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Biomedical subjects

L A Goldstein

Publications and source records attributed to L A Goldstein.

At least 37 records · Page 2Linked to original sources

Hormonal control of neuron number in sexually dimorphic spinal nuclei of the rat: IV. Masculinization of the spinal nucleus of the bulbocavernosus with testosterone metabolites.

The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic motor nucleus in the rat lumbar spinal cord. SNB motoneurons and their perineal target muscles are present in adult males but reduced or absent in females. This sexual dimorphism is due to the presence of androgen during development; females treated with testosterone (T) perinatally have a masculine SNB system. To assess whether masculinization of the SNB could involve the conversion of testosterone into its active metabolites, dihydrotestosterone (DHT) and estrogen, we examined the development of the SNB in females treated perinatally with estrogen alone or in combination with dihydrotestosterone. Counts of motoneurons in the developing SNB in all groups showed the typical prenatal increase followed by a differential postnatal decline; the incidence of degenerating cells reflected this decline. Motoneuron numbers and the frequency of degenerating cells in females treated with estrogen (E) alone did not differ from those of normal females, with both groups losing large numbers of motoneurons and having a high incidence of degenerating cells. In contrast, females treated with both estrogen and dihydrotestosterone did not show the female-typical decline in motoneuron number and had a low, masculine incidence of degenerating cells. By postnatal day 10, females treated with estrogen and dihydrotestosterone had a fully masculine SNB motoneuron number, suggesting that dihydrotestosterone alone or in conjunction with estrogen may be involved in the development of the sexually dimorphic SNB system.

Animals↗

Identification of mRNA that encodes an alternative form of H-CAM(CD44) in lymphoid and nonlymphoid tissues.

The cluster of differentiation 44 (CD44), hereafter referred to as H-CAM(CD44), represents a novel class of polymorphic (Mr 80,000-215,000) cell adhesion molecules that are involved in cell-cell and cell-matrix adhesion events in a variety of organ systems. We report the detection of distinct mRNAs, in both hematopoietic and nonhematopoietic human cell lines, that encode H-CAM(CD44) with different cytoplasmic domains. Genomic Southern blot analyses indicate that the exons encoding these two cytoplasmic domains are located on the same approximately 16 kilobase (kb) Eco RI restriction fragment. Restriction endonuclease and Southern blot analyses performed on polymerase chain reaction (PCR) amplification copies of these mRNAs confirm that their sequences correspond with previously reported cDNA sequences. A consensus splice donor site which is conserved in human, baboon, and mouse mRNAs that encode a molecule with an elongated cytoplasmic domain (H-CAM-L) is utilized to generate a distinct but low-abundance mRNA species that encodes H-CAM(CD44) with a truncated cytoplasmic domain of only three amino acids (H-CAM-S). Estimations of the relative abundance of these mRNA species in B-lymphoblastoid cells using the PCR amplification technique exhibit average H-CAM-L/H-CAM-S ratios ranging between 100 and 200. Therefore, H-CAM (CD44)-mediated adhesive events may be regulated through a differential capacity of H-CAM-L and H-CAM-S to interact with the cytoskeleton and to participate in intracellular signaling events.

Base Sequence↗

Androgen regulation of dendritic growth and retraction in the development of a sexually dimorphic spinal nucleus.

The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurons whose development and maintenance are under androgenic control. Exposure to androgens early in development permanently alters SNB motoneuron number and soma size; in adulthood, androgens regulate dendritic and synaptic architecture. The present set of experiments investigates the influence of androgens on the development of SNB dendritic morphology. In normal males, SNB dendritic growth is biphasic, reaching exuberant lengths by the fourth postnatal week and then retracting to adult lengths by 7 weeks of age. This dendritic growth is androgen dependent--males castrated on postnatal day (P) 7 and given daily injections of testosterone propionate (TP) had exuberant dendritic lengths similar to those of normal males; dendritic length in oil-treated males remained at P7 levels. The early exuberant dendritic length was retained in TP-treated males through P49. The retraction of SNB dendrites after P28 is also influenced by androgens. Males castrated at P28 and given testosterone implants retained exuberant dendritic length at P49; blank-implanted males had significantly shorter dendritic lengths by P70. These results suggest that androgens are necessary for the early exuberant growth of SNB dendrites. Furthermore, the subsequent retraction of SNB dendrites may be halted when testosterone titers reach a critical level during puberty, stabilizing their adult length.

Androgens↗

A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins.

Lymphocyte interactions with high endothelial venules (HEV) during extravasation into lymphoid tissues involve an 85-95 kd class of lymphocyte surface glycoprotein(s), gp90Hermes (CD44). We report here the cloning of cDNA for gp90Hermes expressed in a mucosal HEV-binding B lymphoblastoid cell line, KCA. Northern hybridization revealed the presence of three invariant RNA bands at 1.5, 2.2, and 4.5 kb in mucosal HEV-, lymph node HEV-, or dual-binding cells. The deduced amino acid sequence predicts a mature protein with a C-terminal cytoplasmic tail, a hydrophobic transmembrane domain of 23 amino acids, and an N-terminal extracellular region of 248 amino acids. A proximal extracellular domain is the probable region of O-glycosylation and chondroitin sulfate linkage and displays at least two of the three immunodominant epitope clusters of native gp90Hermes. A distal region contains the majority of potential N-glycosylation sites and cysteines, and exhibits a striking homology to tandemly repeated domains of the cartilage link and proteoglycan core proteins. No significant similarities were found to the immunoglobulin, integrin, or cadherin gene families. Thus gp90Hermes represents a novel class of integral membrane protein involved in lymphocyte-endothelial cell interactions and lymphocyte homing.

Aggrecans↗

Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin.

The biosynthesis of rat haptoglobin, a hetrotetrameric glycoprotein (alpha 2 beta 2), requires the post-translational cleavage of its glycosylated primary translation product (prohaptoglobin) into alpha- and beta-subunits (Hanley, J. M., Haugen, T. H., and Heath, E. C. (1983) J. Biol. Chem. 258, 7858-7869). To elucidate the site(s) at which proteolytic cleavage occurs in prohaptoglobin, we have isolated a recombinant plasmid whose cDNA insert encodes for the carboxyl terminus of the alpha-subunit, the alpha beta-subunit junction, and the beta-subunit region, and also the entire 3'-untranslated region (142 base pairs) and poly(A) tail (55 base pairs) of the mRNA. A single arginine residue was found at the alpha beta-subunit junction region -Val-Gln-Arg-Ile-Ile-Gly-Gly-of prohaptoglobin. The sequence homology of this region with serine protease precursors suggests that post-translational processing of prohaptoglobin involves cleavage of the Arg-Ile bond and extraction of the Arg residue. The rat beta-subunit shows a high degree (approximately 80%) of sequence homology with its human counterpart although it possesses only two of the four N-glycosylation sites present in human haptoglobin beta-subunit.

Amino Acid Sequence↗

Comparative ontogenesis of gamma-glutamyl transpeptidase in rat tissues.

In rats, placental gamma glutamyl transpeptidase (GGTP) specific activity declined linearly during the last third of gestation. In contrast, the kidney enzyme activity progressively increased 15-fold. In the gut, peak activity was reached at mid-lactation (age 12 days). Hepatic GGTP levels were maximal during the foetal stage. Brain GGTP was negligible at birth and attained its highest specific activity at weaning.

Aging↗

Esophageal perforations: a 15 year experience.

A review of 44 patients with 50 esophageal perforations from 1966 through 1980 is presented. The age span was 15 months to 94 years and the male to female ratio was 1 to 1. Each case was studied with regard to presentation, etiology, treatment and complications. Twenty-two cases of esophageal perforation followed instrumentation, including 6 secondary to Mosher bag dilatation for achalasia. Of the remainder, seven patients had spontaneous perforation, five had external trauma, five had intraoperative injury, two had caustic ingestion, and one each had foreign body ingestion, Zollinger-Ellison syndrome and an incarcerated paraesophageal hiatal hernia. Management was nonoperative in 12 patients, primary repair and drainage was performed in 23 patients, and 9 patients underwent drainage and diversion. This series plus 824 patients with esophageal perforation accumulated from a review of the literature emphasizes the importance of the influence of different methods of treatment and time lapse between occurrence and therapy. The type of perforation had no significance on this series. As a result of the experience gained from this series, a treatment protocol is proposed for the management of esophageal perforation.

Adolescent↗

Factor-dependent dissociation of wheat germ ribosomes.

Ribosome dissociation factor has been found in wheat germ acetone powder extracts. Further purification of the crude extract by pH an ammonium sulfate fractionations, DEAE-cellulose and CM-Sephadex column chromatography has resulted in the separation of two active fractions. The possibility that ribosome dissociation activity exhibited by either fraction is due to protease or nuclease is considered unlikely, based on results of experiments involving ribosome dissociation kinetics, subunit structural integrity, and treatment with a serine protease inhibitor. Wheat germ ribosome dissociation factor is not species-specific. Dissociation factor from both fractions will promote the dissociation of Escherichia coli 70-S as well as Artemia salina 80-S ribosomes. Although both dissociation factor activities show the same dependence on K+ and Mg2+ for optimal activity, the two activities exhibit significant differences in their sensitivity to sulfhydryl reagents and heat, and in their dependence on incubation temperature for activity. Certain properties of both factors suggest that neither factor is initiation factor eIF-3; however, the possibility that one or both factors are subunits of initiation factor eIF-3 remains to be determined.

Animals↗

Guidelines for the management of lumbosacral spondylolisthesis associated with scoliosis.

Lumbosacral spondylolisthesis, when it is associated with scoliosis, presents special problems which require special consideration in management. Lumbosacral spondylosisthesis associated with a major thoracic curve, presents two separate problems. Treatment of the lumbosacral spondylolisthesis depends upon the severity of the lesion and symptoms. The thoracic curve is treated as required, depending upon the severity of the scoliosis and the stage of spinal maturation. Lumbosacral spondylolisthesis associated with a thoracolumbar or lumbar curve requires treatment of the curves above, along with the spondylolisthesis. Do not fuse the lumbosacral joint in an uncorrected position.

Adolescent↗