ml/100 g spleen weight. The increase in spleen volume could be separated into an initial phase associated with passive distension of capacitance vessels (Phase-1) followed by a more continuous increase in spleen volume (Phase-2). We used techniques designed to distinguish these components of the volume response to PV elevation, and found Phase-2 rates of increase in spleen volume of 5--10 ml min-1 mm Hg-1 100 g-1 expressed in terms of PV elevation and terminal, drained and trimmed spleen weight. Splenic venous haematocrit determination showed selective sequestration of RBCs during the Phase-2 volume response to PV elevation which was related to the extent of the PV elevation. Both the Phase-2 volume response and the haematocrit changes were reduced by splenic nerve stimulation or i.a. infusions of adrenaline but were unaffected by i.a. infusions of bradykinin.

Animals↗
PubMed1984

Protective effect of bone marrow and spleen suspensions on radiation-induced leukemogenesis in C57BL/6 mice.

The present experiments are an attempt to precise the type and localization of the cells involved in the protective effect of hemopoietic suspensions against the radiation-induced thymic lymphosarcoma (TLS) of C57BL/6 mice. Inocula containing variable numbers of BM or spleen CFUs from 60-day-old and 360-day-old donors were tested. According to their origin, the suspensions differed with respect to the CFU replication rate, the CFU ability to differentiate towards the T lineage and the content of the suspensions in thymic precursors. Two levels of inhibition were observed: BM suspensions from 60-day-old donors containing 1,500 CFUs had the best protective effect: 14.5% of TLS; 1,500 CFUs from 360-day-old donors were slightly but not significantly less efficient (28.5%). The second level of inhibition (36-46% of TLS) was obtained with all the following inocula: a) 1,200 and 300 spleen CFUs or 300 and 95 BM CFUs from 60-day-old donors, b) 1,500 spleen CFUs from aged donors. Seventy-six spleen CFUs from 60-day-old donors, 120 BM or 175 spleen CFUs from aged donors had no effect. These results suggest that in addition to the high replication rate of the BM CFUs as compared with spleen CFUs, cells endowed with an optimal protective effect are present in BM suspensions and are either absent or present in very small amount in spleen suspensions. These cells which induce an early repopulation of the thymus might correspond to thymic precursors.

Animals↗
PubMed2006

MDCT and superparamagnetic iron oxide (SPIO)-enhanced MR findings of intrapancreatic accessory spleen in seven patients.

The aim of this study is to retrospectively evaluate intrapancreatic accessory spleen (IPAS) with mutidetector computed tomography (MDCT) and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) with emphasis on the role of SPIO-MRI for the diagnosis of IPAS. Seven patients (four men and three women; mean age, 50.7 years) with IPAS underwent quadriphasic MDCT and SPIO-enhanced MRI. IPAS was diagnosed histopathologically (n = 2) or by scintigraphy (n = 5). Two radiologists evaluated CT and MRI in consensus for the location and size of each lesion and compared its attenuation on CT and signal intensity (SI) on MRI with those of the pancreas and spleen. For quantitative analysis, another radiologist calculated the mean lesional, pancreatic, and splenic attenuations or SIs on MDCT or MRI in each patient. All lesions were located in the pancreatic tail. The average lesion size was 1.5 +/- 0.5 cm. All IPASs except one appeared high-attenuating to the pancreas and were isoattenuating to the spleen on all dynamic CT phases. The IPASs were hypointense and hyperintense compared with the pancreas on unenhanced T1- and T2-weighted images, respectively, and their SI was similar to that of the spleen. On SPIO-enhanced, T2-weighted images, a similar degree of signal drop to that of the spleen was noted in all lesions. The results of the quantitative analysis were compatible with those of the subjective analysis. In most IPASs, the attenuation on CT and SI on MRI were identical to those of the spleen, and on SPIO-enhanced MRI, the degree of the signal drop in all lesions was similar to that of the spleen.

Adult↗
PubMed2000

Signal changes in liver and spleen after Endorem administration in patients with and without liver cirrhosis.

The goal of this study was compare the effect of Endorem on the signal intensity of the spleen in patients with normal liver tissue and in patients with liver cirrhosis. Thirty patients with normal liver tissue and 47 with liver cirrhosis were examined before and after i.v. Endorem administration. The patients were examined with a 1.5-T magnet system (Magnetom Vision) using a semiflexible cp-array coil. Three different pulse sequences were used: a T1-weighted gradient-echo sequence, a T2-weighted fast spin-echo sequence with spectral fat suppression, and a T2*-weighted gradient-echo sequence. The signal-to-noise ratios (SNRs) of two areas of the liver and spleen were determined. The mean SNRs of the liver and spleen in patients with and without liver cirrhosis were compared. For assessment of statistical significance, the t-test at a level of P < 0.05 was applied. After i.v. administration of Endorem, no differences were seen with the T1-weighted gradient-echo sequence for the liver and spleen and, with the T2-weighted fast spin-echo sequence, no differences were found for the spleen. Significant differences between both groups were seen for the liver with the T2-weighted fast spin-echo sequence. The SNR in the noncirrhotic liver group was 57.4% lower than the SNR in the cirrhotic liver group. With the T2*-weighted gradient-echo sequence, the SNRs of the liver and spleen in the noncirrhotic liver group, compared with the cirrhotic liver group, were 126.8% and 45.6% less, respectively. The effect of Endorem on the liver in patients with Child C-stage liver cirrhosis was 32.1% less than in patients with Child B-stage liver cirrhosis. Likewise, the Endorem effect on the spleen was 27.1% less in patients with Child C-stage compared with Child B-stage liver cirrhosis. Hepatic and splenic uptake of Endorem is significantly decreased in patients with liver cirrhosis.

Adult↗
PubMed2004

Accessory spleens: preoperative diagnostics limitations and operational strategy in laparoscopic approach to splenectomy in idiopathic thrombocytopenic purpura patients.

AIM: The preoperative detection of accessory spleen (AS) is still a very important and serious problem. The aim of the study was to assess the reasons for failure and the long-term results of laparoscopic splenectomy (LS) in patients with idiopathic thrombocytopenic purpura (ITP). METHOD: Fifty-eight ITP patients underwent LS between June 1998 and December 2002. There were 42 women and 16 men. Preoperatively, we performed computed tomography (CT) and sonography to evaluate the size of the spleen and possibly to recognize the presence of the accessory spleens, which were found preoperatively in three cases. RESULTS: Intraoperatively, ASs were found in the course of laparoscopy in six cases overall, three preoperatively false negative. During follow-up (median time 31 months), in three patients the low platelet count was recognized, respectively after 5 months and 1.5 and 1.8 years. In all those cases scintigraphy was performed and in one case the residual accessory spleen, missed both in preoperative examination and during laparoscopy, was revealed. In two other patients, in spite of thrombocytopenia, no residual spleens were found. CONCLUSION: We conclude that the problem of accessory spleens can be managed by careful videoscopic examination of the abdominal cavity during splenectomy, while the use of preoperative imaging techniques in detection of accessory spleens is still limited by the insufficient sensitivity of the examination.

Adult↗
PubMed1983

S-adenosylhomocysteine hydrolase activity, deoxyadenosine triphosphate accumulation, and competence of thymocyte and spleen leucocyte response to mitogens in coformycin-treated mice.

The inhibition of S-adenosylhomocysteine hydrolase and accumulation of dATP in thymus, spleen and other tissues of mice treated with the adenosine deaminase inhibitor coformycin were studied in parallel with the competence of thymocytes and spleen leucocytes to undergo mitogen-induced transformation. Newborn mice were lethally sensitive to daily injections of coformycin, 0.2 mg/kg, whereas adult mice were not. Developmental profiles of enzymes of nucleoside metabolism showed adenosine deaminase and purine nucleoside phosphorylase to be greatest in thymus around day 20 and to decrease for animals older than 60 days. The most notable change was a 3-fold increase in spleen leucocyte adenosine deaminase activity between days 10 and 30. Adenosine deaminase activity was reduced to less than 10% of normal in tissues of newborns treated with coformycin for 12-14 days. S-Adenosylhomocysteine hydrolase was also reduced to 5-40% of normal with no evidence of tissue specificity. Both thymocytes and erythrocytes of coformycin-treated mice accumulated dATP whereas spleen leucocytes did not. For coformycin-treated mice, spleen leucocyte and thymocyte response to concanavalin A (Con A) was reduced to 20 and 60% of controls respectively. Coformycin, 3.6 microM, also potentiated the in vitro toxicity of adenosine and deoxyadenosine toward thymocytes or spleen leucocytes by approximately an order of magnitude. Our observations are consistent with dATP being involved in impairment of thymocyte responsiveness; however, it appears unlikely that either dATP elevation or S-adenosylhomocysteine hydrolase inhibition is involved in the mechanism of impairment of spleen leucocyte response by coformycin.

Adenosylhomocysteinase↗
PubMed1984

Heme metabolism in liver and spleen of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-treated rats.

The effect of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), an anticancer alkylating agent of the nitrosourea group, on liver and spleen enzymes involved in the control of heme metabolism was studied. A single oral dose of 50 or 100 mg/kg CCNU caused a time-dependent loss in weight of both spleen and liver. Seven days after CCNU treatment (100 mg/kg) the weights were at 45 and 65% of controls respectively. The activity of delta-aminolevulinic acid synthetase (ALA-S), the rate-limiting enzyme in heme biosynthesis, declined in spleen and liver to 11 and 24% of control values, respectively, 7 days after CCNU treatment. Heme oxygenase activity, the rate-limiting enzyme of heme breakdown, was moderately increased in liver and spleen following CCNU administration. In liver, heme oxygenase activity was 142% of control values at 24 hr, and in spleen the activity was 180% of controls at 1 week. Pretreatment of the animals with phenobarbital (PB) (40 mg/kg/day, i.p.) for 4 days caused a reversal in the decline of liver weight with no effect on the decline in spleen weight following CCNU treatment. Similarly, PB pretreatment reversed the decline in hepatic ALA-S activity after CCNU administration but had no effect on the decline in splenic ALA-S activity. This study indicates that CCNU causes significant decreases in the activity of enzymes of heme biosynthesis in spleen and liver. The CCNU hemotoxicity in the liver was reversed by PB pretreatment whereas the splenic hemotoxicity was unchanged.

5-Aminolevulinate Synthetase↗
PubMed1983

Neonatal splenic suppressor cells in the chicken. I. In vivo suppression of the immune response to bovine serum albumin by normal and tolerized neonatal spleen cells.

The presence of active splenic suppressor cells in neonatal chickens, either normal or tolerant to bovine serum albumin (BSA), was examined by assessment of their effect on both primary and adoptively transferred secondary responses to BSA or sheep red blood cells (SRC). Both normal and BSA tolerized spleen cells were shown to be highly suppressive of secondary anti-BSA responses generated by specifically primed adult spleen cells in inert recipients. Suppression of the secondary anti-BSA response by normal spleen cells was slightly less effective than that seen with BSA tolerant spleen cells. Transfer of BSA tolerant spleen cells into normal recipients, followed by BSA challenge, prevented any significant primary anti-BSA response. In contrast, transfer of normal spleen cells into normal recipients, followed by BSA challenge, failed to show any suppression of the resulting primary response. Neither normal nor BSA tolerant neonatal spleen cells were capable of suppressing either primary or secondary responses to SRC. Thus, chickens tolerized to BSA have suppressor cells specific for the tolerizing antigen. We present evidence that both the tolerance associated suppressors and the suppressors detected in normal neonatal chickens are T cells.

Aging↗
PubMed1983

Alternative induction of alpha/beta interferons and gamma interferon by listeria monocytogenes in mouse spleen cell cultures.

Production of interferon (IFN) by Listeria monocytogenes (LM) in nonimmunized mouse spleen cell cultures was studied. IFN-gamma defined by virtue of its acid stability and antigenicity was produced in spleen cell cultures obtained from ddY mice, C57BL/6 mice, and BALB/c mice in response to heat-killed (HK) LM within 24 hr. On the other hand, production of IFN-alpha/beta was demonstrated in spleen cell cultures obtained from one of four nude mice (BALB/c, nu/nu). Therefore, it is important to know the reason why the spleen cells of mice other than nude mice did produce only IFN-gamma, but did not produce IFN-alpha/beta in response to HK-LM. Spleen cells obtained from ddY mice were fractionated, and the cellular source for IFN production of either IFN-alpha/beta or IFN-gamma induced by HK-LM was investigated. IFN-gamma was produced only by a mixture of T lymphocytes (nylon wool-nonadherent, Thy-1-positive cells) and macrophages by HK-LM. Neither T lymphocytes nor macrophages alone produced IFN by HK-LM. Macrophage-depleted spleen cells produced neither IFN-gamma nor IFN-alpha/beta, but these cells acquired the ability to produce IFN-alpha/beta, not IFN-gamma, only when they had been treated with IFN-alpha/beta. A possible mechanism of both IFN-gamma and IFN-alpha/beta induction by Listeria in mouse spleen cell cultures is discussed.

Animals↗
PubMed1985

Mechanisms in opposite modulation of spleen cell and lymph node cell responses to mitogens following muramyl dipeptide treatment in vivo.

It has been reported that a muramyl dipeptide (MDP) treatment regimen (200 micrograms MDP per mouse, Days -4, -3, -2, and -1) that, given prophylactically, affords protection against several infectious agents also induces lymph node hyperplasia, lymph node cell (LNC) hyperresponsiveness to mitogens, and spleen cell hyporesponsiveness to mitogens. The purpose of the present work was to extend those studies and delineate cellular mechanisms involved in these phenomena. It has been found that hyperresponsiveness of LNC was prolonged (7 days) posttreatment; in contrast, hyporesponsiveness of spleen cells was transient and rebounded by Day 4 posttreatment. Hyperresponsiveness of LNC and hyporesponsiveness of spleen cells actively enhanced and depressed normal lymphoid cell responses, respectively, in cell mixing experiments. Hyporesponsiveness of spleen cells was associated with the plastic-nonadherent, non-B-cell fraction and nylon wool-nonadherent subpopulations. Indomethacin (10(-6) M) did not abrogate hyporesponsiveness of spleen cells. These data suggest that splenic suppressor T cells result from MDP treatment and were responsible for spleen cell hyporesponsiveness. On the other hand, hyperresponsiveness of LNC was associated with the nylon wool-adherent cell subpopulations and a higher percentage of nonspecific esterase-positive cells. Hyporesponsiveness of spleen cells was associated with deficient production of interleukin 2 (IL-2), but not of interleukin 1 (IL-1). In contrast, hyperresponsiveness of LNC was not explained by enhanced IL-1 or IL-2 production.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

IL-1 secretion and membrane IL-1 expression by neonatal spleen cells during soluble antigen presentation.

Antigen presentation and IL-1 production by neonatal spleen cells were studied in a murine model. The T-helper-cell line (D10-G4.1) (D10), which is specific for soluble antigen presented on syngeneic antigen-presenting cells and dependent on IL-1 for its proliferation, was used as an indicator cell for the ability of syngeneic neonatal or adult spleen cells to present antigen and produce IL-1. The antigen-presenting capacity of neonatal spleen cells is low as attested by D10 proliferation. During antigen presentation there is an augmentation of IL-1 production by the antigen-presenting spleen cell population. However, neonatal spleen cells do not respond to the same levels as do adult spleen cells. These reduced levels of secreted IL-1 cannot be attributed to a low potential for producing IL-1 as attested by the high levels of IL-1 made by these cells after induction by a crude IL-1 inducer factor (IL-1-IF) and by the stimulus of the IL-1-IF produced by D10 cells during antigen presentation by paraformaldehyde-fixed adult cells. The spontaneous expression of membrane IL-1 by neonatal cells is low. Membrane IL-1 levels on neonatal cells can be brought to adult levels by induction with IL-1-IF. Neonatal spleen cells have an impaired capacity to process and/or present soluble antigen. This impairment leads to a decreased stimulus of the T helper cell to produce inducer factors and thus a reduced level of IL-1 production by the neonatal cells during antigen presentation.

Age Factors↗
PubMed1990

Differential response of B cells in the lymph node and the spleen to bacterial lipopolysaccharide.

In vivo polyclonal activation of B cells in the lymph nodes and the spleens of mice injected with bacterial lipopolysaccharide (LPS) was compared. The peak of anti-trinitrophenylated sheep red blood cells plaque-forming cell (PFC) response in the lymph node was reached 6-8 days after the injection of LPS while that in the spleen was reached at 2 days. The maximal increase in the total number of Ig-producing cells in the lymph node also occurred at the later stage. These differences in time courses of polyclonal activation of B cells between the lymph node and the spleen were not due to the absence of B cells in the lymph node, migration of PFC from the spleen to the lymph node, or qualitative differences of B cells. This phenomenon was dependent on the environmental difference between the lymph node and the spleen, because B cells from the lymph node could respond to LPS rapidly in the spleen. Further, the polyclonal activation of B cells was accelerated in the lymph nodes of mice receiving prior injection of LPS. In in vitro cultures of lymph node cells of those mice, a significant amount of interleukin-1 could be detected by stimulation of LPS. It was possible that the delayed activation of B cells in the lymph node was due to the time lag necessary for construction of the environmental condition suitable for activation of B cells, whereas in the spleen this condition can be provided without delay.

Animals↗
PubMed1988

High and low spleen rates distinguish two populations of women living under the same malaria endemic conditions in Madang, Papua, New Guinea.

In a malariometric survey of 594 non-pregnant women living in 17 villages in Madang Province, Papua New Guinea, village groups were identified with average spleen rates of less than 35%, 40-49% and greater than or equal to 50%, with no difference in parasite rates between groups. Most villages where a non-Austronesian language was spoken had high spleen rates, but the association was not consistent. Some women were not indigenous to the study area and to control for the effects of migration on spleen rates, women were grouped according to their area of origin. This analysis, which cuts across village groups, identified 2 subpopulations, one with a high, and the other with a low spleen rate (relative risk 2.23; P less than 0.0001). Persistent splenomegaly was observed more frequently in the high spleen rate population (P less than 0.025) which also showed a significantly increased spleen size (P less than 0.01). The existence of 2 subpopulations living under the same conditions of malaria endemicity, but with different splenic responses to malaria, suggests an altered host immune response to malaria in the high spleen rate group. The absence of intermarriage between these two subpopulations indicates genetic differences distinguish them.

Adult↗
PubMedDate not supplied

Low molecular weight DNA polymerase: decreased activity in spleens of old Balb/c mice.

The DNA polymerase activities in the spleens of young adult (3-8 months) and senescent (24-30 months) female BALB/c mice have been examined. Comparisons were made by direct assay of activated DNA-dependent and (rA)n-(dT)n-dependent activities in extracts from cytoplasmic and neclear fractions and also by sucrose gradient sedimentation analysis of the two major forms of DNA polymerase activity was equivalent in the spleens of young and old BALB/c mice. The low molecular weight DNA polymerase activity was decreased in the spleens of old BALB/c mice. This decreased activity was reflected most markedly in the nuclear fraction of the spleens. Mixing experiments did not indicate the presence of inhibitors in the nuclear extract from the old mouse spleens. Stepwise extractions of isolated nuclei with increasing NaCl concentrations showed consistent results without revealing any difference in extractability of the low molecular weight DNA polymerase from the old mouse chromatin. Isolated low molecular weight DNA polymerase preparations from the young and old BALB/c mouse spleens are similar in chromatographic migration, sucrose gradient sedimentation, heat lability in vitro and Km of substrates. The low molecular weight DNA polymerase activity was not found to decline in livers and kidneys of 24 to 30-month-old BALB/c mice, nor in spleens of 30 to 34-month-old BC3F1 mice.

Animals↗