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Biomedical subjects

D L Brown

Publications and source records attributed to D L Brown.

At least 91 records · Page 5Linked to original sources
PubMed1998

Benign and malignant ovarian masses: selection of the most discriminating gray-scale and Doppler sonographic features.

PURPOSE: To determine the gray-scale and Doppler sonographic features that best enable discrimination between malignant and benign ovarian masses and develop a scoring system for accurate diagnosis with these features. MATERIALS AND METHODS: Gray-scale and Doppler sonographic features of 211 adnexal masses were correlated with the final diagnosis; the most discriminating features for malignancy were selected with stepwise logistic regression. RESULTS: Twenty-eight masses were malignant and 183 benign. All masses with a markedly hyperechoic solid component or no solid component were benign. For masses with a nonhyperechoic solid component, additional features that allowed statistically significant discrimination of benignity from malignancy were, in decreasing order of importance, (a) location of flow at conventional color Doppler imaging, (b) amount of free intraperitoneal fluid, and (c) presence and thickness of septations. A scoring formula that made use of values based on the logistic regression equation had an area under the receiver operating characteristic curve of 0.98 +/- 0.01. The cutoff score with the highest accuracy had a sensitivity of 93% and specificity of 93%. CONCLUSION: A solid component is the most statistically significant predictor of a malignant ovarian mass. A multiparameter scoring system that uses three gray-scale and one Doppler feature, developed by means of stepwise logistic regression, has high sensitivity and specificity for predicting malignancy.

Adolescent↗
PubMed1998

Paraovarian cystadenomas and cystadenofibromas: sonographic characteristics in 14 cases.

PURPOSE: To describe the sonographic features of paraovarian cystadenomas. MATERIALS AND METHODS: We searched the computerized pathology and radiology databases for cases of histopathologically proved paraovarian cystadenomas from January 1993 through December 1996 in which preoperative sonography had also been performed. Fourteen paraovarian cystadenomas or cystadenofibromas were identified in 14 patients aged 20-57 years. Sonographic and pathologic findings were correlated. RESULTS: Three of the masses appeared as simple cysts sonographically. Of the remaining 11 masses, nine had solid nodular areas within the cyst; three had septations; and four had a thick wall, an irregular wall, or both at sonography. At sonography, four masses were thought to arise outside the ovary, four were erroneously thought to arise in the ovary, and the location was uncertain in six. CONCLUSION: Paraovarian cystadenomas are cystic masses that usually contain one or more small solid nodules and occasionally contain septations.

Adenofibroma↗
PubMed1998

Acute delirium after withdrawal of amantadine in Parkinson's disease.

We present three patients who, after long-term therapy with amantadine (4 to 18 years), experienced an acute delirium with confusion, disorientation, agitation, and paranoia on withdrawal. These patients had Parkinson's disease for 5 to 29 years; mean age was 73 years. All had a history of varying degrees of dementia and transient hallucinations in the past. Adjustment of other medications was ineffective in improving their condition and no other cause was found. Only with reinstitution of amantadine did the patients return to baseline status (usually within days).

Acute Disease↗
PubMed1998

Splenic T lymphocytes die preferentially during heat-induced apoptosis: NuMA reorganization as a marker.

We are investigating nuclear events during apoptosis in mouse splenic lymphocytes cultured immediately after isolation (controls) or after heat treatment (42 degreesC, 30 minutes), and have found that hyperthermia increased the level of apoptosis to double that of spontaneous apoptosis in controls within 6 hours. Immunolabelling for Nuclear Mitotic Apparatus Protein (NuMA) suggested that splenocytes were responding heterogeneously to the heat treatment. Whereas all nuclei in controls and about half of nuclei in heat-treated samples showed the usual diffuse nucleoplasmic labelling, 40-60% of nuclei in heated samples also contained numerous bright spots. We then examined whether the heterogeneity in NuMA organization might be an indication of a differential response of B and T lymphocytes to hyperthermia, and whether the presence of NuMA spots is related to the apoptotic process. NuMA labelling of heated fractionated splenocyte populations showed that 90% of nuclei in T-enriched cultures (less than or equal to 4% IgG+ cells), but only 25% of nuclei in B-enriched samples (less than or equal to 80% IgG+ cells), contained spots. As well, 2 hours after heat treatment of unfractionated cultures, greater than or equal to 90% of nuclei that were accumulating DNA strand breaks, as detected by TUNEL, exhibited NuMA spots. These data indicate that cells with NuMA spots are targetted for, or have initiated, the death program. Since most T cells, but few or no B cells, were spotty after heating, we conclude further that hyperthermia induces apoptosis preferentially in splenic T lymphocytes. The observation that the proportion of T cells was, on average, threefold greater in control than in heated samples after 24 hours in culture reinforces this conclusion.

Animals↗
PubMed1998

Sonographic evaluation of the placental cord insertion site.

OBJECTIVE: Velamentous and marginal umbilical cords are uncommon abnormalities of placental cord insertion that can entail significant fetal risk. We undertook this investigation to assess the ability of prenatal sonography to reveal abnormal insertions of the umbilical cord into the placenta. SUBJECTS AND METHODS: Forty-six patients had both prenatal sonographic evaluation of the placental cord insertion site and postnatal pathologic examination. Distance from the insertion site to the nearest placental edge was categorized by sonography and pathology as normal if greater than 1 cm and abnormal if less than or equal to 1 cm. Sonographic and pathologic findings were compared. RESULTS: Thirty-eight singleton and eight twin pregnancies, for a total of 54 cord insertions, were studied. Of the 43 sonographically normal insertions, 38 had normal pathologic findings, and the remaining five insertions had abnormal pathologic findings (all marginal cord insertions). All 11 insertions that showed abnormality on sonography were abnormal on pathologic examination (seven marginal and four velamentous insertions). Sonography was able to reveal a difference between the two types of abnormal insertions in only a single patient, in whom the cord insertion changed from marginal to velamentous during a 7-week interval. Sonography had an overall sensitivity of 69% (11/16), a specificity of 100% (38/38), and an accuracy of 91% (49/54) for revealing abnormal placental cord insertion sites. CONCLUSION: Targeted sonographic examination of the placental site of umbilical cord insertion will reveal abnormal placental cord insertions, although distinguishing the specific type of abnormal insertion may require the use of color Doppler imaging.

Chorion↗
PubMed1998

Complications of percutaneous ethanol ablation.

Percutaneous ethanol injection therapy performed with sonographic visualization is a steadily growing therapeutic method that can be used in the ablation of solid and cystic masses in a variety of anatomic locations. Ethanol has been used for many years as an angiographically administered agent for vascular embolization of tumors such as hepatic and renal neoplasms. It was first used as a percutaneously injected agent for the sclerosis of renal cysts. Local infiltration or intravascular injection of ethanol leads to cell death by causing cell membrane lysis, protein denaturation, and vascular occlusion. Because of the initial success in the sclerosis of renal cysts, percutaneously injected ethanol is now used in the ablation of hepatic cysts and solid tumors, such as hepatocellular carcinomas. As a treatment agent, ethanol combines the benefits of being widely available, inexpensive, efficacious, and relatively easy to administer. Optimal results require that the radiologist have considerable experience in ultrasonographic scanning techniques and facility with percutaneous needle insertion under real-time visualization. Alternatively, the radiologist may choose CT as a method to visualize needle placement. Percutaneous ethanol injection therapy usually is an effective alternative to conventional surgical resection of liver lesions and has a low complication rate. We present two patients in whom hypotensive complications occurred during percutaneous ethanol injection therapy and discuss the likely causative mechanisms.

Aged↗
PubMed1998

Infraclavicular brachial plexus block: parasagittal anatomy important to the coracoid technique.

UNLABELLED: Infraclavicular brachial plexus block is a technique well suited to prolonged continuous catheter use. We used a coracoid approach to this block to create an easily understood technique. We reviewed the magnetic resonance images of the brachial plexus from 20 male and 20 female patients. Using scout films, the parasagittal section 2 cm medial to the coracoid process was identified. Along this oblique section, we located a point approximately 2 cm caudad to the coracoid process on the skin of the anterior chest wall. From this point, we determined simulated needle direction to contact the neurovascular bundle and measured depth. At the skin entry site, the direct posterior insertion of a needle will make contact with the cords of the brachial plexus where they surround the second part of the axillary artery in all images. The mean (range) distance (depth along the needle shaft) from the skin to the anterior wall of the axillary artery was 4.24 +/- 1.49 cm (2.25-7.75 cm) in men and 4.01 +/- 1.29 cm (2.25-6.5 cm) in women. Hopefully, this study will facilitate the use of this block. IMPLICATIONS: We sought a consistent, palpable landmark for facilitation of the infraclavicular brachial plexus block. We used magnetic resonance images of the brachial plexus to determine the depth and needle orientation needed to contact the brachial plexus. Hopefully, this study will facilitate the use of this block.

Adult↗
PubMed1997

High-speed rotational atherectomy of human coronary stenoses: acute and one-year outcomes from the New Approaches to Coronary Intervention (NACI) registry.

High-speed rotational atherectomy (RA) is a new percutaneous procedure for treatment of coronary stenoses that operates by the unique mechanism of plaque abrasion. This article reports acute (in-hospital) outcomes and 1-year follow-up in a large cohort of patients treated with this device by NACI investigators. A total of 525 patients with 670 lesions treated with RA form the substrate of this report. Patients tended to be older (mean age 64.8 years) than those in previously reported series of percutaneous transluminal coronary angioplasty (PTCA), with more extensive disease and more complex lesions. Calcification was present in 54% of lesions, and eccentricity in 41%. Balloon angioplasty postdilation was performed after RA in 88% of cases. Angiographic and procedural success (angiographic success without death, Q-wave myocardial infarction [MI] or emergency coronary artery bypass graft [CABG] surgery) rates were 89% and 88%, respectively. Acute in-hospital events included 4 deaths (1%) and 1 emergency CABG surgery (0.4%). MI occurred in 6% of patients, consisting predominantly of non-Q-wave MI (5%). After RA, angiographic complications included coronary dissection (12%), abrupt closure (5%), side branch occlusion (3%), and distal embolization (3%). Most of these were resolved after postdilation except for coronary dissection, which was present in 15% of lesions treated. Mean length of stay was 3 days. At 1-year follow-up, 27% of patients required target lesion revascularization and 30% had experienced death, Q-wave MI, or target lesion revascularization. Preprocedural characteristics that independently predicted 1-year death, Q-wave MI, or target lesion revascularization were male gender, high risk for surgery, target lesions that were proximal to or in bifurcations, eccentric, long, or highly stenosed. RA, even when applied to lesions of traditionally unfavorable morphology, appears to provide reasonable procedural and angiographic success rates. Restenosis and progression of disease contribute to subsequent clinical and procedural events.

Aged↗
PubMed1997

A Leu117-->Trp mutation within the RGD-peptide cross-linking region of beta3 results in Glanzmann thrombasthenia by preventing alphaIIb beta3 export to the platelet surface.

We report a case of Glanzmann thrombasthenia in a Pakistani child whose platelets express less than 10% of the normal amount of alphaIIb beta3 on their surface. Single-stranded conformation polymorphism analysis of the exons of the patient's alphaIIb and beta3 genes showed an abnormality in exon 4 of the beta3 gene. Direct sequence analysis showed that the patient was homozygous for a T --> G nucleotide substitution in this exon, resulting in the replacement of a highly conserved Leu at position 117 with Trp. Heterologous expression of alphaIIb beta3 containing the beta3 mutation in COS-1 cells confirmed the pathogenicity of the Leu117 --> Trp substitution and showed that it resulted in the intracellular retention of malfolded alphaIIb beta3 heterodimers. Additional site-directed mutagenesis at position 117 indicated that, although the smaller hydrophobic amino acid Val could be substituted for the wild-type Leu, the larger hydrophobic amino acids Trp and Phe or the charged amino acids Asp and Lys were not tolerated. These studies indicate that Leu117 in beta3 plays a critical role in attaining the correct folded conformation of alphaIIb beta3. These studies also suggest that the hydrophobic side chain of Leu117 is likely folded into the interior of beta3, where it serves to stabilize internal packing of the protein and determines its overall shape.

Alleles↗
PubMed1997

Development and validation of a noninvasive method to determine arterial pressure and vascular compliance.

The ability not only to record automated systolic and diastolic pressure, but also to derive measurements of the rate of pressure change during the cardiac cycle, would have great potential clinical value. A new method has been developed to obtain pressure measurements at 20-ms intervals by oscillometric cuff signal pattern recognition. Derivation of noninvasive pressure measurements is based on a T tube aorta and straight tube brachial artery, and assumes that the systolic phase of the suprasystolic cuff signal and the diastolic phase of the subdiastolic cuff signal most closely approximate systolic and diastolic aortic pressures, respectively. Arterial pressures obtained by this method were compared with simultaneous invasive measurements from the thoracic aorta in 36 patients. Good agreement was observed between noninvasive and invasive methods for systolic (146 +/- 4 vs 145 +/- 5 mm Hg), diastolic (80 +/- 2 vs 77 +/- 2 mm Hg), and mean (100 +/- 3 vs 100 +/- 3 mm Hg) arterial pressures, and correlation coefficients were r = 0.94, 0.91, and 0.95, respectively. To assess the validity of measurements of the rate of pressure change, oscillometric cuff signals from a subgroup of 14 patients were analyzed in detail for the peak positive pressure derivative (dP/dt(Max)), peak negative pressure derivative (dP/dt(Min)), and time interval between peak positive and peak negative pressure derivatives [t(pp)]. Results (mean +/- SEM) were: [table in text]. The incorporation of measurements of the rate of pressure change into a physical model of the brachial artery was used to derive vascular compliance. A significant correlation was observed between vascular compliance derived from the oscillometric signal and determinations by either thermodilution or Fick methods and noninvasive pressures (n = 20, r = 0.83, p <0.001). Day-to-day variability for blood pressure and vascular compliance derived by the noninvasive method did not differ by >4%, representing a reproducible measure of vascular structure and function. We conclude that the measurement of absolute pressure and rate of pressure change show good correlation with catheter data and that vascular compliance can be reliably assessed by this new method. The technology should provide a valuable noninvasive tool for the assessment of both cardiac function and vascular properties.

Adult↗
PubMed1997

Conformationally constrained [p-(omega-aminoalkyl)phenacetyl]-L-seryl-L-lysyl dipeptide amides as potent peptidomimetic inhibitors of Candida albicans and human myristoyl-CoA:protein N-myristoyl transferase.

MyristoylCoA:protein N-myristoyltransferase (NMT) covalently attaches the 14-carbon saturated fatty acid myristate, via an amide bond, to the N-terminal glycine residues of a variety of cellular proteins. Genetic studies have shown that NMT is essential for the viability of the principal fungal pathogens which cause systemic infection in immunosuppressed humans and hence is a target for development of fungicidal drugs. We have generated a class of potent peptidomimetic inhibitors of the NMT from one such fungal pathogen, Candida albicans. The N-terminal tetrapeptide from a substrate analog inhibitor, ALYASKL-NH2, was replaced with an omega-aminoalkanoyl moiety having an optimal 11-carbon chain for inhibition (11-aminoundecanoyl-SKL-NH2, 3a, IC50 = 1.2 +/- 0.14 microM). A series of replacements for the C-terminal Leu established that residues containing a lipophilic side chain were most effective, with cyclohexylalanine having the greatest potency (3g, IC50 = 0.36 +/- 0.06 microM). Removal of the carboxamide moiety led to a metabolically stable dipeptide inhibitor containing an N-(cyclohexylethyl)lysinamide (17e, IC50 = 0.11 +/- 0.03 microM). Partial rigidification of the flexible aminoundecanoyl chain produced the dipeptide p-(omega-aminohexyl)phenacetyl-L-seryl-L-lysyl-N-(cyclohexyleth yl)amide (26b, IC50 = 0.11 +/- 0.04 microM). Subsequent incorporation of an alpha-methyl substituent into 26b provided the dipeptide analog [2-[p-(omega-aminohexyl)phenyl]propionyl]-L-seryl-L-lysyl-N-(cyclohex ylethyl)amide, a very potent inhibitor (48, IC50 = 0.043 +/- 0.006 microM), which retained the three essential elements required for recognition by the acyl transferase's peptide binding site.

Acyltransferases↗
PubMed1997

Scanning alanine mutagenesis and de-peptidization of a Candida albicans myristoyl-CoA:protein N-myristoyltransferase octapeptide substrate reveals three elements critical for molecular recognition.

Candida albicans produces a single myristoyl-CoA:protein N-myristoyltransferase (Nmt) that is essential for its viability. An ADP-ribosylation factor (Arf) is included among the few cellular protein substrates of this enzyme. An octapeptide (GLYASKLS-NH2) derived from a N-terminal Arf sequence was used as the starting point to identify elements critical for recognition by the acyltransferases's peptide-binding site. In vitro kinetic studies, employing purified Nmt and a panel of peptides with single Ala substitutions at each position of GLYASKLS-NH2, established that its Gly1, Ser5, and Lys6 residues play predominant roles in binding. ALYASKLS-NH2 was found to be an inhibitor competitive for peptide (Ki = 15.3 +/- 6.4 microM) and noncompetitive for myristoyl-CoA (Ki = 31.2 +/- 0.7 microM). A survey of 26 derivatives of this inhibitor, representing (i) a complete alanine scan, (ii) progressive C-terminal truncations, and (iii) manipulation of the physical-chemical properties of its residues 1, 5, and 6, confirmed the important stereochemical requirements for the N-terminal amine, the beta-hydroxyl of Ser5, and the epsilon-amino group of Lys6. Remarkably, replacement of the the N-terminal tetrapeptide of ALYASKLS-NH2 with an 11-aminoundecanoyl group produced a competitive inhibitor, 11-aminoundecanoyl-SKLS-NH2, that was 38-fold more potent (Ki = 0.40 +/- 0.03 microM) than the starting octapeptide. Removing the primary amine (undecanoyl-SKLS-NH2), or replacing it with a methyl group (dodecanoyl-SKLS-NH2), resulted in 26- and 34-fold increases in IC50, confirming the important contribution of the amine to recognition. Removal of LeuSer from the C terminus (11-aminoundecanoyl-SK-NH2) yielded a competitive dipeptide inhibitor with a Ki (11.7 +/- 0.4 microM) equivalent to that of the starting octapeptide, ALYASKLS-NH2. Substitution of Ser with homoserine, cis-4-hydroxyproline, or tyrosine reduces potency by 3-70-fold, emphasizing the requirement for proper presentation of the hydroxyl group in the dipeptide inhibitor. Substituting D- for L-Lys decreases its inhibitory activity >100-fold, while deletion of the epsilon-amino group (Nle) or masking its charge (epsilon-N-acetyl-lysine) produces 4-7-fold attenuations. L-His, but not its D-isomer, can fully substitute for L-Lys, producing a competitive dipeptide inhibitor with similar potency (Ki = 11.9 +/- 1.0 microM). 11-Aminoundecanoyl-SK-NH2 and 11-aminoundecanoyl-SH-NH2 establish that a simple alkyl backbone can maintain an appropriate distance between three elements critical for recognition by the fungal enzyme's peptide-binding site: a simple omega-terminal amino group, a beta-hydroxyl, and an epsilon-amino group or an imidazole. These compounds contain one peptide bond and two chiral centers, suggesting that it may be feasible to incorporate these elements of recognition, or functionally equivalent mimics, into a fully de-peptidized Nmt inhibitor.

Acyltransferases↗
PubMed1997

Differential expression of 92-kDa gelatinase in primary atherosclerotic versus restenotic coronary lesions.

Rupture of atherosclerotic plaque resulting in intravascular thrombosis and myocardial infarction (MI), while a common sequelae of de novo atherosclerotic lesions, is an uncommon consequence of restenosis. We hypothesize that the rarity of MI associated with restenotic lesions is a result of cellular and biochemical modifications induced by the local response to mechanical injury rendering the site resistant to rupture. Clinical and angiographic features of patients presenting with symptomatic primary (n = 24) or restenotic coronary lesions (n = 12) who underwent directional atherectomy were compared. Histologic analysis and immunostaining for 92-kDa gelatinase were performed on each atherectomy specimen. There was no significant difference between the 2 groups regarding age, gender, incidence of diabetes, smoking, hypertension, hypercholesterolemia, or previous MI. Lesion length, extent, and distribution of disease and percent stenosis were not significantly different between groups. However, 8% of primary lesions were hypercellular compared with 75% of restenotic specimens (p = 0.0001). Hypercellularity in restenotic specimens was shown by adjacent section staining to be composed of smooth muscle cells. Ninety-two kDa gelatinase was expressed in 79% of primary lesions versus 0% of restenotic specimens (p = 0.0001). Thrombus was identified in 54% of primary lesions versus 22% of restenotic lesions (p <0.05). These findings suggest that, independent of clinical or angiographic influences, balloon injury induces increased lesion cellularity and reduced expression of 92-kDa gelatinase, possibly resulting in a reduced propensity for plaque rupture and thrombosis.

Aged↗
PubMed1997

Selective peptidic and peptidomimetic inhibitors of Candida albicans myristoylCoA: protein N-myristoyltransferase: a new approach to antifungal therapy.

MyristoylCoA: protein N-myristoyltransferase (NMT) catalyzes the cotranslational covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often essential for expression of the biological functions for these proteins. Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable association with membranes. The partitioning of N-myrisotylproteins is therefore often modulated by "switches" that function through additional covalent or noncovalent modifications. Candida albicans, the principal cause of systemic fungal infection in immunocompromised humans, contains a single NMT gene that is essential for its viability. The functional properties of the acylCoA binding site of human and C. albicans NMT are very similar. However, there are distinct differences in their peptide binding sites. An ADP ribosylation factor (Arf) is included among the few cellular protein substrates of the fungal enzyme. Alanine scanning mutagenesis of an octapeptide derived from an N-terminal Arf sequence (GLYASKLS-NH2) disclosed that Gly1, Ser5, and Lys6 play predominant roles in binding. ALYASKLS-NH2 is an inhibitor competitive for peptide [Ki(app) = 15.3 +/- 6.4 microM] and noncompetitive for myristoylCoA. Remarkably, replacement of the N-terminal tetrapeptide with an 11-aminoundecanoyl group results in a competitive inhibitor (11-aminoundecanoyl-SKLS-NH2) that is approximately 40-fold more potent [Ki(app) = 0.40 +/- 0.03 microM] than the starting octapeptide. Removal of Leu-Ser from the C-terminus generates a competitive dipeptide inhibitor (11-aminoundecanoyl-SK-NH2) with a Ki(app) of 11.7 +/- 0.4 microM, equivalent to that of the starting octapeptide. A derivative dipeptide inhibitor containing a C-terminal N-cyclohexylethyl lysinamide moiety has the advantage of being more potent (IC50 = 0.11 +/- 0.03 microM) and resistant to digestion by cellular carboxypeptidases. Rigidifying the flexible aminoundecanoyl chain results in very potent general NMT inhibitors (IC50 = 40-50 nM). Substituting a 2-methylimidazole for the N-terminal amine and adding a benzylic alpha-methyl group with R stereochemistry to the rigidifying element produces even more potent inhibitors (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to human enzyme. A related less potent member of this series of compounds is fungistatic. Its growth inhibitory effects are associated with a reduction in cellular protein N-myristoylation, judged using cellular Arf as a reporter. These studies establish that NMT is a new antifungal target.

Acyltransferases↗
PubMed1997

Altered sensitivity of posttranslationally modified microtubules to methylmercury in differentiating embryonal carcinoma-derived neurons.

The effects of methylmercury (MeHg) on microtubules (MTs) in differentiating neurons derived from retinoic acid-induced embryonal carcinoma (EC) cells in culture were examined by immunofluorescence microscopy. Undifferentiated EC cells contained mostly kinetically labile tyrosinated (TYR) MTs which extended from the centrosome and a small population of stable acetylated (ACT) MTs usually (but not exclusively) associated with the centrosome. TYR MTs of undifferentiated cells underwent concentration- and time-dependent disassembly upon exposure to low concentrations of MeHg (1-2 microM), whereas ACT MTs were resistant to MeHg at low concentrations, with many remaining intact even in 5 microM MeHg. After 2 days in retinoic acid the appearance of short neuritic processes was indicative of early differentiation. TYR MTs predominated both in the short neurites and cell soma and remained susceptible to low concentrations of MeHg. ACT MTs also extended into the short neurites but were most often found in small bundles within the perikarya. ACT MTs remained more resistant to MeHg than TYR MTs. The neuron-specific tubulin isotype betaIII was first detected during the second day of differentiation. MTs labeled with antibodies to betaIII showed similar sensitivity to MeHg as TYR MTs, suggesting that MTs containing betaIII were largely tyrosinated. After 4 and 6 days of differentiation a greater number of betaIII-positive neurons were present with progressively longer and often branching neurites. TYR MTs were present in cell soma and neurites while ACT MTs were found almost exclusively in neurites. TYR MTs remained highly susceptible to MeHg (most notably in perikarya) in comparison to ACT MTs at all stages of differentiation; however, with increasing time in culture, even TYR MTs gained appreciable stability to MeHg. These data indicate that microtubules in developing neurons become progressively more resistant to disassembly by MeHg, suggesting that the most critical period of MT susceptibility occurs very early in development in vivo.

Antibodies, Monoclonal↗