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Biomedical subjects

P Goldstein

Publications and source records attributed to P Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1986

Nuclear aberrations and loss of synaptonemal complexes in response to diethylstilbestrol (DES) in Caenorhabditis elegans hermaphrodites.

In Caenorhabditis elegans, loss of viability and fertility is observed after treatment with DES. The decrease in life span is associated with senescent morphology of meiotic prophase nuclei, such that nuclei from young and old specimens cannot be differentiated. Aging in oocytes at the pachytene stage of meiotic prophase is manifested by nucleo-cytoplasmic aberrations, increased density of the nucleoplasm and cytoplasm and decrease in numbers of mitochondria. Increasing concentrations of DES are characterized by concomitant decrease in fertility and increased production of abnormal gametes. At DES concentrations higher than 1.25 micrograms/ml, synaptonemal complexes (SC) are absent from the nuclei, thus, effective pairing and segregation of homologous chromosomes is not possible. The absence of SCs may be the result of: a premeiotic colchicine-like effect that influences pairing of chromosomes; changes in the structure of the DNA due to DES binding that results in changes in expression of the DNA; and changes in temporal DNA synthesis in response to DES. Since the SC is essential for regulating pairing and subsequent separation of bivalents, the lack of an SC explains the loss of fertility, due to the production of unbalanced gametes, observed in DES-treated specimens.

Animals↗
PubMed1986

Alloimmunization by hr'(c), hemolytic disease of newborns, and perinatal management.

A study was made of hr'(c) hemolytic disease to determine its natural history and to develop criteria for its management. Anti-c is 0.52 as frequent as anti-D(Rho) in gravid women. Seventy-four percent of infants born of c-alloimmunized women mated to c-positive men show serologic evidence of hemolytic disease of newborns. Up to 40% of affected infants require transfusion. There is evidence that ABO incompatibility between mother and fetus protects against alloimmunization. Although alloimmunization is frequently related to fetomaternal bleeding, severe hemolytic disease appears to be associated with previous maternal transfusion. Maternal antiglobulin titers of less than 1:16 are usually associated with mild disease or none at all. Women with higher titers, whose mates are hr'(c)-antigen positive, are candidates for amniotic fluid pigment analysis.

ABO Blood-Group System↗
PubMed1986

The synaptonemal complexes of Caenorhabditis elegans: pachytene karyotype analysis of hermaphrodites from the recessive him-5 and him-7 mutants.

The him-5 and him-7 mutants (high incidence of males) of Caenorhabditis elegans both showed increased rates of X chromosome non-disjunction (16% and 3%, respectively) but him-7 also had a high frequency of autosomal non-disjunction (34%). Synaptonemal complex (SC) karyotype analysis revealed a haploid chromosome number of six in each strain. Alterations in him-7 nuclear morphology were observed but there were no aberrations in SC structure that could account for the increased frequency of autosomal non-disjunction. However, the frequency of X-chromosome non-disjunction occurred at predicted rates on the basis of the number of disjunction regulator regions (DRRs) present on the SCs. The observation that the levels of X-chromosome non-disjunction were not influenced by the increase in the frequency of autosomal non-disjunction supports the notion that the X chromosome is subject to separate controls during meiosis. The him-7 mutant is nested within the rad-4 map region on linkage group V, however, SC analysis did not reveal the physical position on the chromosome because of synaptic adjustment.

Animals↗
PubMed1985

Kell alloimmunization, hemolytic disease of the newborn, and perinatal management.

The relative frequency of Kell (K:1) antibodies in pregnant women and a series of cases of Kell hemolytic disease of newborns were evaluated to review the strategy of managing potential disease. Among reproductive-aged women, Kell antibodies are about 60% as frequent as Rho (D) antibodies, but Kell disease is only 3% as common as Rho hemolytic disease. The reason is related to frequent transfusion-alloimmunization by Kell antigen and the low frequency of the K:1 gene among fathers. Kell hemolysis is severe in about half of cases. Amniocentesis is indicated in only a few circumstances: previous child with erythroblastosis fetalis, significant increase in maternal Coombs titer, presence of Kell antigen in the father, and after comparison of the relative risks of hemolytic disease and amniocentesis in each patient. Screening for Kell antigen before transfusing premenopausal women would be a means of avoiding erythroblastosis, but the rarity of severe disease does not justify this approach.

Adolescent↗
PubMed1984

The synaptonemal complexes of Caenorhabditis elegans: pachytene karyotype analysis of the rad-4 radiation-sensitive mutant.

In the rad-4 mutant of C. elegans there is a specific increase in the number of 'Disjunction Regulator Regions' (DDR) present on the synaptonemal complexes (SC) in pachytene nuclei. These DRRs either promote disjunction or inhibit nondisjunction of the X-chromosome as evidenced by the 10-fold decrease in the rate of X-chromosome nondisjunction as compared to the wild-type. The structure of the tripartite SC is normal, thus, the decrease in the rate of X-chromosome nondisjunction in the rad-4 mutant is not related to the structure of the SC but may be related to the number of DRRs. Other changes are also associated with the sensitivity to irradiation, i.e. the pachytene nuclear morphology is altered such that nuclei and nucleoli are 50% the size of wild-type. In addition, the autosomal: X-chromosome size ratio is reduced in the rad-4 mutant. That there are six SCs confirms n = 6 in this mutant and of these six SCs three can be identified: (1) the XX bivalent, SC No. 1, is the shortest and pairs synchronously with the autosomes; (2) the longest bivalent, SC No. 6, carries the nucleolar organizer region at one extreme end; and (3) SC No. 5 has two DRRs located approximately one micron apart from each other.

Animals↗
PubMed1984

The effect of alpha-tocopherol on premenstrual symptomatology: a double-blind study. II. Endocrine correlates.

In a randomized, double-blind, dose-response study, alpha-tocopherol significantly ameliorated symptoms in three of the four classes of the premenstrual syndrome (PMS). Alpha-tocopherol treatment had no significant effect on serum concentrations of testosterone, dehydroepiandrosterone sulfate (DHEA-S), estradiol, and progesterone. However, independent of treatment, a significant correlation emerged between temporal changes in one PMS category and changes in DHEA-S concentrations. These results suggest that improvement in PMS severity is not mediated through direct effects of alpha-tocopherol on serum steroids. Androgens, however, may play a role in some PMS symptomatology.

Clinical Trials as Topic↗
PubMed1984

Sterile mutants in Caenorhabditis elegans: the synaptonemal complex as an indicator of the stage-specific effect of the mutation.

Two sterile mutants of Caenorhabditis elegans hermaphrodites have been examined using the electron microscope and serial section analysis. The F4 and F80 mutants were described previously ( Mounier and Brun , 1980), and they were shown to be blocked at the start of oogenesis. In the F4 mutant, normal sperm are produced and the pachytene nuclei contain tripartite synaptonemal complexes (SC) between the homologously paired chromosomes. In the F80 asynaptic mutant, only a few sperm are produced and they have abnormal morphology. Whereas SCs and SC associated structures (termed 'SC knobs') are present in the F4, these structures are absent from the F80 . The mutation in F80 affects gametogenesis prior to the pachytene stage of meiosis and pairing of homologous chromosomes apparently does not occur. The SC knobs may influence the regulation of the disjunction of the chromosomes. For that reason, these structures are now termed 'disjunction regulator regions'.

Animals↗
PubMed1983

Serum unconjugated estriol concentrations before and after the oxytocin challenge test: an index of fetal well-being.

Serum unconjugated estriol concentrations before and after the oxytocin challenge test (stress test) were measured in 54 high-risk, obstetric patients. Six of the stress test results were positive, and eight were equivocal. Eleven patients demonstrated decrements in estriol of greater than or equal to 25% after stress tests, and the infants of six of these patients demonstrated perinatal morbidity. Three patients exhibited positive stress test results but had estriol concentrations which were unaltered by the stress test; all were delivered vaginally of healthy infants shortly after the stress test. The coefficient of correlation between the stress test and perinatal outcome was 0.58 (P less than 0.001). When the estriol and stress test results were combined to predict outcome, a multiple correlation coefficient of 0.71 was obtained (P less than 0.001). This increment represents a significant (P less than 0.001) and substantial (18%) improvement in the prediction of perinatal outcome. These findings indicate that the measurement of changes in estriol with the stress test significantly improves one's ability to define the fetus at risk.

Estriol↗
PubMed1983

Episiotomy pain: efficacy and safety of fluproquazone compared to aspirin and placebo.

The analgesic efficacy of fluproquazone at 100 mg and 200 mg doses, was measured in 160 patients with episiotomy pain and was compared to that of aspirin (650 mg) and placebo. The 100-mg dose of fluproquazone was more effective in relieving episiotomy pain than the 200-mg dose of fluproquazone, aspirin or placebo in terms of mean pain intensity scores after 1 h. All active compounds were more effective than placebo by all criteria.

Adolescent↗
PubMed1982

Volume regulation of human peripheral blood lymphocytes and stimulated proliferation of volume-adapted cells.

Human peripheral blood lymphocytes exposed to hypotonic media (Ca/Mg-free, room temp.) first swell and then shrink. This shrinking response is characterized by a simple exponential with a half-time of 1.44 +/- 0.60 min (n = 11) and its extent but not the half-time for a given hypotonicity is influenced by [K+]0. Using K-selective electrodes, we observe a change in [K+]0 when cells are diluted into hypotonic media. A half-time of 1.55 +/- 0.06 min (n = 4) was obtained. A similar half-time was obtained by assay of total cell K using atomic absorption spectroscopy. At all osmolarities [K+]i was decreased from control values and was constant as [K+]0 was increased. Short-term incubation with ouabain (10(-4) M) had no effect. Decreasing osmolarities progressively inhibited phytohemagglutinin-stimulated DNA synthesis, yet cell number and viability remained unaltered. Our evidence indicates that the volume response is mediated by a change in the passive permeability of the plasma membrane to K and/or to the accompanying anions, and that the consequently volume-adapted cells are growth-inhibited.

Cell Division↗
PubMed1982

The synaptonemal complexes of caenorhabditis elegans: comparison of wild-type and mutant strains and pachytene karyotype analysis of wild-type.

Normal synaptonemal complexes (SCs), consisting of two lateral elements and a central element, are present in wild-type, him-4 and him-8 mutant strains in both hermaphrodites and males of caenorhabditis elegans. Thus, the increase in rate of nondisjunction in the him mutants is not related to aberrant SC morphology. The wild-type hermaphrodite has six SCs, as determined from 3-D reconstruction analysis of serial section from electron microscopy. Thus, n=6 and this confirms early reports based on cytological studies with the light microscope. Only one end of the SC is attached to the nuclear envelope while the other end is free in the nucleoplasm and there is no apparent bouquet formation. Either end of the SC can attach to the nuclear envelope. The pairing behavior of the XX bivalent is normal and occurs synchronously with the autosomes. Electron dense bodies, or knobs, are associated with the SC via the central element and displace the chromatin for a distance of 200 nm. Each pachytene nucleus of the wild-type hermaphrodite has six such structures that are randomly dispersed along the bivalents such that some SCs have one or two knobs while others have none. Their function is unknown.

Animals↗
PubMed1982

The synaptonemal complexes of Caenorhabditis elegans: pachytene karyotype analysis of male and hermaphrodite wild-type and him mutants.

Only five synaptonemal complexes (SC), representing the 5 autosomes, are present in wild-type, him-4 and him-8, Caenorhabditis elegans males, whereas there are six SCs, accounting for 5 autosomal bivalents and the XX bivalent, in the C. elegans hermaphrodite. The univalent X chromosome of the male is present as a heterochromatic 'X-body' in spermatocyte pachytene nuclei. The XX bivalent in wild-type, him-4 and him-8 hermaphrodites (SC1, 2.5 microns in length) represented 6% of the total karyotype length and a SC of this size is missing from the respective male karyotypes. This corresponds with the fact that the total male karyotype length is only approximately 94% that of the hermaphrodite. Associated with the central element of the SC are structures termed 'SC knobs' that were first described in the wild-type hermaphrodite. The six SC knobs present in the wild-type hermaphrodite oocyte pachytene nuclei and the two SC knobs in the male spermatocyte pachytene nuclei are apparently randomly placed with the exception that they are never found at the ends of the SC. This is also true in him-4 and him-8 in which case there are 3 and zero SC knobs in the hermaphrodites, respectively, and one SC knob each in the male pachytene nuclei. The decrease in number of SC knobs in hermaphrodite to male represents a true sex difference. The presence or absence of the SC knobs may influence the X chromosome nondisjunction process and this effect is not localized to the region of the SC on which the SC knob is located.

Animals↗
PubMed1982

The synaptonemal complexes of meloidogyne: relationship of structure and evolution of parthenogensis.

The synaptonemal complexes of three amphimictic (meiotic) strains of Meloidogyne are examined in this study. M. microtyla (n = 19) has a tripartite synaptonemal complex (SC) comprised of two lateral elements and one central region with a distinct central element. The central region of the SC in both M. carolinensis (n = 18) and M. megatyla (n = 18) lack a distinct central element. The evolutionary history is different in the strains since M. microtyla has arisen by a mechanism involving an increase in chromosome number (from an ancestral stock of n = 18) while both M. carolinensis and M. megatyla have maintained the number of chromosomes of the ancestral stock. The structure of the SCs of the latter two strains are identical to the structure of the SC of the meiotic parthenogenetic M. hapla. Thus, the pachytene karyotype of M. carolinensis was reconstructed to establish the pairing pattern and identify any changes that may be related to the different morphology of the SC in an amphimictic stock. Although recombination nodules (RN) have been observed in the parthenogenetic M. hapla, none of the three amphimictic strains had any SC associated structures that resembled a RN.

Animals↗
PubMed1981

Pachytene karyotype analysis of tetraploid Meloidogyne hapla females by electron microscopy.

Pairing of homologous chromosomes results in the formation of 34 synaptonemal complexes (SC) at pachytene, corresponding to the 34 bivalents at metaphase I. No multivalent associations were observed and pairing occurs two-by-two. The modified SC, which lacks a central element, does not affect the pairing process. Only one end of the SC is attached to the nuclear envelope, although either end can attach. Total SC length and the number of recombination nodules in the tetraploid were about 1.5 times greater than in the diploid.

Aneuploidy↗
PubMed1981

alpha-Tocopherol and serum lipoproteins.

Twenty-six patients with clinically confirmed mammary dysplasia and five age-matched controls were treated with alpha-tocopherol, 600 mg/day. Serum samples collected on the 21st day of the menstrual cycle were analyzed for cholesterol in lipoprotein fractions, isolated by a combination of precipitation and ultracentrifugation techniques. Eighty-five percent of patients showed objective and subjective remission from disease following therapy. In mammary dysplasia patients, the ratio of serum cholesterol/high density lipoprotein cholesterol was higher than those in age-matched controls, an abnormality which was corrected by alpha-tocopherol therapy. Furthermore, as a result of therapy, high density lipoproteins increased and ester cholesterol associated with low density lipoproteins decreased. The results suggest that alpha-tocopherol may serve as an effective agent in treating patients with benign disease, as well as correct the inherent abnormality in serum cholesterol distribution in mammary dysplasia patients.

Breast Diseases↗
PubMed1981

Serum hormones and lipoproteins in benign breast disease.

Seventeen young women with clinically confirmed mammary dysplasia and six age-matched controls were treated with alpha-tocopherol. Serum samples collected during the luteal phase of each woman at monthly intervals for the 4-month duration of the study were analyzed for serum luteinizing hormone, follicle-stimulating hormone, and prolactin concentrations by radioimmunoassay and for lipoprotein levels by a combination of precipitation, ultracentrifugation, and enzymatic techniques. Fifteen patients showed objective and subjective remission from disease. While prolactin levels did not change significantly, elevated levels of luteinizing and follicle-stimulating hormones were decreased to normal levels. Ratios of serum cholesterol to high-density lipoprotein cholesterol decreased; high-density lipoprotein and free cholesterol associated with low-density lipoproteins increased as a result of therapy. The results suggest that alpha-tocopherol may serve as an effective agent not only to treat patients with benign breast disease but also to normalize abnormal hormone and lipid levels in subjects at high risk for breast cancer.

Breast Diseases↗