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S R Russell

Publications and source records attributed to S R Russell.

At least 19 recordsLinked to original sources
PubMed1994

A Drosophila melanogaster chromosome 2L repeat is expressed in the male germ line.

We describe the initial characterisation of a Drosophila melanogaster locus, Mst40 (Male-specific transcript), that was cloned on the basis of its male-specific transcription during the third larval instar. Corresponding low molecular weight poly(A)+ mRNAs are abundant in primary spermatocytes, but in no other larval or adult tissue. During early embryogenesis Mst40 expression is complex; initially transcription is detected during early cleavage stages. This early expression appears as two discrete dots of hybridisation associated with each nucleus. Subsequently, the transcripts are abundant in the cytoplasm of the newly formed pole cells. In the genome Mst40 sequences are located in region 40, at the base of chromosome 2L, close to, or within, the beta-heterochromatin. The Mst40 sequences are organised as a tandemly arrayed 1.4 kb repeat unit. The repeat is conserved in all D. melanogaster strains examined but absent from other Drosophila species studied. The locus does not correspond to any known complementation groups in the region and has yet to be assigned a function.

Amino Acid Sequence↗
PubMed1993

Expression of human platelet glycoprotein Ib alpha in transgenic mice.

Platelets are cytoplasmic fragments of megakaryocytes and, therefore, their membrane proteins cannot be manipulated by expression methods in culture. To overcome this limitation, we have expressed human glycoprotein (GP) Ib alpha in transgenic mouse megakaryocytes and found that it was present on the surface of platelets associated with the mouse GP Ib beta subunit. This finding demonstrates that assembly of the heterooligomeric GP Ib complex occurs through mechanisms conserved across species. In contrast, the receptor function of GP Ib exhibited restricted species specificity, since only the chimeric complex containing human GP Ib alpha bound human von Willebrand factor and supported platelet aggregation mediated by ristocetin. These studies demonstrate the transgenic engineering of a platelet adhesion receptor under control of the human GP Ib alpha promoter and illustrate a new approach to manipulate platelet receptors and study structure-function relationships in hemostasis and thrombosis.

Animals↗
PubMed1993

The effects of feed restriction on reproductive function in Swiss CD-1 mice.

Many test compounds used in toxicity studies produce a "systemic" toxicity manifested as reduced body weight gain. While it is known that reduced weight gain during juvenile growth reduces or delays reproductive competence, the effects of adult-onset feed restriction (FR) and inhibited weight gain on the reproductive system of mice are poorly known. To gain some information on the effects of graded body weight reduction, or reduced body weight gain, on commonly used reproductive endpoints, the studies reported below were conducted at two laboratories, using adult mice that were maintained at 90, 80, and 70% of concurrent control body weight (CBW) for up to 21 weeks. Estrous cyclicity and fertility in the females were significantly affected. While male fertility was variably affected, there was a significant decrease in the number of epididymal sperm and in the number of testicular spermatids in the 70% CBW groups. Testis weight was conserved in both studies; relative testis weight increased in all FR groups. These data can improve the interpretation of future studies by helping to separate chemically induced changes from those produced by reduced body weight gain.

Animals↗
PubMed1993

Drosophila melanogaster male germ line-specific transcripts with autosomal and Y-linked genes.

We have identified of set of related transcripts expressed in the germ line of male Drosophila melanogaster. Surprisingly, while one of the corresponding genes is autosomal the remainder are located on the Y chromosome. The autosomal locus, at 77F on chromosome arm 3L, corresponds to the previously described transcription unit 18c, located in the first intron of the gene for an RI subunit of cAMP-dependent protein kinase. The Y chromosome copies have been mapped to region h18-h19 on the cytogenetic map of the Y outside of any of the regions required for male fertility. In contrast to D. melanogaster, where Y-linked copies were found in nine different wild-type strains, no Y-linked copies were found in sibling species. Several apparently Y-derived cDNA clones and one Y-linked genomic clone have been sequenced. The Y-derived genomic DNA shares the same intron/exon structure as the autosomal copy as well as related flanking sequences suggesting that it transposed to the Y from the autosomal locus. However, this particular Y-linked copy cannot encode a functional polypeptide due to a stop codon at amino acid position 72. Divergence among five different cDNA clones ranges from 1.5 to 6% and includes a large number of third position substitutions. We have not yet obtained a full-length cDNA from a Y-linked gene and therefore cannot conclude that the D. melanogaster Y chromosome contains functional protein-coding genes. The autosomal gene encodes a predicted polypeptide with 45% similarity to histones of the H5 class and more limited similarity to cysteine-rich protamines. This protein may be a distant relative of the histone H1 family perhaps involved in sperm chromatin condensation.

Amino Acid Sequence↗
PubMed1993

Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment.

The platelet GP Ib-IX receptor supports platelet adhesion and activation by binding to vWf in the exposed subendothelial matrix. An abnormal GP Ib-IX complex exists in platelet-type or pseudo-von Willebrand disease and has a characteristic increased affinity for soluble vWf resulting in impaired hemostatic function due to the removal of larger vWf multimers from the circulation. Genetic studies within an afflicted family have demonstrated that the disease is linked to a Gly233-->Val amino acid substitution within the alpha-subunit of the oligomeric GP Ib-IX complex (Miller, J.L., D. Cunningham, V.A. Lyle, and C. L. Finch. 1991. Proc. Natl. Acad. Sci. USA. 88:4761-4765). To evaluate the functional consequences of this mutation, we constructed a recombinant analogue of the alpha-subunit of GP Ib containing Val233. Experiments comparing molecules with either Gly233 or Val233 revealed that the Val substitution generates a molecule with increased affinity for vWf. The recombinant fragment reproduces the functional abnormality of the GP Ib-IX complex in platelet-type von Willebrand disease, thus establishing the molecular basis of the bleeding disorder within this family. Moreover, it becomes apparent that structural elements responsible for the regulation of hemostasis through modulation of vWf affinity for platelets reside within the alpha-subunit of the GP Ib-IX complex.

Amino Acid Sequence↗
PubMed1993

Point mutation in a leucine-rich repeat of platelet glycoprotein Ib alpha resulting in the Bernard-Soulier syndrome.

Leucine-rich repeats are a conserved structural motif, of yet undefined significance, found in a group of proteins from different species. Among these are the four components of the human platelet glycoprotein Ib-IX-V complex, a membrane receptor that performs an essential role in the thrombogenic function of platelets by interacting with the adhesive protein, von Willebrand factor. We have found that a single amino acid substitution (Ala156-->Val) within one of the six leucine-rich repeats in the alpha-subunit of glycoprotein Ib results in a variant form of the congenital bleeding disorder, Bernard-Soulier syndrome, characterized by giant dysfunctional platelets. Genetic studies of the propositus and his family members were complemented by immunological and functional analysis of expressed recombinant GP Ib alpha fragments to demonstrate that the observed mutation is the cause of defective von Willebrand factor binding. These studies define the molecular basis of the Bernard-Soulier syndrome within this family and demonstrate that structural integrity of a leucine-rich repeat is necessary for normal function of the glycoprotein Ib-IX-V receptor complex and, possibly, for normal platelet morphology.

Amino Acid Sequence↗
PubMed1992

Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ib alpha involved in platelet transfusion refractoriness.

The platelet-specific alloantigen, Siba, located within the alpha-subunit of the glycoprotein (GP) Ib-IX membrane receptor, has been found to be involved in the pathogenesis of platelet transfusion refractoriness. We have identified the existence of a naturally occurring threonine/methionine dimorphism at position 145 of the GPIb alpha sequence, and determined that the Siba antigen corresponds to the molecule containing methionine145. The diallelic codons can be detected by restriction enzyme analysis of amplified genomic DNA fragments from the GPIb alpha gene. Evaluation of 61 healthy blood donors showed that the allele frequencies are 89% and 11% for the threonine145 and methionine145 codons, respectively. A positive correlation exists between platelet reactivity with the anti-Siba antibody and the presence of a methionine145-encoding allele. Moreover, recombinant expression of two soluble GPIb alpha fragments differing only at residue 145, provided definitive evidence that the human anti-Siba antibody reacts only with the molecule containing methionine145. These results explain the structural basis of the Siba human alloantigen system and define screening methodologies useful in transfusion medicine to match donor and recipient platelets accordingly.

Amino Acids↗
PubMed1992

Chondroitin sulfate-induced generation of epiretinal membranes.

Previous investigations have examined the role of serum and retinal pigment epithelium-derived factors in the elaboration of epiretinal membranes. Alternatively, the contribution of the insoluble interphotoreceptor matrix, known to contain chondroitin-sulfate-containing proteoglycans, in the generation of epiretinal membranes, has not been evaluated, to our knowledge. To investigate the potential role of chondroitin sulfates in eliciting epiretinal membranes, chondroitin sulfate glycosaminoglycans were injected into the vitreous cavity of rabbits. Examination demonstrated epiretinal membranes in 86% of eyes receiving chondroitin-6-sulfate. Temporal development of chondroitin sulfate glycosaminoglycan-induced epiretinal membranes was categorized into three distinct stages: a preretinal cell stage 1 to 3 weeks following injection, a glial "tuft" stage at 3 to 6 weeks, and a "mature" complex membrane stage at 6 weeks or later. Our results suggest that intravitreal administration of chondroitin sulfate glycosaminoglycan, components of insoluble interphotoreceptor matrix proteoglycans, may elicit the generation of epiretinal membranes, even in the absence of retinal disruption.

Animals↗
PubMed1992

Methods for assessing rat sperm motility.

Computer-assisted sperm analysis (CASA) systems are becoming more widely used. With this spread of technology come more data from toxicology studies, designed to determine if treatment with putative toxicants affects sperm motion parameters. While these CASA methods provide us with more ways to evaluate toxicity and thus perhaps increase our chances of successfully protecting human health, there is also a greater likelihood that different laboratories will use different methods of collecting data on sperm motility. Different systems used with different methods in different laboratories will inevitably generate data that are difficult to compare. In a prospective attempt to address this issue of comparability and limit the problems, a group of individuals using CASA systems to analyze rat sperm motility convened to discuss methodologic issues, share data, and try to reach a consensus about methods for performing these studies. This article shares those meetings and data in the hope that common methods will enhance interlaboratory comparisons.

Animals↗
PubMed1992

Hemorrhagic detachment of the internal limiting membrane after penetrating ocular injury.

During surgery to remove an intraocular gunshot pellet, a loculated "preretinal" hemorrhage was identified. This provided an opportunity to evaluate the structural identity of the inner wall, presumably representing detached posterior vitreous. The preretinal membrane was excised and evaluated using lectin histochemical analysis. All lectins tested bound to the excised tissue, supporting the conclusion that the membrane was a hemorrhagic internal limiting membrane detachment resulting from direct penetrating ocular injury. During intraoperative biomicroscopic examination, this detachment was indistinguishable from a subhyaloid hemorrhage. Because there are no natural history studies on internal limiting membrane loss and damage to retinal visual function, caution is urged in the surgical management of these lesions.

Adult↗
PubMed1991

Distribution of glycoconjugates in the human retinal internal limiting membrane.

The internal limiting membrane (ILM), or basal lamina, of the neural retina is located between the end feet of retinal Müller cells and the vitreous cortex. Recent studies of ILM substructure and histochemistry suggest that the ILM lamina rara externa, a region of the ILM likely to mediate vitreoretinal adhesion, is rich in noncollagen glycoconjugates. To characterize the spatial distribution and temporal expression of ILM glycoconjugates further, fetal and adult human retinas were examined using lectin histochemistry. Eyes from early fetal (13-15 weeks of gestation), midfetal (17-20 weeks of gestation), late fetal (23-26 weeks of gestation), full-term (38-41 weeks of gestation), early adult (17-20 yr of age), and late adult (57-84 yr of age) stages were examined. Although a number of significant observations pertaining to the distribution and temporal expression of ILM-associated glycoconjugates are described, two may have a significant relationship to vitreoretinal adhesion. In contrast to laminin and fibronectin, which are detectable throughout the retinal ILM at both young and older adulthood, erythrina cristagalii (ECA), a lectin with high binding affinity for galactose beta (1,3) N-acetyl-glucosamine, binds strongly to the ILM of young eyes but does not bind to the ILM of eyes from older donors. In addition, dolichos bifloris (DBA), a lectin with high binding affinity for N-acetylgalactosamine, does not bind to the ILM at early fetal stages, but binds at the midfetal stage, a time which corresponds with the onset of tertiary vitreous elaboration. More significantly, the DBA-binding glycoconjugate is neural retina ILM specific; it is not present in the basal lamina of the ciliary epithelium. Based on the known oligosaccharide composition of nonocular forms of human laminin, fibronectin, and collagen type I, and on the distribution of these molecules in the basal laminas of both the retina and ciliary epithelium, the authors conclude that the molecule bound by DBA has not been identified previously as a component of the ILM. Further characterization of ILM-associated molecules will be important to understand vitreoretinal adhesion and clinical disorders where adhesion is anomalous.

Adolescent↗
PubMed1990

Autosomal dominant neovascular inflammatory vitreoretinopathy.

Twenty-eight of 61 members of a six-generation family are affected by an autosomal dominant eye disease which has not been described previously. Affected patients are asymptomatic in early adulthood, but have vitreous cells and the selective loss of the b-wave on the electroretinogram. Later, peripheral retinal scarring and pigmentation, peripheral arteriolar closure, and neovascularization of the peripheral retina at the ora serrata or occasionally neovascularization of the optic disc develop. Cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma can cause profound visual loss. Vitrectomy reduces traction on the retina and allows for retinal reattachment. The role of argon laser photocoagulation or cryopexy in reducing the neovascular complications remains uncertain.

Adult↗
PubMed1990

Direct and feeder vessel photocoagulation of retinal angiomas with dye yellow laser.

Dye yellow laser photocoagulation (577 nm) was used to treat 14 retinal angiomas in nine patients. Eight patients had von Hippel-Lindau disease. Treatment was applied either directly to the tumor surface or to the feeding artery. Seven of eight angiomas that were treated directly and five of six that had feeder vessel treatment only were ablated successfully using dye yellow laser alone (mean follow-up, 11.1 months). An average of 2.2 treatments for feeder vessel and 1.1 treatments for direct ablation was required. Neither treatment caused decreased vision or severe complications. Dye yellow laser photocoagulation allows for effective treatment of retinal angiomas even when applied to the feeder vessel alone.

Adult↗
PubMed1990

Nonsense mutation in the glycoprotein Ib alpha coding sequence associated with Bernard-Soulier syndrome.

Three distinct gene products, the alpha and beta chains of glycoprotein (GP) Ib and GP IX, constitute the platelet membrane GP Ib-IX complex, a receptor for von Willebrand factor and thrombin involved in platelet adhesion and aggregation. Defective function of the GP Ib-IX complex is the hallmark of a rare congenital bleeding disorder of still undefined pathogenesis, the Bernard-Soulier syndrome. We have analyzed the molecular basis of this disease in one patient in whom immunoblotting of solubilized platelets demonstrated absence of normal GP Ib alpha but presence of a smaller immunoreactive species. The truncated polypeptide was also present, along with normal protein, in platelets from the patient's mother and two of his four children. Genetic characterization identified a nucleotide transition changing the Trp-343 codon (TGG) to a nonsense codon (TGA). Such a mutation explains the origin of the smaller GP Ib alpha, which by lacking half of the sequence on the carboxyl-terminal side, including the trans-membrane domain, cannot be properly inserted in the platelet membrane. Both normal and mutant codons were found in the patient, suggesting that he is a compound heterozygote with a still unidentified defect in the other GP Ib alpha allele. Nonsense mutation and truncated GP Ib alpha polypeptide were found to cosegregate in four individuals through three generations and were associated with either Bernard-Soulier syndrome or carrier state phenotype. The molecular abnormality demonstrated in this family provides evidence that defective synthesis of GP Ib alpha alters the membrane expression of the GP Ib-IX complex and may be responsible for Bernard-Soulier syndrome.

Adult↗
PubMed1989

Vitrectomy for complicated retinal detachments secondary to branch retinal vein occlusions.

Combined rhegmatogenous and traction retinal detachments associated with branch vein occlusions occurred in five eyes of five patients between Jan. 1, 1986 and Dec. 31, 1987. Four patients underwent surgery with pars plana vitrectomy and intravitreal gas, with or without scleral buckling. One patient refused treatment. All operated on eyes had attached retinas at a mean follow-up of seven months. Because posterior traction plays an important role in these unusual detachments, consideration should be given to pars plana vitrectomy and air-fluid exchange rather than scleral buckling alone.

Adult↗
PubMed1989

Reproductive toxicity of three phthalic acid esters in a continuous breeding protocol.

A continuous breeding protocol was utilized to examine the reproductive toxicity of three phthalate esters. CD-1 mice were given diets with either di-n-propyl phthalate (DPrP: 0.0, 1.25, 2.5, or 5.0%), di-n-pentyl phthalate (DPP: 0.0, 0.5, 1.25, or 2.5%), or di-n-octyl phthalate (DOP: 0.0, 1.25, 2.5, or 5.0%). Both male and female mice (20 pairs per treatment group, 40 pairs of control animals) were dosed for 7 days prior to and during a 98-day cohabitation period. Reproductive function was evaluated during the cohabitation period by measuring number of litters per pair, live pups per litter, and pup weight. There was no apparent effect on reproductive function in the animals exposed to DOP at dose levels sufficient to cause a significant increase in liver weight. Both DPP and DPrP were toxic to the reproductive system as evidenced by a complete inhibition of fertility at 1.25 and 2.5% DPP or 5.0% DPrP, and reduced fertility (litters/pair and live pups/litter, 0.5% DPP; live pups/litter, 2.5% DPrP). Toxicity of DPP had a strong male component and female component, whereas DPrP was more toxic to the female than the male reproductive system. DPP and DPrP treatment was associated with decreased body weight, increased liver weight, decreased testis and epididymis weights, decreased epididymal sperm concentration, and elevated seminiferous tubule atrophy. A comparison of seven phthalate esters tested using this continuous breeding protocol indicates the relative order of reproductive toxicity as diethylhexyl, dihexyl, dipentyl, dibutyl, dipropyl; diethyl and dioctyl are nontoxic.

Animals↗