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Biomedical subjects

E Weiler

Publications and source records attributed to E Weiler.

At least 19 recordsLinked to original sources
PubMed1999

Apparent trans-chromosomal antibody class switch in mice bearing an Igh(a) mu-chain transgene on an Igh(b) genetic background.

Native high molecular weight dextran induces a thymus-independent response in BALB/c mice. When the dextran epitope is linked to a protein carrier the response becomes thymus-dependent. IgG antibodies produced after secondary immunization had epitope specificity and idiotope of myeloma M104E. The antibody of M104E (mu, lambda1) is representative for antibodies produced by mice with immunoglobulin haplotype Igh(a) in response to immunization with dextran B1355S. Myeloma product and physiological antibodies share specificity for the alpha(1-3) glucosidic linkage and have idiotopes in common. Mice with haplotypes other than Igh(a) (e.g. Igh(b)) are unable to yield this type of response. A complete rearranged immunoglobulin mu-chain gene with a VDJ-region from BALB/c (Igh(a)) myeloma protein M104E had been introduced into the genome of BALB/c congenic mice having the haplotype Igh(b). As was shown previously in our laboratory the M104E mu-chain transgene confers Igh(a)-type reactivity to Igh(b) mice. In experiments described in this report we used the thymus-dependent form of the antigen to immunize mice bearing the M104E mu-chain, either alone or together with the lambda1-chain, as a transgene on an Igh(b) genetic background. Serological analysis revealed a class switch to IgG very similar to that seen in BALB/c mice with respect to magnitude, kinetics, epitope and idiotope specificity. The pattern of IgG subclass expression was indistinguishable in mu-chain transgenic Igh(b) and normal BALB/c mice. The class switch occurred even though, as is shown here, the transgene had become incorporated in a site not linked to the Igh locus on chromosome 12. We propose a model for this apparent trans-chromosomal class switch recombination which is based on mechanisms known for conventional switch recombination.

Animals↗
PubMed1999

Proliferation in the vomeronasal organ of the rat during postnatal development.

We investigated proliferation of sensory cell precursors in the rat vomeronasal organ (VNO) at various postnatal ages from birth (P1) to P666. In the rat, which continues to grow during most of its adult life, proliferation might be related to growth and/or replacement. Proliferating cells were labelled by BrdU injection, and histological sections of the VNO were evaluated after immunohistochemical detection of BrdU. Proliferation density (number of proliferating cells/section) decreased dramatically from 115 at P1 to 27.2 at P21, although the area increased. Adult values were reached at P66-P333 (10.3 cells/section); at P400-P666 the value was 8.6 cells/section. Distribution of labelled cells changed considerably with age: in neonates the cells were nearly equally distributed throughout the sensory epithelium, whereas from P21 onwards most proliferating cells were concentrated in clusters near the boundaries with non-sensory epithelium. Labelled cells in the sensory neuronal layer were adjacent to the undulating basement membrane-bordering capillaries that intrude into the sensory epithelium, indicating that they were true basal cells. The volume of the sensory epithelium increased between P1 and P66, and remained constant thereafter, although the length still increased. Length and volume of the sensory epithelium were related to body size, not to sex; males and females of the same body size had the same VNO size. The complex changes in proliferation pattern during postnatal development indicate differential growth and replacement. We suggest that in adults the labelled cell clusters near the boundaries are a pool for growth, whereas proliferation in the central parts represents a replacement pool.

Aging↗
PubMed1999

Mitral cell loss following lateral olfactory tract transection increases proliferation density in rat olfactory epithelium.

Olfactory sensory neurons are replaced throughout the life of vertebrates by proliferation of basal cells and differentiation of the new cells into neurons. Removal of their target, the olfactory bulb, increases proliferation twofold because sensory neurons die prematurely, suggesting that the olfactory bulb provides a trophic substance required for survival. We asked whether mitral cells, a major postsynaptic target of olfactory sensory neurons, are involved in their survival. We report here that depletion of mitral cells increases proliferation and cell death in the olfactory sensory neuron population. Mitral cell loss was induced unilaterally by transection of their axons in the lateral olfactory tract in 18-day-old rats. At all time points after surgery (3 weeks, 7 weeks, 3 months, 14 months) there was a 29% mean reduction in the number of mitral cells ipsilateral to the transection. The surviving mitral cells were smaller than controls and had less rough endoplasmic reticulum. In the olfactory epithelium, proliferation density (BrdU-positive cells/mm epithelial length) in the progenitor basal cells was increased by an average of 20-25% at all time points, as was the number of TUNEL-positive dying cells. The results are consistent with the notion that mitral cells, or the synaptic sites on them, are a source of trophic factor required for maintenance of the lives of olfactory sensory cells. The target field of postsynaptic neurons remaining after lateral olfactory tract transection is insufficient to maintain normal survival of all existing olfactory neurons. In unperturbed animals the proliferation density declines in an age-dependent manner and interestingly the decline on the tractotomized side is parallel. This suggests that with age the sensory cells are less dependent on their targets.

Aging↗
PubMed1999

The vomeronasal organ of the male ferret.

The vomeronasal organ (VNO) is known to play a major role in sexual behavior in many mammals. This study is the first report that the adult male ferret has a VNO, which is considerably smaller and morphologically different from the usually crescent-shaped epithelium in several mammalian species, particularly rodents. There were no differences in the size or structure of the ferret VNO between the mating season in spring and the sexually quiescent season in autumn, although plasma testosterone, testis size and brain size are dramatically increased in spring and behavior changes significantly. The histological data suggest that the VNO might be not as important a structure in male ferret sexual behavior as in rodents.

Animals↗
PubMed1998

Selective and reversible reduction of odor sensitivity in the rat by concanavalin A.

Rats were trained using an olfactometer to detect low concentrations of ethyl acetate (EA) or dimethyl disulphide vapor (DMDS). Concanavalin A (ConA) applied to the olfactory mucosa had no effect on ability of rats to detect low concentrations of EA but produced a marked deficit in detection in DMDS. DMDS detection performance returned to control levels 3 days after the ConA treatment. These results provide the first behavioral evidence for odor-specific inhibition by chemical modification of the olfactory epithelium and support the notion that ConA selectively inactivates one or more types (subclasses) of olfactory receptor proteins.

Acetates↗
PubMed1998

Proliferation decrease in the olfactory epithelium during postnatal development.

Olfactory sensory cells are replaced continuously throughout the life of an animal. In postnatal rats proliferation density decreases dramatically, and continues to decrease into adulthood at least up to 11 months of age. This is true in both the basal cell and supporting cell populations. However, correlation analysis revealed there was no correlation in mitotic rate between the two cell types, suggesting that proliferation of the two cell types is regulated differently. With age, the rat body size and the area covered by olfactory epithelium increases. We present evidence that supporting cell proliferation provides only for growth, whereas proliferation of basal cells provides for both growth and replacement. Further, we present evidence that in older animals the sensory cells live longer than they do in younger animals.

Aging↗
PubMed1998

Supporting cell proliferation in the olfactory epithelium decreases postnatally.

It is well known that progenitor cells in the basal layer of olfactory epithelium proliferate continuously throughout life; the offspring of these dividing cells produce replacements for receptor neurons. In the rat the number of proliferating basal cells/mm length of epithelium (proliferation density) decreases with postnatal age while the area of the olfactory sheet increases. The supporting cells, which act as the glia of the olfactory epithelium, also divide. We examined in detail some aspects of the dynamics of olfactory supporting cell proliferation to determine whether their rate of proliferation changes with age, and how it compares with the rate in basal progenitor cells. Using BrdU to label dividing cells, we determined the proliferation density of supporting cells and basal cells in 10 microm coronal sections from six different anterior-posterior regions in rats ranging in age from birth (P1) until P333. We observed a dramatic decrease in supporting cell proliferation density from P1 (80 cells/mm) to P11 (32 cells/mm) to P21 (12 cells/mm); the density decreases continuously to P333 (0.4 cells/mm). This reduction was even more dramatic than that in the basal cell population (Weiler and Farbman, 1997). Analysis of the data for correlation between basal and supporting cell proliferation revealed a weak correlation in neonates but no correlation in older animals. This suggests that the mechanisms that regulate proliferation of the two cell types are different. Our data also indicate that the proliferation of supporting cells is related only to growth in surface area of the epithelium. No turnover seems to occur in the supporting cells as it does in the olfactory neurons, where proliferation of basal cells is necessary for both growth and replacement.

Aging↗
PubMed1997

Proliferation in the rat olfactory epithelium: age-dependent changes.

Vertebrate olfactory sensory neurons are replaced continuously throughout life. We studied the effect of age on proliferation in olfactory epithelium in postnatal rats ranging in age from birth (P1) until P333. Using BrdU to label dividing cells, we determined the proliferation density of basal cells, i.e., the number of labeled nuclei/unit length (240 microm) of olfactory epithelium in coronal sections from six different anterior-posterior levels from each animal. A total length of >1 m of olfactory epithelium was counted in each age group. We observed a dramatic decrease of proliferation density from P1 through P333. At P1, proliferation density is 151 cells/mm; it decreases to approximately half at P21 (70 cells/mm), and half again at P40 (37 cells/mm). At P333 the proliferation density was only 8/mm, approximately 5% of that seen at P1. The changes were clearly related to age and not to body weight, because the values were essentially identical for males and females of the same age but of different body weight. Proliferating cells appear in patches that, after P40, become more separated from one another and contain fewer cells. In 6- and 11-month-old rats, 30 and 45% of all units contained no labeled cells. We confirmed the data of others that the olfactory surface area continuously increases with age; we showed that there is a reciprocal relationship between proliferation density and surface area. The proliferating cells provide neurons to sustain growth as well as to replace dying cells.

Aging↗
PubMed1995

Effects of age, education, and living environment on Boston Naming Test performance.

The 60-item Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 1983) was administered to 323 normal elderly subjects between the ages of 65 and 97. The combined effects of age, education, and living environment (institutionalized/independent living) on total test score was determined. These three variables accounted for 32% of the variance in BNT performance. Educational background accounted for the greatest proportion of the variance, followed by age and living environment. There was also a significant interaction between age, education, and living environment. Overall, increased age adversely affected BNT scores. However, institutionalized subjects with a sixth-ninth grade education performed poorly on the BNT regardless of age. In addition, there was little difference in BNT performance according to age or living environment for the well educated. (The only exceptions were the oldest institutionalized subjects, who performed poorly on the BNT regardless of level of education.) The data presented in this study should be helpful for those clinicians who administer the BNT to elderly patients who are institutionalized or who have a limited educational background.

Activities of Daily Living↗
PubMed1995

Stimulation of the same B-cell population by thymus-independent dextran and by thymus-dependent oligosaccharide-carrier.

The immune response of adult BALB/c mice against the bacterial antigen dextran B1355S (Dex) is well characterized as thymus independent (TI type 2) and Igha linked. The antisera consist of mainly IgM/lambda antibodies directed against the alpha(1-->3) glucosidic linkage. This study describes the immune response against the alpha(1-->3) linkage in the thymus dependent form (TD), i.e. tetra- or heptasaccharides (N4 or N7) of glucose as hapten coupled to chicken serum albumin (CSA) as carrier. Whereas athymic BALB/c-nu/nu mice did not respond to the TD antigens N4-CSA and N7-CSA, euthymic BALB/c showed high anti-Dex antibody titres of IgM and, after 2 degrees immunization, a class switch to IgG (mainly IgG1) isotypes with lambda light chains. The hapten N4 inhibited Dex-binding of M104E or of antisera from Dex or N4-CSA or N7-CSA immunized mice at 1.7-10 x 10(-4)M. The idiotype composition of these antibodies resembled those after Dex immunization. We conclude that the same Dex-specific precursor B cells have been stimulated by either form of antigen. The ontogenic development of a Dex-specific response could not be accelerated by the aid of T cells, even of adult origin. It seems, therefore, that the maturation of antigen specific B cells is the limiting step in ontogeny.

Age Factors↗
PubMed1993

The thymus-independent antigen alpha(1-3) dextran elicits proliferation of precursors for specific IgM antibody-producing cells (memory cells), which are revealed by LPS stimulation in soft agar cultures and detected by immunoblot.

Single antibody-forming cells (AFC) specific for alpha(1-3) dextran (Dex) from i.p.-immunized BALB/c mice were enumerated in soft agar cultures by blotting on antigen-precoated membranes and subsequent staining via enzyme-coupled anti-IgM antibodies. Short cultures (2 h) revealed AFC as harvested ex vivo, while in long-term cultures (4 days), in the presence of lipopolysaccharide (LPS) as B cell mitogen, cells or colonies developed by differentiation in vitro. Whereas the spleen contained most AFC ex vivo in a sharp-peak response at 4 and 5 days after i.p. injection of Dex in aqueous solution, peritoneal exudate cells (PEC) contained only very few AFC. However, the same PEC population developed Dex-specific cells or colonies after 4 days of culture. The isotype of antibodies was IgM. The frequency of these Dex-specific LPS-inducible precursor cells rose exponentially in the course of the immune response to a broad plateau and was still, 11 weeks after Dex injection, approximately 40-fold higher than in non-immunized mice. Since these cells increased in frequency after antigen injection, and since they could not be detected as AFC during 2 h ex vivo, they were regarded as memory cells. They seemed to be arrested in vivo, but could be induced to differentiation and/or proliferation in vitro. Although these cells had the functional characteristics of memory cells as defined above, they produced anti-Dex antibodies of IgM isotype. Their population might be critical for the protection of the peritoneal cavity against microbial invasion from the intestines, and it may be significant in this context that we could evoke a peritoneal memory cell response only when antigen was injected intraperitoneally, but not intravenously. In athymic BALB/c-nu/nu mice only few of these Dex-specific memory cells were found. It is possible that T cells exert a regulatory influence on this pathway of differentiation.

Animals↗
PubMed1991

Neonatal complement depletion results in predominant expression of a myeloma M 104E private idiotope among anti-dextran antibodies.

Myeloma M 104E (IgM, lambda 1) with specificity for the alpha(1----3) glucosidic linkage of dextran B 1355 S (Dex) carries two idiotopes (Id) as defined by isogenic anti-idiotype mAb. The public Id is not influenced by two amino acid replacements in CDR 2 nor by an alternative D region sequence. It is shared by all or nearly all humoral antibodies in the primary immune response against Dex of mice carrying haplotype Igha. The private Id-5' appears to depend on the integrity of the VH germ-line sequence and on the particular M 104E D region sequence. It is present on a highly fluctuating but usually small fraction of primary anti-Dex antibody. We report here that this situation is changed when mice are treated with Cobra venom anti-complement factor (CVF), after birth and thereby were deprived of complement for the first two weeks of life. When immunized with Dex as adults the majority of anti-Dex Ab carried the M 104E Id-5. Thus, humoral antibody in CVF-treated animals resembled the Ly-1+ anti-Dex precursor B cell population in the peritoneal cavity, while anti-Dex Ab in animals not treated with CVF more closely corresponded to the Ly-1- precursor B cell pool in spleen (H.-P. Lehmann and G. Lehle, Eur. J. Immunol. 1991. 21: 1201).

Animals↗
PubMed1991

The effects of rate, sequencing, and memory on auditory processing in the elderly.

Auditory sequencing, rate, and memory were evaluated in three age groups with a series of subtests that require the identification of tones (Repetition Test; Tallal & Piercy, 1973). The older elderly group (M age = 80), but not the younger elderly group (M age = 70), performed significantly (p less than .05) poorer than the young adult group (M age = 25) when auditory memory of 4 and 5 tones was required and when the interstimulus interval was decreased. Performance was not related to hearing sensitivity, thus suggesting that changes in the auditory mechanism that occur with age may encompass more than a loss of hearing sensitivity. Moreover, performance on the Repetition Test did correlate with memory for digits, which indicates a relationship between auditory processing and higher cortical functions.

Acoustic Stimulation↗
PubMed1990

Effects of lead and a low-molecular-weight endogenous plasma inhibitor on the kinetics of sodium-potassium-activated adenosine triphosphatase and potassium-activated p-nitrophenylphosphatase.

1. Lead, ouabain and an endogenous plasma inhibitor were all found to be potent inhibitors of purified hog cerebral cortex sodium-potassium-activated adenosine triphosphatase and potassium-stimulated p-nitrophenyl-phosphatase. 2. The kinetic characteristics of inhibition of both enzymes by lead and the endogenous plasma inhibitor differed in several respects. For sodium-potassium-activated adenosine triphosphatase, lead and the endogenous plasma inhibitor were non-competitive inhibitors with respect to potassium; lead was competitive with respect to sodium, whereas the endogenous plasma inhibitor had no effect; lead was competitive with respect to magnesium adenosine triphosphate, whereas the endogenous plasma inhibitor was uncompetitive. For potassium-activated p-nitrophenylphosphatase, both lead and the endogenous plasma inhibitor were competitive with respect to potassium; lead showed a mixed type of inhibition with respect to p-nitrophenylphosphate, whereas the endogenous plasma inhibitor was non-competitive. 3. Lead and the endogenous plasma inhibitor exhibited synergistic inhibitory activity on sodium-potassium-activated adenosine triphosphatase. 4. These results suggest that lead could play a contributory role in the pathogenesis of essential hypertension via an additive inhibition of vascular smooth muscle sodium-potassium-activated adenosine triphosphatase.

4-Nitrophenylphosphatase↗
PubMed1989

Effects of a human-derived sodium transport inhibitor on in vitro vascular reactivity.

Concentrations of sodium-transport inhibitors (STI) which block the sodium-potassium-ATPase pump are increased in the plasma and urine of volume-expanded and low-renin hypertensive humans and animals. To evaluate the physiologic relevance of STI to blood-pressure-raising mechanisms, we have examined the in vitro properties of STI extracted from the urine of human subjects. STI produced a significant (by ANOVA: P less than .01) dose-contraction response in the isolated rabbit femoral artery. Moreover, small noncontractile doses of STI in this in vitro preparation produced a fivefold leftward shift in the contraction dose-response curve of norepinephrine (P less than .01) and a threefold shift for angiotensin II (P less than .01); at lower, physiologic, concentrations of these vasoconstrictor hormones the amplifications in contraction caused by STI ranged from 100% to 500%. In studies in calcium-free tissue bath solutions, the direct contractile action of STI was abolished; however, its amplification of responses to norepinephrine remained, suggesting that this latter effect of STI is not entirely dependent upon calcium influx into vascular smooth muscle cells. The glycoside ouabain produced effects identical to those of STI in arteries, but its actions on a rabbit atrium preparation were different: ouabain stimulated powerful inotropic effects, whereas human STI failed to cause myocardial contractions even though the amounts of STI administered had the same sodium-transport inhibitory capacity as the ouabain. Thus, the actions of human STI are primarily in the peripheral circulation, where they directly produce arterial contractions and also enhance contractile responses to other pressor hormones, suggesting that they may have a role in regulating systemic blood pressure.

Angiotensin II↗
PubMed1988

A map of VH genes located next to the DH region in the Igh locus of two congenic Igh-recombinant mouse strains.

A new congenic mouse strain (C57BL/6-Igh-Vb-Ca) with a recombinant chromosome 12 is described. It carries the Igh-1a allele, but shows the serological characteristics of C57BL/6 when analyzed for idiotype expression with respect to the antigens dextran and (4-hydroxy-5-iodo-3-nitrophenyl)acetyl (NIP). We analyzed liver DNA from one animal for restriction fragment length polymorphism by hybridization to probes detecting members of nine VH gene families and DH segments, and compared it to DNA from animals carrying the nonrecombinant haplotypes Igha and Ighb, respectively. The breakpoint of recombination maps to the region carrying members of VH gene families VGAM3.8, PC7183 and Q52. The CB8KN strain which according to the serological analysis carries a recombinant Igh locus (Igh-Va-Cb) on BALB/c background was also analyzed. In this strain the breakpoint of recombination again maps to the region carrying members of VH gene families VGAM3.8, PC7183 and Q52. Our results show that the VH genes of families PC7183 and Q52 are interspersed and map to the region next to the DH locus. At least one gene from the VGAM3.8 family also maps to this region in the Igha and the Ighb haplotype.

Animals↗