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Biomedical subjects

M A Lane

Publications and source records attributed to M A Lane.

At least 109 records · Page 6Linked to original sources

Effect of immune manipulation on natural immune responses to murine mammary tumor antigens.

The virus-host relationship in BALB/cfC3H virgin female mice neonatally infected with an oncogenic virus (mammary tumor virus) (MuMTV) was significantly altered by a brief immunosuppressive treatment during young adult life. Natural immune responses were augmented and changed. The ability of lymphoid cells to attack target cells expressing MuMTV-associated antigens was significantly increased, and a new component, a non-T-cell reactivity, was added to the T-cell reactivity found in normal females. Serum blocking factors were both quantitatively and qualitatively altered.

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Innervation of heart cells in culture by an endogenous source of cholinergic neurons.

Hearts of embryonic mice 9 days in utero were found to have an endogenous source of cholinergic neurons which can survive in dispersed cell cultures. These neurons are electrically excitable, have ultrastructural characteristics of cholinergic embryonic neurons, and functionally innervate heart cells in culture. The nature of the innervation described is muscarinic cholinergic.

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Antibody in the sera of tumor-bearing mice that mediates spleen cell cytotoxicity toward the autologous tumor.

Pretreatment of MTV-induced BALB/cfC3H mammary tumor cells with autologous serum results in increased spleen cell cytotoxic activity and the recruitment of previously inactive spleen cells to cytotoxic activity against the target cells. These recruiting antibodies are tumor-specific for individual tumors; pretreatment with such serum of target cells of an MTV-induced mammary tumor obtained from a different BALB/cfC3H female results in blocking of spleen cell activity. The autologous recruiting factors are active at dilutions of 1000 or more of whole serum are found in the 19S fraction after gel filtration.

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Complexity of factors in sera of different mice that affect MTV-induced mammary tumor cells.

Specific spleen cell activity in microcytotoxicity assay can be altered by pretreatment of target mammary tumor virus (MTV)-induced mammary tumor cells with serum. Serum from both BALB/cfC3H females neonatally infected with MTV and BALB/c females horizontally exposed to MTV antigens will block specific spleen cell activity against isologous mammary tumor cells. On fractionation of sera, blocking factors are localized in the 7s fraction. The 19s fraction contains recruiting factors that are not detectable in the unfractionated serum; these factors are active against isologous tumors and are thus distinct from the tumor-specific recruiting factors previously described in the sera of tumor-bearing females, which are active only against the autologous tumor. Antibodies mediating complement-dependent cell lysis are also detectable after serum fractionation.

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Stimulation of immune mechanisms against mammary tumors by incomplete T cell depletion.

When BALB/cfC3H females are subjected to continous suction thymectomy, a procedure that results in retention of thymic remnants, the latent period before tumor development is significantly prolonged. However, when BALB/cfC3H females are thymectomized by control suction, a procedure which removes thymic lobes completely, there is no effect on mammary tumorigenesis. Our results show that incomplete T cell depletion causes premature onset of non-T cell cytotoxicity, an augmentation of T cell cytotoxicity, and an alteration in a serum-blocking activity to mammary tumor target cells as tested in microcytotoxicity assay. On the other hand, complete neonatal thymectomy effectively and completely abrogates immune response to mammary tumor target cells. The inability of completely thymectomized mice to generate an immune response to MTV suggests (but does not prove) that MTV-induced mammary tumor target cell surface antigens are thymus-dependent.

Aging↗

In vitro detection of immune responses to MTV-induced mammary tumors: qualitative differences in response detected by time studies.

Both BALB/cfC3H females neonatally infected with mammary tumor virus (MTV) and MTV-free BALB/c females possess spleen cells capable of significant activity against target-MTV-induced mammary tumor cells in in vitro microcytotoxicity tests. The responses of the BALB/cfC3H and BALB/c females are different, however, on the basis of time studies. Further, the reactivity characteristic of virgin BALB/cfC3H females is increased in parous females, and part of this reactivity is subsequently lost in multiparous females bearing large tumors. BALB/cfC3H females possess reactive spleen cells as early as 3 weeks of age, indicating that response to MTV antigens develops soon after birth in these neonatally infected mice.

Age Factors↗

Non-T cell killing of mammary tumor cells by spleen cells: secretion of antibody and recruitment of cells.

Both T cell-mediated killing and non-T cell-mediated killing of target MTV-induced mammary tumor cells can be detected in microcytotoxicity assay tests of spleen cells from mice immunologically responsive to either the histocompatibility antigens or the virus-associated antigens of the target cells. The non-T cell-mediated cytotoxicity is antibody-dependent; otherwise inactive cells (null cells) can be recruited to activity by target cell-specific factors obtained from the supernatant of short-term cultures of sensitized B cells or provided by the introduction of a small number of sensitized B cells to the wells of the assay plate.

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Characterization of cytotoxic effector cells in the mouse mammary tumor system.

Cell types involved in the immune response in vitro to MTV-induced BALB/cfC3H mammary tumors have been studied with techniques designed to inactivate or deplete different cytotoxic effector cells from spleen cells populations. The minimal activity of spleen cells from neonatally MTV-infected virgin BALB/cfC3H females is dependent upon the presence of T cells. Spleens from multiparous BALB/cfC3H females bearing small tumors are similar to those of tumor-free multiparous females. However, after the tumors grow to large size, the activity of the non-T cell population is no longer detectable. The cytotoxic activity of spleen cells from BALB/c females older than 14 weeks (supposedly not infected with MTV) is not dependent upon the presence of T cells. No activity is shown by spleen cells from BALB/c females younger than 14 weeks. Positive control spleen cells were obtained from C3H female mice who had been immunized to BALB/c histocompatibility antigens by a skin allograft; both a T cell and a non-T cell response were found.

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Blocking of spleen cell activity against target mammary tumor cells by viral antigens.

Spleen cells from BALB/c females exposed to or neonatally infected with mammary tumor virus (MTV) are cytotoxic to MTV-induced mammary tumor cells in microcytotoxocity assay. This activity can be partially or completely blocked by pretreatment of spleen cells with MTV purified from milk. Murine leukemia virus (MuLV) has no effect. T cell responses of virgin and multiparous BALB/cfC3H females are effectively blocked. Non-T cell responses of multiparous BALB/cfC3H females or of virgin BALB/c females are blocked by some but not all of the MTV antigen preparations. MuLV, but not MTV, can block activity of spleen cells from MuLV-sensitized donors against target MuLV-producing tumor cells.

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Evaluating measures of hematology and blood chemistry in male rhesus monkeys as biomarkers of aging.

Reliable and valid biomarkers of aging can provide valuable tools for examining the effectiveness of interventions that may influence the rate of aging processes. However, a standardized method for identifying biomarkers of aging has yet to be developed. The current analysis focused on hematology and blood chemistry variables obtained from a 5-year longitudinal study of male rhesus monkeys (N = 29) on a diet restriction regime known to retard aging processes and extend lifespan in laboratory rodents (70% of the diet intake of controls). For the current analysis, the major screening criteria for identifying candidate biomarkers of aging were cross-sectional and longitudinal correlation with chronological age (CA) and stability of individual differences. Six potential variables from the battery of blood chemistry tests were identified: 1) serum glutamic oxalacetic transaminase; 2) alkaline phosphatase; 3) total protein; 4) globulin; 5) blood urea nitrogen to creatinine ratio; and 6) phosphates. When submitted to principle component analysis, these variables loaded onto a single component that accounted for over 50% of the total variance to indicate marked covariance among them. By applying the factor score coefficients from the first principle component, an equation was derived for estimating a biological age score (BAS) for each individual monkey. A comparison of BAS between control and diet-restricted monkeys revealed no statistically significant difference at present; however, the slope of the regression of BAS onto CA appeared steeper for the control group compared to the experimental group. Thus, while demonstration of the validity of the candidate biomarkers awaits further evidence, a strategy by which additional biomarkers of aging can be identified is proposed as an improvement over past approaches.

Aging↗

Age-related decline in striatal volume in monkeys as measured by magnetic resonance imaging.

Age-related declines in striatal markers for the dopamine system have been demonstrated in several species. The current study investigated structural changes during aging in the rhesus monkey striatum. Male monkeys were studied using a volumetric spoiled gradient recall (SPGR) magnetic resonance imaging protocol. The caudate nucleus and putamen were segmented by manual tracing using landmarks made in the orthogonal planes. The whole brain volume (defined as volume of gray and white matter plus cerebrospinal fluid in ventricles and sulci) was measured using a semi-automated algorithm. There was no correlation between age and whole brain volume. There were age-related declines in normalized (i.e. brain region/whole brain volume) caudate nucleus and putamen volumes. Monkeys in the young group (n = 7, 39-45 months old) had larger volumes of both the caudate nucleus and putamen than animals in the middle-age (n = 5, 120-180 months) or old (n = 7, 291-360 months) groups. The current results provide normative data to assess potential interventions (e.g. caloric restriction) in the aging process.

Aging↗

Nonhuman primate models of skeletal and reproductive aging.

BACKGROUND: Bone loss, osteoarthritis (OA) and age-related changes in reproduction are some of the most apparent and troubling results of advancing age in the human population. The significance of these changes underscores the need for developing appropriate animal models to study aging of bone and the reproductive system. OBJECTIVE: This review surveys the literature regarding the current state of nonhuman primates (NHP) as models for skeletal and reproductive aging in humans. RESULTS: Several species of NHP exhibit age-related bone loss as well as changes in the mineral content and architecture of bone that are similar to those reported in humans. In addition, since aged females of some species of NHP exhibit cessation of menses and serum hormone profiles consistent with those described in peri- and premenopausal women, they provide useful models of postmenopausal bone loss. Sensitivity to surgical estrogen depletion and hormone replacement has also been demonstrated in female NHP. Spontaneous development of degenerative arthritis, analogous to humans in age at onset, joint involvement and histologic changes, suggest that NHP are suitable for the study of human OA. Many similarities exist between female NHPs and women in age-related changes in reproductive function including hormone concentrations, menstrual cycling, fertility and the development of endometriosis. Changes in male sexual behavior and fertility with age are also comparable in men and male NHP. CONCLUSIONS: Genetic similarity, long lives and similar reproductive endocrinology suggest that NHPs are likely candidates as models of skeletal and reproductive aging in humans. Current data confirm that several species of NHP exhibit changes in bone and reproduction that are comparable to those known to occur in humans.

Aging↗