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Biomedical subjects

R P Erickson

Publications and source records attributed to R P Erickson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Expression of carbonic anhydrase II (CA II) promoter-reporter fusion genes in multiple tissues of transgenic mice does not replicate normal patterns of expression indicating complexity of CA II regulation in vivo.

Although the proximal, 5' 115 bp of the human carbonic anhydrase II (CA II) gene was sufficient for expression of a reporter gene in some transfected cell lines, we found previously that 1100 bp of this promoter (or 500 bp of the mouse CA II promoter) was not sufficient for expression in transgenic mice. We have now studied the expression of linked reporter genes in mice transgenic for either (1) 11 kb of the human 5' promoter or (2) 8 kb of the human 5' promoter with mouse sequences from the first exon, part of the first intron (since a CpG island spans this region), and the 3' sequences of the gene. Expression was found in both cases, but the tissue specificity was not appropriate for CA II. Although there was a difference in the sensitivity of the assays used, the first construct led to expression in many tissues, while the second construct was expressed only in spleen. These findings indicate considerable complexity of DNA control regions for in vivo CA II expression.

Animals↗
PubMed1995

Environmental pollutants alter taste responses in the gerbil.

Taste and smell are chemical senses that play a crucial role in food selection. Damage to taste and smell receptors can impair food intake, nutritional status, and survival. The purpose of this study was to determine the effects of 11 environmental pollutants (nine insecticides and two herbicides) on electrophysiological taste responses in the gerbil. Integrated chorda tympani (CT) recordings were obtained from gerbils to a range of tastants before and after a 4-min application of 1 of 11 environmental pollutants. The taste stimuli were: sodium chloride (100 mM), calcium chloride (300 mM), magnesium chloride (100 mM), HCl (10 mM), potassium chloride (500 mM), monosodium glutamate (MSG) (50 mM), sucrose (100 mM), fructose (300 mM), sodium saccharin (10 mM), quinine HCl (30 mM), and urea (2 M). The nine insecticides included organophosphorous, carbamate, and pyrethroid insecticides. The seven organophosphorous insecticides tested were: acephate, carbofuran, chlorpyrifos, chlorpyrifos oxon, demeton, malathion, and methamidophos. The carbamate insecticide carbaryl and the pyrethroid insecticide fenvalerate were also tested. Two herbicides, paraquat and glyphosate, were tested, and dose-response curves for each of these two herbicides were also determined. All of the 11 insecticides and herbicides had an effect on some of the taste stimuli tested. Application of 10 mM methamidophos exhibited the greatest amount of suppression on the 11 taste solutions. Each taste stimulus was significantly suppressed with the exception of 2 M urea. Herbicides paraquat and glyphosate also reduced responses to several tastants. These data indicate that environmental pollutants can modify taste responses in the gerbil.

Animals↗
PubMed1995

A family with unusual Waardenburg syndrome type I (WSI), cleft lip (palate), and Hirschsprung disease is not linked to PAX 3.

An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate crossover which has occurred between PAX 3 DNA markers and the disorder in this family. This family may also have anticipation of the WSI traits as the proband's grandmother is nonpenetrant, his mother has dystopia canthorum, and severe cleft lip (palate), while the proband has dystopia canthorum, severe cleft lip (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated in this Waardenburg-like syndrome with Hirschsprung disease and cleft lip (palate).

Base Sequence↗
PubMed1995

Clinical traits and molecular findings in 46,XX males.

46,XX maleness is characterized by the presence of testicular development in subjects who lack a Y chromosome. The majority of affected persons have normal external genitalia, but 10-15% show various degrees of hypospadias. Several hypotheses have been proposed to explain the etiology of this constitution: translocation of the testis-determining factor (TDF) from the Y to the X chromosome, mutation in an autosomal or X chromosomal gene which permits testicular determination in the absence of TDF, and undetected mosaicism with a Y-bearing cell line. We report the phenotypic data and results of molecular analyses performed in six sporadic Mexican males with 46,XX karyotype. Molecular studies revealed Yp sequences in two individuals (ZFY+ SRY+) with different phenotypes, a third one presented with a smaller segment of Yp (ZFY- SRY+) and complete virilization, while the remaining three were Y-negative and showed hypospadias. In all subjects a hidden mosaicism with a Y-bearing cell line was ruled out due to the absence of Y-centromeric sequences. Our data demonstrate that the phenotype does not always correlate with the presence or absence of Y-sequences in the genome, and confirm that 46,XX maleness is a genetically heterogeneous condition.

Adolescent↗
PubMed1995

Modulation of rat chorda tympani nerve activity by lingual nerve stimulation.

1. A subpopulation of lingual nerve (LN) fibers surround and/or terminate in taste buds in fungiform papillae. One possible function of these fibers is to modulate chorda tympani fiber (CT) or taste responses. To test this hypothesis, the rat LN was stimulated electrically at various voltages (to 20 V), and single- and multiunit CT responses to water-0.1 M NaCl cycles were recorded before, during, and after LN stimulation. 2. When a thermally controlled water-0.1 M NaCl stimulus cycle was applied onto the tongue's surface, the surface temperature remained constant, independent of the stimulation voltage. In the absence of a liquid stimulus, the tongue's surface temperature increased approximately 4 degrees C upon LN stimulation for voltages > or = 5 V. This temperature increase, caused by vasodilation by way of the axon reflex flare mechanism, was taken as evidence that LN stimulation induces peptide release. 3. Comparison of CT activity before LN stimulation with the activity either during or after stimulation revealed statistically significant changes in CT activity. During LN stimulation the CT activity decreased. After LN stimulation, the variability in amount of CT activity increased. 4. In rats treated postnatally with subcutaneous injections of capsaicin to reduce or eliminate polymodal nociceptors, LN stimulation did not produce increases in the tongue's surface temperature or changes in CT activity. 5. Changes in CT activity could be detected seconds after LN stimulation, suggesting that the intragemmal and/or perigemmal LN fibers modulate CT activity. 6. The physiological implications of this study suggest that CT responses to salt can be modulated by endogenous compounds (probably peptides), eating foods that activate LN responses (e.g., foods that are very acidic or contain capsaicin) may modulate taste responses, and peri- and intragemmal fibers should be considered an integral part of the taste receptor system.

Animals↗
PubMed1995

A "balanced" Y;16 translocation associated with Turner-like neonatal lymphedema suggests the location of a potential anti-Turner gene on the Y chromosome.

A male patient with Turner-like hydrops in the newborn period (Bonnevie-Ullrich syndrome) was studied. The karyotype was 46,X,t(Y;16)(q11.2;q24) in 100 cells. Chromosome painting with the heterochromatic Y chromosome-specific long arm repeat DYZ2 disclosed that all the hybridization was on the derivative 16. This was confirmed by chromosome painting with DYZ1, the other major Y long arm heterochromatic repeat, and DYZ3, the Y alphoid, centromeric repeat which showed chromosomal separation of the 2 stained regions. To further localize the breakpoint, FISH was performed using individual YACs from a Y-YAC contig (Foote et al., 1992). This disclosed two YACs (yOX111 and yOX123) which hybridized to both the Y and der16 chromosomes. The YACS spanning the translocation breakpoint region were located just proximal to the Y heterochromatin boundary. The recent discovery of a candidate gene for the azoospermia factor (AZF) in this region (Ma et al., 1993) suggests the possibility that there are several Y-expressed genes adjacent to the heterochromatin boundary (as there are near the pseudoautosomal boundary) which may include a gene involved with lymphedema which is disrupted by the translocation in this patient.

Chromosome Mapping↗
PubMed1994

Female pseudohermaphroditism with multiple caudal anomalies: absence of Y-specific DNA sequences as pathogenetic factors.

46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosomes (46,XX); one had a 46,XX,del(10)(q25.3-->qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Y chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY (Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone.

Abnormalities, Multiple↗
PubMed1994

Detection of circular and linear transcripts of Sry in pre-implantation mouse embryos: differences in requirement for reverse transcriptase.

Sry is the testes determining factor gene located on the Y chromosome. Expression of Sry had previously been found to occur during a short time frame of 10.5 to 12.5 days post coitum in the developing genital ridge. A recent study of the Sry transcript from adult testes found that the most abundant transcript is circular in nature. We have performed reverse transcription polymerase chain reactions with RNA from mouse preimplantation embryos ranging from the 2 cell stage to the blastocyst stage and report the detection of both circular and linear forms of Sry in the preimplantation embryo. In addition, we also demonstrate that the well described reverse transcriptase activity of Taq polymerase leads to a major difference in the mode of detection of the two forms.

Animals↗
PubMed1994

Zfy is transcribed in the normal mouse epididymis and in the XXSxr ("sex reversed") testis.

The presence of the mutation Sex reversed (Sxr), a copy of a Y-chromosomal segment that gets transferred to an X chromosome, causes the resulting XXSxr mice to develop as apparent males. However, several features of male sexual development are abnormal in these animals. The testes are small and aspermatogenic, and the epididymides lack the initial segment. Testes and epididymides show abnormalities of extracellular matrix. In this study we examined transcription of the conserved Y chromosomal gene Zfy, which has an X-chromosomal homologue (Zfx). Northern blotting showed Zfy to be expressed in the testes of XXSxr animals, except for those that carry the coat-marker gene Tabby (Ta), despite the lack of germ cells in XXSxr mice. Reverse transcription polymerase chain reaction (RT-PCR) studies detected Zfy in mRNA in testes even when Ta was present. RT-PCR also demonstrated Zfy transcription in epididymides of normal males, though not in XXSxr mice. Previous authors reported an absence of Zfy transcription in XXSxr testes; Zfy transcription in normal testes has been ascribed to germ cells. Our observation indicates that this idea requires re-evaluation. The occurrence of Zfy transcription in the normal epididymis is similarly a novel finding that may help explain those aspects of epididymal development that occur in the absence of androgen.

Animals↗
PubMed1994

Transcription of circular and noncircular forms of Sry in mouse testes.

Although its expression in adult testis was immediately apparent, the role for Sry (sex determining region, Y) in testicular function remains elusive. We have performed transcriptional studies in an effort to elucidate potential roles of Sry by studying the time and location of its transcription in mouse testes. Northern analyses and more sensitive nuclease protection assays detected transcripts in 28-day-old testes and beyond. The highly sensitive technique of reverse transcription polymerase chain reaction (RTPCR) could not detect Sry expression in 14-day testes when primers for the most conserved portion of the gene, the high mobility group (HMG) box, were used, but primers for the circular form detected Sry transcription at all postnatal stages studied. The same HMG box primers were able to detect expression of Sry in XX, Sxra or Sxrb testes. This suggested that Sry is expressed in cells other than germ cells, which was confirmed with studies on fractionated cells--RTPCR detected transcription of Sry in the highly pure interstitial cell fraction. However, Leydig cells and a Leydig cell tumor were negative for Sry expression. We performed in situ studies in an attempt to localize the expression of Sry in the testes. Abundant expression of an Sry cross-hybridizing transcript was found in spermatogonia, in early spermatocytes, and in some interstitial cells with antisense probes to the HMG box or a more specific, 3' region, whereas the sense probe gave little or no hybridization. It is probable that the circular transcripts, which are seen in reverse transcriptase positive (RT+) and RT- reactions by PCR because of the RT activity of Taq polymerase, are responsible for the hybridization seen in spermatogonia and spermatocytes, whereas linear and circular forms are detected later. Thus Sry is expressed in pre- and postmeiotic germ cells and in somatic cells of the testes.

Animals↗
PubMed1994

Bone marrow transplantation demonstrates that carbonic anhydrase II deficiency limited to bone marrow-derived cells affects ammonium chloride tolerance in mice.

Bone marrow transplantation (BMT) in mice was utilized to determine the relative importance of carbonic anhydrase II (CA II) deficiency in blood compared to kidney in the pathogenesis of the ammonium chloride intolerance observed in CA II-deficient mice. "Normal" BMT experiments utilized normal donors and CA II-deficient recipients (NL-->DEF), "reverse" BMT experiments utilized CA II-deficient donors and normal recipients, and control BMT experiments utilized normal mice with a hemoglobin polymorphism (Hbb d/s). Unstressed urinary pH was not significantly altered by normal or reverse BMT, nor was any change induced by control BMT. However, DEF-->NL mice showed markedly altered weight changes when placed on oral ammonium chloride, an effect apparently secondary to dehydration due to decreased water intake. In addition, some CA II-deficient mice have a urinary concentrating defect. Red blood cell and kidney CA II deficiency contribute additively to these effects.

Ammonium Chloride↗
PubMed1994

Taste perception of monosodium glutamate (MSG) in foods in young and elderly subjects.

The purpose of this study was to determine the concentrations at which young and elderly subjects were able to detect and recognize monosodium glutamate (MSG) and MSG with 0.5 mM inosine-5'-monophosphate (IMP) in various food media including meats, vegetables, and soups. The most preferred concentration levels of MSG and MSG (with IMP) in the foods were also determined. Detection thresholds for MSG (with IMP) in foods were elevated in elderly subjects compared with young subjects. The detection thresholds for elderly subjects for MSG with IMP in foods were an average of 2.8 times higher than the same detection thresholds for young subjects. The variability among subjects in the ability to detect MSG (with or without IMP) in every food was far greater than the variability found previously in water solutions, especially for young subjects. Adding 0.5 mM IMP to the MSG did not significantly affect detection thresholds in foods. However, preference scores of both young and elderly subjects were significantly higher for the MSG with IMP condition than the MSG alone condition for some foods. Optimally preferred concentration levels of MSG in foods tended to be lower than the level at which MSG is detected or recognized in the food but above the detection threshold for MSG in water. The mechanism by which MSG can be preferred at a subthreshold concentration in foods is not fully understood. One possibility is that MSG synthesizes with food chemicals and forms a new taste quality.

Adult↗
PubMed1994

Modulators of the adenylate cyclase system can alter electrophysiological taste responses in gerbil.

The adenylate cyclase system has been implicated in taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alter taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to bitter, sweet, salty, sour, and glutamate tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryl-adenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The tast compounds tested were: NaCl (30 mM), monosodium glutamate-MSG (50 mM), sucrose (30 mM), HCl (5 mM and 10 mM), KCl (300 mM), quinine HCl (30 mM), MgCl2 (30 mM), erythromycin (0.7 mM and 1 mM), HCl (5 mM and 10 mM), and urea (2 M). The main findings were as follows. NaF (20 mM) significantly inhibited responses to bitter compounds up to 35% and enhanced the response to sucrose by 30%. NaCl (20 mM), used as a control for NaF, inhibited most responses up to 78% with no enhancement of sucrose as seen with NaF. 8BrcAMP (1.16 mM) reduced the responses to bitter-tasting quinine HCl, MgCl2, and erythromycin but not to urea.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

The effect of sweeteners on bitter taste in young and elderly subjects.

The purpose of this study was to quantify the degree of reduction in perceived bitterness by sweeteners at both threshold and suprathreshold concentrations of bitter compounds. Detection and recognition thresholds were determined for six bitter compounds (caffeine, denatonium benzoate, magnesium chloride, quinine hydrochloride, sucrose octaacetate, and urea) in the absence and presence of several suprathreshold concentrations of five sweeteners. The sweeteners were: sucrose, aspartame, sodium saccharin, mannitol, and sorbitol. Polycose was also tested along with the sweeteners. The degree to which bitter thresholds were affected by the addition of sweeteners was dependent on the chemical classification of the sweeteners and their concentrations. In general, the natural sweeteners, sucrose, mannitol, and sorbitol, were more effective than the noncaloric sweeteners, aspartame and sodium saccharin, in elevating the detection and recognition thresholds of the bitter compounds. A sweetness intensity approximating that of 6% sucrose (0.175 M sucrose) or greater was required to elevate thresholds. For elderly subjects, sweeteners did not significantly elevate thresholds for denatonium benzoate and sucrose octaacetate. The degree to which sorbitol and sucrose can decrease the perceived bitterness intensity of suprathreshold concentrations of the six bitter compounds was also determined. The concentrations of sweeteners and bitter compounds were selected to be of moderate to high subjective intensity. The levels of sweeteners used in the mixtures were: sucrose (none, 0.946 M, and 2.13 M) and sorbitol (none, 2.1 M, and 3.68 M). Both sweeteners significantly reduced the bitterness ratings of almost every concentration of the six bitter compounds. The greatest reductions in bitterness were 87.0% for 0.192 microM denatonium benzoate mixed with 2.13 M sucrose and 84.7% for 1.8 M urea mixed with 3.68 M sorbitol.

Adult↗
PubMed1994

Transcription of paternal Y-linked genes in the human zygote as early as the pronucleate stage.

Global activation of the embryonic genome occurs at the 4- to 8-cell stage in human embryos and is marked by continuation of early cleavage divisions in the presence of transcriptional inhibitors. Here we demonstrate, using reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of transcripts for two paternal Y chromosomal genes, ZFY and SRY in human preimplantation embryos. ZFY transcripts were detected as early as the pronucleate stage, 20-24 h post-insemination in vitro and at intermediate stages up to the blastocyst stage. SRY transcripts were also detected at 2-cell to blastocyst stages. The expression of SRY and ZFY at these early stages and the faster cleavage rate of male embryos observed in many mammalian species focuses attention on the role of events in sex determination prior to gonad differentiation.

Base Sequence↗
PubMed1994

Pulmonary atresia associated with maternal 22q11.2 deletion: possible parent of origin effect in the conotruncal anomaly face syndrome.

A blind study was designed to test the hypothesis that some persons with a relatively rare cardiac malformation, pulmonary atresia with ventriculoseptal defect (PA/VSD), have a recognisable phenotype. Fourteen patients with cyanotic congenital heart lesions were examined by dysmorphologists blinded to the type of cardiac malformation. Six children were judged to have a similar craniofacial appearance; all had PA/VSD. These children were not originally considered to fall within the classic phenotypes of the DiGeorge sequence or the velocardiofacial syndrome, both of which have been shown to be associated with deletions of 22q11. More recently, 22q11 deletions have been documented in the conotruncal anomaly face syndrome and apparently isolated conotruncal heart defects. A new acronym, CATCH 22 syndrome (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia) has been suggested to encompass this very broad phenotypic spectrum. A preliminary molecular study was conducted using the dinucleotide repeat D22S264 located on chromosome 22q11.2. All cases tested with the subtle but recognisable phenotype had deletions, all lacking the maternal contribution at this locus, suggesting there may be a parent of origin effect.

Base Sequence↗
PubMed1994

Classification of taste responses in brain stem: membership in fuzzy sets.

1. Classification methods in sensory systems in general, and gustation in particular, tend to place each of the relevant objects, such as stimuli or neurons, into one class each. Some of these methods are based on the responsiveness of neurons to various stimuli; in these, each group must contain a variety of nonidentical members because of the individuality of each neuron or stimulus. 2. The "fuzzy" set method is appropriate for more accurate classification in such heterogeneous populations. In this method each member is given graded membership in several sets rather than membership in only one set. In the present paper we subjected previously published data on the responses of individual taste neurons to a variety of stimuli to fuzzy set analysis. 3. We found that the amounts of response of 46 neurons in the solitary nucleus of the rat to NaCl, HCl, sucrose, quinine HCl, and KCl could accurately be accounted for by giving each a grade of membership in three sets; the same held in the parabrachial nucleus of the rat for the responses of 41 neurons to the first four of these stimuli. The response was calculated as the sum of the products of the stimulus times neuron ratings in each set. 4. Temporal patterns of response have often been related, but with only moderate success, to the identity of the stimulus or neuron. These patterns could be accurately accounted for with the present method. Each of the products of designated parts of the stimulus ratings times the neuron ratings gave the basis for accurate description of the temporal course of the response of each neuron to each stimulus. 5. This method appears to account for the varieties of amount and temporal pattern of response of taste neurons with a simple mathematical process of few parameters. This suggests that within the known complexities of receptor mechanisms and mechanisms of neural processing, the neural message is reduced to a rather simple form. 6. The fuzzy set approach, which is based on disclosing underlying sets rather than placement of heterogeneous members into one of several essentialistic groups, may be useful in disclosure of the underlying mechanisms producing the neural responses in taste.

Animals↗