PubMed Health⌕ Search

Biomedical subjects

J E Nelson

Publications and source records attributed to J E Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1995

A haploid expressed gene cluster exists as a single chromatin domain in human sperm.

Mammalian spermiogenesis is marked by the initial disruption of the nuclear-histone-DNA complex by the transition proteins for ultimate replacement with protamines. The genes for three of these low molecular weight basic nuclear proteins exist as a single linear array of PRM1, PRM2, and TNP2 on human chromosome 16p13.2. To begin to address the mechanism governing their transcriptional potentiation, a region of approximately 40 kilo-bases of the human genome encompassing these genes was introduced into the germ line of mice. Fluorescence in situ hybridization and Southern analysis showed that this segment of the human genome integrated into independent chromosomal sites while maintaining its fidelity. Transcript analysis demonstrated that the expression of the endogenous mouse protamine Prm1 and Prm2 genes as well as the mouse transition protein Tnp2 gene were expressed along with their human transgene counterparts. The pattern of expression of these transgenic human genes within this multigenic cluster faithfully represented that observed in vivo. In addition, all members of this transgenic gene cluster were expressed in proportions similar to those in human testis. Copy number-dependent and position-independent expression of the transgenic construct demonstrated that the corresponding biological locus was contained within this segment of the human genome. Furthermore, DNase I sensitivity established that in sperm the human PRM1-->PRM2-->TNP2 genic domain was contained as an approximately 28.5-kilobase contiguous segment bounded by an array of nuclear matrix associated topoisomerase II consensus sites. This is the first description of a multigenic male gamete-specific domain as a fundamental gene regulatory unit. A model of haploid-specific gene determination is presented.

Amino Acid Sequence↗
PubMed1995

Coordinate expression of the PRM1, PRM2, and TNP2 multigene locus in human testis.

Maintenance of the transcriptionally inert state of the mature human spermatozoon requires the expression of the various members of the human protamine gene cluster prior to the final stages of spermatogenesis. During this process, known as spermiogenesis, round spermatids morphologically differentiate into mature spermatozoa. The expression of the PRM1, PRM2, and TNP2 genes facilitates the compaction and condensation of the genetic material within the developing spermatid. To understand better the coordinate control governing this transformation, we have examined the localization and distribution of the human protamines PRM1 and PRM2 and transition protein TNP2 transcripts during human spermatogenesis. The stage-specific expression of these transcripts was determined by in situ hybridization analysis using [alpha-35S]-labeled cRNA probes. PRM1, PRM2, and TNP2 transcripts were abundant in association with round and elongating spermatids, located in the adluminal region of the seminiferous epithelium. They were not observed in association with spermatogonia, spermatocytes, Sertoli cells, or interstitial cells. These data indicate that the human PRM1, PRM2, and TNP2 transcripts are expressed postmeiotically in round and elongating spermatids. The quantitative evaluation of each transcript was determined as a function of the relative optical density per unit area. In all cases examined, the relative level of each transcript was consistent with the following pattern, PRM2 > PRM1 congruent to TNP2.

Chromosomal Proteins, Non-Histone↗
PubMed1995

Computer assisted promoter analysis of a human sperm specific nucleoprotein gene cluster.

The promoter regions of the clustered human spermatid-specific nucleoprotein PRM1, PRM2 arid TNP2 genes were compared to define regulatory elements that may govern their expression. Sequence alignment revealed two wll conserved motifs, despite a lack of extensive homology. They are located at similar positions within the first 400 nt of their 5' UTRs. Conservation of these motifs may reflect selective evolutionary pressure to maintain their structure. This supports the view that these elements assume a central role in the coordinate regulation of this gene cluster during spermiogenesis. The distribution of binding sites of known transcription factors was also assessed within the regions flanking the 5' ends of these genes. This analysis should prove useful in directing studies that define the signals necessary for the coordinate regulation of this spermatid specific gene cluster.

Base Sequence↗
PubMed1995

Mapping the clonally unstable recombinogenic PRM1-->PRM2-->TNP2 region of human 16p13.2.

We have isolated a human cosmid clone encompassing approximately 40 kb of the chromosome 16p13.2 region. This region contains the protamine genes PRM1 and PRM2 and the transition protein gene TNP2. To facilitate the characterization of this under represented region of the chromosome 16 physical map, a detailed map of this cosmid clone was constructed. Analysis revealed that this gene cluster was nestled amid numerous repetitive elements. Under representation of this segment may be attributed to these repetitive sequence elements scattered throughout this region rendering this locus clonally unstable. Verification of the map by cosmid and genomic Southern analysis resolved discrepancies within the literature and showed that this highly repetitive DNA sequence containing cosmid was representative of this region of the human genome. This dynamic and recombinogenic region continues to evolve.

Blotting, Southern↗
PubMed1994

Characterization of a human locus in transition.

The spermatid-specific nucleoprotamine genes PRM1 and PRM2 and the transition protein gene TNP2 are clustered at a single site on human chromosome 16p13.2. To begin to understand the mechanism governing their genesis and coordinate regulation the primary sequence of this approximately 40.6 kilobase region was determined. This cluster of genes is embedded within a series of repetitive elements, including numerous Alu elements distributed at a frequency of > 1 Alu element/kilobase. Multiple Alu elements have integrated into separate truncated L1 sequences within this region. Many of these Alu elements are tandemly inserted or clustered. The role of repetitive elements in the genomic organization and evolution of this gene cluster is discussed. Computer-assisted sequence analysis revealed the presence of structural sequence elements often associated with the boundary regions of active transcriptional domains. Further analysis identified a CpG island at the 3' end of this segment of chromosome 16 and other candidate coding segments within this region indicative of an additional linked gene. These sequence landmarks are commensurate with the complexity of the region.

Base Sequence↗
PubMed1994

Hearing, vocalization and the external ear of a marsupial, the northern Quoll, Dasyurus hallucatus.

As part of a continuing study of the development of the marsupial auditory system, auditory brainstem responses (ABR) were recorded and an ABR audiogram was constructed for five female Northern Quolls (Dasyurus hallucatus), which are nocturnal carnivores. The best frequency for hearing lies between 8 and 10 kHz, and at 50 dB SPL there is a range from about 0.5 to 40 kHz. Vocalizations of adult quolls and pouch-young were recorded with a digital audio tape recorder, and the power spectra of representative calls were compared with the ABR audiogram. The common adult vocalizations have most energy at the lower end of the hearing range, whereas frequencies that are dominant in the isolation calls of the pouch-young lie close to the best frequency of hearing. Samples of nocturnal sounds of the habitat of the quoll were also recorded and analyzed. Power spectra have peak energy at frequencies between 2 and 5 kHz, with a smaller contribution above 10 kHz. The spectrum contains relatively little power at the best frequency of hearing. Measurements of the sound pressure level at the external ear canal as a function of stimulus frequency and location in space suggest that the directional amplifying properties of the pinna will operate most effectively on sound frequencies at the upper end of the quoll's hearing range, a region that may be important in prey detection. Comparisons are made with other mammalian nocturnal carnivores and with other marsupials. We speculate that, for nocturnal carnivores, one role of the low-frequency part of the hearing range concerns the recognition of adult conspecifics, the mid-frequency range is important for the detection of pouch-young, and the upper range may be particularly concerned with prey/predator detection.

Animals↗
PubMed1994

Cervical vertebral osteomyelitis presenting as a retropharyngeal abscess.

Retropharyngeal abscess as a manifestation of nontuberculous cervical vertebral osteomyelitis in adults has been described rarely in the literature. We report a case of cervical vertebral osteomyelitis that was caused by Staphylococcus aureus and that presented as a retropharyngeal abscess in a 66-year-old man. In addition, we review related cases.

Aged↗
PubMed1994

The persistent computed tomography nephrogram: its significance in the diagnosis of contrast-associated nephrotoxicity.

A study was undertaken to find out if there is a quantitative relationship between the development of contrast-associated nephrotoxicity (CAN) and the mean renal cortical attenuation (RCA) as seen on computed tomography (CT) examination of the kidneys 24 hours after injection of contrast medium. 96 patients undergoing aortography were selected, who were considered "high risk" either because of the presence of a baseline serum creatinine (Cr) of 123.76 mumol l-1 (1.4 mg dl-1) or higher, or who were 73 or older with or without elevated creatinine levels. A CT study of the kidneys at approximately 24 h was correlated with baseline serum creatinine as well as 24 h Cr (48-72 h Cr when available). Medical history and medications were recorded. Eight of 96 patients had RCA of 108-236 HU at 24 h CT and all developed significant CAN of varying degree; 3/96 had RCA ranging from 48 to 67 HU and had transient CAN; two other patients with RCA of 67-90 HU developed CAN; and there was increased incidence of CAN in patients: (a) with pre-existing renal insufficiency; (b) with diabetes with renal insufficiency; (c) on diuretics; (d) who were older; and (e) had a unilateral atrophic kidney. It was concluded that a 24 h CT study evaluating the RCA had better predictive value for the development of CAN than a 24 h creatinine level.

Age Factors↗
PubMed1994

Magnesium sulfate potentiates several cardiovascular and metabolic actions of terbutaline.

beta-Adrenergic agonists are useful for the emergency treatment of asthma. Recently, magnesium sulfate (MgSO4) has also been shown to be efficacious in this situation. beta-Agonists have unwanted cardiovascular and metabolic actions: increased systolic blood pressure, corrected QT interval (QTc), serum glucose and insulin, and decreased RR interval, diastolic blood pressure, serum potassium, phosphate, and calcium. As beta-agonists and MgSO4 quite possibly will be used in combination, we sought to determine how MgSO4 would affect these actions. Healthy young male adults were administered two doses of terbutaline sulfate, 0.25 mg subcutaneously, 30 min apart on two separate occasions, in a randomized, double-blind fashion. On one occasion, 4 g of MgSO4 was administered intravenously over the same 30-min period. On the other, normal saline solution was given as a placebo. Cardiovascular and metabolic variables were measured sequentially for 2 h. Data at 60 min with p values given for a summation of all time points are as follows: MgSO4 increased terbutaline's effects on the RR interval by 0.09 s, p < 0.0001; QTc interval by 0.01 s, p < 0.0007; diastolic blood pressure by 8 mm Hg, p = 0.0001; serum calcium by 0.13 mg/dl, p = 0.01; and glucose by 9 mg/dl, p < 0.0001. MgSO4 also mitigated the systolic blood pressure elevating the effect of terbutaline by 5 mm Hg (p = 0.007). The magnitude of the response potentiations was modest. We conclude that combining terbutaline and MgSO4 is unlikely to result in serious short-term adverse events, if used acutely in patients with relatively normal cardiac and metabolic function. MgSO4 may act by potentiating the effect of beta-agonists on magnesium requiring enzymes such as adenyl cyclase.

Adult↗
PubMed1994

ISWAC: proposed system for the integrated assembly of chromosomes.

The generation of a physical map as an integral part of sequence project management is a problem that present computer systems do not address. Primarily, the analysis performed is based solely on the information available from a single knowledge level. Management systems that are currently available do not adequately model the multi-layer top down strategy that is most often utilized to manage large scale sequencing projects. Single layered approaches reflect an algorithmic inadequacy since interacting data sets are required to provide a good solution. The analysis tool that is currently under development termed ISWAC, the Integrated System for Wholistic Assembly of Chromosomes, overcomes these limitations by integrating information available from five layers of knowledge. These knowledge layers utilize information from the linkage map, physical map, restriction map, clone strategy map and the DNA sequence itself. The approach we are implementing, reviews current project status and continually refines the experimental strategy necessary to efficiently complete the sequencing task. To facilitate project completion the system is designed to interactively recommend strategies based on partial information. The utility of this tool is enhanced by implementing knowledge representation techniques that allow reasoning with approximate concepts characteristic of these data-sets. In addition, the raw physical data is maintained within an integrated map database to ease data verification. This paper presents the first discussion of the design specifications for a computer system to assimilate the various forms of data that are being generated as part of the human genome project. It was specifically written to stimulate discussion regarding data standardization, translation, analysis and most important, an understandable user-interphase for the molecular biologist. We would hope that interested readers would respond by assisting in the definition of a set of universal data standards and adopting them in their laboratories.

Algorithms↗
PubMed1993

Linkage of human spermatid-specific basic nuclear protein genes. Definition and evolution of the P1-->P2-->TP2 locus.

Protamines and transition proteins are highly basic sperm-specific nuclear proteins that serve to compact the DNA within the condensing spermatid nucleus. It has been proposed that the genes for protamine P1 and P2 and transition protein 2 may be clustered at a single loci. This may have marked implications for their evolution and coordinate developmental regulation. The cloning of a contiguous segment encompassing this region would directly address these issues. We have utilized a cloned segment of the human protamine P1 gene to isolate a human cosmid clone which contains the genes for protamines P1 and P2 and transition protein TP2. Sequence and hybridization analysis of this cosmid showed that the TP2 gene resided 3' of the P2 gene at a distance of approximately 7 kilobases (kb). This establishes the order of this gene cluster within a 13-kb region of 16p13.13-16p13.2 to be P1-->P2-->TP2. Similar to their spatial order, comparative computer-assisted sequence analysis predicts an identical relative rank order of emergence. Accordingly we propose that this gene cluster may have arisen from the P1 gene through a series of gene duplication events.

Amino Acid Sequence↗
PubMed1993

A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder.

OBJECTIVE: To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride. DESIGN: Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine. SETTING: Outpatient clinic. PATIENTS: A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study. MEASURES: Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale. RESULTS: Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity. CONCLUSION: Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.

Adolescent↗
PubMed1993

Association of binge eating disorder and psychiatric comorbidity in obese subjects.

OBJECTIVE: The authors determined the prevalence of binge eating disorder in a self-referred study group of moderately and severely obese subjects and investigated whether binge eating disorder was associated with psychiatric disorders, a history of psychotherapy, a family history of psychiatric illness, or a history of sexual abuse. METHOD: They interviewed 89 obese women and 39 obese men (body mass index > 30 kg/m2) who were not currently in weight loss treatment, using the Binge Eating Disorder Clinical Interview, the Structured Clinical Interview for DSM-III-R, and the Structured Clinical Interview for DSM-III-R Personality Disorders. RESULTS: Forty-three (34%) of the subjects met criteria for binge eating disorder--33 women and 10 men. Black and white subjects had similar rates of binge eating disorder. Subjects with binge eating disorder were significantly more likely than those without the disorder to have a lifetime prevalence of a DSM-III-R axis I or axis II diagnosis and to have undergone psychotherapy or counseling. The lifetime rates of major depression, panic disorder, bulimia nervosa, borderline personality disorder, and avoidant personality disorder were all significantly higher in subjects with binge eating disorder. The rate of reported sexual abuse was not higher among subjects with binge eating disorder; however, they were significantly more likely to have a family history of substance abuse. The relative risks for psychiatric disorders were higher in both moderately and severely obese subjects with binge eating disorder than in those without the disorder. CONCLUSIONS: Among both moderately and severely obese subjects, binge eating disorder is associated with higher rates of axis I and axis II psychiatric disorders.

Adolescent↗
PubMed1992

Purification of cloned and genomic DNA by guanidine thiocyanate/isobutyl alcohol fractionation.

We have developed a rapid and efficient method to purify cloned or high molecular weight eukaryotic DNA from cell lysates using guanidine thiocyanate and isobutyl alcohol. This simple two-step extraction procedure utilizes isobutyl alcohol to fractionate DNA away from cell lysates containing guanidine thiocyanate, yielding a relatively large quantity of pure DNA. The yield of DNA is approximately twice that obtained by the organic extraction method. DNA purified with this chaotropic-based protocol is suitable for a variety of applications including restriction analysis, double-stranded sequencing, PCR, subcloning, and transcription.

Butanols↗
PubMed1992

The development of righting reflexes in the pouch young of the marsupial Dasyurus hallucatus.

The development of righting was studied in the young of Dasyurus hallucatus, a small marsupial from northern Australia. Young were tested from birth to weaning. Righting began at 40 days, when tactile input on the snout triggered rotation to prone. Over the next 15-20 days, asymmetrical tactile input on the body triggered righting movements by the hindlegs (and later by the forelegs). Vestibular righting reflexes developed after these tactile righting reflexes. Furthermore, asymmetrical vestibular righting (i.e., when the young are held laterally in the air) developed before symmetrical vestibular righting (i.e., when held downward by the pelvis or placed supine in water). Vestibular righting triggered by falling supine in the air did not develop until about 80 days. This study further demonstrates that righting behavior does not consist of a single, integrated motor pattern, but a suite of motor patterns having independent control mechanisms and patterns of development.

Aging↗