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Biomedical subjects

K A Rose

Publications and source records attributed to K A Rose.

15 recordsLinked to original sources

Ecological forecasts: an emerging imperative.

Planning and decision-making can be improved by access to reliable forecasts of ecosystem state, ecosystem services, and natural capital. Availability of new data sets, together with progress in computation and statistics, will increase our ability to forecast ecosystem change. An agenda that would lead toward a capacity to produce, evaluate, and communicate forecasts of critical ecosystem services requires a process that engages scientists and decision-makers. Interdisciplinary linkages are necessary because of the climate and societal controls on ecosystems, the feedbacks involving social change, and the decision-making relevance of forecasts.

Agriculture↗

A survey of the accessibility of chiropractic clinics to the disabled.

OBJECTIVE: To determine to what degree chiropractic clinics are complying with the Americans with Disabilities Act (ADA), which mandates that health care clinics be accessible to the disabled. METHODS: A survey was developed and mailed to 200 chiropractic clinics in Orange and Los Angeles counties. The survey asked about the essential necessities for health care clinics to be accessible to the wheelchair-bound, the blind, and the deaf. It also sought to discover how many disabled patients these clinics were treating and the attitudes of practitioners and staff toward this population. RESULTS: The response rate was 50.5%. Accessibility for the wheelchair-bound was high. Accessibility for the blind was limited by a lack of Braille signs. Accessibility to the deaf was limited by lack of telecommunications device for the deaf or use of sign language interpreters. Most clinics were treating few or no disabled patients and did not perceive a need to become more accessible. CONCLUSION: There appears to be poor compliance with the ADA in chiropractic clinics in Los Angeles and Orange counties. Although data are lacking, it appears likely that the disabled population is being underserved by the chiropractic profession. Education for chiropractors on the rights and needs of the disabled population is necessary to give this group equal access to chiropractic health care.

Attitude of Health Personnel↗

Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone.

Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7alpha-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7alpha-hydroxy DHEA but not with 7beta-hydroxy DHEA; when [7alpha-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7alpha position. Brain extracts also efficiently liberated tritium from [7alpha-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7alpha-hydroxy DHEA. We conclude that Cyp7b is a 7alpha-hydroxylase participating in the synthesis, in brain, of neurosteroids 7alpha-hydroxy DHEA, and 7alpha-hydroxy pregnenolone.

17-alpha-Hydroxypregnenolone↗

Changes in the receptive fields of cat retinal ganglion cells affected by pressure on the optic nerve.

In the cat optic nerve a lesion was induced by brief application of pressure. It selectively blocked impulse conduction in large diameter fibres of the retinal ganglion cells. Electrophysiological examination of single optic axons several weeks later demonstrated a gross alteration of the visual properties of the affected BT/Y ganglion cells. It is suggested that the alteration of receptive field properties may reflect the cellular and dendritic response to distant focal injury of the axon.

Animals↗

Correlations between observability of the spatial frequency doubled illusion and a multi-region pattern electroretinogram.

A glaucoma screening device based on the visibility of the spatial frequency doubled (FD) illusion will be marketed by Welch Allyn Ltd in the next year (ANU Patients (Australia) 611,585, (USA) 5,065,767 and application PL 3130). An underlying assumption of the method is that retinal processes are being tested. To test this assumption we compared the visibility of the FD illusion over a range of conditions and in the same spatial locations as a multi-region pattern electroretinogram (PERG). Grating speed and contrast were good predictors of the psychometric functions and PERG amplitude and phase.

Electroretinography↗

A multiple-frequency, multiple-region pattern electroretinogram investigation of non-linear retinal signals.

It has been proposed that the spatial frequency doubled (FD) illusion may originate from Y-like non-linear retinal ganglion cells. If the contrast of multi-frequency stimuli is increased, Y cells show a phase advance in the self-sum frequencies but not in other output frequencies. We looked for these effects with a multi-region pattern electroretinogram (PERG) displaying the sum of two temporal frequencies in each visual field location. Regional variation was found in the recorded sum and difference frequencies. The results indicate that PERG signals become dominated by responses from Y-like cells when the FD illusion is seen.

Contrast Sensitivity↗

A novel cytochrome P450 expressed primarily in brain.

hct-1 (hippocampal transcript) was detected in a differential screen of a rat hippocampal cDNA library. Expression of hct-1 was enriched in the formation but was also detected in rat liver and kidney, though at much lower levels; expression was barely detectable in testis, ovary, and adrenal. In liver, unlike brain, expression was sexually dimorphic; hepatic expression was greatly reduced in female rats. In mouse, brain expression was widespread, with the highest levels being detected in corpus callosum; only low levels were detected in liver. Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that metabolize a range of substrates including steroids, fatty acids, and xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid sequence) to cholesterol 7 alpha-hydroxylase (CYP7) and contains a postulated steroidogenic domain present in other steroid-metabolizing CYPs but clearly represents a type of CYP not previously reported. Genomic Southern analysis suggests that a single gene corresponding to hct-1 is present in mouse, rat, and human. hct-1 is unusual in that, unlike all other CYPs described, the primary site of expression is in the brain. Similarity to CYP7 and other steroid-metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism in brain, notable because of the documented ability of brain-derived steroids (neurosteroids) to modulate cognitive function in vivo.

Amino Acid Sequence↗

Comparison of genotyping and serotyping methods for the identification of hepatitis C virus types.

The usefulness of identification of hepatitis C virus (HCV) genotype has recently been investigated for the clinical management of patients infected by HCV. In the present study, the HCV genotype infecting 127 patients was determined by two different methods: HCV genotyping using a dot-blot assay with type-specific probes derived from the 5'-UTR of HCV genome and HCV serotyping using an ELISA system in which type-specific antibodies against the NS4 region were detected. Overall, a good correlation of the two methods was observed, the main discrepancy being 4 patients with sequence-confirmed HCV-2 (2 cases) and HCV-3 (2 cases) genotypes recognized as HCV-1 by serotyping. Mixed infections were not detected by either method. In 19 PCR negative sera, in which the HCV genotype could not be evaluated, no particular serotype profile was observed. In conclusion, the molecular and serological techniques are almost equivalent in determining the viral type, although in individual cases, especially in PCR negative patients, the clinical meaning of the serotyping result remains to be determined.

Base Sequence↗

Increased basal arterial smooth muscle glucose transport in the Zucker rat.

Insulin has recently been reported to stimulate glucose transport in vascular smooth muscle cells (VSMC). This observation suggests a role for this hormone in hypertension associated with insulin resistance. To determine whether VSMC glucose transport abnormalities exist in a state of insulin resistance, we studied basal and insulin-stimulated glucose transport in VSMC derived from Zucker lean (normotensive, insulin sensitive) and obese (hypertensive, insulin resistant) rats. Basal glucose transport, as measured by tracer quantities of [3H]2-deoxyglucose, was 4.2 +/- 0.8 and 7.4 +/- 0.9 fmol/10(6) cells/min for lean and obese cells, respectively (P < .05). Kinetic analyses utilizing variable concentrations of unlabeled 2-deoxyglucose in the media revealed that increased transport in the obese rat was due to an increased Vmax of the transporter system: Vmax = 5.9 +/- 0.8 and 12.1 +/- 1.2 fmol/10(6) cells/min for lean and obese cells, respectively (P < .05); no changes in Km were noted for the two populations: Km = 1.14 +/- 0.24 and 0.96 +/- 0.10 mmol/L. Insulin (10 microU/mL) increased the Vmax of the transporter in both preparations, but greater stimulation was seen in the lean VSMC: 32 +/- 4.8% v 11.5 +/- 2.1% (P < .05). Insulin had no effect on the Km of the transporter in either strain. These data suggest that increased basal glucose transport in obese VSMC may predispose the vessel to increased glucose-mediated events, while blunted insulin-stimulated glucose transport in these cells mirrors insulin-resistant glucose disposal in other tissues of the obese rat.

Analysis of Variance↗

Insulin and insulin-like growth factor-1 modulation of glucose transport in arterial smooth muscle cells: implication of GLUT-4 in the vasculature.

Insulin modulates many physiological processes in vascular smooth muscle cells (VSMC) such as contractility, proliferation, and ion homeostasis. However, hormonal modulation of glucose transport has not been explored in pure populations of these cells. This study demonstrates that insulin and insulin-like growth factor-1 (IGF-1) increase glucose transport in a7r5 clonal and freshly prepared Sprague-Dawley aortic (SDa) VSMC. In a7r5 cells, physiologic (10(-12) to 10(-9) mol/L) insulin concentrations increase transport by 8% to 15%, whereas supraphysiologic concentrations (10(-9) to 10(-6) mol/L) increase transport by up to 60% (P < .05 v no increase over all concentrations tested). In SDa cells, insulin was more potent, displaying maximum transport stimulation of 70% at 10(-8) mol/L (P < .05 v a7r5 cells). Insulin regulation of glucose transport occurs by a protein synthesis-independent pathway as 10 mumol/L cycloheximide was without effect. Insulin produces these effects within 20 min of treatment, and cytochalasin B (10 mumol/L) inhibits both basal and insulin-stimulated glucose transport by 93% and 96%, respectively. Stimulation of insulin receptors alone, with 2.5 pg/mL insulin receptor-specific antibody, stimulates glucose transport by 20%, suggesting transport can be stimulated by an IGF-1 receptor independent mechanism. However, IGF-1 is a more potent stimulator of transport in both cell lines studied, with maximal stimulation (10(-8) mol/L IGF-1) of 60% and 80% in a7r5 and SDa cells, respectively (P < .05 v 10(-8) mol/L insulin in both cell lines). Insulin stimulation of glucose transport is specific for [D+]-glucose; [L-]-glucose does not compete for transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV): use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3.

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV.

Amino Acid Sequence↗

Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression.

The effects of expression of human c-myc and both mutated (T24) and normal forms of human Ha-ras-1 were studied in an aneuploid rat fibroblast line (208F). Mutated T24 Ha-ras was also studied in a near-diploid cell derived from early passage Chinese hamster lung fibroblasts (CHL). In contrast to the parental fibroblasts, cells expressing any of the human oncogenes engendered rapidly growing tumours in immune-suppressed animals. Blood- and lymph-borne metastases were observed from both ras- and myc-expressing cells. In general ras-expressing cells were more aggressive than those expressing myc. In the 208F background, expression of c-myc was associated with an incidence of mitosis similar to that in tumours expressing T24 Ha-ras, but incidence of single cell death by apoptosis was higher. Quantitatively, expression of human oncogene mRNA was constant during growth in vivo, and similar to that sometimes observed in human neoplasms. Of 9 endogenous proto-oncogenes, 7 showed no change in expression from the parental fibroblasts, but c-abl and c-fos were strongly expressed in all cells expressing human ras or myc. Thus these tumorigenic cells, although transfected with single human oncogenes, all expressed oncogenes with both nuclear- and membrane-associated products.

Animals↗

Electron paramagnetic resonance saturation studies of P-700+ reaction center chlorophyll in plant photosynthesis.

Electron paramagnetic resonance (EPR) power saturation and saturation recovery methods have been used to determine the spin lattice, T1, and spin-spin, T2, relaxation times of P-700+ reaction-center chlorophyll in Photosystem I of plant chloroplasts for 10 K less than or equal to T less than or equal to 100 K. T1 was 200 mus at 100 K and increased to 900 mus at 10 K. T2 was 40 ns at 40 K and increased to 100 ns at 10 K. T1 for 40 K less than or equal to T less than or equal to 100 K is inversely proportional to temperature, which is evidence of a direct-lattice relaxation process. At T = 20 K, T1 deviates from the 1/T dependence, indicating a cross relaxation process with an unidentified paramagnetic species. The individual effects of ascorbate and ferricyanide on T1 of P-700+ were examined: T1 of P-700+ was not affected by adding 10 mM ascorbate to digitonin-treated chloroplast fragments (D144 fragments). The P-700+ relaxation time in broken chloroplasts treated with 10 mM ferricyanide was 4-times shorter than in the untreated control at 40 K. Ferricyanide appears to be relaxing the P-700+ indirectly to the lattice by a cross-relaxation process. The possibility of dipolar-spin broadening of P-700+ due to either the iron sulfur center A or plastocyanin was examined by determining the spin-packet linewidth for P-700+ when center A and plastocyanin were in either the reduced or oxidized states. Neither reduced center A nor oxidized plastocyanin was capable of broadening the spin-packet linewidth of P-700+ signal. The absence of dipolar broadening indicates that both center A and plastocyanin are located at a distance at least 3.0 nm from the P-700+ reaction center chlorophyll. This evidence supports previous hypotheses that the electron donor and acceptor to P-700 are situated on opposite sides of the chloroplast membrane. It is also shown that the ratio of photo-oxidized P-700 to photoreduced centers A and B at low temperature is 2 : 1 if P-700 is monitored at a nonsaturating microwave power.

Binding Sites↗

Detection of human Ha-ras transcripts in tumor cells by in situ hybridization.

We demonstrate the development of a method for identification of human Ha-ras transcripts in cytological and histological preparations of rodent fibroblasts by RNA-RNA in situ hybridization. Fibroblasts, expressing human Ha- ras at high or a very low level, provide a biological model system to optimize in situ hybridization. For rapid detection we used the radiographic signal from cell smears, in directly overlaid x-ray film. Certain pretreatments of slides are shown to increase nonspecific probe binding. The methods described can be used for rapid detection of oncogene expression in small numbers of cultured cells, without prior extraction and purification of their RNA.

Genes, ras↗

Electrical shock injury.

OBJECTIVE: To discuss the case of a patient who received an electrical shock injury to the back of his head and was co-managed by a neurologist and a chiropractor. The common manifestations of electrical shock injuries are presented. CLINICAL FEATURES: The patient was a 31-yr-old man. His initial symptoms consisted of headaches, dizziness, pain in the suboccipital area, tingling down both arms to the hands, nausea, blurred vision, increased sweating, chest pain, loss of appetite and memory lapses. The patient received a neurological examination, MRI of the brain, EEG, brain stem auditory evoked response and EKG. The neurologist's diagnosis was post-traumatic head syndrome following electrocution. INTERVENTION AND OUTCOME: He was treated by a neurologist and a chiropractor, with fair results. Chiropractic treatments were directed toward correcting the fixations, fibrotic tissue and joint proprioception in his neck using manipulation, physical therapy and active care exercises. CONCLUSION: Electrical shocks commonly cause immediate damage to the heart, nervous system and musculoskeletal system. They can also cause delayed complications days to years later, including cholelithiasis, cataracts and nervous system conditions such as ALS. Chiropractors can play an important role in managing the musculoskeletal manifestations of electrical shock injuries.

Adult↗