A review and critical analysis of treatment research related to articulation and phonological disorders. This article contains a summary of aspects of research designs and strategies found in 63 published reports in which the effectiveness of treatment of articulation or phonological disorders was evaluated. These research reports were published in four nationally refereed journals that contained most of the literature published in the decades of the 1970s and 1980s. A total of 91 items were evaluated in each report by two reviewers working independently, including types of research designs, details about subjects, sampling, and types of independent and dependent variables used by researchers. Comparisons were made within each decade and across both decades to identify strengths and limitations. Some significant differences in research designs and variables under investigation occurred between the decades. A critical analysis was performed, and suggestions for changes are discussed.


Assessment of sensitivity to interpersonal stress in stutterers. The Willoughby Personality Schedule-R was administered to adult male Yugoslav stutterers who were not yet in treatment. Internal consistency of the WPS-R was assessed by computing item-scale score correlations. Twenty-two of 25 items were significantly correlated with WPS-R total score. Confirmatory factor analysis revealed three separate and reliable dimensions: Social Isolation (ssca .85), Social Confidence (ssca .74), and Social Sensitivity (ssca = .62), that were identical to those previously found for American stutterers. Although WPS-R scores were unrelated to several measures of stuttering severity, analysis of extreme scores suggested support for the hypothesis that general anxiety moderates stuttering severity. Overall the results are consistent with the contention that hypersensitivity to interpersonal stress is manifested in stutterers as general anxiety, which is better conceptualized as occurring along a continuum than as reflecting generic "overwhelming anxiety" in stutterers.


The use of artificial neural networks to estimate speech intelligibility from acoustic variables: a preliminary analysis. Previous research has used regression analysis to attempt to predict the intelligibility of hearing-impaired speakers from acoustic speech parameters. Improvement of prediction may be achieved by the use of computerized artificial neural networks to process mathematically the acoustic input variables as part of the intelligibility process. A preliminary scheme for estimating speech intelligibility from acoustic parameters using a neural network is outlined and preliminary data illustrate its use.


The effect of gender upon nasalance scores among normal adult speakers. Nasometry, pressure-flow, and fundamental frequency data were obtained from 15 normal female speakers and 15 normal male speakers all of whom were over the age of 18 and had Mid-Atlantic dialects. The nasalance scores and nasal cross-sectional areas of these two groups did not differ. The nasalance scores based on three standardized reading passages were not highly correlated with nasal cross-sectional area or voice fundamental frequency. The clinical significance of these findings is discussed.


Esophageal speaker articulation of /s,z/: a dynamic palatometric assessment. Esophageal talker linguapalatal contact patterns and durations during /s/ and /z/ productions were examined using dynamic palatometry instrumentation. It was found that sibilant groove narrowing is a physiologic compensation for a reduced air supply in esophageal speech. The place of esophageal /s, z/ articulation was on the anterior portion of the alveolar ridge as seen in normal speakers. Average medial groove width for esophageal /s/ was narrower than the 5-7-mm groove characteristic of normal speakers. Groove widths averaged 3 mm for /s/ and 4 mm for /z/. Systematic changes in groove widths across speech sounds, syllable position, and vowel context were also observed. Use of a narrower lingual groove was interpreted as a significant articulatory maneuver to meter out a limited intraoral air supply and effect more normal fricative durations.


Structuring HIV prevention service delivery systems on the basis of social science theory. In order to identify the optimal configuration of HIV prevention programs, it is necessary to examine different theoretical models of behavior change. Cognitive/decision-making theories of human behavior change are compared to social learning theories vis-a-vis their influence on the structure of service delivery systems. Cognitive/decision-making theories ascribe behavior change to the provision of new information and favor the development of homogeneous interventions providing clients with information about risk behaviors. These interventions are easily standardized across delivery sites and various target populations. Social learning theories view behavior change as a series of stages and recognize the influence of sociocultural variables. They favor multiple heterogeneous interventions in a variety of settings, with the provision of skills training as well as information. Ongoing HIV prevention research indicates that social learning theories provide a more accurate paradigm of human behavior change for the complex behaviors related to HIV risk. Public health agencies must therefore continue to strengthen organizational and referral relationships with community-based organizations that can provide the specialized prevention interventions called for by social learning theory. This will require ongoing collaboration and technical assistance.


Utilization of pediatric health services in Jerusalem. The high rate of utilization of health services and rising health care costs in Israel, have prompted the need for reform of the health care system. Preventive and curative aspects of mother and child health care in Israel have traditionally been addressed by independent but parallel health systems. Prior to the pilot integration of these services, current patterns of utilization of health services by children during their first year of life, and determinants of use, were analyzed. Mothers of 651 children from five neighborhoods, representing the middle-low, middle and upper social class Jewish population were interviewed. Overall, a high degree of compliance with recommended visits to the preventive family health centers was found, with an average of eleven visits to the public health physician or nurse. The children also made an average of 12 visits to curative practitioners. Combined with all other health care consultations, these children averaged 26 health care visits in the first year of life. This pattern of frequent visitations, and its determinants, is discussed in context of the current framework of parallel health care systems. Multivariate analysis revealed that the birth order of the child was the key factor in determining the number of preventive visits, while the mother's perception of her child's health status held the major influence on the number of curative visits. No association between utilization of services and social class was discovered. Comparison of utilization patterns arising from this study with subsequent investigation of the planned integrated services allows for the assessment of the effects of a major change in the structure and delivery of pediatric services.


Predictors of participation in a school-based anti-tobacco activism program. This study investigated the predictors of participation in a school-based, anti-tobacco activism program. Subjects in this study consisted of 7th grade students participating in the intervention component of Project S.H.O.U.T., a tobacco use prevention program in San Diego County, California. In the activism component, a newsletter containing an activism contest was distributed to each student. Small prizes were awarded to contest winners at each school. "Activism" included letter and petition writing, anti-tobacco poster contests, merchant education, peer surveys and magazine subscription cards. A total of 170 students participated in the activities, with 81.1 percent participating two or more times. Of those who participated, 59 percent were female and 60 percent were White, non-Hispanic. Two sets of logistic analyses were conducted. Variables such as SES, gender, ethnicity, friends' tobacco use and parental tobacco use were used to predict participation in activism activities. The choice of variables was intended to provide information regarding activism participation in reference to known tobacco risk factors. Results of the first analysis indicated that students with a higher SES, and in an urban vs. rural location were more likely to participate in the activism activities. The second analysis used the same set of characteristics to predict "ever-use" of tobacco. Results of this analysis indicated that male gender, low grades, White, non-Hispanic ethnicity, friends' and parents' tobacco use were positively associated with tobacco experimentation.


Health risks associated with residential exposure to extremely low frequency electromagnetic radiation. Extremely low frequency electromagnetic radiation has received considerable attention recently as a possible threat to the health of persons living near high tension electric power lines, distribution substations, and even in close proximity to common household electric appliances. Results of epidemiological and laboratory research are examined to assess risks associated with magnetic fields generated by extremely low frequency electromagnetic sources. Health risks associated with such fields include a wide variety of ills ranging from disruption of normal circadian rhythms to childhood cancers. Risk assessment has been particularly difficult to determine in light of an ostensible lack of a dose-response relationship. Current media sensation fueled in part by an equivocal position adopted by the United States Environmental Protection Agency has contributed to the controversy. Recommendations for prudent avoidance of possible dangers are presented along with policy implications concerning health risks associated with magnetic fields.


The why, when and whether of condom use among female and male drug users. Eight focus groups consisting of all male, all female and mixed male and female drug users were conducted to gain an in-depth understanding of beliefs and behavior regarding the use of family planning services and contraceptives, particularly condom use in an effort to reduce the perinatal transmission of HIV. While participants often supported the use of condoms because of STDs and AIDS, their unplanned pregnancies and STD histories indicated in-consistent use, depending on the partner and the circumstances. The vast majority of both men and women did not like to use condoms because it interfered with the spontaneity and pleasure of sexual relations, though women seemed more willing to use condoms than their partners. Participants varied in their knowledge about the benefits of using a condom, in how and when to put it on, in the associations they made between condom use and trust and commitment, in the type of partner and conditions under which they would use condoms and in their willingness to consider condom use as an integral part of their lives. Issues of trust, commitment and condom use did not seem to have been resolved in the drug using community, particularly among younger people who appeared to have more difficulty in negotiating condom use. Promoting the use of condoms needs to be considered as part of a larger, multifaceted behavior change effort.


Development of astroglial cells in the proliferative matrices, the granule cell layer, and the hippocampal fissure of the hamster dentate gyrus. The histogenesis of the hamster dentate gyrus was studied with light and electron microscopy and antisera against the astrocyte-associated antigens vimentin and GFAP, in order to follow the differentiation of radial glial cells and astrocytes. The formation of the stratum granulosum is preceded by the establishment of successive dentate matrices, which are formed by cells that leave the ventricular neuroepithelium and occupy positions above the fimbria (suprafimbrial), below the pial surface (subpial), and within the dentate hilus (hilar dentate matrix). The subpial dentate matrix invades the marginal zone of that region of the cerebral wall, where the stratum granulosum will later develop. From the beginning of its existence on embryonal day 13 (E13) up to its disappearance about postnatal day 7 (P7), it is characterized by a high content of GFAP-positive cells and mitoses. This indicates early gliogenesis in the dentate anlage, long before the appearance of the stratum granulosum. Many of the bipolar GFAP-positive cells are oriented parallel to the pial surface and have focal contacts to the pial basement membrane. The establishment of the subpial dentate matrix splits the primordial radial glial scaffold of the hippocampal/dentate anlage into two bundles: 1) the suprafimbrial bundle that retains its original radial position between ventricle and pial surface; and 2) the dorsal glial bundle that traverses the ventral tip of the pyramidal cell layer of future CA3. The latter is pushed dorsolaterally, away from the pial surface, by the enlargement of the subpial dentate matrix and, later, by the suprapyramidal blade. The latter emerges around birth as small radial columns of granule cells located between the bent basal parts of the ventralmost fibers of the dorsal glial bundle and the subpial dentate matrix. From the beginning of its existence it is traversed by unipolar "secondary" radial glial fibers that appear to originate from the subpial dentate matrix. Both the supra- and the infrapyramidal blades seem to elongate by the addition of postmitotic granule cells and "secondary" radial glial cells from the subpial dentate matrix to the growing end of the primordial stratum granulosum. The hilar dentate matrix that is localized in the prospective hilar region, inside the growing stratum granulosum, also contains glial cells that seem to be incorporated into the stratum granulosum. The dentate gyrus is demarcated from the CA1 region of the hippocampus proper by GFAP-positive cells that populate the hippocampal fissure, and that also originate from the subpial dentate matrix.(ABSTRACT TRUNCATED AT 400 WORDS)


A crustacean neuronal cytoskeletal protein with characteristics of neurofilaments and microtubule-associated proteins. The purpose of this study was to characterize further a unique protein that is a component of the cytoskeleton of crayfish neurons. This protein, referred to as P600, is unique because it is unusually large (Mr greater than 600 kD), and because it has characteristics in common with both mammalian microtubule-associated proteins and neurofilaments. Immunohistochemical techniques have shown that P600 colocalizes with microtubules and is a component of the fibrous side-arms that extend from microtubules (Weaver and Viancour, Brain Res. 544:49, 1991). We have developed a method for obtaining purified P600 by using gel filtration techniques. When viewed by negative staining electron microscopy, P600 obtained by that method produced 11 nm-wide beaded filaments. The number of filaments was strictly related to the P600 concentration in a column fraction. A small amount of P600 consistently copurified with taxol-stabilized microtubules. The proportion copurifying with microtubules was increased by using apyrase to deplete ATP, or by using a nonhydrolyzable ATP analogue to compete with ATP. Immunogold labeling localized P600 near the ends of a subset of the fibrous side-arms extending from endogenous axonal microtubules. Several polyclonal antibodies against mammalian microtubule-associated proteins were tested for P600 labeling on immunoblots, and positive labeling was obtained with an antiserum directed against a region of microtubule-associated protein 1B that has microtubule binding activity. Epitope homology between P600, mammalian microtubule-associated protein 1B, and the mammalian mid-molecular weight neurofilament subunit is discussed in the context of possible evolutionary relationships among these cytoskeletal proteins.


Effects of ethanol on development of dorsal raphe transplants in oculo: a morphological and electrophysiological study. The purpose of this project was to investigate ethanol influence on the development of serotonin-containing (5-HT) neurons of the dorsal raphe nucleus in rat. Fetal tissue of embryonic day 17 from the dorsal brainstem was grafted to the anterior chamber of the eye of adult albino rats. The experimental group was exposed to 16% ethanol in the drinking water, and the control group received water ad libitum. After 4 weeks, morphological and electrophysiological evaluations were performed. Immunohistochemical analysis showed that 5-HT-immunoreactive fibers from ethanol-treated transplants had a disturbed outgrowth pattern into the host iris as compared to the control group. Furthermore, the outgrowth area and axon bundle formation was significantly greater in the control group than in the ethanol group. Electrophysiological recordings revealed a dose-dependent biphasic effect of locally applied ethanol on transplanted monoaminergic neurons. Low doses of ethanol (0.5-3 mM) induced an increase in basal firing rate of control neurons, while higher doses (10-100 mM) caused inhibition. However, monoaminergic neurons in the ethanol group showed a decreased neuronal sensitivity to locally applied ethanol. The same dose of locally applied ethanol which produced an excitation of neuronal activity in the ethanol transplants produced an inhibition in the control grafts. The dose-response curve was shifted to the right. The present results suggest that chronic ethanol exposure during early development leads to altered axonal outgrowth from brainstem 5-HT neurons, as well as decreased sensitivity of these neurons to locally applied ethanol.


Destruction of meningeal cells over the medial cerebral hemisphere of newborn hamsters prevents the formation of the infrapyramidal blade of the dentate gyrus. Meningeal cells participate in the development of the cerebellum both by stabilizing the extracellular matrix of the pial surface and by organizing the radial glial scaffold and the lamination of the cerebellar cortex. In the present study we investigated possible influences of meningeal cells on the development of the dentate gyrus, whose ontogenesis has many similarities to that of the cerebellum. Meningeal cells were selectively destroyed by injecting newborn hamsters with 25 micrograms 6-hydroxydopamine (6-OHDA) into the interhemispheric fissure. Twenty-four hours postinjection (p.i.) the meningeal cells over the medial cerebral hemispheres were completely destroyed. Thirty days p.i. the infrapyramidal blade of the dentate gyrus was almost completely missing, while the suprapyramidal blade was hypertrophied, extending with its medial tip almost up to the medial surface of the cortex. In order to ascertain that this maldevelopment was caused by the destruction of meningeal cells, another group of hamsters was pretreated with normetanephrine (NMN) which inhibits the extraneuronal uptake of 6-OHDA into meningeal cells. In this group the meningeal cells were unaffected by the treatment, and the morphology of the dentate gyrus was normal 30 days p.i. of 6-OHDA plus NMN. When the meningeal cells were destroyed in later stages of development (postnatal days 1-5), alterations of the dentate gyrus could be induced only up to the fourth postnatal day; thereafter, 6-OHDA treatment left it unchanged. This indicates a critical period of meningeal cell influence that coincides with the period of existence of the subpial dentate matrix. Analysis of the time course of the defective development revealed that in the first 5 days p.i. 1) meningeal cells over the medial cerebral hemisphere were destroyed and removed, 2) the pial basement membrane over both the dentate anlage and the diencephalon thinned and ruptured, and the adjacent brain parts fused focally, 3) many cells of the subpial dentate matrix disappeared from their subsurface position, 4) the number of "immature" cells increased in the hilus and the subgranular zone of the suprapyramidal blade, 5) the suprapyramidal blade elongated and thickened considerably, while the infrapyramidal blade did not form. Beyond 5 days p.i. those parts of the pial surface of the dentate anlage that had not fused with the diencephalon were repopulated with meningeal cells. This reappearance of meningeal cells was accompanied by 1) the restitution of the normal morphology of the basement membrane, 2) the reappearance of neuronal and glial cells below the pial surface, and 3) the formation of fragments of the infrapyramidal blade which later developed a normal appearing lamination.(ABSTRACT TRUNCATED AT 400 WORDS)


Pyramidal neurons of the rat cerebral cortex, immunoreactive to nicotinic acetylcholine receptors, project mainly to subcortical targets. Cortical neurons immunoreactive to nicotinic acetylcholine receptors (nAChR) of the rat brain were characterized with monoclonal antibodies directed to ACh-binding subunits (alpha 4) or to ACh-structural subunits (beta 2). A heterogeneous population of nAChR-LI neurons was found in all cortical regions. The most prominent immunoreactive neurons were pyramids of layers V and II-III. The nonpyramidal positive neurons were fusiform horizontally oriented neurons of layer VIb, small cells of layer I and round or ovoid neurons of layers II-V. Double labeled experiments (immunohistochemistry and fluorescent retrograde tracers) showed that cholinoceptive pyramidal neurons of layer V project mainly to subcortical targets such as caudate-putamen, superior colliculus, and pontine nuclei, while very few nAChR positive neurons connect to other cortical areas. These findings suggest that the mainly excitatory effect that has been attributed to the cholinergic innervation upon the cortical neurons may have a greater influence upon the cortico-subcortical output than the corticortical one.


A unique morphological subtype of horizontal cell in the rabbit retina with orientation-sensitive response properties. Intracellular recordings were obtained from horizontal cells in the rabbit retina to assess the orientation sensitivity of their visual responses to moving and stationary rectangular slits of light. Cells were subsequently labeled with horseradish peroxidase (HRP) for morphological identification. The responses of A-type horizontal cells and those of the somatic and axon terminal endings of B-type horizontal cells (with the exception of one cell) were found to be insensitive to the orientation of light stimuli. However, 20 horizontal cells encountered within or just superior to the visual streak displayed clear orientation-sensitive response properties. These cells were divided into two groups: the majority (70%) showed preference for light stimuli oriented parallel to the visual streak, whereas the remainder preferred stimuli oriented orthogonal to the visual streak. Analysis of the shape of the receptive fields of these cells by means of a narrow, displaced slit of light revealed an anisotropy with the major or elongated axis of the receptive field of each cell aligned along the same angle as its physiological preferred orientation. Morphologically, the orientation-sensitive horizontal cells formed a homogeneous group with an architecture corresponding to that of elongated A-type or Ae-type horizontal cells reported previously in the rabbit retina. These cells showed a marked elongation of their dendritic arbors with the major axes oriented either parallel or orthogonal to the visual streak. Furthermore, the orientation of the dendritic arbor of each cell matched that of its physiological preferred orientation. The present results, then, suggest strongly that the orientation sensitivity of Ae-type horizontal cells results directly from the asymmetry in their dendritic arbors. The spatial location and specialized physiology of Ae-type horizontal cells suggest that they play a role in the formation of orientation-sensitive properties exhibited by more proximal neurons in the rabbit retina.


Morphological variations among output neurons of the olfactory bulb in the frog (Rana ridibunda). Morphological properties of putative output cells have been studied in detail in the olfactory bulb of frogs (Rana ridibunda). Intracellular injection of Lucifer Yellow was used to reconstruct individual neurons. Ten different anatomical features related to cell shape and position were studied quantitatively. The results show that output cells, generally considered to be a homogeneous group in the olfactory bulb of amphibians, are, in fact, quite different in their morphology. Using multidimensional analysis to examine differences among the output neurons, we found that they might be divided into at least two groups. In one group, the cell somata were located near the glomerular layer and the dendrites lay at large angles with respect to each other. In the other group, the cell somata were farther from the glomerular layer and their dendrites lay at smaller angles. From their morphology, these two cell groups appear to be homologous, respectively, to the superficial/middle tufted cells and deep tufted/mitral cells of mammals.


Isthmotectal axons make ectopic synapses in monocular regions of the tectum in developing Xenopus laevis frogs. During the development of binocular maps in the tectum of Xenopus laevis, axons that relay input from the ipsilateral eye via the nucleus isthmi undergo a prolonged period of shifting connections. This shifting accompanies the dramatic change in eye position that takes place as the laterally placed eyes of the tadpole move dorsofrontally. There is a concomitant expansion of the proportion of tectum that receives contralateral retinotectal input corresponding to the binocular portion of the visual field. Electrophysiological recording demonstrates that ipsilateral units are present in those rostral tectal zones, and anatomical methods show that the isthmotectal axons arborize densely in the rostral region but also extend sparser branches into the caudal zone, which is occupied by contralateral inputs with receptive fields in the monocular zone of the visual field. A mechanism that aligns the ipsilateral and contralateral maps is activity-dependent stabilization of isthmotectal axons that exhibit firing patterns correlated with those of nearby retinotectal axons. In order for activity patterns to function in stabilizing correct connections and promoting the withdrawal of incorrect connections, synaptic communication of some sort is hypothesized to be essential. We have investigated whether isthmotectal axons make morphologically identifiable synapses during development and where such synapses are located. We find evidence for morphologically identifiable synapses in all regions of the tectum, along with many growth cones and structures that are probably immature synapses. As in the adult, the synapses contain round, clear vesicles, have asymmetric specializations, and terminate on structures that appear to be dendrites. In both adult and tadpole, the rarity of serial synapses involving isthmotectal terminals suggests that the interactions between retinotectal and isthmotectal inputs are mediated by postsynaptic dendrites.


Selective vulnerability of the hippocampal pyramidal neurons to hypothyroidism in male and female rats. Thyroid hormone deficiency has long been considered to affect profoundly such cognitive functions as learning and memory, which are known to depend on the structural integrity of the hippocampal formation. Since we previously found that the number of granule cells of the dentate gyrus is reduced in hypothyroid animals, we decided to extend our observations to the pyramidal cells of the hippocampus in order to gain further insight into the effects of hypothyroidism upon the other neuronal links of the hippocampal trisynaptic circuitry, inasmuch as CA1 neurons are known to be particularly vulnerable to aggressive agents. Groups of 6 male and 6 female rats aged 30 and 180 days were analysed separately after being treated as follows: (1) hypothyroid from day 0 until day 30 (30-day-old hypothyroid group); (2) respective 30-day-old control; (3) hypothyroid from day 0 until day 180 (180-day-old hypothyroid group); (4) hypothyroid until day 30 and thenceforth maintained euthyroid (recovery group); (5) hypothyroid since day 30 (adult hypothyroid group); and (6) respective 180-day-old control. The volume of the pyramidal cell layer of the CA1 and CA3 regions and the numerical density of the respective neurons were evaluated, thereby allowing us to estimate the total number of pyramidal cells in each hippocampal region. The areal density and the mean nuclear volume of CA1 and CA3 pyramidal cells were also estimated. In the CA3 region, we found that hypothyroidism, whatever its duration and time of onset, induces a reduction in the volume of the pyramidal cell layer and a parallel increase in the numerical density of its neurons, without interfering with the total number of pyramidal cells. Conversely, in the CA1 region, thyroid hormone deficiency started either neonatally or during maturity was found to lead to a decrease in the total number of pyramidal cells. Reductions ranging between 14.2 and 22.5% were found in 30 and 180-day-old hypothyroid groups. The reestablishment of a euthyroid state did not ameliorate the referred neuronal loss. The present results support the view that hypothyroidism induces small alterations in the structural organization of the hippocampal CA3 region, contrary to what happens in CA1 in which neuronal death occurs. Furthermore, the data presented herein demonstrate that the total number of CA1 pyramidal cells displays sexual dimorphism that is not affected by thyroid hormone manipulations.(ABSTRACT TRUNCATED AT 400 WORDS)


GABA-immunoreactive terminals synapse on primate spinothalamic tract cells. Gamma-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the vertebrate nervous system. Several lines of evidence suggest that GABA plays an important role in the processing and modulation of sensory input in the spinal cord dorsal horn. In the present study, the relationship between GABA-immunoreactive (GABA-IR) terminals and spinothalamic tract (STT) cells in the monkey lumbar cord was investigated. Physiologically characterized STT cells, one located in lamina V and two located in lateral lamina IV, were intracellularly injected with horseradish peroxidase (HRP). A fourth STT cell, located in lamina I, was retrogradely labeled following injection of HRP into the contralateral thalamus. Immunogold labeling of ultrathin sections through the cell bodies and proximal dendrites of the STT neurons demonstrated that the percentage of the GABA-IR terminals in contact with these profiles was 24.7% and 36%, respectively. The average STT surface length contacted by GABA-IR terminals for cell bodies and proximal dendrites was 18.2% and 26.7%, respectively. For the lamina I cell, 7 out of 35 (20%) of the terminals were GABA-IR and they covered 9.6% of the surface analyzed. These data demonstrate that GABA-IR terminals synapse directly on STT cells, constituting a substantial proportion of the terminal population on these cells. Furthermore, compared to the cell bodies, a greater percentage of the input on the proximal dendrites is GABAergic. These anatomical data are consistent with the findings of a previously published iontophoretic study that demonstrated that GABA can exert a strong inhibitory influence on STT cells. These findings are discussed in relation to GABAergic involvement in tonic and phasic inhibition of STT neurons.


Nuclear clefting in dorsal root ganglion neurons: a response to whole body vibration. Normal adult rabbits were studied in a whole body vibration model which simulates the type of environmental exposure associated with vibration-induced low back pain. This model has previously been shown to induce changes in pain-related neuropeptides in the dorsal root ganglion. Following two weeks of daily exposure to whole body vibration, dorsal root ganglia were excised from control and vibrated rabbits and prepared for ultrastructural evaluation. Of over 1,200 cells sampled, 190 appropriately sectioned cells were analyzed: 32 from immobilized controls, 44 from normal controls, and 114 from vibrated animals. Analysis of nuclear contours revealed more prevalent and more extensive clefting of the nuclear membrane in vibrated cells. The membrane lining these clefts was traversed by numerous pores; density of these pores was 46% greater than in adjacent nonclefted segments (p less than .001). Number of clefts per nucleus was increased by 39% in vibrated animals. Cleft area represented 1.19% of nuclear area in vibrated cells compared to 0.74% in controls (p less than .001). Numerous mitochondria and free ribosomes and abundant rough endoplasmic reticulum were located within the cleft spaces of vibrated cells. Pores in the cleft membrane appeared normal, supporting the conclusion that the clefts are structural alterations rather than fixation or sectioning artifacts. Changes in dorsal root ganglion neuropeptides seen in previous studies of vibrated animals may result from increased or redirected cellular synthesis. Ultrastructural changes seen in these vibrated dorsal root ganglion neurons are consistent with such an alteration in metabolism and could reflect increased synthesis of pain-related neuropeptides.


Spatial representation of frequency-modulated signals in the tonotopically organized auditory cortex analogue of the chick. For auditory communication, many birds, including domestic chicks, use a variety of frequency-modulated (FM) sounds. As a first approach to the spatial representation of such sounds in the central auditory system, we have analyzed 2-deoxyglucose (2DG) patterns that were produced by FM stimuli in the tonotopic map of the auditory forebrain area (field L/hyperstriatum ventrale complex) of domestic chicks. Linear FM signals, varying in the depth and range of modulation, and in the direction and rate of the frequency change, were tested. Also included were signals designed to mimic species-specific FM calls. All FM stimuli activated those regions of the map in which frequencies contained in the stimulus spectra were tonotopically represented. However, frequency and amplitude of the FM spectra were not faithfully reproduced by activation of the complete corresponding tonotopic space. FM signals that differed only in the direction of modulation, and therefore had identical long-term spectra, induced maximum 2DG activation at different locations of the tonotopic gradient. FM signals that differed in the rate of change of frequency produced maxima of 2DG uptake at different positions along an isofrequency dimension of the map. These results suggest that the direction of modulation may be represented in a complex fashion along the tonotopic axis of the structure, whereas the rate of change of frequency may be represented along an isofrequency dimension. None of the experiments provided evidence of FM-selective regions within the auditory forebrain complex. However, numerous telencephalic areas, in addition to the primary auditory area, were strongly activated in chicks stimulated with artificial "species-specific" FM signals. These areas could be involved in the processing of biologically relevant stimuli, requiring attention, recognition, and interpretation of the signals.


5'-nucleotidase: a new marker for striosomal organization in the rat caudoputamen. The distribution of the adenosine-producing ectoenzyme 5'-nucleotidase was studied by means of a histochemical lead technique in the caudoputamen of normal adult rats and of rats in which injections either of 6-hydroxydopamine in the medial forebrain bundle or of ibotenic acid in the caudoputamen had been made 1-3 weeks previously. The patterns of striatal 5'-nucleotidase activity in these animals were compared in serial sections to the patterns of calbindin-D28k immunoreactivity and of 3H-naloxone ligand binding, which respectively mark the known matrix and striosome (patch) compartments of the caudoputamen. In the normal rats, 5'-nucleotidase activity was differentially concentrated in striosomes, where it produced a dense staining of the neuropil. The enzymatic staining followed a striosomal distribution in all but the caudal caudoputamen. Within the striatal matrix, 5'-nucleotidase staining also observed a lateromedial density gradient. Depletion of the dopamine-containing nigrostriatal innervation of the caudoputamen with 6-hydroxydopamine did not alter the striosomal selectivity of 5'-nucleotidase activity. Destruction of intrastriatal neurons by ibotenic acid led to a strongly 5'-nucleotidase-positive gliosis within the resulting necrotic region. Elsewhere in the caudoputamen, the enzyme's striosomal distribution was not detectably altered. We conclude that 5'-nucleotidase histochemistry provides an advantageous tool for detecting the striosomal architecture of the rat's caudoputamen. Moreover, 5'-nucleotidase is prominently associated with glial membranes in the central nervous system, so that the concentration of this enzyme in striosomes could mark these as sites of selective glial populations within striatum. These properties and actions of 5'-nucleotidase in purinergic neurotransmission and in neuroadhesion may contribute to the specialized functions of striosomes and matrix.


Genesis of neurons in the retinal ganglion cell layer of the monkey. We have analyzed the genesis of various neuronal classes and subclasses in the ganglion cell layer of the primate retina. Neurons were classified according to their size and the time of their origin was determined by pulse labeling with 3H-thymidine administered to female monkeys 38 to 70 days pregnant. All offspring were sacrificed postnatally, and their retinas processed for autoradiography. The somata of cells in the retinal ganglion cell layer generated on embryonic day (E) 38 ranged from 9 to 14 microns in diameter. Between E40 and E56, the minimum soma diameter remained around 8-9 microns, while the maximum gradually increased to 22 microns. As a consequence, the means of the distributions of labeled cells also increased with age, from 11.8 microns diameter for cells generated on E38 to 14.6 microns diameter at E56. Over this period the percentage of labeled cells in the 10.5-16.5 microns and greater than 16.5 microns diameter range gradually increased. The proportion of the labeled cells in the less than 10.5 microns diameter range decreased from E38 to E45, but subsequently increased rapidly. At the end of neurogenesis in the retinal ganglion cell layer, around E70, most labeled cells were considerably smaller (7-9 microns) than those generated earlier. Our results indicate that within the ganglion cell layer of the macaque, neurons of small caliber are generated first, followed successively by medium sized cells. Large, putative P alpha cells are generated late. The production between E56 and E70 of cells with the smallest somata suggests that the last-generated neurons in the ganglion cell layer are predominantly displaced amacrine cells. Within the same sector of retina, different classes of neurons in the ganglion cell layer of the rhesus monkey appear to have a sequential schedule of production.


Vasopressin innervation of sexually dimorphic structures of the gerbil forebrain under various hormonal conditions. The distribution of vasopressin-immunoreactive fibers in the forebrain of male and female gerbils was studied, focusing on the lateral septum and the sexually dimorphic area (SDA) found at the border between the medial preoptic area and the anterior hypothalamus. To study hormonal influences on the densities of these fibers, some animals of each sex were gonadectomized or gonadectomized and given testosterone. Others were given sham operations. High densities of vasopressin-immunoreactive fibers were found in the lateral septum. In the SDA, the densities of these fibers varied considerably. Many were found in the medial half of the medial SDA, but few in the lateral SDA. Vasopressin-immunoreactive fibers were also sparse in the lateral half of the medial SDA, except for a dense cluster in the SDA pars compacta of males. Similar but smaller clusters were seen in the same location in females although the SDA pars compacta could not be detected in Nissl-stained sections from the female brains. Fiber densities in two areas, the lateral septum and the lateral SDA, were sensitive to gonadal steroids. In both cases, castration reduced fiber density and testosterone enhanced it. In addition, fiber densities in two areas, the lateral septum and the medial SDA, were sexually dimorphic. In each case, fiber density was greater in males. There was no hormonal effect, however, on the fiber densities in the medial SDA. The fact that the fiber plexuses in the lateral septum and the medial SDA respond differently to gonadal steroids suggests that they arise from different cells and possibly from different areas of the brain. The vasopressin-immunoreactive fibers in the lateral septum probably come from steroid-sensitive vasopressin neurons in the bed nucleus of the stria terminalis. Those in the medial SDA may originate in the dorsal aspect of the suprachiasmatic nucleus where vasopressin-immunoreactive cell bodies were seen.


Dendritic morphology of pyramidal neurones of the visual cortex of the rat. IV: Electrical geometry. Features of the dendritic morphology of pyramidal neurones of the visual cortex of the rat that are relevant to the development of models of their passive electrical geometry were investigated. The sample of 39 neurones that was used came from layers 2/3 and 5. They had been recorded from and injected intracellularly with horseradish peroxidase (HRP) in vitro as part of a previous study (Larkman and Mason, J. Neurosci 10:1407, 1990). These cells had been reconstructed and measured previously by light microscopy. The relationship between the diameters of parent and daughter dendrites during branching was examined. It was found that most dendrites did not closely obey the "3/2 branch power relationship" required for representation of the dendrites as single equivalent cylinders. Estimates of total neuronal membrane area ranged from 27,100 +/- 7,900 microns2 for layer 2/3 cells to 52,200 +/- 11,800 microns2 for thick layer 5 cells. Dendritic spines contributed approximately half the total membrane area. Both neuronal input resistance and the ratio of membrane time constant to input resistance were correlated with neuronal membrane area as measured anatomically. The relative electrical lengths of the different dendrites of individual neurones were investigated, by using simple transformations to take account of the differences in diameter and spine density between dendritic segments. A novel "morphotonic" transformation is described that represents the purely morphological component of electrotonic length. Morphotonic lengths can be converted into electrotonic lengths by division by a "morphoelectric factor" ([Rm/Ri]1/2). This procedure has the advantage of separating the steps involving anatomical and electrical parameters. These transformations indicated that the dendrites of the apical terminal arbor were much longer electrically than the basal or apical oblique dendrites. In relative electrical terms, most apical oblique trees arose extremely close to the soma, and terminated at similar distances to the basals. These results indicate that the dendrites of these pyramidal cells cannot be represented as single equivalent cylinders. The electrotonic lengths of the dendrites were calculated by using the electrical parameters specific membrane capacitance (Cm), intracellular resistivity (Ri), and specific membrane resistivity (Rm). Conventional values were assumed for Cm (1.0 muFcm-2) and Ri (100 omega cm), but three different Rm values were used for each cell. Two of these were within the conventionally accepted range (10,000-20,000 omega cm2), while the third value was an order of magnitude higher, in line with some recent evidence from modeling and whole-cell recording studies.(ABSTRACT TRUNCATED AT 400 WORDS)


Position of growth cones within the retinal nerve fibre layer of fetal ferrets. Optic axons are added to the retinal nerve fibre layer of fish along its vitreal border in a chronotopic manner. Likewise, the optic tract of all vertebrate species acquires axons preferentially along the superficial surface of the pathway. We have examined the developing retina of fetal ferrets (Mustela putorius furo) aged between embryonic day 27 (E27) and E34 to see whether a similar segregation of growth cones is apparent within the mammalian retinal nerve fibre layer. The distributions of growth cone, "wrist" (thick trailing portion of the growth cone), axonal, and glial profiles were determined from electron micrographs, and expressed as a percentage of neural profiles for several retinal locations. The retinal nerve fibre layer of fetal ferrets contains radially elongated bundles of fibres composed of axonal, wrist, and growth cone profiles. Glial processes of varying density divide the adjacent bundles, occasionally subdividing them in the plane of the retina, and give rise to endfeet lining the basal lamina and separating the optic axons from the latter. Growth cones within the developing fibre layer represented about 2.4% of profiles at E28, while at later developmental stages (E34), this value fell to about 0.6%. During this period of axonal outgrowth, growth cones were not preferentially segregated toward the vitreal basal lamina or the glial endfeet within the nerve fibre layer. Rather, they were found scattered throughout the axon bundles of the fibre layer. While there were differences in the proportion of immature profiles found within the vitreal half compared to the scleral half of the fibre layer, such that more growth cones and wrists were found vitreally, there was no clear accumulation of them in association with features of the vitreal margin. The present results show that young and old optic axons course together throughout the depth of the nerve fibre layer. A chronotopic mode of pathway genesis such as seen in the optic fibre layer of fish or in the optic tract of mammals is not present in the nerve fibre layer of ferrets. Differences in growth cone behaviour in the optic fibre layer and tract indicate that the mechanisms governing pathway formation differ along its course.


The organization of the thalamocortical connections of the mediodorsal thalamic nucleus in the rat, related to the ventral forebrain-prefrontal cortex topography. The medial and central segments of the mediodorsal nucleus of the thalamus (MD) receive afferents from the ventral forebrain, including the piriform cortex, the ventral pallidum, and the amygdaloid complex. Because MD is reciprocally interconnected with prefrontal and agranular insular cortical areas, it provides a relay of ventral forebrain activity to these cortical areas. However, there are also direct projections from the piriform cortex and the amygdala to the prefrontal and agranular insular cortices. This study addresses whether this system has a "triangular" organization, such that structures in the ventral forebrain project to interconnected areas in MD and the prefrontal/insular cortex. The thalamocortical projections of MD have been studied in experiments with injections of retrograde tracers into prefrontal or agranular insular cortical areas. In many of the same experiments, projections from the ventral forebrain to MD and to the prefrontal/insular cortex have been demonstrated with anterograde axonal tracers. The connections of the piriform cortex (PC) with MD and the prefrontal/insular cortex form an organized triangular system. The PC projections to the central and medial segments of MD and to the lateral orbital cortex (LO) and the ventral and posterior agranular insular cortices (AIv and AIp) are topographically organized, such that more caudal parts of PC tend to project more medially in MD and more caudally within the orbital/insular cortex. The central and medial portions of MD also send matching, topographically organized projections to LO, AIv and AIp, with more medial parts of MD projecting further caudally. The anterior cortical nucleus of the amygdala (COa) also projects to the dorsal part of the medial segment of MD and to its cortical targets, the medial orbital area (MO) and AIp. The projections of the basal/accessory basal amygdaloid nuclei to MD and to prefrontal cortex, and from MD to amygdaloceptive parts of prefrontal cortex, are not as tightly organized. Amygdalothalamic afferents in MD are concentrated in the dorsal half of the medial segment. Cells in this part of the nucleus project to the amygdaloceptive prelimbic area (PL) and AIp. However, other amygdaloceptive prefrontal areas are connected to parts of MD that do not receive fibers from the amygdala. Ventral pallidal afferents are distributed to all parts of the central and medial segments of MD, overlapping with the fibers from the amygdala and piriform cortex. Fibers from other parts of the pallidum, or related areas such as the substantia nigra, pars reticulata, terminate in the lateral and ventral parts of MD, where they overlap with inputs from the superior colliculus and other brainstem structures.(ABSTRACT TRUNCATED AT 400 WORDS)


Time course of dorsal root axon regeneration into transplants of fetal spinal cord: I. A light microscopic study. Cut dorsal root axons regenerate into intraspinal transplants of fetal spinal cord and establish synaptic connections there. The aims of the present study were to describe the progression of dorsal root growth within the transplants and the maturation of transplant morphology and to determine whether the regenerated dorsal root axons persist within the transplants or eventually withdraw. Embryonic (E) day 14 spinal cord was grafted into the lumbar enlargement of adult Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and juxtaposed to the transplants. The morphology of the transplants was examined from 1 day to over 1 year after surgery, and the regenerated dorsal roots were labeled with immunohistochemical methods to study the subset that contains calcitonin gene-related peptide (CGRP). Embryonic spinal cord transplants survived and grew within the host spinal cord in over 90% of the animals. Transplant volume increased and the morphology of the transplants matured over the first 12 weeks and then did not change for 48-60 weeks. During the first week the transplants were composed of dissociated neurons, glia, and hematogenous cells with considerable extracellular space between them. Subsequently, the grafted neurons became densely aggregated, and non-neuronal elements such as inflammatory cells and myelin debris disappeared. CGRP-immunoreactive dorsal roots began to regenerate into the transplants within 24 hours, formed dense bundles by 4 days, and were still present at 60 weeks, the longest survival period examined. Myelination of axons within transplants began at 2 weeks. Quantitative analysis showed that the area of the transplants occupied by CGRP-labeled axons and the distribution area of the labeled axons within the transplants increased until 12 weeks and persisted unchanged for over 48 weeks. These results indicate that regenerated dorsal root axons are permanently maintained within transplants of embryonic spinal cord and suggest that the transplants can contribute to the permanent restoration of damaged intraspinal neural circuits.


Effects of advancing age on peripheral nerve regeneration. Following axotomy, the regrowth of peripheral axons takes longer in older individuals than in young ones. The present study compares the crush-induced process of degeneration and regeneration in the buccal branch of the facial motor nerve in groups of rats aged 3 months and 15 months. Observations are based on qualitative and quantitative analyses of the nerve 20 mm from the site of injury in rats 1, 2, 4, 16, 21, 28, and 56 days after crush. The buccal branch is purely motor and contains a unimodal population of about 1,600 axons commonly in a single fascicle. During the first 28 days post crush (dpc) in the 3-month animals, the progression of myelin and axon degeneration, myelin clearance, regrowth of axon sprouts, and axon maturation are relatively synchronized and uniform. In the older rats, the degeneration of myelin and axons, myelin clearance, and the appearance of axon sprouts at the site of sample are all delayed. In the younger animals, axon sprouts increase in numbers from their first appearance at 4 dpc through the 2 weeks examined following the restoration of whisking behavior. The numbers of regenerating older axons increase at a rate comparable to that in the younger animals through the time that bilaterally symmetrical whisking behavior is evident, but afterwards the number of axon sprouts decreases. At 2 months after crush the young animals have 30% more fibers in the buccal branch than control nerves, while the older animals have fewer than control numbers. In the 3-month regenerated nerve, 2 months post crush, 30% of the regenerated fibers are of very small caliber, less than 3 microns2 in cross sectional area, and typically these small axons have unusually thick myelin sheaths; the older nerves do not have such a skewed distribution of axon areas. The older regenerated axons at 2 months post crush have an unusually high density of microtubules compared to the younger regenerated ones (and controls), and the ratio of neurofilaments to microtubules is very low. The conclusions are that motor neurons in older animals regenerate damaged axons after a delay not apparent in the young; the strong regenerative response apparent initially in animals of both age groups is not maintained in the older animals; and the relationship between the numerical density of cytoskeletal elements and the axon cross-sectional area deviates from normal in the regenerated axons of the older animals.


Expression of s-laminin and laminin in the developing rat central nervous system. The extracellular matrix component, s-laminin, is a homologue of the B1 subunit of laminin. S-laminin is concentrated in the synaptic cleft at the neuromuscular junction and contains a site that is adhesive for motor neurons, suggesting that it may influence neuromuscular development. To ascertain whether s-laminin may also play roles in the genesis of the central nervous system, we have examined its expression in the brain and spinal cord of embryonic and postnatal rats. S-laminin was not detectable in synapse-rich areas of adults. However, s-laminin was present in discrete subsets of three laminin-containing structures: (1) In the developing cerebral cortex, laminin and s-laminin were expressed in the subplate, a transient layer through which neuroblasts migrate and cortical afferents grow. Both laminin and s-laminin disappeared as embryogenesis proceeded; however, laminin was more widely distributed and present longer than s-laminin. (2) In the developing spinal cord, laminin was present throughout the pia. In contrast, s-laminin was concentrated in the pia that overlies the floor plate, a region in which extracellular cues have been postulated to guide growing axons. (3) In central capillaries, s-laminin appeared perinatally, an interval during which the blood-brain barrier matures. In contrast, laminin was present in capillary walls of both embryos and adults. To extend our immunohistochemical results, we used biochemical methods to characterize s-laminin in brain. We found that authentic s-laminin mRNA is present in the embryonic brain, but that brain-derived s-laminin differs (perhaps by a posttranslational modification) from that derived from nonneural tissues. We also used tissue culture methods to show that glia are capable of synthesizing "brain-like" s-laminin, and of assembling it into an extracellular matrix. Thus, glia may be one cellular source of s-laminin in brain. Together, these results demonstrate that s-laminin is present in the developing central nervous system, and raise the possibility that this molecule may influence developmental processes.


Cholinergic innervation of the human striatum, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus. The anatomical organization of cholinergic markers such as acetylcholinesterase, choline acetyltransferase, and nerve growth factor receptors was investigated in the basal ganglia of the human brain. The distribution of choline acetyltransferase-immunoreactive axons and varicosities and their relationship to regional perikarya showed that the caudate, putamen, nucleus accumbens, olfactory tubercle, globus pallidus, substantia nigra, red nucleus, and subthalamic nucleus of the human brain receive widespread cholinergic innervation. Components of the striatum (i.e., the putamen, caudate, olfactory tubercle, and nucleus accumbens) displayed the highest density of cholinergic varicosities. The next highest density of cholinergic innervation was detected in the red nucleus and subthalamic nucleus. The level of cholinergic innervation was of intermediate density in the globus pallidus and the ventral tegmental area and low in the pars compacta of the substantia nigra. Immunoreactivity for nerve growth factor receptors (NGFr) was confined to the cholinergic neurons of the basal forebrain and their processes. Axonal immunoreactivity for NGFr was therefore used as a marker for cholinergic projections originating from the basal forebrain (Woolf et al., '89: Neuroscience 30:143-152). Although the vast majority of striatal cholinergic innervation was NGFr-negative and, therefore, intrinsic, the striatum also contained NGFr-positive axons, indicating the existence of an additional cholinergic input from the basal forebrain. This basal forebrain cholinergic innervation was more pronounced in the putamen than in the caudate. The distribution of NGFr-positive axons suggested that the basal forebrain may also project to the globus pallidus but probably not to the subthalamic nucleus, substantia nigra, or red nucleus. The great majority of cholinergic innervation to these latter three structures and to parts of the globus pallidus appeared to come from cholinergic neurons outside the basal forebrain, most of which are probably located in the upper brainstem. These observations indicate that cholinergic neurotransmission originating from multiple sources is likely to play an important role in the diverse motor and behavioral affiliations that have been attributed to the human basal ganglia.


Spatial density and immunoreactivity of bipolar cells in the macaque monkey retina. The anatomical substrates of spatial and color vision in the primate retina are investigated by measuring the immunoreactivity and spatial density of bipolar, amacrine and horizontal cells in the inner nuclear layer of the macaque monkey retina. Bipolar cells can be distinguished from amacrine and horizontal cells by their differential immunoreactivity to antisera against glutamate, glycine, GABA, parvalbumin, calbindin (CaBP D-28K), and the L7 protein from mouse cerebellum. The spatial density of bipolar cells is compared to the densities of photoreceptors and ganglion cells at different retinal eccentricities. In the centralmost 2 mm, cone bipolar cells outnumber ganglion cells by about 1.4:1. The density of cone bipolar cells is thus high enough to allow for input to different (parasol and midget) ganglion cell classes by different (diffuse and midget) bipolar cell classes. The density gradient of cone bipolar cells follows closely that of ganglion cells in central retina but falls less steeply in peripheral retina. This suggests that the convergence of cone signals to the receptive fields of ganglion cells in the peripheral retina occurs in the inner plexiform layer. The density of cone bipolar cells is 2.5-4 times that of cones at all eccentricities studied, implying that cone connectivity to bipolar cells remains constant throughout the retina. Different subgroups of bipolar cells are distinguished by their relative immunoreactivity to the different antisera. All rod and cone bipolar cells show moderate to strong glutamate-like immunoreactivity. The bipolar cells that show weak to moderate GABA-like immunoreactivity are also labeled with the antiserum to the L7 protein and are thus identified as rod bipolar cells. Nearly half of all cone bipolar cells showed glycine-like immunoreactivity. The results suggest that the inhibitory neurotransmitter candidates GABA and glycine are segregated respectively in rod and cone bipolar cell pathways. A diffuse, cone bipolar cell type can be identified by the anti-parvalbumin and the anti-calbindin antisera. All horizontal cells show parvalbumin-like immunoreactivity. Nearly all amacrine cells show GABA-like or glycine-like immunoreactivity; a variety of subpopulations also show immunoreactivity to one or more of the other markers used.


Quantitative analysis of bulbospinal projections from the rostral ventrolateral medulla: contribution of C1-adrenergic and nonadrenergic neurons. The contribution of C1-adrenergic and nonadrenergic neurons to the spinal projection from the rostral ventrolateral medulla (RVLM) and their relative innervation density throughout thoracic spinal segments were examined by combining the Fluorogold (FG) retrograde tracing technique with immunofluorescent labeling for the epinephrine-synthesis enzyme phenylethanolamine N-methyltransferase (PNMT). The results indicate that the RVLM-spinal projection is comprised of both PNMT-positive and PNMT-negative neurons located in the subretrofacial area of the RVLM, approximately 1 to 1.7 mm rostral to obex. The bulbospinal projection from the RVLM is predominantly ipsilateral, and bulbospinal neurons do not appear to be organized within the RVLM in a manner indicating their segmental termination site. Eighty-one percent (+/- 4%, n = 2) of the PNMT-positive cells in the ipsilateral subretrofacial RVLM were retrogradely labeled after unilateral FG injections into multiple thoracic levels of the intermediolateral cell column (IML). Following single level FG injections, the number of retrogradely labeled PNMT-positive neurons in the subretrofacial RVLM decreased with injections in more caudal thoracic segments, indicating a heavier innervation of the upper thoracic IML by C1 neurons. PNMT-negative neurons were the main component of the RVLM-spinal population with 63 +/- 8% (n = 7) of the non-PNMT-containing neurons within the ipsilateral subretrofacial RVLM innervating all thoracic levels of the IML. The results indicate that both C1-adrenergic and nonadrenergic neurons in the RVLM make a substantial contribution to the innervation of the IML.


Morphology of intracellularly labeled interneurons in the dentate gyrus of the immature rat. Although many aspects of the morphological development of interneurons in the dentate gyrus have been described, the full extent of their dendrites and local axon projections in immature rodents has not been examined. Here intracellular labeling was used to assess the branching patterns of interneurons in the dentate gyrus of rat pups between 7 and 9 days of age. Labeled neurons were located within or just below the granule cell layer, and most were classified as GABAergic basket neurons on the basis of their dendritic morphologies. All labeled interneurons exhibited immature characteristics. Spines were present on cell bodies and dendrites, and growth cones were visible on some dendrites and axons. In spite of these immature features, the dendrites and axon arbors of the labeled neurons were extensive. Many apical dendrites reached the top of the molecular layer, and a number of basal dendrites extended to the CA3 pyramidal cell layer of the hippocampus. Elaborate axon plexuses were present within the dentate gyrus itself, and axon collaterals of several neurons extended beyond the dentate gyrus to branch within regions CA3 and CA1 of the hippocampus. These results indicate that the dendrites and axon collaterals of dentate interneurons are extensive at a time when the principal neurons, the granule cells, are still proliferating. These data are consistent with the idea that GABAergic interneurons may influence granule cell development in the dentate gyrus, as well as pyramidal cell maturation in the hippocampus proper.


The human transient subpial granular layer: an optical, immunohistochemical, and ultrastructural analysis. The cytological features, origin, migration, and fate of the subpial granular layer cells of the human embryonic cerebral cortex are studied with light and electron microscopy, Golgi impregnations, and immunocytochemical staining with the microtubule associated protein 2 and glial fibrillary acidic protein antibodies. Subpial granular layer (SGL) cells form a distinct neuronal population in the molecular layer, characterized by a small dark nucleus with abundant chromatin clumps and prominent nucleoli, and a lightly stained cytoplasm containing few organelles. Somata and processes of SGL cells are intensively stained with microtubule-associated protein 2 antibody but do not express glial fibrillary acidic protein antibody. These cells apparently originate from the olfactory germinative zone. They follow two major strands from the olfactory subventricular zone to the subpial region. Subsequently, they migrate tangentially at the subpial level to all cortical regions, as is observed on Golgi and ultrastructural preparations. They constitute a transient population that penetrates the deep molecular layer and subsequently disappear from it. Several cytological features of these cells suggest an inward migration with growth of a radial process toward the cortical plate and subsequent nuclear translocation. The fate and the role of this new phylogenetic neuronal population has yet to be determined although the abundance of degenerating SGL cells in the deep molecular layer suggests at least partial degeneration.


Time of ganglion cell genesis in relation to the chiasmatic pathway choice of retinofugal axons. The time of generation of retinal ganglion cells in fetal cats has been related to the course taken later by their axons in the optic chiasm. The ganglion cells were labelled with tritiated thymidine either on embryonic day (E) 26 or on E-30. When the cats were mature, ganglion cells were retrogradely labelled with horseradish peroxidase injected into one optic tract. The distribution of double-labelled cells showed that cells in the temporal retina generated on E-26 all have axons that take an uncrossed course in the chiasm, whereas, of the cells generated on E-30 in the temporal retina, some take a crossed course and others take an uncrossed course. The uncrossed axons of the E-26 cohort come from cells having a central distribution on the retina. For the E-30 cohort, the uncrossed axons come from cells having a relatively peripheral distribution, whereas the crossed axons come from more central cells. The present results suggest that the mechanism which serves to direct temporal retinal axons into the ipsilateral optic tract weakens as development proceeds. In principle, the change may occur in either a chiasmatic signal, read by temporal but not nasal optic axons, or in a retinal label, carried by temporal but not nasal cells and their processes. Since temporal retinal cells born concurrently at different places can project to opposite optic tracts, a retinal signal that deteriorates with time in a centroperipheral fashion is favored by the present results.


Fine structure and blood-brain barrier properties of the central nervous system of a dipteran larva. Using scanning and transmission electron microscopy, we studied basic ultrastructure, membrane specializations, and blood-brain barrier properties of the ventral ganglion and abdominal nerves of the last (third) instar larva of a dipteran fly, Delia platura. Both ganglion and nerves are covered with a non-cellular neural lamella. A monolayer of flattened perineurial cells lies beneath the neural lamella. Perineurial cells contain stores of metabolites and nutrients and these cells extensively interdigitate with one another. An extensive extracellular series of channels pervades perineurial cells. Glial cells beneath the perineurium envelope but do not entwine axons. In a minority of cases, adjacent axons in nerve and neuropil appear to be contiguous without glial intervention. Extensive (pleated) septate junctions with triangular septa are present between perineurial cells. Hemidesmosomes, half desmosomes (a first report for invertebrates), and desmosomes were also observed. Although no tight junctions were discovered, an effective blood-brain barrier exists, and tracer (ionic lanthanum) in no case reached neuronal surfaces. Extracellular tracer halted within the extensive septate junctions between perineurial cells. We postulate that in the absence of tight junctions the functional blood-brain barrier is effected by the septate junctions in the central nervous system of the Delia larva.


Contractile proteins in the hyaline cells of the chicken cochlea. Hyaline cells are a single layer of epithelial cells found at the inferior edge of the sensory epithelium in the chick cochlea. They rest directly above a specialized region of the basilar membrane at a point where it connects to the fibrocartilaginous skeleton of the cochlear duct. The basal cytoplasm of the hyaline cells contains a bundle of linearly aligned actin filaments that resemble stress fibers in their organization. The actin filaments are anchored in the basal plasma membranes of the cells, which are, in turn, associated with the underlying basal lamina and the extracellular matrix of the basilar membrane. We have used a combination of transmission electron microscopy, differential-interference-contrast and epifluorescence light microscopy, and confocal laser scanning microscopy to study the composition and organization of these actin bundles within the hyaline cells. The bundles are arranged into triangular wedges that are oriented radially across the basilar membrane. Each cell contains one or two actin wedges. Adjacent cells can have them aligned in opposite directions so that in a whole-mount surface preparation they appear as interdigitations. Immunofluorescent staining of the hyaline cells has shown that smooth muscle myosin and alpha-actinin are co-localized to the actin bundles. Smooth muscle myosin is also found throughout the cytoplasm of the cells. The fact that hyaline cells in the chick cochlea are contacted by efferent nerve fibers suggests that these cells may regulate tension on the basilar membrane via the specialized bundle of actin filaments.


Projections from the commissural subnucleus of the nucleus of the solitary tract: an anterograde tracing study in the cat. The commissural subnucleus (COM) of the nucleus of the solitary tract (NTS) is known to receive primary afferents from the lungs and other viscera innervated by the vagus nerve, and thus to participate in central autonomic and respiratory control. The aim of the present study was to identify the areas of terminal arborizations of COM neurons in order to examine brainstem sites which may be involved in reflex responses mediated by these neurons. The projections were studied in cats, using biocytin as an anterograde tracer. Labeled fibers and terminal boutons were visualized by horseradish-peroxidase histochemistry, 2-3 days after microinjection of the tracers into the COM 1-2 mm caudal to the obex. Labeled axons were examined in the brainstem from the rostral pons to the caudal medulla and were found bilaterally, with an ipsilateral predominance, mainly in the following regions: (1) The dorsolateral rostral pons. Terminal boutons were observed in the lateral and medial parabrachial nuclei, Kölliker-Fuse nucleus, and around the mesencephalic trigeminal tract. This area corresponds to the pontine respiratory group also known as the "pneumotaxic center." (2) The pontine area dorsolateral to the superior olivary nucleus. This region contains the A5 noradrenergic cell group; (3) Near the ventral surface, below the facial nucleus. This area overlaps with the 'retrotrapezoid nucleus.' (4) Respiration-related areas of the medulla, including the dorsal and ventral respiratory groups, and the Bötzinger complex. (5) The dorsal motor nucleus of the vagus. These results suggest that the COM is involved in reflex arcs, which have both respiratory functions and autonomic functions. The pathway to the dorsolateral pons, which has been identified in our recent electrophysiological study is likely to play a role in mediating respiratory responses from pulmonary rapidly adapting receptors. Other pathways may represent additional projections from second-order neurons receiving input from this group of lung receptors, or projections from as yet unidentified neurons that relay information from different afferents terminating in the COM.


Corticotectal projections in the cat: anterograde transport studies of twenty-five cortical areas. Retrograde transport studies have shown that widespread areas of the cerebral cortex project upon the superior colliculus. In order to explore the organization of these extensive projections, the anterograde autoradiographic method has been used to reveal the distribution and pattern of corticotectal projections arising from 25 cortical areas. In the majority of experiments, electrophysiological recording methods were used to characterize the visual representation and cortical area prior to injection of the tracer. Our findings reveal that seventeen of the 25 cortical areas project upon some portion of the superficial layers (stratum zonale, stratum griseum superficiale, and stratum opticum, SO). These cortical regions include areas 17, 18, 19, 20a, 20b, 21a, 21b, posterior suprasylvian area (PS), ventral lateral suprasylvian area (VLS), posteromedial lateral suprasylvian area (PMLS), anteromedial lateral suprasylvian area (AMLS), anterolateral lateral suprasylvian area (ALLS), posterolateral lateral suprasylvian area (PLLS), dorsolateral lateral suprasyvian area (DLS), periauditory cortex, cingulate cortex, and the visual portion of the anterior ectosylvian sulcus. While some of these corticotectal projections target all superficial laminae and sublaminae, others are more discretely organized in their laminar-sublaminar distribution. Only the corticotectal projections arising from areas 17 and 18 are exclusively related to the superficial layers. The remaining 15 pathways innervate both the superficial and intermediate and/or deep layers. The large intermediate gray layer (stratum griseum intermedium; SGI) receives projections from almost every cortical area; only areas 17 and 18 do not project ventral to SO. All corticotectal projections to SGI vary in their sublaminar distribution and in their specific pattern of termination. The majority of these projections are periodic, or patchy, and there are elaborate (double tier, bridges, or streamers) modes of distribution. We have attempted to place these findings into a conceptual framework that emphasizes that the SGI consists of sensory and motor domains, both of which contain a mosaic of connectionally distinct afferent compartments (Illing and Graybiel, '85, Neuroscience 14:455-482; Harting and Van Lieshout, '91, J. Comp. Neurol. 305:543-558). Corticotectal projections to the layers ventral to SGI, (stratum album intermediale, stratum griseum profundum, and stratum album profundum) arise from thirteen cortical areas. While an organizational plan of these deeper projections is not readily apparent, the distribution of several corticotectal inputs reveals some connectional parcellation.


Further study of the aberrant optic nerve projection to olfactory cortex. When implanted into the cerebral hemisphere, the regenerating optic nerve of the adult frog (Rana pipiens) forms a well-defined terminal field in the pars ventralis of the lateral (olfactory) cortex, and sometimes expands medially into the postolfactory eminence. These adjacent areas receive their normal input from the main olfactory bulb. The aberrant projection extends caudally toward the core neuropil of the medial amygdaloid nucleus, which receives its normal input from the accessory olfactory bulb, but does not enter this vomeronasal sector of the amygdala. The present study tests whether: 1) optic fibers would innervate the vomeronasal amygdala after surgical ablation of the accessory olfactory bulb, 2) the projection would transpose into adjacent cortex after olfactory cortex lesions, and 3) the projection would overflow into adjacent areas after being amplified by hemisection at the di-telencephalic junction (to minimize escape of fibers into the diencephalon). The retinal projection always terminated in the olfactory cortex when this area was intact, or in spared fragments of it after radical cortical lesions, but never entered the vomeronasal amygdala in any specimen, as studied by autoradiographic and horseradish peroxidase tracing techniques. With forebrain hemisection, the cortical terminal field increased in thickness but remained confined to the olfactory area. However, the interruption of the lateral forebrain bundle induced a new projection to the striatum in a region neighboring but separate from the olfactory cortical field. These findings support the hypothesis that retinal fibers have a specific affinity for primary olfactory cortex that is not normally allowed expression in development. Retinal fibers may also have a latent affinity for the striatum that is unmasked after deafferentation.


Afferents to the oculomotor nucleus in the goldfish (Carassius auratus) as revealed by retrograde labeling with horseradish peroxidase. The goal of this work was to compare the distribution and morphology of neurons projecting to the oculomotor nucleus in goldfish with those previously described in other vertebrate groups. Afferent neurons were revealed by retrograde labeling with horseradish peroxidase. The tracer was electrophoretically injected into the oculomotor nucleus. The location of the injection site was determined by the antidromic field potential elicited in the oculomotor nucleus by electrical stimulation of the oculomotor nerve. Labeled axons whose trajectories could be reconstructed were restricted to the medial longitudinal fasciculus. In order of quantitative importance, the afferent areas to the oculomotor nucleus were: (1) the ipsilateral anterior nucleus and the contralateral tangential and descending nuclei of the octaval column. Furthermore, a few labeled cells were found dorsomedially to the caudal pole of the unlabeled anterior octaval nucleus; (2) the contralateral abducens nucleus. The labeled internuclear neurons were arranged in two groups within and 500 microns behind the caudal subdivision of the abducens nucleus; (3) a few labeled cells were observed in the rhombencephalic reticular formation near the abducens nucleus, most of which were contralateral to the injection site. Specifically, stained cells were found in the caudal pole of the superior reticular nucleus, throughout the medial reticular nucleus and in the rostral area of the inferior reticular nucleus; (4) eurydendroid cells of the cerebellum, located close to the contralateral eminentia granularis pars lateralis, were also labeled; and (5) a small and primarily ipsilateral group of labeled cells was located at the mesencephalic nucleus of the medial longitudinal fasciculus. The similarity in the structures projecting to the oculomotor nucleus in goldfish to those in other vertebrates suggests that the neural network involved in the oculomotor system is quite conservative throughout phylogeny. Nevertheless, in goldfish these projections appeared with some specific peculiarities, such as the cerebellar and mesencephalic afferents to the oculomotor nucleus.


Epidermal dendritic cells in psoriasis possess a phenotype associated with antigen presentation: in situ expression of beta 2-integrins. Epidermal dendritic cells (DCs) isolated from psoriasis possess greatly enhanced T lymphocyte-activating properties compared with DCs from normal skin, suggesting that DCs in psoriasis express surface antigens crucial for antigen presentation. These include beta 2-integrins and intercellular adhesion molecule (ICAM)-1. Our purpose was to determine DC phenotype in psoriatic compared with normal epidermis with respect to these molecules. Tissue sections were single labeled with a peroxidase antiperoxidase (PAP) immunohistochemical technique and double labeled where necessary with a combination of a PAP and an alkaline phosphatase-anti-alkaline phosphatase technique. In psoriatic compared with normal skin, decreased numbers of DCs expressed CD1a (p less than 0.05), whereas increased numbers of DCs expressed class II major histocompatibility antigens (p less than 0.05). In normal skin positive staining for CD18 was not observed, whereas in psoriasis both CD1a+ and CD1a- DCs expressed beta 2-integrins, LFA-1 (CD11a/CD18), and gp 150/95 (CD11c/CD18). DCs in atopic dermatitis and lichen planus were also found to express beta 2-integrins. Neither MAC 1 (CD11b/CD18) nor ICAM-1 was observed on DCs. These data are consistent with either migration of dendritic antigen-presenting cells into the epidermis or in situ cytokine modulation of Langerhans cell phenotype in inflamed skin. Furthermore, they indicate that epidermal DCs in psoriasis and other cutaneous inflammatory diseases express molecules that are known to be crucial for Langerhans cell-driven T-cell activation in vitro.


Oral lesions in systemic lupus erythematosus. Do ulcerative lesions represent a necrotizing vasculitis? It has been suggested that oral lesions in patients with systemic lupus erythematosus (SLE) may be grouped clinically as erythema, discoid lesions, or oral ulcerations. Oral ulcerations have been said to foretell a severe systemic disease flare and the proposal that oral ulcers represent a mucosal vasculitis has been suggested to explain this hypothesis. Our objective was to test the hypothesis that oral ulcers in patients with SLE result from vasculitis. We studied 10 patients with American College of Rheumatology (ACR) criteria for a diagnosis of SLE who had oral lesions of lupus (six prospectively and four retrospectively) clinically and by routine and immunofluorescence microscopy. Biopsy specimens were reviewed in a single-blinded fashion. In our patients, no oral lesion, regardless of morphology, demonstrated vasculitis histologically. All lesions demonstrated an interface mucositis. Our data strongly contradict the hypothesis that leukocytoclastic vasculitis explains a possible unproven correlation between oral ulceration and disease flares in patients with SLE.


Immunoelectronmicroscopic differentiation of linear IgA bullous dermatosis of adults with coexistence of IgA and IgG deposition from bullous pemphigoid. The differentiation between linear IgA bullous dermatosis (LABD) and bullous pemphigoid (BP) is sometimes difficult in patients who have both IgA and IgG deposition in a linear pattern at the basement membrane zone. We address whether two cases of acquired subepidermal blistering disease with coexistence of IgA and IgG deposition in a linear pattern at the basement membrane zone are LABD or BP. The two cases were investigated by immunoelectron microscopy and compared with two typical cases of LABD. In both cases, the deposition of IgA and IgG was ultrastructurally localized below the lamina densa in close association with anchoring fibrils, as was seen in two cases of typical LABD. These findings indicate that our two cases of acquired blistering disease with co-existence of IgA and IgG deposition are LABD, rather than BP.


Dysplastic nevi can be diagnosed and graded reproducibly: a longitudinal study. Poor interobserver reproducibility in diagnosing and grading dysplastic melanocytic nevi is often cited as evidence against the ability of pathologists to recognize such an entity. We attempted to examine the diagnostic profiles of melanocytic lesions of two dermatopathologists in a stable population base. All 2600 melanocytic neoplasms were diagnosed at Stanford University Medical Center during the past 4 years by one dermatopathologist from 1987 to 1989 and a different dermatopathologist in 1990 and 1991. The two independently evaluated these lesions unaware of the other's criteria. The diagnostic profile of the two pathologists shows a striking degree of similarity: 76.7% versus 75.3% of all nevi were diagnosed as acquired melanocytic nevi, 8.8% versus 12.0% were diagnosed as mildly dysplastic, 7.0% versus 6.8% as moderately dysplastic, and 2.7% versus 1.6% as severely dysplastic. Our findings suggest that the two pathologists are using reproducible criteria for diagnosing and grading dysplastic nevi.


The Tzanck smear: can dermatologists accurately interpret it? The Tzanck preparation is a standard technique for the rapid diagnosis of herpes simplex and varicella-zoster virus infections. This study was designed to determine the ability of practicing dermatologists to interpret Tzanck preparations accurately. Dermatologists at different levels of training interpreted a series of Tzanck preparations under test conditions. Second- and third-year residents had a pooled average for correct responses of 91%; dermatologists in practice less than 10 years, 84%; dermatologists in practice more than 10 years, 67%. Dermatologists are able to use the Tzanck preparation effectively for diagnosing herpetic infections. Second- and third-year residents who are most likely to be diagnosing blistering eruptions in immunosuppressed or otherwise critically ill patients are especially accurate interpreters.


Cutaneous Bowen's disease. An analysis of 1001 cases according to age, sex, and site. There are no large studies of Bowen's disease that have analyzed its distribution according to age, sex, and site. This study was performed primarily to determine whether there were significant sex and site differences in the distribution of Bowen's disease. One thousand one skin biopsy specimens of Bowen's disease were analyzed according to age, sex, and site of origin. This study revealed that the most common site of Bowen's disease was the head and neck (440 lesions), whereas specimens from the lower limbs (298 lesions) and upper limbs (198 lesions) outnumbered specimens from the torso (65 lesions). Of 298 specimens from the lower limbs, 72.1% were from women; 79.3% of the 87 specimens from the scalp and ears were from men. Eighty percent of the 85 specimens of Bowen's disease from the cheeks were from women. These results indicate that cutaneous Bowen's disease occurs mainly on sun-exposed sites. This is also supported by the predominance of Bowen's disease on the lower limbs in women and on the scalp and ears in men. The basis for the female predominance on the cheeks is unknown, but may reflect the increased vulnerability to sun damage of superficial vellus hair follicles that predominate on the cheeks in women. This finding may provide indirect support for the hypothesis that some forms of Bowen's disease have a follicular histogenesis.


Serum adenosine deaminase activity in systemic sclerosis (scleroderma) and related disorders. Adenosine deaminase (ADA) activity in serum is mainly derived from T lymphocytes. Our purpose was to clarify the significance of ADA activity in systemic sclerosis (PSS) and related disorders. ADA activity was determined with an enzymatic method in 34 patients with PSS, 4 with mixed connective tissue disease (MCTD), 6 with dermatomyositis (DM), 11 with localized scleroderma (LS), and 13 with other collagen diseases. Serum ADA activity was elevated over the mean (+2 standard deviations) of the control in 85% of the patients with PSS, all with MCTD, 83% of those with DM, and 82% of those with LS. The mean values in 10 PSS patients with anti-topoisomerase I antibodies, 14 patients with anti-RNP antibodies, 12 patients with anticentromere antibodies (ACAs), and 5 patients without antinuclear antibodies (ANAs) were 26.1, 24.9, 22.6, and 16.8 IU/L, respectively. In most cases, except for ACA-positive patients, serum ADA activity changed almost in parallel with ANA titers. These results support the notion that T cells are involved in the pathogenesis of PSS and related disorders.


Perineal ecthyma gangrenosum in infancy and early childhood: septicemic and nonsepticemic forms. Ecthyma gangrenosum is characterized by necrotic ulcerations surrounded by an erythematous halo. It is secondary to Pseudomonas aeruginosa infection. Most lesions are located in the anogenital and axillary areas, but the route of infection is generally difficult to establish. We report six children with perineal ecthyma gangrenosum and discuss predisposing factors, origin, and route of infection. This was a retrospective clinical study. Three children had blood cultures positive for P. aeruginosa, and one died. Predisposing factors were present in all cases; two had received chemotherapy (neuroblastoma, acute lymphoblastic leukemia), and two had idiopathic granulocytopenia. The last two patients previously had received treatment with systemic antibiotics and had abnormal granulocyte killing several months later. Septicemic ecthyma gangrenosum can be rapidly fatal in young children and requires aggressive antibiotic therapy. Benign ecthyma gangrenosum in healthy infants may result from a modification of bowel microflora after antibiotic therapy in conjunction with maceration in the diaper area. However, careful evaluation and long-term follow-up must be done to detect neutropenia, functional abnormalities of granulocytes, or a possible immune deficiency.


Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy. This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease. Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls. Files of patients from the original photopheresis study centers were reviewed and their current status was documented. The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy. Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.


Elevation of fasting serum lipids in patients treated with low-dose cyclosporine for severe plaque-type psoriasis. An assessment of clinical significance when viewed as a risk factor for cardiovascular disease. Hyperlipidemia has received little attention as a side effect of cyclosporine therapy for severe psoriasis. We report changes in fasting serum lipids in patients treated with low-dose oral cyclosporine for psoriasis and discuss their significance. Twenty-two patients with severe, recalcitrant, plaque-type psoriasis were treated with cyclosporine, 5 mg/kg/day, for 12 to 16 weeks. Fasting serum lipid levels (triglycerides, cholesterol, and high-density lipoproteins) were measured at 2-week intervals. The mean serum triglyceride level increased from 117.8 +/- 11.7 mg/dl before initiation of therapy to 183.9 +/- 31.4 mg/dl after 2 weeks of treatment, without further significant change during the remainder of the study (p less than 0.007). A significant elevation of serum cholesterol from 207.1 +/- 8.1 mg/dl initially to 247.4 +/- 10.2 mg/dl after 2 weeks of treatment occurred (p less than 0.001) and persisted with continued cyclosporine therapy. No consistent alteration in high-density lipoprotein was noted (p less than 0.42). Serum lipids should be closely monitored in psoriasis patients receiving intermediate or long-term therapy with cyclosporine, especially in the presence of elevated baseline values.


Dermabrasion: therapy and prophylaxis of the photoaged face. For many years dermabrasion has been used for the treatment of photoaged facial skin. However, there is a paucity of correlative studies that document the beneficial histopathologic effects of dermabrasion with clinical changes. Moreover, long-term follow-up and comparative studies that document these therapeutic results are lacking. Our purpose was to study patients with photoaged facial skin by comparing the preoperative and postoperative clinical and histopathologic changes that occur as a result of surgical dermabrasion of aged and photodamaged facial skin. Twelve patients 40 years of age and older with significant photoaging and dermatoheliosis were treated with full-face dermabrasion. Predermabrasion biopsy specimens were compared with matched postdermabrasion biopsy specimens taken at various time intervals from 6 months to 8 years after dermabrasion. Microscopic normalization of the actinically damaged epidermis and papillary dermis was manifested clinically by the replacement of dermatoheliosis with supple, smooth-textured facial skin that remained clinically evident well beyond 8 years after dermabrasion. In addition, the necessity for the continued treatment of premalignant and malignant lesions was virtually eliminated during the 8-year postdermabrasion period. Not only is dermabrasion a beneficial therapeutic option for aged and photo-damaged skin, but it also is a valid means of prophylaxis against neoplastic changes.


Wiskott-Aldrich syndrome: new molecular and biochemical insights. The Wiskott-Aldrich syndrome is an uncommon X-linked recessive disease characterized by eczema, thrombocytopenia, and immunodeficiency. The clinical features begin early in life and include recurrent infections, bleeding, and severe eczema. Unless the condition is treated by bone marrow transplantation, the prognosis of Wiskott-Aldrich syndrome is grave, and premature death caused by sepsis, hemorrhage, or lymphoreticular malignancy is common. Although the biochemical defect responsible for the syndrome is not known, recent investigations with restriction fragment length polymorphisms have mapped the Wiskott-Aldrich syndrome locus to the proximal portion of the short arm of the human X chromosome (Xp11). The isolation of these DNA markers makes feasible both carrier detection and prenatal diagnosis of Wiskott-Aldrich syndrome and provides an important adjunct to the management of Wiskott-Aldrich syndrome for patients and their families. These genetic data, in conjunction with the recent identification of a specific O-glycosylation defect in lymphocytes from patients with Wiskott-Aldrich syndrome, present an opportunity for the eventual isolation of the Wiskott-Aldrich syndrome gene and identification of the underlying cellular defect. We review the clinical and laboratory features of this syndrome and summarize the new molecular and biochemical approaches that can be used in diagnosis, genetic counseling, and treatment.


Reactive lentiginous hyperpigmentation after cryosurgery for lentigo maligna. Twenty patients treated for lentigo maligna of the face with cryosurgery developed benign lentiginous hyperpigmentation mimicking a recurrence. When cryosurgery is used in the treatment of lentigo maligna, it is important to know whether repigmentation of the scar represents true recurrence or a benign process. Twenty patients were treated with cryosurgery for lentigo maligna of the face. Within a follow-up period of 7 to 80 months, frequent clinical observations were made. Lentiginous hyperpigmentation developed within the treatment area in eight patients. Histologic investigation revealed recurrence of lentigo maligna in three and benign hyperpigmentation in five. Genetic factors and UV exposure after cryosurgery may favor the development of benign lentiginous hyperpigmentation. Because recurrence of lentigo maligna must be considered, histologic evaluation of repigmentation is mandatory.


Pulsed-dye laser therapy for cutaneous Kaposi's sarcoma associated with acquired immunodeficiency syndrome. Cutaneous lesions of Kaposi's sarcoma associated with acquired immunodeficiency syndrome (AIDS-KS) are disfiguring. This study assesses the response of AIDS-KS to pulsed-dye laser (PDL) therapy. The PDL was used to treat 15 AIDS-KS patients. Treatment was repeated at 4-week intervals. On average, patients received three treatments per treated lesion. At 6 weeks' follow-up, the patients' treated lesions were reduced in size when compared with their matched control lesions (p less than 0.002). A complete or partial clinical response occurred in 44% of treated lesions (17 of 39) compared with 18% of matched control lesions (7 of 39) [corrected]. Patients experienced limited pain, infrequent blistering, and no scarring. However, histopathologic findings of treated lesions throughout therapy correlated poorly with clinical response. At 12 weeks, all treated lesions had recurred. PDL therapy for AIDS-KS is not recommended. Although safe, the rapid recurrence of disease at initially responsive sites would require costly, long-term therapy to maintain cosmetic improvement.