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Biomedical subjects

H Baker

Publications and source records attributed to H Baker.

At least 55 records · Page 3Linked to original sources
PubMed1999

Immunoradiometric measurement of pS2 in breast cancer--correlation with steroid receptors and plasminogen activators.

pS2 was measured by radioimmunometric assay in tumour extracts from 197 breast cancer patients. Values ranged from 0 to 50 ng/mg protein (mean 9.6 and median 3 ng/mg). We found no correlation with age, menopausal status, nodal metastases, disease stage or tumour histology. There was, however, a linear relationship with both ER (p < 0.0001) (particularly nuclear ER) and PR (p < 0.0001) expression determined by enzyme immunoassay (ELISA), as well as a good correlation when high and low expressors were stratified on the basis of combined ER/PR expression using consensus cut-off points. Only 15% of ER - ve/PR - ve patients were classified as pS2 + ve compared with 83% of those who were ER + ve/PR + ve. pS2 was also directly correlated with high expression of tPA and inversely with uPA. Comparison with previous studies showed that the current ELISA method produced consistent results, in contrast to other methods, particularly those based on immunohistochemical detection. The close relationship between pS2 and both steroid receptors suggests that pS2 may be important in terms of defining hormone-responsive patients who are likely to benefit from endocrine therapy.

Breast Neoplasms↗
PubMed1999

Pronuclear orientation, polar body placement, and embryo quality after intracytoplasmic sperm injection and in-vitro fertilization: further evidence for polarity in human oocytes?

Three hypotheses were tested: (i) the distance between first and second polar bodies (PB) may relate to embryo morphology, (ii) that the orientation of pronuclei (PN) relative to PB may relate to embryo morphology, (iii) that the placement of a spermatozoon in a fixed plane relative to the first PB [intracytoplasmic sperm injection (ICSI)] may alter PN/PB orientation relative to in-vitro fertilization (IVF). A total of 251 two pronuclear (2PN) embryos (124 ICSI, 127 IVF) from 64 patients was studied. Angles were measured between the PN axis and the nearest PB (alpha), the furthest PB (beta), and between the two PB (gamma). On day 2, the morphological grades of embryos were recorded. gamma ranged from 0 to 150 degrees and was not significantly different for ICSI or IVF embryos of different grades; however, an unusual distribution of gamma suggested different populations of oocytes. The first hypothesis was rejected. alpha and beta ranged from 0 to 90 degrees : alpha did not relate significantly to embryo grade, but beta increased significantly with decreasing quality of ICSI embryos (P < 0.05) and the total group (P < 0.01), supporting hypothesis (ii). The difference in beta between ICSI and IVF embryos was not significant, so hypothesis (iii) was unproven. Significant differences between ICSI and IVF embryos in PN positions, irregular cleavage, and cleavage failure were noted.

Cell Nucleus↗
PubMed1998

Tyrosine hydroxylase expression in primary cultures of olfactory bulb: role of L-type calcium channels.

Sensory activity mediates regulation of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway, in the rodent olfactory bulb. The current studies established for the first time primary cultures of neonatal mouse olfactory bulb expressing TH and tested whether L-type calcium channels mediate the activity-dependent regulation of the dopamine phenotype. After 1 d in vitro (DIV), a small population of TH-immunostained neurons that lacked extensive processes could be demonstrated. After an additional 2 DIV in serum-free medium, the number of TH neurons had doubled, and they exhibited long interdigitating processes. Membrane depolarization for 48 hr with 50 mM KCl produced a further 2.4-fold increase in the number of TH-immunoreactive neurons compared with control cultures. Increased TH neuron number required at least 36 hr of exposure to KCl. Forskolin, which increases intracellular cAMP levels, induced a 1.5- to 1.6-fold increase in the number of TH-immunostained neurons. Combined treatment with KCl and forskolin was not additive. Nifedipine, an L-type calcium channel blocker, completely prevented the depolarization-mediated increase in TH expression but did not block the response to forskolin. Treatment with Bay K8644, an L-type calcium channel agonist, also significantly increased the number of TH-expressing neurons. Depolarization also induced alterations in neuritic outgrowth, resulting in a stellate versus an elongate morphology that, in contrast, was not prevented by nifedipine. These results are the first demonstration that in vitro, as in vivo, depolarization increases TH expression in olfactory bulb and that L-type calcium channels mediate this activity-dependent regulation of the dopamine phenotype.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release.

The N-lobe of human serum transferrin (hTF/2N) has been expressed in baby hamster kidney cells and crystallized in both orthorhombic (P212121) and tetragonal (P41212) space groups. Both crystal forms diffract to high resolution (1.6 and 1.8 A, respectively) and have been solved by molecular replacement. Subsequent refinement resulted in final models for the structure of hTF/2N that had crystallographic R-factors of 18.1 and 19.7% for the two crystal forms, respectively; these models represent the highest-resolution transferrin structures determined to date. The hTF/2N polypeptide has a folding pattern similar to those of other transferrins, including the presence of a deep cleft that contains the metal-binding site. In contrast to other transferrins, both crystal forms of hTF/2N display disorder at the iron-binding site; model building suggests that this disorder consists of alternative conformations of the synergistically bound carbonate anion, the side chain for Arg-124, and several solvent molecules. Subsequent refinement revealed that conformation A has an occupancy of 0.63-0. 65 and corresponds to the structure of the iron-binding site found in other transferrins. The alternative conformation B has an occupancy of 0.35-0.37; in this structure, the carbonate has rotated 30 degrees relative to the iron and the side chain for Arg-124 has moved to accommodate the new carbonate position. Several water molecules appear to stabilize the carbonate anion in the two conformations. These structures are consistent with the protonation of the carbonate and resulting partial removal of the anion from the metal; these events would occur prior to cleft opening and metal release.

Animals↗
PubMed1998

Induction of cell division in olfactory basal epithelium following intranasal irrigation with wheat germ agglutinin-horseradish peroxidase.

The lectin, wheatgerm agglutinin (WGA) conjugated to horseradish peroxidase (HRP), previously was shown to be transported into the central nervous system following application by intranasal irrigation. The current study investigated the hypothesis that uptake of molecules, such as the lectin-conjugate, by olfactory receptor cells would mimic internalization of other substances including odorants. This process would result in both premature death of receptor cells and increased turnover of their precursors, globose basal cells. Tetramethylbenzidine histochemical analysis showed the presence of significant amounts of the lectin-conjugate in both the receptor epithelium and olfactory bulb until at least 2 weeks postintranasal application. Neither supporting nor globose basal cells contained WGA-HRP, suggesting that uptake was primarily into olfactory receptor cells. Cell turnover, assessed by tritiated-thymidine (thymidine) autoradiography, increased both 1 and 2 weeks, but not 3 and 4 weeks, following intranasal irrigation with WGA-HRP. Most of the cells containing thymidine labelling appeared to be globose basal cells, although supporting cells also occasionally exhibited labelling. Survival of either mature or immature receptor cells in the epithelium, indicated by epithelial thickness and cell density of the septal epithelium, also declined following treatment. These data suggest that uptake of substances may result in cell loss from the olfactory epithelium and increased mitotic activity of basal cells.

Administration, Intranasal↗
PubMed1998

AP-1, CREB and CBP transcription factors differentially regulate the tyrosine hydroxylase gene.

The tyrosine hydroxylase (TH) gene encodes the rate-limiting enzyme in the biosynthesis of catecholamines. We have investigated the roles of two elements of the TH promoter, the TH-'Fat Specific Element' (TH-FSE) which binds the Fos-Jun complex, and the cAMP Response Element (CRE), which binds CREB and the co-activator protein, CREB Binding Protein (CBP) in regulating TH gene transcription. In PC12 cells, the TH-FSE was required for induction by NGF while the CRE was required for induction by cAMP. We show that both elements can function independently and contribute strongly to TH promoter basal activity in PC12 cells. We employed transient expression in the F9 teratocarcinoma cell line to vary experimentally the levels of the nuclear regulators implicated in TH control by the PC12 studies. In F9 cells, the TH promoter was strongly activated by Fos and Jun, and by PKA-stimulated CREB protein. In F9 and NIH3T3 cells, CBP, a co-activator which targets Fos-Jun and PKA-stimulated CREB, also induced the TH promoter. Immunohistochemical studies in rat brain regions enriched in dopaminergic neurons, including the midbrain and olfactory bulb (OB), suggest that Fos-Jun and CREB make differential contributions to TH gene activity in different tissues. Whereas changes in Fos protein levels parallel decreases in TH protein upon olfactory deprivation, CBP levels remain unchanged. This suggests that CRE-associated factors, including CBP, are not major regulators in the OB. In contrast, the presence of CREB and the absence of Fos immunoreactivity in midbrain dopaminergic cells suggests that the CRE is the primary regulator in this region.

3T3 Cells↗
PubMed1998

Localization of GTP cyclohydrolase in monoaminergic but not nitric oxide-producing cells.

The first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis is GTP cyclohydrolase (GTPCH). BH4 serves as the essential cofactor for aromatic L-amino acid hydroxylases, such as tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), as well as for nitric oxide synthase (NOS). We hypothesized that to provide access to the cofactor, a close association exists between BH4-synthesizing and BH4-dependent enzymes, and we determined the relationship among GTPCH, neuronal NOS (nNOS), and TH in rat brain and adrenal gland using immunohistochemistry and in situ hybridization. Analyses of adjacent sections revealed specific localization of GTPCH in TH-containing cells of the substantia nigra, ventral tegmental area, hypothalamus, locus ceruleus, and adrenal medulla, and also in TPH-containing cells of the dorsal raphe nucleus and pineal gland. Thus, BH4 can be synthesized in all monoaminergic cells and is readily available for the enzymes requiring it. In contrast, analysis of adjacent sections showed that nNOS was not colocalized with GTPCH. Scattered nNOS-positive cells were found in the cortex, striatum, cerebellum, and olfactory bulb, all areas that receive monoaminergic innervation. The absence of GTPCH in nNOS cells suggests that nitric oxide-producing cells may either obtain biopterin from monoamine-containing processes which terminate in close proximity, or take up biopterin released into the blood. Double labelling of the same section for TH and nNOS revealed the TH nerve terminals connecting with the nNOS-positive cell bodies, suggesting the possibility that the BH4-containing nerve terminals may directly donate this cofactor to the nNOS-containing cells.

Adrenal Glands↗
PubMed1998

A practical assay of lipoate in biologic fluids and liver in health and disease.

A procedure for assaying lipoic acid concentration in biologic fluids and tissues was devised using a eukaryotic protozoan Tetrahymena thermophila. T.thermophila has a specific and sensitive (30 pg/ml) requirement for lipoic acid. Unlike humans and other microorganisms, T.thermophila can not synthesize lipoic acid; hence, its requirement for exogenous lipoic acid is specific. The lipoic acid supplied to T. thermophila by the processing of biologic fluids and tissues during the assay procedure, permits the derivation of a practical assay for lipoate concentration as described here. Lipoate concentration in biologic fluids and tissue obtained from healthy humans, compared to those obtained from patients with renal and liver disease, indicate deviations from normal during disease. Absorption chartings of 200 mg of DL-alpha-lipoic acid in humans indicate a peak concentration of lipoate in plasma 2 h after ingestion and then a steady descent of lipoate to a baseline level after 24 h. With this practical assay, it is now possible to chart lipoate's antioxidant activity and therapeutic action during health and disease.

Absorption↗
PubMed1998

A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers.

AIMS: The aim of this study was to compare the cardiovascular effects of levobupivacaine with those of rac-bupivacaine following i.v. administration to 14 healthy male volunteers. METHODS: Drugs were infused (at 10 mg min(-1)) using a randomized, double-blind, complete crossover procedure with a washout period of at least 1 week. The administration of drug was discontinued on the appearance of defined CNS symptoms or when a total of 150 mg had been given. Parameters measured were arterial blood pressure, heart rate, ECG, ejection fraction, acceleration index, stroke index and cardiac index. RESULTS: The mean doses administered were 56.1 mg and 47.9 mg for levobupivacaine and rac-bupivacaine respectively and the maximum mean plasma concentrations were 2.62 and 2.25 microg ml(-1) respectively. Despite the dose and plasma concentrations being comparable, levobupivacaine produced a statistically significant smaller reduction in mean stroke index (-5.14 vs -11.86 ml m(-2), P=0.001), acceleration index (-0.09 vs -0.20 s(-2), P=0.011) and the ejection fraction (-2.50 vs -4.29%, P=0.024). Both levobupivacaine (non significant) and rac-bupivacaine (significant) produced small increases in the PR interval and the corrected QT interval and although the effects of rac-bupivacaine appeared to be greater the difference between the two drugs was not significant. CONCLUSIONS: In conclusion, this study has shown that following i.v. administration levobupivacaine produces significantly less effects on cardiovascular function than does rac-bupivacaine. In particular the negative inotropic effect for levobupivacaine was less than that for rac-bupivacaine as indicated by changes in stroke index, acceleration index and ejection fraction.

Adult↗
PubMed1998

Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease.

OBJECTIVE: We wanted to know if alterations in plasma cobalamin (B12) concentration and B12 carriers, e.g., holotranscobalamins (holo TC), occur in blood and liver tissue from patients with severe alcoholic liver disease. Our purpose was to test the hypothesis that liver disease may disrupt B12 distribution. METHOD: Total B12, as well as B12 bound to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas malhamensis--a protozoan reagent served to measure only metabolically active (true) B12. Total B12 as distributed in holo TC in plasma and liver tissue of healthy subjects (controls) were compared to patients with severe alcoholic liver disease. RESULTS: Severe liver disease initiates highly elevated B12 levels in plasma and a lowered liver tissue total B12 concentration. The percent of B12 distributed to holo TC II is significantly depleted during liver disease. In contrast, holo TC I and III are elevated in plasma during liver disease and contain more B12 than controls. Total B12 and B12 distributed to TC are lower in diseased liver tissue. CONCLUSION: Severe alcoholic liver disease involves leakage of total B12 from liver tissue into the plasma. Holo TC I and III concentration increases in plasma; this preserves the high plasma B12 from being excreted. However, plasma holo TC II B12 distribution is decreased, indicating that there is a depression of exogenous B12 entering the plasma and tissues. In severe liver disease, liver tissue B12 binding and storage by TC is disrupted and causes B12 to leak out of the liver into the circulation. Eventually liver disease could produce enough severe tissue B12 deficits to cause metabolic dysfunction despite elevated plasma total B12. Elevation of plasma B12, accompanied by a lowering of holo TC II distribution, seemed to be a useful index of liver disease severity suggesting preventive treatment.

Humans↗
PubMed1997

Importance of vascular changes in selective neurodegeneration with thiamine deficiency.

These results demonstrate that early alterations in the BBB may underlie selective vulnerability in this model of chronic reduced oxidative metabolism. Changes in the BBB (IgG extravasation) precede alterations in APP processing and cell death. Since thiamine-dependent enzymes are also reduced in the brain in Alzheimer's disease, similar processes may be important in the pathophysiology of the disease.

Amyloid beta-Protein Precursor↗
PubMed1997

Microalbuminuria in patients with non-insulin-dependent diabetes mellitus relates to nocturnal systolic blood pressure.

PURPOSE: Microalbuminuria predicts early mortality in non-insulin-dependent-diabetes mellitus patients (NIDDM). Our objective in the present study was to compare and assess the relationship between 24-hour, day and nocturnal ambulatory blood pressure (BP) and urinary albumin excretion rate (UAE) in microalbuminuric and normoalbuminuric NIDDM and in normal control subjects. PATIENTS AND METHODS: In the present cross-sectional study, 24 hour ambulatory BP (daytime BP and nocturnal BP) and HbA1c were compared in microalbuminuric (n = 10) and nonmicroalbuminuric NIDDM patients (n = 10) and in nondiabetic controls (n = 9). None of the patients were taking antihypertensive agents. RESULTS: In the microlbuminuric group, whereas 24 hour and daytime systolic BP differed significantly from control values (P < 0.025 and P < 0.05 respectively), there was no difference between diabetic groups. However, nocturnal systolic BP in the microalbuminuric group was significantly higher than in the normoalbuminuric diabetic patients (139 vs. 125) (P < 0.05) and a significant difference was also found between the NIDDM patients and the control group (139, 125 vs. 114) (P < 0.025). In multiple regression analysis, only nocturnal systolic BP showed a significant relationship with UAE (P < 0.05). CONCLUSIONS: We suggest that the higher nocturnal systolic blood pressure seen in our microalbuminuric NIDDM patients may contribute to the increased morbidity in this group.

Adult↗
PubMed1997

Subpopulations of stromal cells from long-term human bone marrow cultures: ontogeny of progenitor cells and expression of growth hormone receptors.

Long-term culture of bone marrow derived stromal colony forming cells (S-CFC) in matrix and nutrient defined agar medium resulted in stromal cell colonies that pass sequentially through three distinct morphological stages: firstly, aggregated loose syncytium of round to avoid cells (stage I), a second developmental stage of large branching colonies in which the cells become enlarged, elongated with cytoplasmic projections forming a loosely anastomized network with adjacent cells (stage II), and finally cells become dissociated, loosing their long, thin cytoplasmic filaments and breaking their contacts with one another, but remain large and retain a bi-polar nature (stage III). Cells were also grown in liquid medium in a culture microenvironment closely resembling conditions of haemopoiesis in vitro. Using a panel of well defined monoclonal antibodies reactive against the rat, rabbit and human growth hormone receptors, this study found immunochemical evidence of the presence and localization of binding sites of growth hormone (GH) in the cell membrane and extra-nuclear Golgi area of long-term bone marrow derived human stromal cells in liquid and semi-solid nutrient agar mediums. GH-receptor immunoreactivity was present in small proliferating progenitor cells, myofibroblast-like cells, large reticular fibroblast cells, adipocytes and endothelial cells. Only MAb known to be reactive against human tissue resulted in strong immunoreactivity. The expression of GH-receptors not only on small proliferating, but also on the well differentiated cells, indicates a role for growth hormone on non-progenitor cells. GH-receptor immunoreactivity on differentiating and/or differentiated cells suggests that GH is also necessary for, or has a trophic function in differentiation. We propose that direct GH action is necessary not only for differentiation of progenitor cells as implied by the dual effector hypothesis, but also their subsequent clonal expansion, differentiation and maintenance.

Animals↗
PubMed1997

Antisense inhibition of 5-hydroxytryptamine2a receptor induces an antidepressant-like effect in mice.

Treatment with different antidepressants is invariably accompanied by the down-regulation of the 5-hydroxytryptamine2A (5-HT2A) receptor. To determine whether receptor down-regulation is an essential part of antidepressant action, we manipulated levels of the 5-HT2A receptor by using a nonpharmacological approach. Here, we report that down-regulation of the 5-HT2A receptor by intracerebroventricular injection of antisense oligonucleotides resulted in an antidepressant-like effect in mice. Animals with 5-HT2A receptor deficiency showed less immobility in the Porsolt's forced swim test, a well established animal model that is used to identify drugs with an antidepressant effect. The overall locomotor activity of the receptor-deficient animals was not altered, demonstrating the specificity of the behavioral change in the Porsolt's forced swim test. Reduced immobility in this test was accompanied by a greater c-Fos response in piriform cortex. Because 5-HT2A receptors have been localized on gamma-aminobutyric acid interneurons, the inhibitory activity of these neurons may be impaired at low receptor levels, leading to a greater c-Fos response in the piriform cortex and increased mobility in the Porsolt's forced swim test. These experiments demonstrate that down-regulation of the 5-HT2A receptor alone is sufficient to achieve an antidepressant-like effect in mice and suggest that receptor down-regulation may be an essential part of the antidepressant drug action.

Animals↗
PubMed1997

Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in goldfish.

Electrophysiological, ultrastructural, and immunohistochemical techniques were utilized to describe the excitatory and inhibitory vestibular innervation of extraocular motor nuclei in the goldfish. In antidromically activated oculomotor motoneurons, electrical stimulation of the intact contralateral vestibular nerve produced short-latency, variable amplitude electrotonic excitatory postsynaptic potentials (EPSPs) at 0.5-0.7 ms followed by chemical EPSPs at 1.0-1.3 ms. Stimulation of the ipsilateral vestibular nerve produced small amplitude membrane hyperpolarizations at a latency of 1.3-1.7 ms in which equilibrium potentials were slightly more negative than resting potentials. The inhibitory postsynaptic potentials (IPSPs) reversed with large amplitudes after the injection of chloride ions suggesting a proximal soma-dendritic location of terminals exhibiting high efficacy inhibitory synaptic conductances. In antidromically identified abducens motoneurons and putative internuclear neurons, electrical stimulation of the contralateral vestibular nerve produced large-amplitude, short-latency electrotonic EPSPs at 0.5 ms followed by chemical depolarizations at 1.2-1.3 ms. Stimulation of the ipsilateral vestibular nerve evoked IPSPs at 1.4 ms that were reversed after injection of current and/or chloride ions. gamma-Aminobutyric acid (GABA) antibodies labeled inhibitory neurons in vestibular subdivisions with axons projecting into the ipsilateral medial longitudinal fasciculus (MLF). Putative GABAergic terminals surrounded oculomotor, but not abducens, motoneurons retrogradely labeled with horseradish peroxidase. Hence the spatial distribution of GABAergic neurons and terminals appears highly similar in the vestibuloocular system of goldfish and mammals. Electron microscopy of motoneurons in the oculomotor and abducens nucleus showed axosomatic and axodendritic synaptic endings containing spheroidal synaptic vesicles establishing chemical, presumed excitatory, synaptic contacts with asymmetric pre- and/or postsynaptic membrane specializations. The majority of contacts with spheroidal vesicles displayed gap junctions in which the chemical and electrotonic synapses were either en face to dissimilar or adjacent to one another on the same soma/dendritic profiles. Another separate set of axosomatic synaptic endings, presumed to be inhibitory, contained pleiomorphic synaptic vesicles with symmetric pre- and/or postsynaptic membrane specializations that never included gap junctions. Excitatory and inhibitory synaptic contacts appeared equal in number but were more sparsely distributed along the soma-dendritic profiles of oculomotor as compared with abducens motoneurons. Collectively these data provide evidence for both disynaptic vestibular inhibition and excitation in all subdivisions of the extraocular motor nuclei suggesting the basic vestibulooculomotor blueprint to be conserved among vertebrates. We propose that unique vestibular neurons, transmitters, pathways, and synaptic arborizations are homologous structural traits that have been essentially preserved throughout vertebrate phylogeny by a shared developmental plan.

Abducens Nerve↗
PubMed1996

Prolonged in vivo gene expression driven by a tyrosine hydroxylase promoter in a defective herpes simplex virus amplicon vector.

A 9.0-kb fragment of the tyrosine hydroxylase (TH) promoter, previously shown to direct tissue-specific expression in transgenic mice, was fused to an Escherichia coli LacZ reporter gene in a defective herpes simplex virus type-1 (HSV-1) amplicon vector (THlac). The HSV immediate early (IE) 4/5 promoter (HSVlac) was used as a control. LacZ gene expression was visualized by X-Gal histochemical and TH immunocytochemical analysis. Two days and 10 weeks after THlac injection into rat caudate nucleus (CN), X-Gal-stained cells were observed in the substantia nigra (SN) and locus ceruleus (LC) ipsilateral to the injection site. These blue cells were TH-positive neurons as evidenced by double labeling with immunocytochemistry. Moreover, the number of X-Gal+, TH+ (double-positive) neurons in the SN increased at 10 weeks as compared to that seen 2 days after THlac injection. In marked contrast, few double-positive nigral neurons were observed either 2 days or 10 weeks after direct injection of THlac into SN. However, neither nigral nor striatal injection of HSVlac resulted in prolonged gene expression. These results suggest that a neuronal, but not a viral, promoter in an HSV vector can produce cell-type-specific, prolonged, and stable gene expression following retrograde transport. In addition, THlac produced infrequent gene expression in TH-negative cells (CN and dorsal to SN) after THlac injection into CN and SN, respectively. Overall, these results suggest that in some in vivo contexts cell-type-preferred expression can be achieved by a cellular promoter in an amplicon vector. Moreover, they underscore the need for the careful and systematic study of neuronal promoters in HSV vectors.

Defective Viruses↗