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P Sanchez

Publications and source records attributed to P Sanchez.

At least 91 records · Page 5Linked to original sources
PubMed1989

Physical linkage of mouse lambda genes by pulsed-field gel electrophoresis suggests that the rearrangement process favors proximate target sequences.

The first complete map of a mammalian immunoglobulin gene locus is presented. Mouse lambda genes were mapped by pulsed-field gel electrophoresis. The gene order is V2-Vx-C2-C4-V1-C3-C1. The distance between V2 or Vx and the C2-C4 cluster is 74 or 55 kilobases (kb), respectively, whereas that between V1 and C3-C1 is only 19 kb; V2 and C3-C1 are at least 190 kb apart. Thus, the distances between the lambda subloci are inversely proportional to their frequencies of rearrangement. The related gene lambda 5 is not within the 500 kb of the lambda locus mapped here.

Animals↗
PubMed1989

Direct administration of testosterone increases rat tibial epiphyseal growth plate width.

Local injection of hormones into the tibial epiphyseal growth plate offers a possible model to answer whether sex steroids can affect bone growth directly. To answer this question, we injected different doses of testosterone enanthate (4, 40, 120 and 400 micrograms/100 g of rat weight) once into the tibial epiphyseal growth plate of castrated 35-day-old male rats. The contralateral tibia was injected with sesame oil and served as control. All animals were sacrificed at age 42 days. Tibias were removed for measurement of epiphyseal growth plate width and blood was collected for measurement of serum IGF-I and testosterone. The lower doses of testosterone enanthate (4, 40 and 120 micrograms/100 g) did not produce any significant change in epiphyseal growth plate width. Testosterone at the largest dose tested (400 micrograms/100 g) increased epiphyseal growth plate width by about 15% compared to control (p less than 0.01). At this dose, serum testosterone was not increased, suggesting that the effect on epiphyseal growth plate width was not due to higher systemic testosterone concentrations. No differences in IGF-I levels were observed among the groups. We conclude that direct administration of testosterone enanthate at a dose of 400 micrograms/100 g into the rat tibial epiphyseal growth plate can increase epiphyseal growth plate width.

Animals↗
PubMed1989

Sleep polygraphic effects of trimipramine in depressed patients. Preliminary report.

Preliminary results are presented from an ongoing study in hospitalised depressed patients. Changes in sleep parameters were assessed on days 1 to 3 and 12 to 14 of a 4-week study in which patients received trimipramine 150 mg on day 1 and 100 mg thereafter. On days 1 to 3 and 12 to 14, 7 depressed patients had a significantly increased total sleep time and sleep efficiency index and a significantly decreased total wake time and number of intrasleep wake episodes per hour of sleep. Trimipramine treatment had no significant effect on REM sleep, percentage of REM sleep, REM duration and REM sleep stability index. However, a significant increase in REM latency was noted on days 1 to 3 but not on days 12 to 14. These polygraphic data suggest that trimipramine effects a very rapid and maintained sleep improvement in these depressed patients without significant alterations to the parameters of REM sleep.

Depressive Disorder↗
PubMed1988

Stimulation of aromatase activity in immature porcine Leydig cells by fibroblast growth factor (FGF).

The effects of fibroblast growth factor (FGF) on testicular aromatase activity has been studied using primary cultures of porcine Leydig cells. After culture for 3 days in the absence or presence of FGF, the ability of the cells to produce estrogen was examined in a 4h-test period in which either (a) hCG (10(-9) M) or (b) androstenedione (3 x 10(-6) M) was added to the medium. FGF produced a 3- to 20-fold increase in estrogen formation from endogenous or exogenous substrate during the test period, in spite of a marked decrease (approximately equal to 60%) in [125I]-hCG binding and no significant change in testosterone concentration. Stimulation of estrogen secretion by FGF was dose-(ED50 approximately equal to 2 ng/ml) and time-dependent, the first and maximal effects were observed after 12h and 48h, respectively. Preliminary tests with several other factors (insulin, EGF, TGF-beta, FSH and hCG) showed that hCG alone directly stimulated aromatase activity. From these findings a role is suggested for FGF as a paracrine/autocrine agent in the control of estrogen secretion by Leydig cells.

Animals↗
PubMed1988

Murine anti-TNP antibodies positive for either lambda 1 or lambda 2 light chains express common idiotypic determinants.

Although the lambda-bearing antibodies represent only 5% of the total mouse serum immunoglobulins, some antigens such as B1355 dextran (alpha (1-3)Dex), the 4-hydroxy-3-nitrophenyl acetyl (NP) and 2,4-dinitro or 2,4,6-trinitrophenyl (DNP/TNP) antigens can induce lambda-positive immune responses. In contrast to the lambda antibody response against alpha (1-3)Dex and NP antigens which is restricted to the lambda 1 isotype it was shown that the response to the DNP (or TNP) antigen uses lambda 1 and lambda 2 and lambda 3 isotypes. The idiotypy of the alpha (1-3)Dex and NP systems has been well characterized contrary to that of the lambda-positive anti-TNP/DNP response which has been poorly studied. In this paper, we describe two idiotopes (Id C19-3 and Id D11-2) shared by two BALB/c monoclonal anti-TNP antibodies (TNP5 and TNP9) which, respectively, use the lambda 1 and lambda 2 light chains. These idiotopes were independently expressed on other monoclonal anti-TNP/DNP antibodies and appear to require the use of a unique VH gene associated with a particular V lambda region. After TNP-Ficoll immunization, BALB/c mice recurrently express both idiotopes on lambda 1 and (lambda 2 + lambda 3) anti-TNP antibodies. In addition, all the mouse strains immunized against TNP-Ficoll give a lambda 1- and (lambda 2 + lambda 3)-positive immune response with the exception of SJL and SJA strains which present a deficit for the expression of lambda 1 light chain. The expression of Id C19-3 was restricted to the strains with the Igh-Va allotypic haplotype (including SJA) whereas the Id D11-2 was extensively expressed in the various strains.

Animals↗
PubMed1988

[Efficacy of the treatment of sleep apnea using naltrexone. A clinical, polygraphic and gasometric study].

Twelve patients with clinical, polysomnographic and oxymetric features of Sleep Apnoea Syndrome (S.A.S.) were recorded, after a 2-week wash-out period, during 2 nights without treatment and 2 nights after receiving 50 mg naltrexone at bed-time. Clinical symptoms improved immediately in four patients, within one month in three patients and after 3 months of treatment in the remaining five ones. Sleep Apnoea index as well as the number, duration and intensity of hypoxic events were dramatically improved by this treatment that has now been prescribed to 25 patients, for more than 2 years in 14 of them.

Blood Gas Analysis↗
PubMed1987

A new variable region in mouse immunoglobulin lambda light chains.

A series of lambda+ murine hybridomas were derived from a BALB/c mouse after a single injection of anti-lambda 2 antibodies coupled to LPS. Nine lambda B cell clones (five lambda 2 and four lambda 3) were expected and seven reacted with antibodies specific for the C lambda 2 constant region but showed a particular isoelectric spectrum. Their RNA products did not hybridize with the V lambda probe. The partial DNA sequence of gene segments coding the unexpected light chain of one hybridoma shows that the V gene segment has only 55% homology with the V lambda 2 gene segment sequence and that J lambda 2 and probably C lambda 2 gene segments are used. Taken together, these results demonstrate the existence of a new lambda light chain.

Animals↗
PubMed1987

Suppressor T cells with histamine type II receptors in chickens bearing chemically induced fibrosarcomas.

Immunity to a local (wing web) challenge with transplantable, chemically induced tumors, such as CHCT-NYU-4, can be transferred to histocompatible SC chickens with intravenously injected splenic T cells from tumor-immune chickens. Simultaneous iv injection of splenic T cells from chickens bearing progressively growing CHCT-NYU-4 prevents the expression of this adoptive systemic tumor immunity. The splenic suppressor T cells are B-L(Ia) positive and adhere to dishes coated with cimetidine-protein conjugate, suggesting that they bear type II histamine receptors (H2R). Intravenous injection of gamma-irradiated CHCT-NYU-4 cells 7 days prior to a local challenge with the same tumor promotes growth of a normally suboptimal tumor cell dose such that the incidence of progressive tumor growth is significantly increased. Concomitant treatment with the H2R antagonist, ranitidine, inhibits tumor growth of an optimal tumor dose challenge and promotes induction of tumor immunity. However, this drug cannot reverse the effect of iv injected tumor cells. Another drug with reported antisuppressor cell activity, cyclophosphamide (50 mg/kg), injected 1 day prior to challenge causes a transient inhibition of tumor growth. Injection of this drug on Day 7 does not have a significant effect by itself but, in combination with the Day-1 pretreatment, a significant inhibition of tumor growth by size and tumor incidence measurements is obtained. These results indicate that manipulation of immunity to transplantable fibrosarcomas in the chicken is possible with drugs acting on suppressor cells.

Animals↗
PubMed1987

Structure of a third murine immunoglobulin lambda light chain variable region that is expressed in laboratory mice.

Recently, we reported evidence for the existence of an immunoglobulin lambda light chain (lambda x) whose variable region differs from those encoded by the known V lambda gene segments V lambda 1 and V lambda 2. Expression of lambda x was detected in some hybridomas elicited by treatment of a BALB/c mouse with rabbit anti-lambda 2 antibodies coupled to bacterial lipopolysaccharide [Sanchez, P. & Cazenave, P.-A. (1987) J. Exp. Med. 166, 265-270]. We constructed a cDNA clone from one hybridoma (B6) that expresses the lambda x chain and determined the complete nucleotide sequence. The deduced amino acid sequence of V lambda x is 30-33% identical with those encoded by V lambda 1 and V lambda 2 and by V kappa gene segments. The third hypervariable region of V lambda x is four codons longer than those of the other murine variable gene segments. The expression of lambda x requires a genomic rearrangement that juxtaposes the V lambda x gene with the J lambda 2-C lambda 2 joining-constant gene pair. Rabbit anti-V lambda x antibodies detected the lambda x light chain in the normal sera of all laboratory mice tested. Lambda x expression seems to be independent of lambda 1 expression, since both SJL and SJA strains, which are defective in lambda 1 production, express normal levels of lambda x chain.

Amino Acid Sequence↗
PubMed1986

Repertoire of murine lambda-positive variable domains: polyclonal induction of lambda isotypes and their associated pattern of antibody specificities.

The diversity of lambda variable (V lambda) domains is extremely restricted when compared to those of VH and V kappa. In addition, each V lambda domain is determined by the C lambda domain. For these reasons, the lambda system is an excellent model for the study of the associated VH region repertoire. The study of V lambda domain diversity has been limited by the small contribution (approximately 5%) of lambda-bearing proteins to the total Ig pool. We now show that treatment of BALB/c mice with rabbit anti-lambda 1 antibodies coupled to lipopolysaccharide induces a production of polyclonal lambda 1 light chain-bearing Ig whereas, conversely, treatment with rabbit anti-lambda 2 antibodies induces a production of polyclonal lambda 2 + lambda 3 light chain-bearing Ig. The antigenic specificities of these two distinct lambda populations were then studied using B1355 dextran, (4-hydroxy-3-nitrophenyl)acetyl (NP) and 2,4-dinitrophenyl (DNP) as antigens. The anti-alpha(1-3)dextran antibody specificity was found to be mediated exclusively by antibodies bearing the lambda 1 isotype whereas the anti-NP and anti-DNP antibody specificities are mediated by both the lambda 1 and lambda 2 + lambda 3 isotypes. In addition, various mouse strains with the VHa or VHb allotypic haplotype and the rlo lambda 1 or r+ lambda 1 phenotype were treated with rabbit anti-lambda 1 antibodies. The lambda 1 anti-NP and anti-DNP antibody specificities were similar in all strains whereas the lambda 1 anti-alpha(1-3)dextran specificity was linked to the presence of the VHa allotypic haplotype. The mouse strains with the rlo lambda 1 or r+ lambda 1 phenotype did not differ in terms of their patterns of lambda 1 antibody specificities.

Animals↗
PubMed1986

Production of auto-anti-idiotypic antibody during the normal immune response. XII. Enhanced auto-anti-idiotypic antibody production as a mechanism for apparent B-cell tolerance in rabbits after feeding antigen.

Rabbits fed trinitrophenylated bovine serum albumin (TNP-BSA) generated fewer anti-TNP plaque-forming cells but greater numbers of hapten (TNP)-augmentable IgM and IgG PFC following immunization with TNP-Ficoll or TNP-Brucella abortus than did animals not previously fed antigen. Spleen and mesenteric and bronchial lymph nodes were similarly affected. In addition more auto-anti-idiotype (Id) antibody (anti-anti-TNP) was eluted by hapten from spleen cells of antigen-fed rabbits than from spleen cells of control rabbits not prefed antigen. Gel filtration studies ruled out the possibility that the Id binding activity in the eluates was due to immune complexes. The isotype of the anti-Id was IgG except in one rabbit where it was IgM. The results are consistent with the interpretation that the production of auto-anti-Id antibody is one of the factors responsible for the specific depression of the IgM and IgG immune responses which follows antigen feeding. In contrast the antigen feeding resulted in priming for an IgA anti-TNP response without detectable hapten-augmentable IgA PFC.

Administration, Oral↗
PubMed1986

Paracrine control of Leydig cell activity by FSH dependent proteins from Sertoli cells: an in vitro study.

The regulating effect of follicle-stimulating hormone (FSH) on Leydig cell function was studied using a model of immature porcine Leydig and Sertoli cells cultured in a hormone supplemented defined medium. FSH pretreatment for 2 days of Leydig cells cultured alone was with no effect. FSH pretreatment of Leydig cells cocultured with Sertoli cells increases Leydig cell activity in an FSH dose-dependent manner with a maximal effect observed at 50 ng/ml porcine FSH (pFSH). Leydig cells cultured for 2 days in conditioned medium (CM) by FSH stimulated (FSH-CM) Sertoli cells, as compared to CM by unstimulated (control) (C-CM) Sertoli cells show an increase of their activity with a maximal effect observed at 50 ng/ml pFSH. Leydig cells cultured in CM as compared to non CM, show a marked development of organelles (smooth endoplasmic reticulum and mitochondria) involved in the steroidogenic activity. The activity of FSH-CM as compared to C-CM on Leydig cell function was non dialyzable and trypsin sensitive. These data suggest that Sertoli cells exert a regulatory action on Leydig cell steroidogenic activity via FSH dependent secreted proteins.

Animals↗
PubMed1986

Inhibition of RNA and DNA synthesis in Sertoli cells by co-culture with spermatogenic cells.

Sertoli cell monolayers were prepared from 30-day-old rat testes and cultured for 7 days to eliminate contaminant germ cells. Some of these monolayers were co-cultured with a spermatogenic cell preparation enriched in pachytene spermatocytes and round spermatids (fraction 3 from a Percoll gradient), isolated from 30-day-old rat testes. After co-culture for 4 to 48 h, germ cells were removed. RNA synthetic activity in rat Sertoli cell cultures alone was 216,800 +/- 66,480 dpm [3H]uridine.2h-1 X 10(6) cells-1 (mean +/- SD) compared to 98,390 +/- 23,595 in rat Sertoli cells which had been co-cultured with germ cells of fraction 3 for 24 h (P less than 0.01). By contrast, RNA synthesis in Sertoli cell monolayers prepared from immature pigs were unaffected by co-culture with rat germ cells. A similar inhibitory effect of germ cells was observed in rat Sertoli cells stimulated with FSH or testosterone. Culture medium, conditioned by 20 h culture of a fresh preparation of rat spermatogenic cells of fraction 3, was active in inducing the inhibitory effect on RNA synthesis in rat Sertoli cells. Co-culture of rat Sertoli cells with germ cells of this fraction also decreased the incorporative of [3H]thymidine into DNA in rat Sertoli cells, from 9061 +/- 3339 to 4766 +/- 526 dpm.2h-1 X 10(6) cells-1 (P less than 0.01), but no such change was found in pig Sertoli cells. A different spermatogenic cell preparation, partially deprived of pachytene spermatocytes (fraction 5), stimulated rat Sertoli cell DNA synthesis (Sertoli alone 7833 +/- 2550, Sertoli cells which had been in co-culture with germ cells of fraction 5, 13,300 +/- 2279 dpm.2h-1 X 10(6) cells-1, P less than 0.05). These inhibitory actions of some germ cells on Sertoli cells were observed together with the previously reported simultaneous stimulatory effect of Sertoli cells on germ cells. These Sertoli cell-germ cell interactions of detected in culture may represent regulatory influences operating in vivo.

Animals↗
PubMed1985

FSH regulates cultured Leydig cell function via Sertoli cell proteins: an in vitro study.

The effects of follicular stimulating hormone (FSH) on testicular steroidogenic activity has been studied by testing the capacity of conditioned medium (CM) by both unstimulated (control) Sertoli cells (C-CM) and FSH stimulated Sertoli cells (FSH-CM) to influence porcine cultured Leydig cell activity. Leydig cells cultured in FSH-CM for 48 hrs, as compared to C-CM, show a significant (P less than 0.05) increase in [125I]-hCG binding (150% +/- 4) and hCG-stimulated testosterone (T) secretion (266% +/- 42). In addition, the stimulating effect of FSH-CM on Leydig cell function as compared to C-CM, is trypsin sensitive, non dialyzable, heat stable, acid resistant and is chromatographed following gel filtration (Sephadex G 100) into two different peaks of activity. These data suggest that FSH regulates Leydig cell function via (at least two types of) Sertoli cell secreted proteins.

Animals↗
PubMed1985

The regulatory locus r lambda 1 affects the level of lambda 1 light chain synthesis in lipopolysaccharide-activated lymphocytes but not the frequency of lambda 1-positive B cell precursors.

Several strains of mice, most notably the SJL strain, have a greatly reduced level of circulating lambda 1 immunoglobulins (r lambda 1 lo phenotype) compared with other mice. The locus responsible for this phenotype has been shown to be closely linked to the structural C lambda 1 gene. Functionally this locus has been said to reduce the number of lymphocytes expressing surface lambda 1 molecules. In order to gain a better understanding of this phenomenon we compared the functional properties of activated B cells secreting lambda 1 immunoglobulins in the splenocytes of both BALB/c and SJL mice. Our results indicate that regulatory T cells, as well as regulatory ontogenetic processes, are not responsible for the r lambda 1 lo phenotype. In addition, limiting dilution analyses revealed that the number of lipopolysaccharide-sensitive precursors of lambda 1-secreting B cells was similar in the splenocytes of the two strains of mice tested. The quantity of lambda 1 molecules produced by a B cell clone, however, was found to be lower in SJL than in BALB/c mice. As the level of lambda 1 mRNA is greatly reduced in lipopolysaccharide blasts of SJL mice, as compared to the mRNA detected in BALB/c blasts, we conclude that the impairment responsible for the r lambda 1lo phenotype is probably transcriptional. We tentatively propose that sequences 5' to the C lambda 1 region are defective in their capacity to enhance the lambda 1 transcripts in SJL mice.

Animals↗
PubMed1985

The expression of a private idiotope requires pretreatment with noncomplementary anti-idiotypic antibodies.

The levan-binding ABPC48 myeloma protein is characterized by 3 idiotopes, (Ids), defined by 3 syngeneic monoclonal anti-idiotypic antibodies (IDA 10, IDA 16 and IDA 17). When BALB/c mice are immunized with levan, they produce anti-levan antibodies, some of which carry the Id 10 and Id 16 but not the Id 17 determinants. In the present study, we attempted to induce the synthesis of Id 17 positive anti-levan molecules. We found that immunization with IDA 17 antibodies alone was ineffective in inducing an Id 17 positive anti-levan response. By contrast, successive immunizations with IDA 10, IDA 16 and IDA 17 antibodies resulted in the synthesis of Id 17 positive anti-levan immunoglobulins. The synthesis of these molecules was concommitant with the induction of Id 10 and Id 16 positive anti-levan antibodies. Thus our data suggest that the Id 17 determinant on anti-levan antibodies is coexpressed with Id 10 and Id 16, and that successive anti-idiotypic treatment may result in the selective expansion of rare ABPC48 cross-reactive idiotype B-cell clone precursors.

Animals↗
PubMed1985

Immune response induced by a single or several syngeneic monoclonal antiABPC48 antiidiotypic antibodies: no predominant coexpression of ABPC48 idiotopes.

BALB/c mice were immunized with monoclonal BALB/c antibodies IDA10, IDA16 and IDA17 raised against the BALB/c ABPC48 myeloma protein. Several procedures of immunization--copolymers with lipopolysaccharide or keyhole limpet hemocyanin, simultaneous or sequential injections of different IDAs--were performed in an attempt to orient the immune response towards the production of ABPC48-like idiotypes. We used a binding assay which identifies two idiotopes on the same molecule to measure the population of antibodies induced in these responses. The expression of ABPC48 cross-reactive idiotypes in immune sera was analyzed. The results show that, with all immunization protocols, immune responses to different monoclonal antiidiotypic antibodies are mostly independent of each other: the coexpression of ABPC48 idiotopes, either private or recurrent on the induced antibodies, is rarely found; it makes it difficult to discriminate by a serological approach between cross-reactive idiotypes and anti-antiidiotypic antibodies. We discuss the interest of combining molecular and serological approaches to identify these two populations of antibodies.

Animals↗