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D A Lewis

Publications and source records attributed to D A Lewis.

358 records · Page 20Linked to original sources

The dopaminergic innervation of monkey entorhinal cortex.

Dopamine has been implicated in the pathophysiology of schizophrenia, and the entorhinal cortex (ERC) is thought to be a site of structural pathology in this disorder. However, relatively little is known about the dopaminergic (DA) innervation of ERC in the primate brain. In this study, immunohistochemical methods and antibodies directed against tyrosine hydroxylase (TH) and dopamine were used to determine the organization of DA axons in the ERC of macaque monkeys. The anti-TH antibody used in this study appeared predominantly to identify DA axons, as demonstrated by its failure to label fibers that were immunoreactive with an antibody against dopamine-beta-hydroxylase in double-labeling experiments. In addition, the regional and laminar distributions of TH-immunoreactive fibers were strikingly similar to those labeled with the anti-dopamine antibody. With both antibodies, cytoarchitectonically identified subdivisions of monkey ERC (Amaral et al., 1987) differed in both the density and laminar distribution of labeled fibers. Immunoreactive processes exhibited a substantial rostral-to-caudal gradient of decreasing density across subdivisions of ERC, and the density of labeled fibers also decreased from medial to lateral in the rostral but not in the caudal subdivisions of ERC. The laminar distribution of labeled fibers differed both between and within subdivisions. For example, in the olfactory and rostral subdivisions of ERC, the superficial layers contained a very high density of immunoreactive processes, whereas in the intermediate region, three bands of labeled fibers were seen in layers I, III-IV, and VI. In addition, radial columns of fibers interdigitated with areas of decreased density were present between layers I and III. Although the overall density of labeled fibers was greater in lateral than in the caudal subdivisions of ERC, these regions had similar laminar distribution patterns. In these areas of monkey ERC, labeled processes were highest in density in deep layer I, and homogeneously distributed in the other cortical layers. These findings demonstrate that the DA innervation of monkey ERC is complex, and follows laminar- and subdivision-specific patterns. These patterns of distribution suggest the possible interactions that DA axons may have with other elements of ERC circuitry, and may provide insight into the possible functional roles of dopamine in ERC in both normal and disease states.

Animals↗

Postnatal development of tyrosine hydroxylase- and dopamine transporter-immunoreactive axons in monkey rostral entorhinal cortex.

Dopamine afferents from the mesencephalon appear to play a critical role in the normal development and cognitive functions of multiple areas of the primate cerebral cortex. In some regions, such as the prefrontal and motor cortices, dopamine innervation changes substantially during postnatal development. However, little is known about the postnatal maturation of dopamine afferents to the primate rostral entorhinal cortex, a periallocortical region that receives a dense dopamine innervation in adults. In this study, we used immunocytochemical techniques and antibodies against tyrosine hydroxylase and the dopamine transporter to examine the postnatal development of dopamine axons in the rostral subdivision of macaque monkey entorhinal cortex. Within animals, the axons labeled with each antibody did not differ in overall density or laminar distribution. Across development, the density of dopamine axons in layers I and VI did not change appreciably. In contrast, the density of labeled axons in layer III significantly increased by a factor of three between birth and 5-7 months of age. The timing of this change differs substantially from that observed in prefrontal cortex, where peak dopamine innervation occurs between 2 and 3 years of age. These findings, in concert with other data, suggest that developmental changes in the dopamine innervation of cortical regions may parallel the functional maturation of those areas.

Aging↗

Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures.

The ability of dopamine to regulate the cognitive functions of the prefrontal cortex (PFC) involves complex modulatory actions on GABA-containing local circuit neurons in addition to pyramidal cells. However, the subclasses of cortical neurons that receive direct dopamine input are not known. We sought to determine whether dopamine terminals innervate the subclasses of local circuit neurons that contain the calcium-binding protein parvalbumin (PV), namely the wide arbor and chandelier neurons that target pyramidal cell soma and axon initial segments respectively. Sections through area 9 of five monkeys were labeled with immunoperoxidase for tyrosine hydroxylase (TH), to identify dopamine terminals, and with immunogold-silver for PV. Electron microscopic examination of the middle cortical layers (IIIb-IV) revealed that TH-positive terminals were sometimes directly apposed to PV-labeled dendrites, and approximately one-third of these contacts exhibited morphological features that are typically associated with symmetric synapses. In contrast, TH-immunolabeled terminals in the superficial layers (I-IIIa) were less frequently apposed to PV-positive dendrites, and none of these contacts exhibited synapse-like morphology. These findings, in concert with previous studies of GABA- or calretinin-containing local circuit neurons, suggest that dopamine's modulatory action in the PFC involves selective effects on only certain interneuron populations, including those that mediate potent inhibitory actions on pyramidal cells.

Animals↗

Tetracycline-resistant Neisseria gonorrhoeae. Characteristics of patients and isolates at a London Genitourinary Medicine Clinic.

OBJECTIVES: To compare auxotypes, serovars, and antibiograms of tetracycline-resistant Neisseria gonorrhoeae (TRNG) and non-TRNG isolated from patients attending an East London Genitourinary Medicine (GUM) Clinic. To obtain plasmid profiles for penicillinase-producing gonococci (PPNG) as well as presumptive TRNG. To identify differences in patient characteristics for the TRNG and non-TRNG patient groups. STUDY DESIGN: Gonococcal isolates were collected from 400 patients attending the GUM clinic at the Royal London Hospital GUM Clinic over a 1-year period. Isolates (378) were tested for susceptibility to various antibiotics, auxotyped, and serotyped. Plasmid profiles were obtained for PPNG and isolates exhibiting high-level tetracycline resistance (TRNG). The presence of the tet M determinant was confirmed using the polymerase chain reaction (PCR). The PCR product was digested with the restriction endonuclease (RE) Hpa II and electrophoresed on a 2.5% agarose gel to determine an "RE pattern." Patient data were collected by retrospective case-note review. RESULTS: TRNG (n = 42) accounted for 11% of the 378 isolates tested, and the remaining 336 (89%) isolates were non-TRNG. Non-requiring auxotrophy and P1B-2 serovar expression occurred more frequently among TRNG. PPNG accounted for 31% of TRNG and 5% of non-TRNG. Chromosomal resistance to penicillin (CMRNG) was absent among TRNG but accounted for 11% of non-TRNG. One TRNG isolate showed decreased susceptibility to ciprofloxacin (MIC 0.25 mg/l). All isolates were sensitive to cefotaxime, cefixime, spectinomycin, and azithromycin. All TRNG possessed the 25.2 MDa plasmid and produced a PCR product of appropriate size after tet M gene sequence amplification. RE digests of the PCR product gave a single pattern. None of the TRNG in contrast to 18% of the non-TRNG were acquired homosexually. Ethnic distribution differed between the patients with TRNG and patients without non-TRNG (Afro-Caribbean 81% versus 58%; white 19% versus 36%). Most TRNG were acquired in the United Kingdom. CONCLUSIONS: TRNG differ from the non-TRNG in their auxotype and serovar distribution. PPNG are more common among the TRNG isolates, whereas CMRNG appear absent. TRNG are isolated more commonly from Afro-Caribbean patients and were not represented among homosexually acquired isolates.

Adolescent↗

Properties of LTP induction in the CA3 region of the primate hippocampus.

Activity-dependent changes in synaptic strength, such as long-term potentiation (LTP), have been proposed to underlie memory storage in the brains of all mammals, including humans. However, most forms of synaptic plasticity, including LTP, are studied almost exclusively in rodents and related species. Thus, the hypothesis that LTP is important in human memory relies on the assumption that LTP is similar in the primate and rodent brains. We have begun to test this hypothesis by studying the properties and mechanisms of LTP induction in area CA3 of hippocampal slices from cynomolgus monkeys. We have found that LTP can be induced reliably at both mossy fiber-CA3 and collateral/associational-CA3 synapses in the primate brain, and that the properties of LTP induction at these synapses are similar to what we and others have observed in experiments using hippocampal slices from rodents. Also, we have investigated the role of opioids in mossy fiber synaptic transmission and LTP and have found no effect of the opioid antagonist naloxone nor the opioid agonist dynorphin on mossy fiber synaptic transmission or potentiation. These data suggest that LTP in the primate and rat brains has a similar induction mechanism and, thus, that the rodent is a useful animal model in which to study synaptic modification such as LTP.

Animals↗

Behçet's syndrome: a review for the genitourinary medicine physician.

Behcet's syndrome is a multisystem disorder due to vasculitis of unknown aetiology. It may present to genitourinary medicine physicians with genital ulceration. Careful history-taking and clinical examination should allow a correct diagnosis which may be confirmed by reference to the new diagnostic criteria including performing a pathergy test. Of particular importance is a prompt referral to an ophthalmologist for an ocular slit-lamp assessment as eye involvement can be severe and therapy needs to be started early in the course of the illness. The management of Behçet's syndrome may also involve rheumatologists, gastroenterologists, neurologists and immunologists. Close liaison between these clinicians may be necessary to provide optimum care for the patient with Behçet's syndrome.

Adult↗

Physiological differences between genders. Implications for sports conditioning.

It is commonly accepted that there are physiological and morphological gender differences. These differences become evident in the specific responses or magnitude of response to various training regimens. Very little difference is seen in the response to different modes of progressive resistance strength training. Men and women experience similar relative strength gains when training under the same programme. The evidence on body composition changes that occur with strength training is equivocal at this point. Researchers, however, suggest that there appears to be less muscle hypertrophy with strength improvement in women when compared to men. The data suggest that there are no differences between genders in central or peripheral cardiovascular adaptations to aerobic training. However, women in general have a reduced O2 carrying capacity. Another factor that may be responsible for the sex differences seen in the metabolic responses to exercise may be the greater, essential sex specific fat of women. Sparling and Cureton (1983) have shown that differences in similarly trained male and female distance runners are due largely to percentage body fat, less to cardiorespiratory fitness and least to running economy. Pate et al. (1985) determined that men and women who are capable of similar performances, in this case a 15 mile race, do not differ in body composition, cardiorespiratory response or metabolic response. There appear to be no differences in relative increases in VO2max for men and women when they are trained under the same intensity, frequency and duration. Mode of training also appears to elicit no sex difference. Hormonal factors lead to greater initial levels of high density lipoproteins in women. This appears to cause a smaller change in the total cholesterol-high density lipoprotein ratio than occurs with aerobic training in men. Generally, the menstrual cycle phase makes no difference to performance in women. The special cases of exercise in hot and cold environments present conflicting evidence. When men and women are matched for surface area:mass, VO2max and percentage body fat, the major disadvantages women have in the heat disappear. The question of gender differences in the cold has yet to be fully explored. When the general population is compared, men appear to have an advantage over women.

Adaptation, Physiological↗

Insuring women's health.

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Delivery of Health Care↗

Cartoid artery calcification in a general dental population: a retrospective study of panoramic radiographs.

To determine the prevalence of carotid artery calcification and the degree of cervical spine imaging for three different brands of panoramic radiograph machines in a retrospective study, all panoramic radiographs exposed between January and June 1994 were reviewed for frequency of cervical spine imaging and radiopacities of the soft tissue in the region of the common carotid artery bifurcation. While carotid artery calcifications are not common in a general dental population, they can be found in up to 5 percent of older patients. Our data support panoramic radiography as a device that may identify patients at risk for developing a cerebrovascular accident, although we do not recommend making this radiograph for calcification detection alone.

Adolescent↗

Analysis of Ginkgo biloba for the presence of ginkgotoxin and ginkgotoxin 5'-glucoside.

Hot water extracts of Ginkgo biloba seeds were analyzed for the presence of ginkgotoxin (4'-O-methylpyridoxine) by reversed-phase liquid chromatography (LC) using methanol-0.05M KH2PO4 (1 + 9, v/v) adjusted to pH 3 as mobile phase. Detection was by fluorescence (excitation 280 nm, emission 370 nm). A straight line calibration curve was obtained for the 10-100 ng injected. After addition of beta-glucosidase (37 degrees C/h), an earlier eluting peak disappeared and the ginkgotoxin peak increased. The identity of the ginkgotoxin was confirmed by LC/MS and LC/MS/MS. LC/MS/MS also confirmed the 5'-glucoside by comparison with the 3-glucoside. This is the first identification of a glucoside of ginkgotoxin in Ginkgo biloba. An unknown compound of MW 267 also observed in the Ginkgo biloba seed extract was shown not to be 3,5'-diacetylginkgotoxin by its different LC retention time. Extraction of ground Ginkgo biloba seeds with boiling water in a Soxhlet for 2 x 2 h yielded a total of 179 microg/g of free ginkgotoxin. The concentration in powder from Ginkgo biloba capsules was several times lower than this (17-64 microg/g) in 3 samples but higher in another (457 microg/g). Canned ginkgo seeds (white nuts) contained no detectable free ginkgotoxin but the glucoside was present. Different extraction times were studied: 0.5 h gave only 52 microg/g free ginkgotoxin in the ginkgo seeds. However, boiling an extract for 4 h showed about 15% loss of ginkgotoxin and its glucoside.

Chromatography, Liquid↗

Family planning needs and services in nonmetropolitan areas.

More than 215 million low- and marginal-income women living in rural areas are still without access to family planning services they want and need. Priority attention to more populous areas where there are no organized programs, or just one agency providing services, is suggested. Increased involvement of hospitals is necessary if the rural-urban gap is to be closed.

Adolescent↗