Biomedical subjects

M P Hill

Publications and source records attributed to M P Hill.

At least 19 recordsLinked to original sources

PubMed2006

Susceptibility of adult Aethina tumida (Coleoptera: Nitidulidae) to entomopathogenic fungi.

Aethina tumida Murray (Coleoptera: Nitidulidae) is an invasive parasite species in populations of honey bees, Apis mellifera L. Aiming toward substitution of chemical control, we here identified a naturally occurring fungal pathogen of adult A. tumida from its endemic range in South Africa [Metarhizium anisopliae (Metschnikoff) Sorokin variety anisopliae strain FI-203]. The susceptibility of adult beetles (n = 400) to this fungus and to three other generalist entomopathogenic fungal isolates [Metarhizium anisopliae, Beauveria bassiana (Balsamo) Vuillemin, and Hirsutella illustris Minter & Brady] was assessed using spore suspension bioassays. The data revealed significantly increased mortality in the B. bassiana (74.00 +/- 8.94%) and M. anisopliae variety anisopliae (28.00 +/- 16.43%) tests but not in the H. illustris (2.00 +/- 4.47%) and M. anisopliae (12.00 +/- 8.37%) groups. The results indicate a potential for entomopathogenic fungi as an alternative control of A. tumida.

Animals↗

PubMed2001

Neural mechanisms underlying peak-dose dyskinesia induced by levodopa and apomorphine are distinct: evidence from the effects of the alpha(2) adrenoceptor antagonist idazoxan.

Dyskinesia, secondary to dopamine replacement therapy, is the major complication of currently available therapies for Parkinson's disease. Alpha(2) adrenoceptor antagonists, such as idazoxan, can significantly reduce levodopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned, nonhuman primate model of Parkinson's disease and in human. This action of adrenoceptor antagonists may involve blockade of the actions of noradrenaline synthesised from levodopa. We hypothesise that, because dopamine receptor agonists, such as apomorphine, cannot be metabolised to produce noradrenaline, activation of adrenoceptors may not be involved in dyskinesia produced by such agents. If this were the case, idazoxan would not be expected to reduce apomorphine-induced dyskinesia. MPTP-lesioned marmosets with stable dyskinesia induced by prolonged levodopa therapy were given an acute challenge with apomorphine (0.3 mg/kg subcutaneously) or levodopa (8.0 mg/kg orally), these doses produced equivalent peak-dose dyskinesia. Idazoxan (2.5 mg/kg p.o.), or vehicle, was then administered with either apomorphine or levodopa. Idazoxan abolished levodopa-induced dyskinesia but did not affect apomorphine-induced dyskinesia (P < 0.05 and P > 0.05, respectively, Wilcoxon matched pairs test). Idazoxan also extended the anti-parkinsonian actions of levodopa but did not affect those of apomorphine. The pharmacological characteristics of the neural mechanisms underlying levodopa-induced dyskinesia and apomorphine-induced dyskinesia in parkinsonism thus appear to be distinct, at least with respect to the involvement of alpha(2) adrenoceptors. Specifically, levodopa, but not apomorphine-induced dyskinesia, involves activation of adrenoceptors. This finding may have major implications for understanding dyskinesia and should be borne in mind when designing clinical studies in which levodopa or dopamine receptor agonist challenges are employed to assess potential anti-dyskinetic properties of drugs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

Antiparkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of Parkinson's disease.

Dopamine-replacement strategies form the basis of most symptomatic treatments for Parkinson's disease. However, since long-term dopamine-replacement therapies are characterized by many side effects, most notably dyskinesia, the concept of a nondopaminergic therapy for Parkinson's disease has attracted great interest. To date, it has proved difficult to devise a nondopaminergic therapy with efficacy comparable to that of dopamine replacement. In animal models of Parkinson's disease, loss of striatal dopamine leads to enhanced excitation of striatal NR2B-containing NMDA receptors. This is responsible, in part at least, for generating parkinsonian symptoms. Here we demonstrate that, in the MPTP-lesioned marmoset, monotherapy with the NR2B-selective NMDA receptor antagonist, ifenprodil, administered de novo, has antiparkinsonian effects equivalent to those of l-DOPA (administered as its methyl ester form). In MPTP-lesioned marmosets, median mobility scores, following vehicle-treatment were 12.5/h (range 6-21), compared to 61/h (range 26-121) in normal, non-MPTP-lesioned animals. Following ifenprodil (10 mg/kg) treatment in MPTP-lesioned marmosets, the median mobility score was 66/h (range 34-93), and following l-DOPA (10 mg/kg i.p.) treatment 89/h (range 82-92). The data support the proposal that NR2B-selective NMDA receptor antagonists have potential as a nondopaminergic monotherapy for the treatment of parkinsonian symptoms when given de novo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson's disease.

In recent years, cannabinoid receptors and their endogenous ligands (endocannabinoids) have been identified within the brain. The high density of CB1 cannabinoid receptors within the basal ganglia suggests a potential role for endocannabinoids in the control of voluntary movement and in basal ganglia-related movement disorders such as Parkinson's disease. However, whether endocannabinoids play a role in regulating motor behavior in health and disease is unknown. Here we report the presence in two regions of the basal ganglia, the globus pallidus and substantia nigra, of the endocannabinoids 2-arachidonoylglycerol (2AG) and anandamide. The levels of the latter compound are approximately threefold higher than those previously reported in any other brain region. In the reserpine-treated rat, an animal model of Parkinson's disease, suppression of locomotion is accompanied by a sevenfold increase in the levels of the 2AG in the globus pallidus, but not in the other five brain regions analyzed. Stimulation of locomotion in the reserpine-treated rat by either of the two selective agonists of D2 and D1 dopamine receptors, quinpirole and R-(+/-)-3-allyl-6-chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (Cl-APB), respectively, results in the reduction of both anandamide and 2AG levels in the globus pallidus. Finally, full restoration of locomotion in the reserpine-treated rat is obtained by coadministration of quinpirole and the selective antagonist of the cannabinoid CB1 receptor subtype, SR141716A. These findings indicate a link between endocannabinoid signaling in the globus pallidus and symptoms of Parkinson's disease in the reserpine-treated rat, and suggest that modulation of the endocannabinoid signaling system might prove useful in treating this or other basal ganglia-related movement disorders.

Animals↗

PubMed2000

Delta-opioid receptor agonists as a therapeutic approach in Parkinson's disease.

Current symptomatic treatments for Parkinson's disease are based largely on dopamine replacement therapies; however, the fact that these treatments are characterized by many long-term side effects has led to widespread interest in nondopaminergic therapies. To date, a nondopaminergic therapy with comparable efficacy to dopamine replacement has not been devised. Here the authors discuss recent findings that systemic administration of a selective delta-opioid receptor agonist has powerful antiparkinsonian effects in rodent and primate models of Parkinson's disease that are equivalent to those of dopamine replacement. delta-Opioid receptor agonists may prove to be useful for the symptomatic treatment of Parkinson's disease in humans.

Journal Article↗

PubMed1999

Antiparkinsonian actions of blockade of NR2B-containing NMDA receptors in the reserpine-treated rat.

Current symptomatic treatment for Parkinson's disease is based largely on dopamine-replacing agents. The fact that long-term treatment with these drugs is characterized by many side effects has lead to widespread interest in nondopaminergic therapies. To date, however, it has proved difficult to devise a nondopaminergic therapy with significant antiparkinsonian efficacy when administered as monotherapy. Overactivity of the striatolateral pallidal pathway, the "indirect" striatal output pathway, is thought be responsible for the generation of parkinsonian symptoms. Indeed, it has been suggested that selective reduction in the activity of the "indirect" pathway may be achieved by blockade of NR2B-containing NMDA receptors. In the present study, we demonstrate that selective blockade of NR2B-containing NMDA receptors with the polyamine antagonists ifenprodil and eliprodil causes a significant increase in locomotor activity in the reserpine-treated rat model of Parkinson's disease (30 mg/kg ifenprodil, 221.2 +/- 54 mobile counts compared to vehicle, 19.6 +/- 6.87, P < 0.001). Additionally, we show that, subsequent to dopamine depletion, the ability of ifenprodil to bind to the polyamine site and inhibit binding of the NMDA channel blocker [3H] MK-801 is increased fourfold (IC50 3.7 +/- 0.4 microM compared to vehicle, IC50 14.3 +/- 2.34 microM, P < 0.01). We suggest that ifenprodil selectively targets the polyamine site on overactive NR2B-containing NMDA receptors. Thus, we propose that NR2B-selective NMDA receptor antagonists may prove useful in the treatment of Parkinson's disease.

Animals↗

PubMed1999

Expression of TGFalpha in meningiomas.

The objective of this study was to examine the expression of transforming growth factor alpha (TGFalpha), a mitogen for many cell types, and its receptor in basic subtypes of meningiomas as well as in meningiomas of varying grade. Formalin-fixed tissues from 26 meningiomas including 15 benign (5 meningothelial, 5 transitional, and 5 fibrous variants), 6 atypical, and 5 malignant examples were immunohistochemically examined for both TGFalpha protein and EGF/TGFalpha receptor protein. In addition, in situ hybridization (ISH) was used to detect TGFalpha mRNA expression. Immunostaining for TGFalpha was strongest in fibrous and atypical meningiomas, followed closely by transitional and malignant tumors. Only weak reactivity was observed in the meningothelial variant. In all but 4 tumors (2 fibrous, 2 atypical), ISH showed TGFalpha mRNA to be present, the signal being stronger in malignant than in conventional or atypical tumors. Lastly, immunostaining for EGF/TGFalpha receptor was positive in all tumors studied. Strong TGFalpha protein expression in meningiomas is commonly associated with fibrous morphology. Although the frequent detection of both TGFalpha protein and its mRNA, as well as of EGF/TGFalpha receptor within tumors of all type and grades, suggests that TGFalpha serves to promote tumor growth, its possible role in tumorigenesis or malignant progression is uncertain. In summary, demonstration of these substances is of no utility in the classification or grading of this common tumor because the differences in their expression among the various meningioma subtypes were not statistically significant.

Adult↗

PubMed1999

Control of glutamate release by calcium channels and kappa-opioid receptors in rodent and primate striatum.

The modulation of depolarization (4-aminopyridine, 2 mM)-evoked endogenous glutamate release by kappa-opioid receptor activation and blockade of voltage-dependent Ca2+ -channels has been investigated in synaptosomes prepared from rat and marmoset striatum. 4-Aminopyridine (4-AP)-stimulated, Ca2+ -dependent glutamate release was inhibited by enadoline, a selective kappa-opioid receptor agonist, in a concentration-dependent and norbinaltorphimine (nor-BNI, selective kappa-opioid receptor antagonist)-sensitive manner in rat (IC50 = 4.4+/-0.4 microM) and marmoset (IC50 = 2.9+/-0.7 microM) striatal synaptosomes. However, in the marmoset, there was a significant (approximately 23%) nor-BNI-insensitive component. In rat striatal synaptosomes, the Ca2+ -channel antagonists omega-agatoxin-IVA (P/Q-type blocker), omega-conotoxin-MVIIC (N/P/Q-type blocker) and omega-conotoxin-GVIA (N-type blocker) reduced 4-AP-stimulated, Ca2+ -dependent glutamate release in a concentration-dependent manner with IC50 values of 6.5+/-0.9 nM, 75.5+5.9 nM and 106.5+/-8.7 nM, respectively. In marmoset striatal synaptosomes, 4-AP-stimulated, Ca2+ -dependent glutamate release was significantly inhibited by omega-agatoxin-IVA (30 nM, 57.6+/-2.3%, inhibition), omega-conotoxin-MVIIC (300 nM, 57.8+/-3.1%) and omega-conotoxin-GVIA (1 microM, 56.7+/-2%). Studies utilizing combinations of Ca2+ -channel antagonists suggests that in the rat striatum, two relatively distinct pools of glutamate, released by activation of either P or Q-type Ca2+ -channels, exist. In contrast, in the primate there is much overlap between the glutamate released by P and Q-type Ca2+ -channel activation. Studies using combinations of enadoline and the Ca2+ -channel antagonists suggest that enadoline-induced inhibition of glutamate release occurs primarily via reduction of Ca2+ -influx through P-type Ca2+ -channels in the rat but via N-type Ca2+ -channels in the marmoset. In conclusion, the results presented suggest that there are species differences in the control of glutamate release by kappa-opioid receptors and Ca2+ -channels.

4-Aminopyridine↗

PubMed1999

The adrenergic receptor agonist, clonidine, potentiates the anti-parkinsonian action of the selective kappa-opioid receptor agonist, enadoline, in the monoamine-depleted rat.

1. The treatment of Parkinson's disease relies predominantly upon dopamine replacement therapy, usually with l-dihydroxyphenylalanine (L-DOPA). However, side-effects of long-term treatment, such as L-DOPA-induced dyskinesias can be more debilitating than the disease itself. Non-dopaminergic treatment strategies might therefore be advantageous. 2. The aim of this study was to investigate the potential anti-parkinsonian efficacy of the kappa-opioid receptor agonist, enadoline, and the alpha-adrenoreceptor agonist, clonidine, both alone or in combination, in the reserpine-treated rat model of Parkinson's disease. 3. Rats were treated with reserpine (3 mg kg-1), and experiments carried out 18 h later, at which time they exhibited profound akinesia (normal animals 1251+/-228 mobile counts h-1, reserpine-treated animals 9+/-2 mobile counts h-1). Both enadoline and clonidine increased locomotion in reserpine-treated rats in a dose-dependent manner. The maximum locomotor-stimulating effect of enadoline alone was seen at a dose of 0.2 mg kg-1 (208+/-63 mobile counts h-1). The maximum effect of clonidine was seen at a dose of 2 mg kg-1 (536+/-184 mobile counts h-1). 4. Co-administration of enadoline (0.1 mg kg-1) and clonidine (0.01 - 0.1 mg kg-1) at sub-threshold doses, synergistically increased locomotion. 5. The synergistic stimulation of locomotion in the reserpine-treated rat involved activation of kappa-opioid receptors and a combination of both alpha1 and alpha2-adrenoreceptors. 6. The results presented suggest a need for further studies on the potential of stimulating kappa-opioid and/or alpha-adrenoreceptors as a therapy for Parkinson's disease. Furthermore, the studies may offer potential mechanistic explanations of the ability of alpha2-adrenergic receptor antagonist to reduce L-DOPA-induced dyskinesia in Parkinson's disease.

Adrenergic alpha-Agonists↗

PubMed1998

Kappa-opioid receptor agonists increase locomotor activity in the monoamine-depleted rat model of parkinsonism.

Excessive glutamate transmission in the basal ganglia is a major factor in the neural mechanisms underlying parkinsonian akinesia. Activation of kappa opioid receptors causes a presynaptic reduction in glutamate release. Kappa opioid receptors are concentrated in those regions of the basal ganglia associated with increased glutamate transmission in parkinsonism. In this study, we use the alpha-methyl-p-tyrosine and reserpine-treated rat model of parkinsonism to investigate whether systemic administration of the kappa opioid agonists enadoline (CI-977) and U69,593 can alleviate the symptoms of parkinsonism either alone or in conjunction with dopamine replacement therapy. We report that, when administered alone, both enadoline and U69,593 can increase locomotion in monoamine-depleted rats. No increase in locomotor activity was seen after kappa opioid agonist administration in non-parkinsonian rats. The responses to kappa opioid agonists were blocked by co-administration of either the nonspecific opioid receptor antagonist naloxone or the selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI). An important finding is that when enadoline and L-dopa are administered together, their anti-akinetic properties are synergistic. Thus, the doses of enadoline and L-dopa required to alleviate akinesia when administered together are lower than either administered alone. These data illustrate the importance of kappa opioid receptors in the neural mechanisms controlling voluntary movement and suggest that kappa opioid agonists may have a role as adjuncts to dopamine replacement in the management of Parkinson's disease.

Animals↗

PubMed1998

Rothmund-Thomson syndrome and tolerance of chemoradiotherapy.

Rothmund-Thomson syndrome (RTS) is a rare disorder with a predisposition for cutaneous and non-cutaneous malignancy. It is speculated that ultraviolet (UV) sensitivity and deficient DNA repair may account for this predisposition and influence the tolerance of chemoradiotherapeutic management. A case is reported of the management of an RTS patient with squamous cell carcinoma of the tongue who demonstrated increased radiosensitivity and tissue intolerance to chemotherapy.

Adult↗

PubMed1995

Modulation of glutamate release by a kappa-opioid receptor agonist in rodent and primate striatum.

The influence of the kappa-opioid receptor agonist, enadoline, on endogenous glutamate release was investigated in rat and marmoset striatal synaptosomes. Enadoline decreased 4-aminopyridine (2 mM)-stimulated glutamate release (rat: IC50 approximately 8.7 microM, marmoset: IC50 approximately 2.9 microM). The effect of enadoline was reversed by nor-binaltorphimine (5 microM). These data indicate that, in the striatum of the rat and marmoset, kappa-opioid receptor agonists can modulate glutamate release. These findings may have implications for the treatment of Parkinson's disease.

4-Aminopyridine↗

PubMed1995

Metabotropic glutamate receptor agonists inhibit endogenous glutamate release from rat striatal synaptosomes.

A striatal synaptosomal preparation was used to assess the action of metabotropic glutamate receptor (mGlu receptor) agonists on 4-aminopyridine (2 mM)-stimulated endogenous glutamate release. 4-Aminopyridine alone increased basal glutamate release by 6.89 +/- 0.74 nmol/mg. The mGlu receptor agonists L-2-amino-4-phosphonobutyric acid (L-AP4) (IC50 approximately 0.2 microM) and (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid (IC50 approximately 0.2 microM) inhibited 4-aminopyridine-stimulated release. The putative mGlu receptor antagonist (S)-alpha-methyl-L-AP4, which itself inhibited 4-aminopyridine-stimulated release (IC50 approximately 10 microM), did not inhibit the effects of the two agonists.

4-Aminopyridine↗

PubMed1994

Glycolysis can prevent non-synaptic excitatory amino acid release during hypoxia.

Release of excitatory amino acids (EAAs) contributes to neuronal death during cerebral ischemia. EAA release occurs by both synaptic and non-synaptic mechanisms. However, studies in vivo yield conflicting estimates of their relative importance. This disparity may reflect differing degrees of substrate deprivation produced by various in vivo models. We used primary rat astrocyte cultures to establish the relationship between substrate deprivation, energy failure, and non-synaptic EAA release. Combined hypoxia and glycolytic blockade produced severe ATP depletion and EAA release (10-fold). In contrast, hypoxia alone caused only a moderate reduction in ATP and did not induce EAA release. These findings suggest that glycolytic metabolism may be an important factor affecting the magnitude of non-synaptic EAA release during ischemia.

Adenosine Triphosphate↗

PubMed1994

Whisker stimulation metabolically activates thalamus following cortical transplantation but not following cortical ablation.

Local cerebral glucose utilization was assessed during whisker stimulation by 2-deoxyglucose autoradiography. Whisker stimulation increased local cerebral glucose utilization in brainstem, thalamus and whisker sensory cortex in normal rats. Whereas whisker stimulation increased glucose metabolism in brainstem, whisker stimulation failed to increase glucose metabolism in thalamus of rats that had whisker sensory cortex ablated 5 h to five weeks previously. The failure of whisker stimulation to activate thalamus after cortical ablations was probably not due to decreased cortical input to thalamus because whisker stimulation activated thalamus after large cortical tetrodotoxin injections. Failure of whisker stimulation to activate thalamus at early times (5 h and one day) after cortical ablations was not due to thalamic neuronal death, since it takes days to weeks for axotomized thalamic neurons to die. The failure of whisker stimulation to activate thalamus at early times after cortical ablations was likely due to the failure of trigeminal brainstem neurons that project to thalamus to activate axotomized thalamic neurons. This might occur because of synaptic retraction, glial stripping or inhibition of trigeminal brainstem synapses onto thalamic neurons. The thalamic neuronal death that occurs over the days and weeks following cortical ablations was associated with thalamic hypometabolism. This is consistent with the idea that the thalamic neurons die because of the absence of a cortically derived trophic factor, since the excitotoxic thalamic cell death that occurs following cortical kainate injections is associated with thalamic hypermetabolism. The glucose metabolism of parts of the host thalamus was higher and the glucose metabolism in surrounding nuclei lower than the normal side of thalamus in rats that sat quietly and had fetal cortex transplants placed into cavities in whisker sensory cortex five to 16 weeks previously. Whisker stimulation in these subjects activated the contralateral host thalamus and fetal cortical transplants. This was accomplished using a double-label 2-deoxyglucose method to assess brain glucose metabolism in the same rat while it was resting and during whisker stimulation. The high glucose metabolism of parts of host thalamus ipsilateral to the fetal cortical transplants is consistent with prolonged survival of some axotomized thalamic neurons. The finding that whisker stimulation activates portions of host thalamus further suggests that the cortical transplants maintained survival of the host thalamic neurons and that synaptic connections between whisker brainstem and thalamic neurons were functional.

Animals↗

PubMed1993

Induction of 70-kDa heat shock protein and hsp70 mRNA following transient focal cerebral ischemia in the rat.

Induction of the 70-kDa heat shock protein (HSP70) was demonstrated immunocytochemically in adult rats 4 h to 7 days following temporary middle cerebral artery (MCA) occlusions lasting 30, 60, or 90 min. Maximal HSP70 induction occurred approximately 24 h following ischemia. Thirty minutes of ischemia induced HSP70 in neurons throughout the cortex in the MCA distribution, whereas 90 min of ischemia induced HSP70 in neurons in the penumbra. HSP70 protein was induced in endothelial cells in infarcted neocortex following 60-90 min of MCA occlusion, and HSP70 was induced in endothelial cells in infarcted regions of lateral striatum following 30-90 min of MCA occlusion. hsp70 mRNA was induced in the MCA distribution in cortex and to a lesser extent in striatum at 2 h to 3 days following 60 min of ischemia. It is proposed that brief ischemia induces hsp70 mRNA and HSP70 protein in the cells most vulnerable to ischemia--the neurons. HSP70 protein is not induced in most neurons and glia following 60-90 min of ischemia in areas destined to infarct, whereas it is induced in vascular endothelial cells.

Animals↗

PubMed1992

[Superficial disseminated porokeratosis with dermal amyloidosis].

A case of non-actinic disseminated superficial porokeratosis with dermal amyloid deposits in a 53 year-old-man is reported. The lesions of the trunk and arms were typical, but annular lesions of the ankles were lichenoid. The amyloid deposits were present under the cornoid lamella in the typical lesions and absent in the annular lesions. The different clinical variants of porokeratosis are discussed. The origin of amyloidosis is debated; it seems to be epidermic, due to degeneration of the keratinocytes. The secondary cutaneous amyloidosis is usually described in association with epithelial tumors or psoriasis, but exceptionally with porokeratosis.

Amyloidosis↗

PubMed1992

[Acquired atrophic pigmented band-like lesions following Blaschko's lines].

Over a seventeen years period we observed 5 patients presenting with very similar lesions the equivalent of which we could not find in the literature. These were pigmented and more or less atrophic bands which exactly followed Blaschko's lines. The lesions appeared during childhood or adolescence, between the ages of 6 and 20 years and always were unilateral. In all cases they were located on the trunk where they formed a recumbent "S" pattern characteristic of Blaschko's lines. They often started 3 to 6 cm away from the posterior midline and ended precisely on the anterior midline. These bands varied in number and in 3 out of 5 cases they were associated with pigmented atrophic bands or lines on the limbs of the same side. The intensity of pigmentation and atrophy was variable. The lesions were asymptomatic and only caused a cosmetic prejudice. They were perfectly fixed, and during a 2 to 30 years observation period they remained unmodified. The five skin biopsies performed on 3 patients showed no abnormality of the epidermis other than irregular and moderate hyperpigmentation of its deep part. In the dermis, there was no distinct pigment incontinence, no inflammation and no alteration of connective tissue texture; the elastic network was invariably normal. The impression of skin atrophy was not due to true dermal hypoplasia and perhaps corresponded to atrophy of the subcutaneous cellular tissue. No biological disturbance was observed. These lesions can easily be distinguished from epidermic naevi, incontinentia pigmenti and areas of hypoplastic dermis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗