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Biomedical subjects

G Smutzer

Publications and source records attributed to G Smutzer.

15 recordsLinked to original sources
PubMed1998

Human olfactory mucosa in schizophrenia.

Recent evidence indicates that developmental anomalies may underlie some symptoms of schizophrenia, while psychophysical studies have demonstrated olfactory deficits in this disease. The postmortem olfactory mucosa of elderly schizophrenic patients was examined to characterize the molecular phenotype of this tissue. The distribution of developmentally regulated cytoskeletal proteins, a synaptic vesicle protein, a neural marker protein, a receptor for trophic molecules, axonal guidance and cell migration proteins, and neuronal and glial cytoskeletal proteins of various degrees of phosphorylation was examined by immunohistochemistry. Both schizophrenic and control subjects exhibited dystrophic neurites that were immunoreactive for synaptophysin, microtubule-associated proteins (MAP1B), and neurofilament proteins. No major histochemical or morphologic differences in either the expression or distribution of these proteins were observed in the olfactory epithelium of schizophrenic compared to control subjects. These studies indicated that dystrophic neurites frequently occurred in the olfactory mucosa of both schizophrenics and neurologically normal adults. The absence of major immunocytochemical abnormalities suggested that olfactory deficits in schizophrenia may be due to more subtle cellular or molecular differences or to abnormalities in olfactory regions of the central nervous system rather than in the olfactory epithelium.

Adolescent↗
PubMed1998

The translational start sites of jawless and cartilaginous fish genes.

Nucleotide sequences that surrounded ATG initiation codons were examined in jawless and cartilaginous fish complementary DNA sequences. Both thymidine and cytidine residues were underrepresented at positions near the initiation codon, while an extremely high frequency of purine nucleotides was observed at position -3. Statistical analysis (chi2) indicated that the greatest compositional bias occurred at nucleotide positions -3 and +4, and suggested that a relatively short consensus sequence surrounded AUG initiation codons of primitive fish genes. ATG triplets within 5' leader sequences were flanked by nucleotides different from those that surrounded ATG initiation codons. Dinucleotide frequency analysis indicated a deficiency in TA and an excess in AA around initiation codons. DNA sequence analysis suggested that low CpG conversion occurred 5' to the translation start of primitive fish genes. The conservation of consensus sequences around initiation codons of primitive fish genes underscores the importance of nucleotide composition for initiation of translation.

Animals↗
PubMed1997

Inositol 1,4,5-trisphosphate receptor expression in odontoblast cells.

The cellular distribution of inositol 1,4,5-trisphosphate receptors was examined in rodent maxillary incisor teeth. In situ hybridization studies with a transmembrane probe of type I inositol 1,4,5-trisphosphate receptor indicated that this receptor/channel was highly expressed in odontoblast cells of incisor teeth. In contrast, very low labeling was observed in dental pulp. Northern analysis showed a message size of approximately 9.5 kilobases for this receptor, and demonstrated that type III inositol 1,4,5-trisphosphate receptor was expressed in incisor teeth. Immunocytochemical studies confirmed that types I and III inositol 1,4,5-trisphosphate receptors were both highly expressed in odontoblasts while very low expression was detected in dental pulp. Finally, antibodies that recognized alpha subunits of the Gq class of GTP binding proteins also stained odontoblasts. These results indicate that receptor-mediated regulation of calcium release through inositol 1,4,5-trisphosphate receptors may occur in odontoblasts of rat incisor teeth. These findings also suggest that inositol 1,4,5-trisphosphate receptor/channels regulate calcium flux in odontoblasts during mineralization of dentin, or in growth and differentiation of incisor tissue.

Animals↗
PubMed1997

Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson's, Alzheimer's with parkinsonism, and Alzheimer's disease.

The molecular characteristics of midbrain dopamine (DA) neurons have been extensively studied in Parkinson's disease (PD). No such studies of the characteristics of midbrain DA neurons in Alzheimer's disease (AD) or Alzheimer's disease with parkinsonism (AD/Park) have been published. We examined the levels of tyrosine hydroxylase (TH) protein, and the expression of TH and dopamine transporter (DAT) mRNAs, in midbrain neurons of PD, AD, and AD/Park cases. In PD, the loss of TH protein in the ventral tier of the substantia nigra pars compacta (SNpc) of the PD group in accompanied by severe losses in the number of neurons that express TH mRNA and DAT mRNA (74% loss). Remaining neurons show a shift to higher concentrations of TH mRNA but a shift to lower concentrations of DAT mRNA per cell. Hence, there is evidence that compensation in the remaining neurons can elevate concentrations of TH mRNA and lower DAT mRNA. Alternatively, there may be a predilection for a loss of neurons with high levels of DAT mRNA and low TH mRNA levels within the SNpc of PD cases. There was no change in TH protein but an elevation of TH mRNA concentrations per neuron without any change in concentrations of DAT mRNA in the AD group. The AD/Park group did not exhibit changes in the level of TH protein, but showed a small loss (26%) of neurons in the SNpc and a greater loss in other regions of the midbrain (43-53%). Remaining DA neurons showed a marked shift to lower concentrations of DAT mRNA per neuron and a nonsignificant shift in cellular concentration of TH mRNA to higher levels. This is consistent with our previous work showing that with AD/Park there is a significant reduction in the number of DAT sites located on DA terminals in the striatum, but the midbrain neurons have not died. Our results indicate that the differential regulation of mRNAs encoding TH and DAT is similar in the parkinsonian disorders (PD and AD/Park) even though the degree of cell death is very different. This might suggest that compensatory events occur in these DA neurons in AD/Park that are similar to those in PD and that result in differential effects on mRNAs encoding TH and DAT proteins.

Aged↗
PubMed1997

Inositol 1,4,5-trisphosphate receptor expression in mammalian olfactory tissue.

Two cDNAs encoding inositol 1,4,5-trisphosphate (IP3) receptors were amplified from rat olfactory tissue, and both exhibited 100% sequence identity to the short (Segment II - ) variant of type I IP3 receptor. Type III IP3 receptor was also expressed in olfactory tissue. The distribution of IP3 receptors included the olfactory epithelium, lamina propria, and glandular tissue. These results demonstrate the co-expression of multiple IP3 receptor subtypes in olfactory cells, and suggest multiple functions for IP3 receptors in this tissue.

Animals↗
PubMed1994

Dinucleotide frequencies and codon usage in jawless and cartilaginous fishes.

Dinucleotide frequencies and codon usage in terms of strong-weak codon choices were examined in gene coding regions of 5 jawless and cartilaginous fish species. These dinucleotide frequencies were then compared to gene-coding regions from a vertebrate and an invertebrate species. These primitive vertebrate fishes exhibited species specificity in the hierarchy of dinucleotide frequencies. The most frequently occurring dinucleotide varied among coding regions of jawless and cartilaginous fishes, but it always contained G. Of the 16 dinucleotides, TA had the lowest frequency of occurrence in all species, and it had considerably lower frequencies in jawless fish genes than in cartilaginous fish genes. Dinucleotide frequency analysis suggested CpG conversion to TG in ray genes. Strong-weak codon usage analysis indicated that all 5 fish species used strong-weak-strong bonding codons most frequently; furthermore, each species used any-weak-strong codons in greater than expected levels. Gene coding regions from all 5 species exhibited a bias toward strong bonding nucleotides at codon position 3, with the greatest bias in sea lamprey genes. This bias may reflect the overall G+C content of localized regions of chromosomal DNA in which these genes reside.

Animals↗
PubMed1988

A fluorescent sterol probe study of cholesterol/phospholipid membranes.

The behavior of dehydroergosterol in L-alpha-dimyristoylphosphatidylcholine (DMPC) unsonicated multilamellar liposomes was characterized by absorption spectroscopy and fluorescence measurements. Dehydroergosterol exhibited a lowered absorption coefficient in multilamellar liposomes while the steady-state fluorescence anisotropy of dehydroergosterol in these membranes decreased significantly with increasing dehydroergosterol concentration, suggesting membrane sterol-sterol interactions. The comparative steady-state anisotropy of 0.9 mole percent dehydroergosterol in multilamellar liposomes was lower than in small unilamellar vesicles suggesting different sterol environments for dehydroergosterol. Dehydroergosterol fluorescence lifetime was relatively independent of membrane sterol content and yielded similar values in sonicated and unsonicated model membranes. In multilamellar liposomes containing 5 mole percent cholesterol, the gel-to-liquid crystalline phase transition of DMPC detected by 0.9 mole percent dehydroergosterol was significantly broadened when compared to the phase transition detected by dehydroergosterol in the absence of membrane cholesterol (Smutzer, G. et al. (1986) Biochim. Biophys. Acta 862, 361-371). In multilamellar liposomes containing 10 mole percent cholesterol, the major fluorescence lifetime of dehydroergosterol did not detect the gel-to-liquid crystalline phase transition of DMPC. Time-correlated fluorescence anisotropy decays of dehydroergosterol in DMPC multilamellar liposomes in the absence and presence of 5 mole percent cholesterol exhibited a single rotational correlation time near one nanosecond that was relatively independent of temperature and low concentrations of membrane cholesterol. The limiting anisotropy of 0.9 mole percent dehydroergosterol decreased above the gel-to-liquid crystalline phase transition in membranes without cholesterol and was not significantly affected by the phase transition in membranes containing 5 mole percent cholesterol. These results suggested hindered rotational diffusion of dehydroergosterol in multilamellar liposomes. Lifetime and time-correlated fluorescence measurements of 0.9 mole percent dehydroergosterol in multilamellar liposomes further suggested this fluorophore was detecting physical properties of the bulk membrane phospholipids in membranes devoid of cholesterol and was detecting sterol-rich regions in membranes of low sterol concentration.

Cholesterol↗
PubMed1988

A fluorescent sterol probe study of human serum low-density lipoproteins.

The fluorescent sterol probe, ergosta-5,7,9,(11),22-tetraen-3 beta-ol (dehydroergosterol), was utilized as a cholesterol analog to label human serum low-density lipoproteins (LDL). Quenching of dehydroergosterol fluorescence by KI indicated that most of the fluorophore was either buried within the outer phospholipid monolayer of LDL or within the neutral lipid core of LDL. The steady-state anisotropy of dehydroergosterol in LDL detected the cholesteric core phase transition near 30 degrees C. Fluorescence lifetime decays for dehydroergosterol contained two components, both below and above the cholesteric phase transition, with the major lifetime component near 1 ns. Neither lifetime component underwent a detectable change in duration at the core phase transition temperature. Time-correlated fluorescence anisotropy decays of dehydroergosterol indicated a single rotational correlation time near 1.7 ns, which was unaffected by the core phase transition. Time-correlated anisotropy decays also suggested hindered rotation of dehydroergosterol in LDL. These results indicate that unesterified cholesterol is primarily located in the outer phospholipid monolayer of LDL, with the majority of cholesterol not in direct contact with the aqueous phase.

Calorimetry↗
PubMed1986

Physical properties of the fluorescent sterol probe dehydroergosterol.

Spectroscopic studies were performed on the fluorescent sterol probes ergosta-5,7,9(11),22-tetraen-3 beta-ol (dehydroergosterol) and cholesta-5,7,9(11)-trien-3 beta-ol (cholestatrienol). In most isotropic solvents, these molecules exhibited a single lifetime near 300 ps. Fluorescence lifetimes in 2-propanol were independent of emission wavelength and independent of excitation wavelength. Excited state behavior of these probes appears relatively simple. In isotropic solvents, dehydroergosterol fluorescence emission underwent at most a small Stokes shift as solvent polarity was modified. Time-resolved anisotropy decays indicated that dehydroergosterol decay was monoexponential, with rotational correlation times dependent on solvent viscosity. When incorporated into L-alpha-dimyristoylphosphatidylcholine liposomes at a concentration of 0.9 mol%, dehydroergosterol fluorescence lifetime decreased at the phase transition of this phospholipid indicating that the sterol probe was detecting physical changes of the bulk phospholipids. Furthermore, total fluorescence decays and anisotropy decays were sensitive to the environment of the sterol. Dehydroergosterol and cholestatrienol are thus useful probes for monitoring sterol behavior in biological systems.

Cholestenes↗
PubMed1985

A fluorescence anisotropy study on the phase behavior of dimyristoylphosphatidylcholine/cholesterol mixtures.

The phase behavior of L-alpha-dimyristoylphosphatidylcholine/cholesterol mixtures was studied in multilamellar vesicles by fluorescence polarization of the sterol molecule dehydroergosterol and of the polyene molecule alpha-parinaric acid. In the absence of cholesterol, dehydroergosterol exhibited an increase in polarization as DMPC vesicles were heated through the phase transition. This rise in polarization anisotropy was observed over a 0.6-1.0 degrees C increase in temperature with the midpoint of the phase transition occurring at 23.6 degrees C. Addition of 5 mol% cholesterol completely obliterated this change in polarization anisotropy through the phase transition of DMPC. alpha-Parinaric acid underwent a characteristic decrease in polarization anisotropy through the phase transition of DMPC. The change in anisotropy through the phase transition was over 4-fold greater than the values observed with dehydroergosterol. Vesicles containing 5 mol% cholesterol in the presence of alpha-parinaric acid underwent a decrease in polarization anisotropy that was over 75% of the original decrease in amplitude observed in the absence of any membrane cholesterol. The difference in sensitivity of the two fluorescent probes to the phase transition of DMPC as a function of membrane cholesterol content may be explained by a preferential partitioning of dehydroergosterol (and cholesterol) into a sterol-rich phase at low sterol concentrations. This partitioning allows dehydroergosterol to detect sterol-rich regions in the membrane bilayer.

Chemical Phenomena↗
PubMed1978

Interactions between photosystem II components in chloroplast membranes. A correlation between the existence of a low potential species of cytochrome b-559 and low chlorophyll fluorescence in inhibited and developing chloroplasts.

1. Chloroplasts inhibited by incubation with hydroxylamine in the light exhibit a low fluorescence yield upon illumination in the presence of dithionite sufficient to completely reduce the primary acceptor, Q. In the absence of magnesium ions, the fluorescence yield is the same as in control chloroplasts, suggesting that the reason for the low yield is a defect in the mechanism by which Mg2+ enhances the fluorescence. These chloroplasts were previouly shown to contain only low potential (Em7.8 = +80 mV) cytochrome b-559 (Horton, P. and Croze, E (1977) Biochim. Biophys. Acta 462, 86-101). 2. In Photosystem II particles, in heat-treated chloroplasts and in trypsin-digested chloroplasts, high potential cytochrome b-559 is absent and the variable fluorescence yield is again low. 3. Peas grown under intermittent light contain only one-fifth of the content of high potential cytochrome b-559 seen in fully greened plants, yet show high rates of water to methyl viologen electron transport. Aquisition of the high potential cytochrome b-559 accompanies synthesis of chlorophyll b, the onset of Mg-stimulated fluorescence and an increased variable yield of fluorescence. A similar correlation was seen during greening of dark-grown barley. 4. It is proposed that the high potential state of cytochrome b-559 is due to the same membrane properties which allow cation enhanced variable fluorescence, so that the presence of low potential cytochrome b-559 is accompanied by a decrease in variable fluorescence yield.

Cell Membrane↗
PubMedDate not supplied

Codon usage in bony fishes.

Bony fishes are excellent experimental models that have been used extensively in biochemical and molecular genetic studies. As proteins are isolated and characterized from these organisms, information on codon usage by bony fishes can be used for subsequent recombinant DNA studies. Codon usage and nucleotide bias within codons from three species of bony fishes and two composites of 14 and 15 bony-fish species were analyzed. Although differences in codon usage increased from seven amino acids between fish species to eight amino acids between fish genera, the small number of differences (3 amino acids) between a single species and a fish composite minus that species suggests that codon usage tables constructed from large numbers of fish species are representative of bony fish in general. Furthermore, we found few differences in codon usage between two vertebrate phyla (fish and rat). Codons in fish DNA sequences end predominantly in G or C, even though the coding sequences are not enriched in these nucleotides. This positional base bias can be used to locate putative protein coding regions in fish DNA sequences.

Amino Acids↗