Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study.

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles (P < 0.001). Further splitting of the historical control group into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed that all groups significantly benefitted (P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method.

Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

Final ART success rates: a 10 years survey.

BACKGROUND: Cumulative pregnancy rates (CPRs) and live birth rates (CLBRs) are much better indicators of success in IVF programmes than cross-sectional figures per cycle or embryo transfer. They allow a better estimation of patient's chances of having a child and enable comparisons between centres and treatment strategies. METHODS: A 10 year cohort study of patients undergoing their first assisted reproductive technique cycle was conducted. Patients were followed until live birth or discontinuation of treatment. All IVF and ICSI cycles and cryo-cycles with embryos derived from frozen pronuclear stage oocytes were included. The CPR and CLBR were estimated using the Kaplan-Meier method for both the number of treatment cycles and transferred embryos. The analysis assumed that couples who did not return for subsequent treatment cycles would have had the same chance of success as those who had continued treatment. RESULTS: A total of 3011 women treated between 1998 and 2007 were included, and 2068 children were born; women already with a live birth re-entered the analysis as a 'new patient'. For 3394 'patients under observation' with 8048 cycles, the CLBR was 52% after 3 cycles (the median number of cycles per patient), 72% after 6 cycles and 85% after 12 cycles. A CLBR of ∼ 50% was achieved for patients aged under 40 years, after the cumulative transfer of six embryos. The mean live birth rate from one fresh cycle and its subsequent cryo-cycle(s) was 33%. Our analysis also shows that ART can reach natural fertility rates but not exceed them. CONCLUSIONS: Most couples with infertility problems can be treated successfully if they continue treatment. Thereby ART can reach natural fertility rates. Even with the restrictions in place as a result of the German Embryo Protection Law, CLBR reach internationally comparable levels.

Isolated CD39 expression on CD4+ T cells denotes both regulatory and memory populations.

Foxp3(+) regulatory T cells (Tregs) express both ectoenzymes CD39 and CD73, which in tandem hydrolyze pericellular ATP into adenosine, an immunoinhibitory molecule that contributes to Treg suppressive function. Using Foxp3GFP knockin mice, we noted that the mouse CD4(+)CD39(+) T-cell pool contains two roughly equal size Foxp3(+) and Foxp3(-) populations. While Foxp3(+)CD39(+) cells are CD73(bright) and are the bone fide Tregs, Foxp3(-)CD39(+) cells do not have suppressive activity and are CD44(+)CD62L(-)CD25(-)CD73(dim/-), exhibiting memory cell phenotype. Functionally, CD39 expression on memory and Treg cells confers protection against ATP-induced apoptosis. Compared with Foxp3(-)CD39(-) naïve T cells, Foxp3(-)CD39(+) cells freshly isolated from non-immunized mice express at rest significantly higher levels of mRNA for T-helper lineage-specific cytokines IFN-gamma (Th1), IL-4/IL-10 (Th2), IL-17A/F (Th17), as well as pro-inflammatory cytokines, and rapidly secrete these cytokines upon stimulation. Moreover, the presence of Foxp3(-)CD39(+) cells inhibits TGF-beta induction of Foxp3 in Foxp3(-)CD39(-) cells. Furthermore, when transferred in vivo, Foxp3(-)CD39(+) cells rejected MHC-mismatched skin allografts in a much faster tempo than Foxp3(-)CD39(-) cells. Thus, besides Tregs, CD39 is also expressed on pre-existing memory T cells of Th1-, Th2- and Th17-types with heightened alloreactivity.

Relevance of anti-Mullerian hormone measurement in a routine IVF program.

BACKGROUND: Diminished ovarian reserve has become a major cause of infertility. Anti-Mullerian hormone (AMH) seems to be a promising candidate to assess ovarian reserve and predict the response to controlled ovarian hyperstimulation (COH). This prospective study was conducted to evaluate the relevance of AMH in a routine IVF program. METHODS: Three hundred and sixteen patients were prospectively enrolled to enter their first IVF/ICSI-cycle. Age, FSH-, inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses. RESULTS: A total of 132 oocyte retrievals were performed. A calculated cut-off level < or =1.26 ng/ml AMH alone detected poor responders (< or =4 oocytes) with a sensitivity of 97%, and there was a 98% correct prediction of normal response in COH if levels were above this threshold. With levels <0.5 ng/ml, a correct prediction of very poor response (< or =2 oocytes) was possible in 88% of cases. Levels of AMH > or =0.5 ng/ml were not significantly correlated with clinical pregnancy rates. CONCLUSIONS: AMH is a predictor of ovarian response and suitable for screening. Levels < or =1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count. Measurement of AMH supports clinical decisions, but alone it is not a suitable predictor of IVF success.

Construction of a defective retrovirus containing the human hypoxanthine phosphoribosyltransferase cDNA and its expression in cultured cells and mouse bone marrow.

Defective ecotropic and amphotropic retroviral vectors containing the cDNA for human hypoxanthine phosphoribosyltransferase (HPRT) were developed for efficient gene transfer and high-level cellular expression of HPRT. Helper cell clones which produced a high viral titer were generated by a simplified method which minimizes cell culture. We used the pZIP-NeoSV(X) vector containing a human hprt cDNA. Viral titers (1 X 10(3) to 5 X 10(4)/ml) of defective SVX HPRT B, a vector containing both the hprt and neo genes, were increased 3- to 10-fold by cocultivation of the ecotropic psi 2 and amphotropic PA-12 helper cells. Higher viral titers (8 X 10(5) to 7.5 X 10(6] were obtained when nonproducer NIH 3T3 cells or psi 2 cells carrying a single copy of SVX HPRT B were either transfected or infected by Moloney leukemia virus. The SVX HPRT B defective virus partially corrected the HPRT deficiency (4 to 56% of normal) of cultured rodent and human Lesch-Nyhan cells. However, instability of HPRT expression was detected in several infected clones. In these unstable variants, both retention and loss of the SVX HPRT B sequences were observed. In the former category, cells which became HPRT- (6-thioguanine resistant [6TGr]) also became G418s, indicative of a cis-acting down regulation of expression. Both hypoxanthine-aminopterin-thymidine resistance (HATr) and G418r could be regained by counterselection in hypoxanthine-aminopterin-thymidine. In vitro mouse bone marrow experiments indicated low-level expression of the neo gene in in vitro CFU assays. Individual CFU were isolated and pooled, and the human hprt gene was shown to be expressed. These studies demonstrated the applicability of vectors like SVX HPRT B for high-titer production of defective retroviruses required for hematopoietic gene transfer and expression.

Neurobiological bases of age-related cognitive decline in the rhesus monkey.

The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age-related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer I in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an age-related loss of cortical neurons or synapses, as has long been assumed.

Neuronal population of area 4 during the life span of the rhesus monkey.

One right or left area 4 of each of 19 rhesus monkeys, ranging in age from 1 day to 35 years, was processed (frozen sectioned at 30 or 40 microns) for light microscopic analysis to assess age-related changes in the neuronal population. All neurons were examined regardless of their size. In addition, Betz cells were analyzed separately; to be regarded as Betz cells, pyramidal somata had to display a minimum height of 38 microns. A significant loss of approximately one-third was observed in the total number of neurons in maturing monkeys (less than 5.5 years). In contrast, in maturing rhesus monkeys significant increases with age were observed in the mean number of Betz cells, and in the means of Betz cell area, height, width, perimeter, and estimated volume. In adult monkeys (greater than 4.5 years), no age-associated loss of neurons was observed. Also, no loss of Betz cells occurred, although the perimeter, area, and estimated volume of Betz cells decreased slightly, but significantly, with increasing age in adult monkeys. Lipofuscin granules were discernable in Betz cells beginning at the age of 5 years and their number increased with increasing age. In the older rhesus monkeys, the lipofuscin granules were so large and numerous that in some Betz cell somata they displaced the nucleus from its usual location in the center of the cell. No age-related change in thickness of area 4 was found.

beta-Amyloid (A beta) deposition in the brains of aged orangutans.

While aged monkeys of several species show cerebral amyloid deposition in senile plaques and blood vessels similar to that seen in human aging and Alzheimer's disease (AD), studies of great apes have been limited. Using histological and immunohistochemical methods, we examined the brains of four orangutans aged 10, 28, 31, and 36 years. We encountered sparse beta-amyloid (A beta)-immunoreactive, silver-negative plaque-like structures in the brains of the three older apes. The 36-year-old orangutan also evidenced small A beta-positive deposits in subcortical white matter and sparse vascular amyloid deposition, primarily in meningeal vessels. Neurofibrillary tangles were not detected on silver stains or on tau or ubiquitin immunohistochemistry. Many of the A beta-positive plaque-like deposits in the orangutans were apolipoprotein E-immunoreactive, as we have previously reported in aged rhesus monkeys and an aged chimpanzee. Also, paralleling our earlier findings in these nonhuman primates, A beta 40 in plaques was more prominent in the orangutan than is typically seen in human aging, AD, and Down syndrome. These intriguing species differences may provide clues to the mechanisms of amyloid deposition and the development of neuropathologic changes in AD.

Brain weight does not decrease with age in adult rhesus monkeys.

Cross-sectional studies on adult human autopsy material have shown that younger cohorts have heavier brains than older groups. We sought to determine whether a similar pattern is present in the rhesus monkey, a species that serves as a useful model of human brain and cognitive aging. Data were obtained from necropsies of 399 rhesus monkeys (180 females; 219 males), of ages covering the entire adult lifespan of this species. In addition to fresh brain weight, variables considered were age, sex, body weight, heart weight, identity of the prosector, and circumstance of death. Initial bivariate analyses revealed a significant sex difference in brain weight (mean for males: 96.1 g; for females: 86.1 g; p < 0.001), as well as significant correlations of brain weight with body weight (r = 0.20, p < 0.01 for females; r = 0.27, p < 0.001 for males), and heart weight (r = 0.27, p < 0.001 for females; r = 0.38, p < 0.001 for males). Identity of prosector, circumstance of death, and age were not significantly related to brain weight in bivariate analyses. Multiple linear regression, controlling for possible confounding effects of body weight and sex, also suggested that brain weight is stable throughout adulthood in the rhesus monkey.

A beta40 is a major form of beta-amyloid in nonhuman primates.

Because aged nonhuman primates show beta-amyloid (A beta) deposition in senile plaques and blood vessels similar to that seen in human aging and AD, we used C-terminal specific antibodies to A beta40 and A beta42 to investigate A beta peptide length in the brains of 11 aged rhesus monkeys and a 59-year-old chimpanzee. In contrast to AD, where the earliest and most prominent form of A beta in senile plaques is A beta42, in the monkey, A beta40-positive plaques predominated. The ratio of A beta40:A beta42-positive plaques averaged 2.08 in the monkey, as compared to a mean ratio of 0.37 in 68 human AD subjects (p < 0.001). A beta40 was also more prominent in the chimpanzee than in humans. Possible explanations for these findings include species differences in the cleavage of A beta from the amyloid precursor protein or in the activity of a putative carboxy peptidase forming A beta40 from A beta42 in situ.

An autoradiographic investigation of the subcortical visual system in chimpanzee.

Based on one adult chimpanzee monocularly injected with radioactive proline, retinofugal fibers were found to terminate bilaterally in the suprachiasmatic, pregeniculate, lateral geniculate, olivary, pretectal and lateral terminal nuclei, and the superior colliculi; the existence of a dorsal terminal nucleus of the accessory optic system is in doubt. In the ipsilateral geniculate nucleus, the fibers terminate in layers 2, 3 and 5; in the contralateral nucleus, they end in layers 1, 4 and 6. Midway through the geniculate nucleus, layers 3 and 4 split medially into two daughter layers each. In the superior colliculi, most of the retinal terminals are aggregated superficially in a band located in the stratum griseum superficiale. The contralateral band is interrupted by gaps; the ipsilateral band has fewer gaps, is slightly thicker and located more deeply. There is a limited second tier of terminals in the contralateral superficial gray.

Subcortical projections to the occipital and parietal lobes of the chimpanzee brain.

The subcortical sources of afferents to occipital and parietal cortex were studied in two chimpanzees with the aid of retrogradely transported horseradish peroxidase (HRP). In chimpanzee 1, HRP was injected into right cortical areas 17 and 18; chimpanzee 2 received HRP into right areas 17, 18, 19, and 39. The following subcortical structures were found to project to area 17 and/or area 18: locus coeruleus, dorsal raphe nucleus, nucleus annularis, nucleus centralis superior, pontine reticular formation, mesencephalic reticular formation, dorsal hypothalamus, lateral hypothalamus, nucleus basalis of Meynert, nucleus of the diagonal band of Broca, claustrum, nucleus basalis lateralis amygdalae, lateral geniculate nucleus, inferior pulvinar, lateral pulvinar, nucleus limitans, medial magnocellular part of the nucleus ventralis anterior, nucleus paracentralis, and nucleus centralis medialis thalami. Some of these structures may also project to area 19 and/or area 39. The following thalamic nuclei were found to project to area 19 and/or area 39 but not to areas 17 and 18: nucleus lateralis posterior, nucleus centralis lateralis, nucleus medialis dorsalis, nucleus ventralis lateralis, nucleus ventralis anterior nucleus lateralis dorsalis, and nucleus anterior ventralis. In several Instances, the HRP-labeled cells traversed specific nuclear borders, extending uninterruptedly from one classically defined nucleus into another. These results in the chimpanzee largely confirm data from a number of other mammalian taxa on the subcortical sources of afferents to the posterior cortex. Because of the close biological relationship between chimpanzee and man, we feel confident that such projections are also features of the human brain.

Ultrastructure of neurons in the nucleus basalis of Meynert in squirrel monkey.

The nucleus basalis of Meynert in the squirrel monkey exhibits numerous labeled neurons following the retrograde transport of horseradish peroxidase from occipital cortical injection sites. The typically large, often clustered, labeled cells are seen most frequently in association with the fibrous bordering structures of the substantia innominata and in the internal and external laminae of the globus pallidus. Ultrastructurally the copious cytoplasm of nucleus basalis neurons abounds with organelles. Large, vacuolated lipofuscin granules proliferate as a function of age and are not evident in younger monkeys. Approximately 4% of the somal surface is occupied by symmetrical synapses with either flat or pleomorphic vesicles. The remainder is covered mostly by neuroglial processes. Somatic spines bearing synapses are occasionally observed. In the neuropil surrounding nucleus basalis somata, the synapses onto dendrites and spines are mostly asymmetrical with large, round vesicles. Labeled nucleus basalis cells in the substantia innominata immediately lateral to the optic tract are larger and rounder than cells in the internal and external pallidal laminae. However, no remarkable ultrastructural differences were observed between nucleus basalis somata in the substantia innominata and external pallidal lamina, or between horseradish peroxidase-labeled and unlabeled large cells.

Anatomical consequences of long-term monocular eyelid closure on lateral geniculate nucleus and striate cortex in squirrel monkey.

The effects of long-term monocular deprivation on the geniculostriate system in squirrel monkeys were studied with neuroanatomical methods. Four neonates were visually deprived by monocular eyelid suture during their first 10 days of life and survived from 9 to 40 months. In the lateral geniculate nucleus (LGN), deprivation resulted in severe cell size changes. Neurons in the deprived laminae were smaller compared to those in the undeprived laminae. Deprivation left the reciprocal connections between LGN and striate cortex intact: After horseradish peroxidase (HRP) injections into striate cortex, retrogradely transported enzyme labeled a wedge of neurons in deprived and undeprived LGN laminae; anterogradely transported HRP filled preterminal and terminal axons in this wedge. Following 3H-proline injections into the deprived eye for transneuronal transport, autoradiography showed in the ipsilateral striate cortex a silver grain distribution over most of layer IVc similar to that in normal squirrel monkeys, except for a small strip in the anterior calcarine fissure. Here, a few, irregularly spaced "patches" of higher grain density occurred deep in layer IVc. Layer IVc of contralateral area 17 was also uniformly labeled over most of its extent, except for a very few and inconspicuous accumulations of slightly increased silver grains. After visual stimulation of the deprived eye, the 14C-2-deoxyglucose method showed in the contralateral striate cortex some alternating "patches" of higher uptake superimposed on the heavy labeling in layer IVc. Layer IVc in the ipsilateral cortex was more uniformly labeled. Regularly spaced arrays of labeled "puffs" in layers II/III were present in both hemispheres. Cytochrome oxidase staining showed no change in the distribution pattern of the enzyme in the deprived monkeys from the basic pattern of normal adults. No changes in cell sizes were found in layer IVc in cresyl-violet-acetate-stained sections. These results lead to the conclusion that in area 17 of squirrel monkeys there is no distinct segregation of inputs from the two eyes into anatomically discrete ocular dominance columns and they support the view of a predominantly binocular organization of area 17.

Complementary laminar terminations of afferents to area 17 originating in area 18 and in the lateral geniculate nucleus in squirrel monkey.

The projections from area 18 and the lateral geniculate nucleus onto area 17 of the squirrel monkey (Saimiri) were investigated with retrograde (horseradish peroxidase) and anterograde (tritiated proline) labelling techniques, and the (Fink-Heimer) silver impregnation method for degenerating axons and their terminals. The association fibers from area 18 terminated in all layers of area 17 except in layer IV and in the lower aspect of layer IIIc. The greatest number of terminals were in layers I, V and VI. The bulk of geniculocortical fibers terminated in layer IV and the lower aspect of layer IIIc; a minority of the geniculocortical fibers terminated in layer VI and the lower aspect of layer IIIb. Thus, the majority of fibers from the two sources investigated terminate in a complementary laminar fashion in area 17. The portion of area 17 on the lateral surface of the hemisphere, where the central visual field is represented, received a less dense projection from the geniculate nucleus than the striate cortex in the calcarine fissure, where the peripheral visual field is represented. Ocular dominance columns were not apparent in the striate cortex. No evidence was found that the lateral geniculate nucleus projects to area 18. The results of combined injections of horseradish peroxidase and tritiated proline in area 17 indicated a point-to-point reciprocity between area 17 and the ipsilateral lateral geniculate nucleus.

Anatomical organization of long ascending propriospinal neurons in the cat spinal cord.

Retrograde transport of lectin-HRP conjugate (WGA-HRP) was used to examine the anatomical organization of long ascending propriospinal neurons (LAPNs) projecting to the cervical enlargement (C5-T1) and to the upper part of the cervical cord (C3-4) in cats. Small injections (0.05-1.0 microliter) of dilute (1-4%) WGA-HRP were made into the C5-T1 or C3-4 regions. The field potential evoked from stimulation of the superficial radial nerve served to position the micropipette delivering injections. Small and localized populations of labelled LAPNs were found in the dorsal horn (laminae IV-V), the intermediate zone (dorsal and medial lamina VII), and the ventral horn (ventral lamina VII, laminae VIII and IX). Ventral horn LAPNs projecting to the C5-T1 region were preferentially located in rostral lumbar regions. Ventral LAPNs projecting to the C3-4 region were more caudally situated. No regional differences in distribution of dorsal horn and intermediate zone LAPNs were noted in comparing the results of C3-4 with C5-T1 injection protocols. It is concluded that the caudally located ventral LAPNs may exert their influence on cervical motor output through C3-4 propriospinal interneurons. Other LAPNs are considered to exert their effect more directly, either at the C5-T1 or the C3-4 levels.

Competition between an aphakic and an occluded eye for territory in striate cortex of developing rhesus monkeys: cytochrome oxidase histochemistry in layer 4C.

Monkey models were used to examine the effects of competition for cortical territory between two eyes which were deprived simultaneously, but each eye experienced a different type of deprivation. We wanted to determine whether, under this condition of binocular unequal deprivation, the postnatal process of segregation into ocular dominance columns proceeds according to the same rules as those that apply to competition between a deprived and an undeprived fellow eye. Our models involved surgical removal of the natural lens from one eye in newborn rhesus monkeys. The resulting aphakia was corrected optically to a near point with extended-wear contact lenses. The fellow eyes were either left unmanipulated or occluded with opaque contact lenses for varying periods during the day. At the end of the rearing period, some monkeys from each experimental group had either one eye enucleated or sustained injury to the retinal ganglion cells of one eye. The histochemical reaction for cytochrome oxidase was used to reveal the widths of ocular dominance columns in layer 4C of striate cortex in these monkeys. Under all experimental conditions, the axons related to the two eyes occupied segregated fields. The amount of cortical territory related to the aphakic, optically corrected eye depended on the manipulations of the fellow eye. In competition with an unmanipulated fellow eye, the aphakic eye's territory was greatly reduced. In competition with a part-time occluded eye, its territory was reduced to a lesser degree, depending on the duration of the occlusion. In competition with a continuously occluded eye, however, the space related to the aphakic, optically corrected eye was slightly greater than that related to the occluded eye. Since neither the aphakic nor the continuously occluded eye receives normal visual input, they are both impaired. Therefore, they may compete on an almost equal basis for synaptic territory in layer 4C of striate cortex. Moreover, it is likely that activities originating in the aphakic and the continuously occluded eye are asynchronous, and that this condition is sufficient to drive the postnatal segregation of inputs from the two deprived eyes.

Distribution of muscarinic cholinergic receptor proteins m1 to m4 in area 17 of normal and monocularly deprived rhesus monkeys.

Antibodies to muscarinic cholinergic receptor proteins m1 to m4 were used in striate cortex tissue of normal rhesus monkeys to determine the laminar distribution of these proteins with special attention to geniculorecipient layers. The normal patterns were compared to those of monkeys whose ocular dominance system had been altered by visual deprivation. In normal monkeys, immunoreactivity of all four proteins was localized in complex laminar patterns; m1 was densest in layers 2, 3, and 6, followed by layer 5. In contrast, m2 reactivity was densest in lower layer 4C and in 4A; the latter exhibited a honeycomb pattern. Layers 2 and 3 displayed alternating dense and light regions; this pattern was complementary to that of cytochrome oxidase (CytOx). Laminar immunoreactivity for the m3 receptor was similar to the CytOx pattern, including a honeycomb in 4A and a pattern of alternating darker and lighter patches in layers 2/3. Antibody to m4 reacted most densely with layers 1, 2, 3, and 5, layers 2 and 3 exhibited alternating dark and light regions, and layer 4A had a faint honeycomb. Layer 4C was the lightest band. The differential distribution of these four muscarinic receptor subtypes suggests distinct roles in cholinergic modulation of visual processing in the primate striate cortex. Furthermore, all four muscarinic receptors appear to be insensitive to elimination of visual input via monocular occlusion from birth, to deprivation of pattern vision in one eye during a specific time period in adulthood, and to long-term retinal injury.

Brain weight throughout the life span of the chimpanzee.

Studies on human postmortem material report lower brain weights in older than in younger cohorts, whereas there is no apparent change with age in the rhesus monkey. In view of these contrasting results, we examined the pattern of brain weight across the life span in the chimpanzee, one of the closest biological relatives of humans. To place the study in context of the empirical life expectancy of the chimpanzee, we first performed a survival analysis on data from 275 chimpanzees that were maintained in the colony of the Yerkes Primate Center. The survival analysis revealed the maximum life spans of female and male chimpanzees to be about 59 and 45 years, respectively. We examined fresh brain weights from 76 chimpanzees ranging in age from birth to 59.4 years of age. The brains were taken from 9 infants (birth to 1 year of age), 25 juveniles (1-7 years), 13 adolescents (7-15 years), 21 young adults (15-30 years), and 8 old adults (over 30 years). Adult brain weight was achieved by the age of 7 years. The adolescent and young adult chimpanzees had the largest brain weights; in these two age groups combined, the mean brain weight (+/- standard deviation) was 368.1 g (+/-37.3) for females (n = 17) and 405.6 g (+/-39.4) for males (n = 17). This sex difference was statistically significant (P < 0.01). Simple linear regression performed on the combined material from females and males aged 7 years and older revealed a decline in brain weight with advancing age of 1.1 g/year (P < 0.05). When the effect of sex on brain weight was statistically controlled for, the loss of brain weight with age was 0.9 g/year (P = 0.07). These results suggest that brain weight declines moderately with age in the chimpanzee as it does in humans.