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Biomedical subjects

M A Lane

Publications and source records attributed to M A Lane.

At least 73 records · Page 4Linked to original sources
PubMed1995

Influence of age, sex, and dietary restriction on intracellular free calcium responses of CD4+ lymphocytes in rhesus monkeys (Macaca mulatta).

The influence of aging and dietary restriction on increase in intracellular free calcium ([Ca2+]i) of CD4+ lymphocytes from Macaca mulatta was examined after stimulation with anti-CD3 mAb. We used a flow cytometric assay with the dye indo-1 and either direct or reciprocal immunofluorescent staining to identify CD4+ cells. After stimulation with anti-CD3 mAb, intracellular free calcium responses were reduced in CD4+ lymphocytes from old male and female ad libitum fed monkeys compared to young and adult male or female monkeys. Old female monkeys had significantly lower [Ca2+]i than did old male monkeys. The reduced responses were in part related to a decreased percentage of responding cells. Dietary restriction of males over a four-year period did not alter [Ca2+]i response compared to ad libitum fed male monkeys. Female monkeys of all ages (which were restricted only for four months) also had similar [Ca2+]i responses to ad libitum fed controls. Our data suggest that age-related changes in [Ca2+]i responses are similar between humans and M. mulatta, and that over these intervals, no effects of caloric restrictions can be detected.

Aging↗
PubMed1995

Energy balance in rhesus monkeys (Macaca mulatta) subjected to long-term dietary restriction.

Male rhesus monkeys of various age groups representative of the species life span were fed ad libitum amounts (controls) or 30% less food than control monkeys of comparable age and body weight. Despite significantly lowered energy intake and body weight, the amount of energy lost in the feces, and fecal energy density (concentration) were not altered in diet-restricted (DR) monkeys, compared to age- and weight-matched controls. Absolute energy expenditure (EE; 24-hr) was consistently lower in DR monkeys, but this trend was not statistically significant. Expressed as a function of metabolic mass (body weight, metabolic body size, lean mass), 24-hr EE was not different in monkeys subjected to long-term DR, compared to controls. Calculations of net energy (intake-loss), as an index of energy balance, revealed that energy expenditure generally exceeded energy intake in all juvenile and adult group monkeys. However, this discrepancy was not statistically different from zero, suggesting that most animals were in energy balance. Also, there was no difference between control and DR animals with respect to energy balance. Diet restriction induced significant reductions in the absolute amount of lean body mass; however, percent (of total weight) lean and fat mass did not differ from controls.

Animals↗
PubMed1995

Aging and food restriction alter some indices of bone metabolism in male rhesus monkeys (Macaca mulatta).

Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. In rats, food restriction delays bone growth and reduces bone density and mineral content. We report the effects of aging and long-term (> 6.0 y) food restriction on several indices of bone growth and metabolism in rhesus monkeys (Macaca mulatta). Food allotments for controls approximated free access consumption, whereas food-restricted monkeys received 30% less food on a body weight basis. Cross-sectional and longitudinal age effects on serum alkaline phosphatase paralleled those reported for humans. Food restriction induced a significant delay in the developmental decline (to adult levels) in total alkaline phosphatase and significantly suppressed serum interleukin 6 concentrations, particularly in younger monkeys. Also, food restriction slowed skeletal growth, as reflected by shorter crown-rump length, and significantly reduced total body bone mineral content, but not bone mineral density, measured by dual energy X-ray absorptiometry. Analyses of serum parathyroid hormone, calcium, phosphate and osteocalcin concentrations suggested that the effects on skeletal growth were not related to alterations in calcium and phosphate homeostasis or a primary defect in bone formation. These findings suggest that long-term food restriction delays skeletal development in male rhesus monkeys while allowing the development of a reduced but otherwise normal skeleton.

Aging↗
PubMed1995

Diet restriction in rhesus monkeys lowers fasting and glucose-stimulated glucoregulatory end points.

Male rhesus monkeys (Macaca mulatta) of different age groups representing the species life span were fed ad libitum or a 30% reduced calorie diet over a 7-yr period. During the first 2-3 yr of this longitudinal study, glucose and insulin levels were not altered by diet restriction (DR). However, reductions in fasting blood glucose became apparent in DR animals after 3-4 yr. At the end of the 6th yr of study, glycated hemoglobin was measured, and intravenous glucose tolerance tests (IVGTTs) were conducted. Maximum glucose levels reached during IVGTTs increased with age but were lower in DR animals compared with controls. Several measures of the insulin response (baseline, maximum, and integrated areas under curve) increased with age and were lower in DR monkeys. With the exception of glycated hemoglobin, which was not different in monkeys subjected to DR, these findings confirm previous studies in rodents demonstrating that DR alters glucose metabolism and may be related to the antiaging action of this intervention.

Aging↗
PubMed1995

The role of p53 mutations in bilateral breast carcinoma.

Mutations of the tumor suppressor gene p53 have been implicated in certain familial cases of breast cancer. We examined a series of 38 cases of nonfamilial bilateral breast cancer using antibodies CM1 and DO7 to p53 wild-type and mutant protein (Novocastra Laboratories) by the avidin-biotin-peroxidase complex method. The two antibodies reacted similarly. Mutant p53 protein was detected in 17 of 76 (22%) tumors but in only 3 of 38 (8%) paired tumors. There were no significant differences in p53 expression between synchronous (< 12 mos) and metachronous tumors (29% vs 17%, P = 0.09) or between first and second tumors (14% vs 26%, P = 0.29). Mutant p53 was detected bilaterally in one metachronous and two synchronous cases, which were amplified and sequenced and two synchronous cases, which were amplified and sequenced by polymerase chain reaction and single strand confirmation polymorphism. One synchronous case showed a bilateral mutation in exon 2-3; the other had a bilateral mutation in exon 8-9. In the metachronous case, a mutation could be demonstrated in only one breast. Analysis of all tumors demonstrated that when p53 protein is overexpressed in the first tumor, there is a 60% probability of overexpression in the second, whereas if absent from the first, it is unlikely to be present in the second. These data suggest that p53 mutations do not play a major role in the pathogenesis of bilateral disease in most women.

Adult↗
PubMed1993

Sperm transport and distribution during the puberal transition in ewe lambs.

Sperm transport through and distribution within the anterior reproductive tract were evaluated at either 2 or 22 h after artificial insemination in ewe lambs at first (1E; n = 15) or third (3E; n = 14) estrus and in mature (MAT; n = 12) ewes. Each ewe was inseminated immediately upon detection of estrus with 7.5 x 10(8) progressively motile sperm placed into the external os cervix. Ewes were hysterectomized at either 2 or 22 h after insemination. Sperm were recovered from the uterus, isthmi, and ampullae by flushing with sterile .9% saline. The distribution of sperm recovered from the uterus, isthmus, and ampulla did not differ (P > .10) among 1E, 3E, and MAT ewes at either 2 or 22 h. However, there was a tendency (P = .08) for more sperm to be recovered from the anterior reproductive tract in 3E and MAT ewes than from that in 1E ewes. There was a time of hysterectomy x anatomical segment interaction (P < .05) for percentage of sperm recovered of the total number of sperm in the inseminate because more sperm were recovered from the isthmus and ampulla at 22 h than at 2 h after insemination. Percentages of 1E, 3E, or MAT ewes from which sperm were recovered from the anterior reproductive tract did not differ (P > .10). However, sperm were recovered from the oviducts in a greater (P < .05) percentage of ewes at 22 h after insemination than at 2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Dietary restriction in nonhuman primates: progress report on the NIA study.

Rhesus and squirrel monkeys have been fed a semisynthetic diet at approximately ad libitum or 30% reduced levels for 3.5 (rhesus group 2) to 4.5 (rhesus group 1 and squirrel) years. Animals have maintained excellent health status as determined by physical examinations, hematology, and blood chemistry. While relative rates of body weight gain in restricted group 1 rhesus and squirrel monkeys have been markedly reduced, DR effects on crown-rump length (body height) have been variable. In addition, numerous physiological and biochemical parameters have been measured, and several exhibit significant cross-sectional age effects. Interestingly, several of these also exhibit possible species and genotype (group 1 and 2 rhesus) differences. A number of physiological parameters are emerging that might be altered by DR; however, further explanation of these effects awaits more extensive and detailed analyses.

Aging↗
PubMed1992

Loss of the 17p chromosomal region in a metastatic carcinoma of the prostate.

Genetic alterations of multiple loci that serve as markers for the induction and progression of disease have been identified in several adenocarcinomas, but not in adenocarcinoma of the prostate. To determine if similar genetic alterations occur in prostate carcinoma and could serve as markers for the extent of clinical disease, we have examined 23 predominantly moderately-differentiated, localized prostate carcinomas and one prostatic dysplasia for changes in the structure and copy number of ten selected genes. These genes include 1) those important to androgen metabolism in the prostate, the androgen receptor and steroid 5 alpha reductase genes; 2) those that map to the 10q (PLAU) and 7q (MET) chromosomal regions found deleted in some prostate carcinomas, and 3) proto-oncogenes (ERBB2, INT2, and MYC) and tumor suppressor gene loci (RB1, TP53 and D17S5) found altered in adenocarcinomas of the breast, colon and lung. Gene alterations were detected in one specimen, a lymph node metastasis from a poorly differentiated tumor. This specimen exhibited loss of heterozygosity for two loci putatively active in tumor suppression, TP53 and D17S5, on the short arm of chromosome 17. This study indicates that gross genetic alterations were not evident and could not be used as markers of tumor development in well- or moderately-differentiated, localized lesions, but that loss of the 17p region may be a useful marker for advanced carcinomas in the prostate.

Adenocarcinoma↗
PubMed1992

In situ dephosphorylation of p53 protein by calf intestinal alkaline phosphatase treatment.

The monoclonal antibody (mAb) 1801 has been reported to identify an N-terminal determinant within the tumor-suppressor protein p53 located between amino acids 32 and 79. This region contains two potential sites for serine phosphorylation at amino acids 33 and 46. Using a novel technique which dephosphorylates proteins in situ in fixed permeabilized cells, we have unmasked determinants in p53 recognized by mAb 1801, allowing additional sites of p53 protein to be detected in immunohistochemically reacted cells. This result indicates that phosphorylation at one or both sites within the determinant recognized by mAb 1801 previously blocked antibody-ligand interaction. It further suggests that in situ dephosphorylation may be of more general use in identifying antibodies which can only bind to epitopes in a particular phosphorylation state.

Alkaline Phosphatase↗
PubMed1991

Identification and initial characterization of glucose-repressible promoters of Streptococcus mutans.

Three catabolite-repressible promoters from Streptococcus mutans have been isolated. These promoters were identified by utilizing the vector pRQ200 which contains a promoterless amylase-encoding gene, a Gram- origin of replication, and an erythromycin-resistance determinant. A library of S. mutans DNA was constructed in pRQ200, amplified in Escherichia coli and integrated by Campbell-type insertion into the S. mutans chromosome following transformation. Colonies exhibiting amylase production on media lacking an extraneous carbohydrate source were screened for diminished amylase production on media containing glucose. The effect of glucose on these promoters has been characterized using a quantitative spectrophotometric assay of amylase activity.

Amylases↗
PubMed1989

Sodium butyrate suppresses the transforming activity of an activated N-ras oncogene in human colon carcinoma cells.

The transforming activity of DNA from a newly established undifferentiated human colon carcinoma cell line (MIP-101) was tested in the NIH-3T3 transfection assay. Southern blot analysis of the transfectant DNA revealed the presence of a human N-ras oncogene. Treatment of MIP-101 cells with the maturational agent sodium butyrate induced a more normal phenotype, including diminished growth rate, elimination of anchorage independent growth, and decreased tumorigenicity (R. Niles, S. Wilhelm, P. Thomas, and N. Zamcheck (1988) J. Cancer Invest. 6, 39). Here we report that there is a significant reduction in the transforming efficiency of the DNA from butyrate-treated MIP-101 cells. A nonspecific reduction in total DNA uptake as an explanation for these findings was eliminated by showing that there was similar uptake and expression of the thymidine kinase gene from the DNA of butyrate-treated and control MIP cells. Butyrate treatment had no detectable effect on the overall structure, methylation, and level of expression of the human N-ras gene from MIP-101 cells. An NIH-3T3 transformant ability after treatment with sodium butyrate. Although butyrate suppressed several transformed properties similar to MIP-101 cells, DNA from control and treated cultures had an identical level of transforming activity. The results suggest that the environment of the MIP cells may contain additional elements not present in the NIH-3T3 transformants which are required to observe the effect of butyrate on reduction of transforming activity.

Butyrates↗
PubMed1989

Cytophotometric assessment of T-2 toxin induced alterations in azure B-RNA and Coomassie-protein in supraoptic-magnocellular neurons of rat hypothalami.

Quantitative cytophotometry was used to monitor T-2 toxin-induced alterations in azure B-RNA and Coomassie-total cell protein in supraoptic-magnocellular neurons of rat hypothalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.00 and 1.50 x LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric azure B-RNA and Coomassie-protein staining of brain sections, scanning-integrating microdensitometry was used to quantify toxin-induced alterations in these well established indices of neuronal toxicity. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in azure B-RNA reactivity were observed in the 0.75, 1.00 and 1.50 x LD50 groups (i.e. 11%, 13% and 8%, respectively); no differences in RNA levels were observed between controls and the 0.50 x LD50 group. In addition, a decrease in Coomassie-total cell protein was seen in animals receiving 0.50, 0.75 and 1.50 x LD50 T-2 toxin (i.e. 33%, 21% and 12%, respectively); however, toxin administration did not alter protein levels in the 1.00 x LD50 group. Furthermore, a dose-dependent decrease in systolic blood pressure was observed at 8 hr. post-injections (i.e., approximately -39%, -52%, -66% and -64% for the 0.50, 0.75, 1.00 and 1.50 x LD50 groups, respectively). Additional observations include pronounced polydipsia, ascites, abdominal and subdural hemorrhage, and horripilation (piloerection) in experimental groups. It is postulated that the T-2 toxin-induced reductions in azure B-RNA and Coomassie-protein represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is advanced that the supraoptic-magnocellular compartment represents an important site in T-2 toxin mycotoxicosis. Moreover, these findings support previous claims that T-2 toxin intoxication may critically impair the vasopressinergic response to toxin-induced cardiovascular collapse.

Animals↗
PubMed1985

The isolation and characterization of the Blym-1 transforming gene.

There are a number of similarities between chicken bursal lymphomas and human Burkitt's lymphomas. Both lymphomas are associated with viral infection, by LLV in bursal lymphomas and Epstein-Barr virus in Burkitt's lymphoma. Avian lymphoid leukosis virus integration is associated with enhanced c-myc expression, while the role EBV plays in tumorigenesis remains unclear. In Burkitt's lymphoma, however, c-myc activation does occur as a result of specific chromosomal translocations involving the human c-myc locus. Furthermore, the activated transforming genes detected by transfection of both bursal lymphoma and Burkitt's lymphoma DNAs are homologous members of the Blym family of genes. These similarities between chicken and human lymphomas provide evidence that viral involvement and oncogene activation are significant in tumor development and suggest they are involved in the multi-step progression to the neoplastic phenotype. The function of the Blym genes remains to be determined. Although the chicken and human Blym genes are only distantly related, they have maintained their homology to the amino-terminal regions of transferrins. This fact may reflect some functional constraint on the evolution of these genes. It is therefore possible that transforming genes such as Blym may function via a transferrin-related mechanism.

Animals↗
PubMed1985

Flower petal microtexture is a tactile cue for bees.

Honeybees are shown to be able to detect, learn, and discriminate between microsculptured epidermes of flower petals. The sensilla trichodea at the tips of the bees' antennae are in the same size range as the microsculptural features of the petals (ca. 10 mum), which presumably deflect these mechanoreceptive sensilla in characteristic ways. Honeybees were trained to associate reward with one floral texture and to choose that over another. Further, the bees also recognized differences in textures at different ends of petals of the same species. The phenomenon is significant in that it suggests another way in which insect pollinators can discriminate between the flowers of different plant species and so act as species isolators. Also, the microsculptural patterns differ from one end of a petal to the other and, therefore, can be used as nectar-guides by foraging bees. This study presents a previously unreported conditioned response to texture by insects and shows the functional significance of a floral character used in plant taxonomy.

Journal Article↗