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Biomedical subjects

D Ritter

Publications and source records attributed to D Ritter.

At least 19 recordsLinked to original sources
PubMed1997

Black children deficient in galactose 1-phosphate uridyltransferase: correlation of activity and immunoreactive protein in erythrocytes and leukocytes.

A recent study found a high prevalence of a missense mutation (S135L) in the gene for galactose 1-phosphate uridyltransferase (GALT) in black children with galactosemia (J Pediatr 1996; 128:89-95). In the present study, GALT activity and GALT protein content were measured in erythrocytes and leukocytes of eight black and seven white galactosemic (GALT-deficient) children, for correlation with the presence of the S135L and Q188R (highly prevalent in white galactosemic children) missense mutations. The S135L mutation was found in 9 of 16 alleles of black children but not in white children; the Q188R mutation was found in 10 of 14 alleles examined in white galactosemic children and in 4 of 16 alleles in black galactosemic children. The GALT activity was near zero in the erythrocytes of white and black galactosemic children (0.26 +/- 0.28 vs 0.33 +/- 0.25 mumol/hr per gram of hemoglobin, respectively; p = 0.61) (normal 17 to 26 mumol/hr per gram), and no correlation of erythrocyte activity with genotype was observed. The GALT activity was higher in the leukocytes of black galactosemic children compared with white children (5 +/- 6 vs 1 +/- 2 mumol/hr per gram, respectively) (normal 172 to 374 mumol/hr per gram), but the difference was not statistically significant (p = 0.11). Analysis by genotype revealed that the two S135L homozygotes had much more leukocyte activity (9 and 17 mumol/hr per gram) than Q188R homozygotes or than all non-S135L allelic genotypes. Compound heterozygotes (S135L/G) had intermediate activity. The GALT protein was not detectable by Western blot in the erythrocytes of either white or black galactosemic children, as determined by antibodies specific for both C- and N-terminal sequences. The GALT protein was undetectable in the leukocytes of white galactosemic children, but leukocytes from black galactosemic children with the S135L mutation contained reduced but readily detectable GALT protein. Erythrocyte galactose 1-phosphate levels were significantly lower in galactosemic children with an S135L mutant allele (1.1 +/- 0.2 gm/dl) compared with children who had other mutations (3.1 +/- 0.9 mg/dl; p = 0.0001). The correlation of protein content data with activity levels in the blood cells suggests that the S135L missense mutation affects the stability of GALT protein to produce a deficiency state.

Adolescent↗
PubMed1997

Regulation of insulin-like growth factor I (IGF-I) gene expression in brain of transgenic mice expressing an IGF-I-luciferase fusion gene.

Insulin-like growth factor I (IGF-I) plays an important role in the development and function of the central nervous system (CNS). Little is known, however, about the factors and mechanisms involved in regulation of CNS IGF-I gene expression. To facilitate our goal to define mechanisms of IGF-I gene regulation in the CNS, we generated several lines of transgenic (Tg) mice that express firefly luciferase (LUC) under control of a 11.3-kb fragment from the 5' region of the rat IGF-I gene. Consistent with expression of the native IGF-I gene in murine brain, expression of the transgene predominated in neurons and astrocytes and used promoter 1, the major IGF-I promoter in the CNS and in most tissues. Transgene messenger RNA and protein expression rapidly increased after birth and peaked at postnatal (P) day 4 in all brain regions studied. LUC activities in all regions then gradually decreased to 0.5-4% of their peak values at P31, except for the olfactory bulb, which maintained about one third of its maximal activity. Compared with littermate controls, administration of dexamethasone decreased LUC activity and transgenic IGF-I messenger RNA abundance, whereas GH significantly increased the expression of the transgene. Addition of GH to cultured fetal brain cells from Tg mice for 12 h also increased LUC activity in a dose-dependent manner (77-388%). These results show that this IGF-I promoter transgene is expressed in a fashion similar to the endogenous IGF-I gene, and thus indicates that the transgene contains cis-elements essential for developmental, GH, and glucocorticoid regulation of IGF-I gene expression in the CNS. These Tg mice should serve as an useful model to study mechanisms of IGF-I gene regulation in the brain.

Aging↗
PubMed1997

Interference with testing for lysergic acid diethylamide.

We found a high rate (4.2%) of positive results for lysergic acid diethylamide (LSD) by Emit in 1898 urine samples that were submitted primarily from psychiatric patients for drugs-of-abuse (DOA) testing. Specimens that tested positive for LSD by Emit subsequently tested negative for LSD with two RIAs. Furthermore, LSD was not detected in randomly selected Emit-positive urine samples by gas chromatography-mass spectrometry. Normal urine samples tested positive for LSD by Emit when they were supplemented with therapeutic medications that were prescribed for patients with positive urine LSD results by Emit. These therapeutic drugs interfered specifically with the Emit assay for LSD, since other Emit DOA tests were not affected by these medications at the tested concentrations.

Enzyme Multiplied Immunoassay Technique↗
PubMed1996

Preoperative glycopyrrolate: oral, intramuscular, or intravenous administration.

STUDY OBJECTIVE: To evaluate the effects of oral, intramuscular (i.m.) and intravenous (i.v. glycopyrrolate on oral and gastric secretions, and to assess how these routes of administration change intubating conditions. DESIGN: Randomized, double-blinded study. SETTING: University hospital operating room. PATIENTS: 37 ASA status I and II general anesthesia patients. INTERVENTIONS: Patients were randomized to receive glycopyrrolate or placebo just before surgery by three routes: oral, i.m., and i.v.. Glycopyrrolate was received once by one route and placebo by the other two routes. A placebo group received three placebos and no glycopyrrolate. MEASUREMENTS AND MAIN RESULTS: Mouth conditions and intubating conditions were qualitatively assessed by the patient and the intubating anesthesiologist. No difference between groups was noted. Oral and gastric volumes were measured and showed significantly less gastric volume for the i.v. group as compared with the other groups. Oral secretions were reduced in both the i.v. and i.m. groups when compared with placebo or glycopyrrolate administered orally. CONCLUSIONS: Preoperative glycopyrrolate is significantly more effective at reducing oral and gastric secretions if administered intravenously immediately before induction.

Adjuvants, Anesthesia↗
PubMed1996

Differentiation of Mycobacterium genavense and Mycobacterium simiae by automated mycolic acid analysis with high-performance liquid chromatography.

Mycobacterium genavense, a fastidious opportunist in patients with AIDS, cannot be identified by conventional biochemical methods. Computerized mycolic acid analysis by high-performance liquid chromatography offers an alternative that distinguishes the mycolic acid profile of M. genavense from those of all other organisms in the database developed at the Centers for Disease Control and Prevention.

Bacterial Typing Techniques↗
PubMed1996

Distribution and regulation of guanylyl cyclase type B in the rat nephron.

C-type natriuretic peptide (CNP) has been localized to the proximal and distal nephron. In this study, we examined the distribution and regulation of the CNP receptor, guanylyl cyclase type B (GC-B), in the rat kidney. GC-B mRNA was detected most frequently in microdissected glomeruli, thin and thick limbs of the loop of Henle, and outer and inner medullary collecting ducts by reverse transcription-polymerase chain reaction (RT-PCR). This pattern of expression is supported by immunofluorescent staining, using anti-GC-B-specific antiserum. Nearly equivalent levels of GC-B and guanylyl cyclase type A (GC-A) mRNAs were found by quantitative RT-PCR (5,662 +/- 1,622 and 5,187 +/- 1,204 molecules of cDNA/microgram total RNA, respectively; means +/- SE, n = 6). Renal inner medulla GC-B mRNA levels, but not renal CNP mRNA levels, were 3.2-fold greater in hypervolemic and 2.3-fold less in hypovolemic rats compared with euvolemic controls. Immunohistochemical staining also supports a greater GC-B expression with increased volume status. These data link hydration status and GC-B expression and suggest an additional and novel mechanism for regulating intravascular volume.

Animals↗
PubMed1996

Axial muscle function during lizard locomotion

It was recently reported that the epaxial muscles of a lizard, Varanus salvator, function to stabilize the trunk during locomotion, and it was suggested that this stabilizing role may be a shared derived feature of amniotes. This result was unexpected because it had previously been assumed that the epaxial muscles of lizards function to produce lateral bending during locomotion and that only in mammals and birds were the epaxial muscles active in stabilizing the trunk. These results and the inferences made from them lead to two questions. (1) Is the pattern of epaxial muscle activity observed in V. salvator representative of a basal lizard condition or is it a derived condition that evolved within lizards? (2) If the epaxial muscles do not produce lateral bending, which muscles do carry out this function? These questions were addressed by collecting synchronous electromyographic (EMG) and kinematic data from two lizard species during walking and running. EMG data were collected from the epaxial muscles of a lizard species from a basal clade, Iguana iguana, in order to address the first question. EMG data were collected from the hypaxial muscles of both Iguana iguana and Varanus salvator to address the second question. The timing of epaxial muscle activity in Iguana iguana relative to the kinematics of limb support and lateral trunk bending is similar to that observed in Varanus salvator, a finding that supports the hypothesis that the epaxial muscles stabilize the trunk during locomotion in lizards and that this stabilizing role is a basal feature of lizards. Therefore, a stabilizing function of the epaxial muscles is most parsimoniously interpreted as a basal amniote feature. In both Iguana iguana and Varanus salvator, the activity of two of the hypaxial muscles, the external oblique and rectus abdominis, is appropriately timed for the production of lateral bending. This indicates that elements of the hypaxial musculature, not the epaxial musculature, are the primary lateral bending muscles of lizards.

Journal Article↗
PubMed1995

Natriuretic peptide receptors A and B have different cellular distributions in rat kidney.

The cellular distribution of guanylyl cyclase coupled natriuretic peptide receptors type A (GC-A) and type B (GC-B) was examined by immunocytochemistry in normal rat kidney, and compared with the distribution of the vacuolar H(+)-ATPase. Staining for GC-A was found in glomeruli, thin limbs of Henle's loop, cortical collecting tubule, and inner medullary collecting duct. Staining for GC-B was found in glomeruli and the same nephron sections as GC-A, with the exception of the thin limbs. In the cortical collecting tubule, GC-A was found in both principal and intercalated cells; GC-B was restricted to the apical pole of alpha intercalated cells. In inner medullary collecting duct cells, GC-A was located on the basal membrane, whereas GC-B was found in the apical pole. The different pattern of polarization of natriuretic peptide receptors in the inner medulla provides a plausible basis for the different physiologic effects of atrial natriuretic factor and C-type natriuretic peptide. The results also suggest the possibility that GC-B is involved in the regulation of bicarbonate transport in the cortical collecting tubule.

Animals↗
PubMed1995

Polarized distribution of renal natriuretic peptide receptors in normal physiology and ischemia.

The polarized expression of guanylyl cyclase-coupled natriuretic peptide receptors, types A (GC-A) and B (GC-B), was measured in inner medullary collecting ducts (IMCD) of normal and ischemic rat kidneys, as well as in IMCD cells. Exposure of normal rat kidney medulla to an anti-GC-A antibody demonstrated a propensity of receptor staining on the cellular basal membrane. The polarization of GC-A receptors was lost in the ischemic kidney. The maximal binding capacity of 125I-atrial natriuretic factor (ANF) to the basal membrane of the inner medullary cell line mIMCD-K2 was five times greater than that to the apical membrane. ANF or C-type natriuretic peptide (CNP) added to the basal side of cultured cells resulted in guanosine 3',5'-cyclic monophosphate formation that was greater than when applied to the apical side. Depletion of ATP stores in cultured cells was followed by an increase of 125I-ANF binding to apical cellular membranes. Similar results were obtained when receptor guanylyl cyclase activity was assayed. In conclusion, these results suggest that functional GC-A and GC-B receptors are present predominantly on the basal membrane of IMCD. However, depletion of cellular ATP stores such as in ischemia is followed by a partial loss of polarization.

Animals↗
PubMed1995

Epaxial muscle function during locomotion in a lizard (Varanus salvator) and the proposal of a key innovation in the vertebrate axial musculoskeletal system

The pattern of electromyographic activity in the epaxial muscles of walking and running lizards (water monitors, Varanus salvator) was quantified with high-speed video and synchronized electromyography. Muscle denervation experiments were performed and ground reaction forces were recorded to evaluate hypotheses of muscle function. Water monitors exhibit unilateral, uniphasic activation of the epaxial muscles ipsilateral to rear limb support. The iliocostalis and longissimus dorsi muscles are active throughout the support phase of the rear limb, while the transversospinalis is active only during the second half of the support phase. The timing of muscle activity does not support the presumed locomotor function of the epaxial muscles of lizards (lateral bending of the trunk). Bilateral denervation of the two most lateral epaxial muscles (iliocostalis and longissimus dorsi) caused no significant change in the amplitude of lateral trunk bending. These two epaxial muscles do not appear to be necessary for lateral bending of the trunk, nor do they appear to be involved in resisting lateral bending of the trunk. On the basis of the data reported in this study, as well as a re-evaluation of previously existing data, it is proposed that the locomotor function of the epaxial muscles of lizards is to stabilize the trunk against the vertical component of the ground reaction forces; i.e. the epaxial muscles function in a postural role during locomotion in lizards, as they do in other amniotes. This proposed postural role of the epaxial muscles may represent a key innovation of amniotes, made possible by the loss of an aquatic larval stage in their common ancestor.

Journal Article↗
PubMed1995

The kinematics and mechanism of prey capture in the African pig-nosed frog (Hemisus marmoratum): description of a radically divergent anuran tongue.

High-speed videography and muscle denervation experiments were used to quantify the feeding kinematics of Hemisus marmoratum and to test hypotheses of muscle function. The feeding behavior of H. marmoratum, which feeds on ants and termites, differs radically from that of other frogs that have been studied. During feeding in H. marmoratum, the tongue 'telescopes' straight out of the mouth, as opposed to the 'flipping' tongue trajectory observed in most other frogs. At the time of prey contact, two lateral lobes of tissue at the tongue tip envelop the prey. These lateral lobes are capable of applying significant pulling forces to the prey and the tongue is, therefore, described as prehensile. The trajectory of the tongue can be adjusted throughout protraction so that the frog can 'aim' its tongue in all three dimensions; distance, azimuth and elevation. Bilateral denervation of the genioglossus muscles results in a complete lack of tongue protraction, indicating that the genioglossus muscle is the main tongue protractor in H. marmoratum, as in other frogs. Thus, H. marmoratum provides strong evidence of functional conservatism of the genioglossus muscle within anurans. Bilateral denervation of the hyoglossus muscle indicates that although the hyoglossus is involved in several aspects of normal tongue retraction, including the prehensile capability of the tongue tip, it is not necessary for tongue retraction. Unilateral denervation of the genioglossus muscle causes significant deviation of the tongue towards the denervated side, providing evidence for a mechanism of lateral tongue aiming. On the basis of the kinematics of prey capture, the anatomy of the tongue and the results of the denervation experiments, we propose that H. marmoratum uses a hydraulic mechanism to protract its tongue.

Animals↗
PubMed1994

Endogenous serum antibodies that interfere with a common thyroid hormone uptake assay: characterization and prevalence.

We identified individuals whose serum contained a substance that produced falsely decreased thyroid hormone (T)-uptake values determined by the Emit (Syva) procedure. Investigation of this interference was prompted by identification of a patient with T-uptake values inconsistent with clinical assessment. IgG depletion and supplementation studies with this patient's serum suggested that the interference was due to endogenous antibodies with specificity for the thyroxine-glucose-6-phosphate dehydrogenase conjugate in the Emit T-uptake assay. The prevalence of the interference was examined by prospectively comparing routine Emit T-uptake values of 1710 patients' samples to T-uptake values obtained by another method. Discrepant samples were also assayed by a radioactive binding triiodothyronine-uptake assay. We identified eight samples that had falsely decreased T-uptake values by Emit, for an overall prevalence of 0.46%. Among 45 consecutive patients with a T-uptake value < 20%, five patients, or 11%, were falsely decreased by Emit and three of these were clearly due to an interfering IgG. We suggest that samples with abnormally low T-uptake values determined by the Emit method be confirmed by an alternative method.

Adult↗
PubMed1993

Seroprevalence of hepatitis B viral markers in 52,000 Alaska Natives.

As a part of a program to screen and immunize as many Alaska Natives as possible against hepatitis B infection, hepatitis B virus seromarkers were measured in 52,022 Alaska Natives between 1983 and 1987. Hepatitis B surface antigen (HBsAg) was found in 1,603 persons (3.1%), and 7,155 persons (13.8%) exhibited hepatitis B virus seropositivity. While the prevalence of total seropositivity increased with increasing age (p < 0.001), the proportion of seropositive persons who were also positive for HBsAg was significantly higher in children under age 5 years than in persons over age 60 (p < 0.001). The total hepatitis B virus seropositivity was significantly higher in males than in females (p < 0.001), and a greater proportion of seropositive males than seropositive females had HBsAg (p < 0.001). The prevalence of HBsAg and total seropositivity differed significantly by geographic region (p < 0.001), ranging from 0.5% to 8.2% for presence of HBsAg and from 5.4% to 29% for total seropositivity. Of persons who were HBsAg positive, hepatitis B e antigen was found in 35.4%, and antibody to hepatitis e antigen was found in 49.6%. The prevalence of hepatitis B e antigen significantly decreased with age, while that of antibody to hepatitis e antigen significantly increased. The prevalence of hepatitis B virus seropositivity is high in Alaska Natives, and there are significant differences in both the prevalence of HBsAg and total hepatitis B virus seromarkers by age, sex, and geographic region.

Adolescent↗
PubMed1993

Positron emission tomography in myotonic dystrophy.

Regional cerebral glucose metabolism (rCMRG1) was studied in three patients with myotonic dystrophy by positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose as the radiotracer. Clinically, all patients presented an organic personality syndrome. Impairment of rCMRG1 was found in all cortical and subcortical regions, particularly in the frontal cortex and the lentiform nucleus. The results suggest that the organic personality changes that occur in myotonic dystrophy reflect widespread cerebral pathology. The metabolic pattern was similar to that seen in normal aging but was qualitatively more severe and is therefore consistent with the classification of myotonic dystrophy as a progeric disease.

Adult↗
PubMed1993

Endogenous antibodies that interfere with thyroxine fluorescence polarization assay but not with radioimmunoassay or EMIT.

We have identified an individual whose thyroxine (T4) concentration was undetectable with Abbott's fluorescence polarization immunoassay (FPIA) but within the reference range by radioimmunoassay or EMIT (Syva). The patient's thyrotropin, triiodothyronine, and T-uptake values were within the normal range. The T4 concentration measured by FPIA increased to normal when the immunoglobulin fraction was selectively removed from the serum. When the patient's immunoglobulin fraction was added to normal serum, the T4 content of the normal serum measured by FPIA became falsely low. The patient's antibody interfered with the T4 FPIA by binding to the fluorescein-T4 conjugate. The T-uptake was less affected by the patient's serum because of the low affinity of the patient's antibody to fluorescein-T4 (K = 3.5 x 10(8) L/mol). The patient's immunoglobulin bound preferentially to fluorescein-T4, in comparison with binding to fluorescein or T4 alone. We conclude that the patient's immunoglobulin bound to an epitope unique to the fluorescein-conjugated T4.

Adult↗