Biomedical subjects

G Shapiro

Publications and source records attributed to G Shapiro.

At least 19 recordsLinked to original sources

PubMed2001

Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years.

OBJECTIVE: Montelukast is a leukotriene receptor antagonist administered orally once daily for treatment of chronic asthma in adults and children. A comprehensive analysis of safety data from double-blind, randomized, placebo-controlled trials with montelukast has not been previously reported. PATIENTS AND METHODS: A pooled analysis of safety data from 11 multicentre, randomized, controlled montelukast Phase IIb and III trials and five long-term extension studies was performed. A total of 3386 adult patients (aged 15-85 years) and 336 paediatric patients (aged 6-14 years) were enrolled in the trials; 2031 adults received montelukast for up to 4.1 years, and 257 children received montelukast for up to 1.8 years. Summary statistics comparing incidences of adverse events among treatment groups were calculated. RESULTS: The overall incidence of clinical and laboratory adverse events among montelukast-treated patients, both adult and paediatric, was similar to that among patients receiving placebo. There were no clinically relevant differences in individual adverse events, including infectious upper respiratory conditions and transaminase elevations, between montelukast and placebo groups. Discontinuations due to adverse events occurred with similar frequencies during placebo, montelukast and inhaled beclomethasone therapy. No dose-related adverse effects of montelukast were observed in adults treated with dosages as high as 200 mg per day (20 times the recommended dose) for 5 months. This tolerability profile montelukast observed in clinical trials has been generally reflected in the post-marketing safety experience seen to date. CONCLUSIONS: These data indicate a tolerability profile for montelukast similar to placebo during both short-term and long-term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6-14 years.

Acetates↗

PubMed2001

Oxidative stress during hemodialysis: effect of heparin.

BACKGROUND: Patients on chronic hemodialysis (HD) are exposed to oxidative stress. An HD session is used in this study as an in vivo model for studying the influence of heparin on oxidative stress caused partially by activated peripheral blood polymorphonuclear leukocytes (PMNLs) during a HD session. METHODS: Each patient underwent HD once with and once without heparin. Oxidative stress was determined by evaluating both the rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNLs and plasma levels of oxidized glutathione (GSSG), both measured before and after the dialysis session. RESULTS: In vitro, heparin reduced the rate of superoxide release from separated PMA-stimulated PMNLs. In vivo, the rate of superoxide release from PMNLs was always increased after the dialysis session, regardless of the presence of heparin. However, in the presence of heparin, this increase was significantly smaller. The augmentation in the rate of superoxide release after the dialysis session without heparin was accompanied by a significant elevation of GSSG, reflecting a preceding oxidation of plasma glutathione. CONCLUSIONS: The increase in both parameters, the rate of superoxide release, and the plasma GSSG concentration after HD treatment suggest that heparin in vivo alleviates the oxidative stress induced by the dialysis process. Based on our results, heparin should be the anticoagulant of choice because of its suppressant action on HD-induced oxidative stress.

Adult↗

PubMed2001

Medical complications in scoliosis surgery.

Several medical complications can occur after scoliosis surgery in children and adolescents. They include the syndrome of inappropriate antidiuretic hormone; pancreatitis; cholelithiasis; superior mesenteric artery syndrome; ileus; pnemothorax; hemothorax; chylothorax; and fat embolism. This review focuses on the pathophysiology, diagnosis, and treatment of the various conditions that occur after correction of spinal deformity. Attention is given to recent literature specifically related to scoliosis surgery. Surgical complications like urinary tract infection, wound infection, and hardware failure will not be addressed.

Adolescent↗

PubMed2001

Involvement of peripheral polymorphonuclear leukocytes in oxidative stress and inflammation in type 2 diabetic patients.

OBJECTIVE: To determine the extent to which peripheral polymorphonuclear leukocytes (PMNs) contributed to oxidative stress (OS) and inflammation in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: PMNs and plasma were separated from blood withdrawn from 18 type 2 diabetic patients and 16 age- and sex-matched normal control subjects. The rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs and the plasma glutathione (GSH) levels served as measures of OS. Inflammation was assessed by PMN recruitment, expressed by peripheral blood PMN counts, and the in vitro survival of PMNs, which reflects cell necrosis. RESULTS: PMA-stimulated PMNs from diabetes released superoxide significantly faster, and plasma-reduced GSH was lower in diabetic patients than in normal control subjects. The rate of superoxide release from diabetic PMNs showed no correlation with the plasma glucose concentrations, whereas a positive linear correlation with HbA1c was found. The in vitro survival of diabetic PMNs was lower than normal control PMNs when each was incubated in its own serum. The in vitro survival of normal control PMNs was reduced when incubated with diabetic serum, whereas normal control sera promoted the survival of diabetic PMNs. Peripheral PMN counts were higher in diabetic patients than in normal control patients. CONCLUSIONS: Type 2 diabetes is accompanied by a priming of PMNs, resulting in OS and increased self-necrosis. Necrosis starts a chain of inflammatory reactions that result in cell recruitment and in the long run, with OS, may result in endothelial dysfunction. Understanding the contribution of PMNs to OS and inflammation in diabetes may illuminate new mechanisms through which endothelial dysfunction evolves and causes angiopathy and atherosclerosis.

Adult↗

PubMed2000

First direct measurement of the parity-violating coupling of the Z0 to the s quark

We present the first direct measurement of A(s), the parity-violating coupling of the Z0 boson to the strange quark, using approximately 550 000 e(+)e(-)-->Z0-->hadrons events recorded by the SLC Large Detector with a polarized e(-) beam. We tagged Z0-->s&smacr; events by the absence of B or D hadrons and the presence in each hemisphere of a high momentum K+/- or K(0)(s). Fitting the polar angle distributions of the strangeness-signed thrust axis gave A(s) = 0.895+/-0.066(stat)+/-0.062(syst). The analyzing power and uu+d&dmacr; background were constrained using the data, greatly reducing any model dependence.

Journal Article↗

PubMed2000

Precise measurement of the b-quark fragmentation function in Z0 boson decays

We have developed a new technique for inclusive reconstruction of the energy of B hadrons. The excellent efficiency and resolution of this technique allow us to make the most precise determination of the b-quark fragmentation function, using e(+)e(-)-->Z0 decays recorded in the SLAC Large Detector experiment. We compared our measurement with the predictions of a number of fragmentation models. We excluded several of these models and measured the average scaled energy of weakly decaying B hadrons to be = 0.714+/-0. 005(stat)+/-0.007(syst)+/-0.002 (model dependence).

Journal Article↗

PubMed2000

Conjugate additions of 1-propenylphosphonates to metalated Schöllkopf's bis-lactim ether: stereocontrolled access to 2-amino-3-methyl-4-phosphonobutanoic acids.

Diastereoselectivity in the conjugate addition of metalated Schöllkopf's bis-lactim ethers 5a-e to (E)- and (Z)-1-propenylphosphonates 4a,b was studied experimentally and theoretically and utilized to achieve a direct and stereocontrolled synthesis of all four diastereoisomers of 2-amino-3-methyl-4-phosphonobutanoic acid, 6a,b and their enantiomers. The relative stereochemistry was assigned from an NMR study of cyclic derivatives 13a,b. According to semiempirical calculations, both in vacuo (PM3) or a dielectric continuum (PM3/COSMO), initial lithium-phosphoryl coordination, without an energy barrier, to form a solvated chelate complex is followed by the rate-determining reorganization to the 1,4-addition product through an eight-membered transition state. The translation of the Z,E geometry into a syn, anti configuration at the adducts originates from an orientational preference in the transition state for a compact disposition of the reaction partners.

Aminobutyrates↗

PubMed2000

Clinical comparability of ventolin formulated with hydrofluoroalkane or conventional chlorofluorocarbon propellants in children with asthma.

BACKGROUND: Aerosolized asthma medications with chlorofluorocarbon (CFC) propellants are being phased out because of environmental concerns about the ozone layer. Medications are being reformulated with non-ozone-depleting propellants. OBJECTIVE: To evaluate the clinical comparability of albuterol sulfate formulated in a new hydrofluoroalkane-134a (HFA) propellant (Ventolin HFA Inhalation Aerosol), and conventional CFC-containing albuterol (Ventolin Inhalation Aerosol) in children with asthma. DESIGN: Randomized, double-blind, placebo-controlled 2-week clinical trial with a 1- to 2-week run-in period. During the run-in, patients took Ventolin CFC as needed. Patients (n = 135) aged 4 to 11 years with asthma then were assigned randomly to treatment with Ventolin HFA, Ventolin CFC, or placebo administered 4 times daily via metered-dose inhaler for 2 weeks. All patients were allowed rescue albuterol use in matching propellant as needed for relief of breakthrough symptoms. The main outcome measure was the mean percentage of predicted peak expiratory flow (PEF) after the morning dose of study drug on day 1 and after 2 weeks as assessed by results of 6-hour serial tests. RESULTS: At day 1, the mean (+/- SE) percentage of predicted PEF increased postdose by 14% (+/- 1%) in the Ventolin HFA group and 13% (+/- 1%) in the Ventolin CFC group compared with 6% (+/- 2%) in the placebo group (P</=.006). At week 2, mean postdose increases were 11% (+/- 1%) in the Ventolin HFA and CFC groups compared with 5% (+/- 1%) in the placebo group (P<.001). There were no significant differences between the Ventolin HFA and CFC groups in postdose increases in pulmonary function, time to onset of response, duration of response, or peak effects. Safety profiles were similar among the 3 groups. CONCLUSION: Ventolin HFA is clinically comparable to Ventolin formulated with the conventional CFC-containing propellant when administered to children with asthma. Arch Pediatr Adolesc Med. 2000;154:1219-1225.

Aerosols↗

PubMed2000

Combined salmeterol 50 microg and fluticasone propionate 250 microg in the diskus device for the treatment of asthma.

Three hundred forty-nine patients with asthma previously treated with medium doses of inhaled corticosteroids during a 2-wk, single-blind, run-in period were randomized to treatment with salmeterol 50 microg combined with fluticasone propionate (FP) 250 microg, salmeterol 50 microg, FP 250 microg, or placebo, each given twice daily through a Diskus device for 12 wk. Mean change in FEV(1) at endpoint was significantly (p </= 0.001) greater with the salmeterol/FP combination product (0.48 L) than with placebo (-0.11 L), salmeterol (0.05 L), or FP (0.25 L). The combination product significantly increased the area under the 12-h serial FEV(1) curve relative to baseline over that with placebo, salmeterol, or FP at Day 1, Week 1, and Week 12 (p </= 0.025). Patients in the combination-product group had a significantly greater probability of remaining in the study without being withdrawn because of worsening asthma than did patients in the placebo, salmeterol, or FP groups (p </= 0.002). The combination product significantly increased (p < 0. 001) morning PEF at endpoint (53.5 L/min) as compared with placebo (-14 L/min), salmeterol (-11.6 L/min), or FP (15.2 L/min). The combination product significantly (p </= 0.011) reduced asthma symptom scores and supplemental albuterol use, and significantly increased the percentage of nights with no awakenings as compared with placebo, salmeterol, and FP (p </= 0.016). Combination treatment with salmeterol 50 microg and FP 250 microg given twice daily from the Diskus device provided better asthma control and greater improvement in pulmonary function than did the individual agents, and may simplify the management of asthma in patients who need both classes of drugs for optimal control of their disease.

Adolescent↗

PubMed1999

Differential effects of the adenosine A(1) receptor allosteric enhancer PD 81,723 on agonist binding to brain and adipocyte membranes.

The benzoylthiophene analog, PD 81,723, has been shown to allosterically enhance agonist binding and functional activation of the mammalian adenosine (ADO) A(1) receptor subtype by putatively maintaining the receptor in a high affinity state. The present studies were conducted to evaluate the ability of PD 81,723 to enhance the binding of [3H]cyclohexyladenosine ([3H]CHA) to A(1) receptors of neural (cerebral cortex) and non-neural (adipocyte) origin in three different species; rat, guinea pig and dog. PD 81, 723 (0.3-100 microM) produced a concentration-dependent enhancement of [3H]CHA binding to rat brain A(1) receptors. These effects were also species-dependent with larger enhancements (150-200% of control) observed in guinea pig and dog brain membranes as compared to the rat (120% of control). In contrast, PD 81,723 did not produce any enhancement of [3H]CHA binding to A(1) receptors in adipocyte membranes from any of the species examined. Additional binding studies were conducted using pharmacological manipulations that have previously been shown to enhance the allosteric effects of PD 81,723. In the presence of 1 mM GTP, the allosteric effects of PD 81,723 (15 microM) were increased in rat, guinea pig and dog brain membranes, however, in adipocyte membranes from each species, no significant alteration in agonist binding was observed. Similarly, the A(1) receptor selective antagonist 8-cyclopentyl-1, 3-dipropylxanthine (added to effectively reduce the intrinsic antagonist properties of PD 81,723) was found to enhance the allosteric effects of PD 81,723 (15 microM) in brain, but produce no alteration of agonist binding in adipocyte membranes from each species. Examination of the dissociation kinetics of [3H]CHA binding from rat brain and adipocyte membranes revealed that PD 81,723 (15 microM) differentially slowed agonist dissociation from brain, but not adipocyte, membranes. Taken together, the present data support the hypothesis that in tissues that are sensitive to PD 81,723, this benzyolthiophene functions to maintain the A(1) receptor in a high-affinity state and that the relative proportions of high-affinity A(1) receptors present in specific tissues may contribute, at least in part, to the apparent differential effects of PD 81,723 on agonist binding. The tissue specific modulation of A(1) receptor function by PD 81,723 also illustrates the possibility that the locus of allosteric modulation by PD 81,723 may be manifest via a specific, but indirect and tissue-dependent, interaction with the A(1) receptor.

Adenosine↗

PubMed1999

Reply

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Journal Article↗

PubMed1999

The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program.

BACKGROUND: Sensitivity and exposure to indoor allergens constitutes a risk factor for the development and persistence of asthma in children. OBJECTIVE: Our purpose was to evaluate the relationship between sensitivity and exposure to inhalant allergens and lung function and bronchial responsiveness in a group of children (n = 1041) aged 8.9 +/- 2.1 years with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). METHODS: With use of the extensive CAMP baseline cross-sectional data on spirometry, bronchial responsiveness, allergen sensitivities, and household allergen levels, the relationship of sensitization and exposure to allergens to lung function and methacholine sensitivity was evaluated. Children who enrolled in CAMP stopped all antiasthma medication except rescue use of albuterol and prednisone for exacerbations during the 5- to 16-week screening period. During the last 2 of these weeks they underwent spirometry and methacholine challenge. Indoor allergen exposures were determined from questionnaires completed by the parent. Household levels of indoor allergens (mite, cat, dog, cockroach, mold) were determined on house dust samples. Allergen sensitivity was determined by percutaneous skin testing with a standard battery of allergens plus locally important pollen and fungal spores. Lung function and bronchial hyperresponsiveness were compared for children sensitive and not sensitive to both indoor and outdoor allergens on skin testing and, if sensitive, for exposed and not exposed to the allergens to which they were positive on skin testing. RESULTS: There was a strong direct correlation between increased sensitivity to inhaled methacholine and skin test sensitivity to tree, weed, Alternaria, cat, dog, and indoor molds. When the relationship was examined by stepwise regression, the skin test sensitivities showing the strongest associations with the concentration of methacholine that caused a 20% fall in FEV(1) were dog (P =.003), Alternaria (P =.01), and cat (P =.05). Children sensitive to any one of the aeroallergens tested were compared for the presence or absence of exposure to that allergen at the time that the methacholine challenge was performed. Those who were sensitive and exposed to weed and cat had greater methacholine sensitivity than those similarly sensitive but not exposed (P =.003 and P =.02, respectively). CONCLUSIONS: Sensitivity to dog or cat dander or Alternaria by skin testing was associated with increased bronchial responsiveness but not decreased lung function in children with mild to moderate asthma. These findings support the important role that sensitization to certain allergens plays in modulating bronchial responsiveness.

Adolescent↗

PubMed1999

Interaction between erythropoietin and peripheral polymorphonuclear leukocytes in hemodialysis patients.

The effect of erythropoietin (EPO) on the oxidative stress and inflammation caused by polymorphonuclear leukocytes (PMNLs) in chronic hemodialysis (HD) patients was investigated in vivo and in vitro. The studies were performed on isolated PMNLs from peripheral blood of healthy controls and HD patients before and following 6 weeks of EPO treatment. The oxidative stress was expressed by the rate of superoxide release from phorbol 12-myristate 13-acetate stimulated PMNLs, and the inflammatory state was evaluated by in vitro PMNL survival, in addition to white blood cell and PMNL counts of the enrolled subjects. Following 6 weeks of EPO treatment, in HD patients, the rate of superoxide release from PMNLs as well as WBC and PMNL counts fell significantly when compared with the pretreatment values. PMNLs from HD patients and healthy controls incubated in vitro with increasing amounts of EPO displayed a significant reduction in their rates of superoxide release and a significant improvement in survival. We have concluded that EPO interacts with PMNLs, attenuating their primed state in HD patients, thus reducing oxidative stress and the extent of inflammation. To the best of our knowledge, this attenuation of the primed state of PMNLs by EPO is a new finding.

Cell Survival↗

PubMed1999

Once-daily inhaled corticosteroids in children with asthma: nebulisation.

Current guidelines on the management of childhood asthma have emphasised the important preventive role of inhaled corticosteroids, which should be used at the lowest possible doses that are compatible with good disease control. However, some children do not respond to inhaled corticosteroids, the most common reasons for which are inability to use conventional hand-held inhalers (plus spacers and face masks) effectively or lack of cooperation with them, particularly among infants and young children. In these patients, nebulisers have proved effective in administering corticosteroids, and this form of delivery is often preferred by both the children and their parents, despite their longer administration times (commonly around 10 minutes). Compliance with these devices may therefore be better than with a conventional pressurised metered-dose inhaler plus spacer and face mask. Recent studies with nebulised budesonide have demonstrated that once-daily administration is as effective in maintaining control of asthma symptoms in children as the usual twice-daily administration. In children with moderately severe persistent asthma, the improvement provided by once-daily nebulised doses of 1.0 mg budesonide has been found to be equivalent to that with twice-daily doses of 0.25 or 0.5 mg, indicating that once-daily therapy is an effective option that can be considered in many patients. In view of the time-consuming nature of nebuliser administration, reduction of the frequency of corticosteroid administration from twice to once daily may be useful in simplifying the treatment programme and improving compliance with it. This may be beneficial in reducing under-utilisation of inhaled corticosteroids in children with asthma and improving long term control of the disease.

Administration, Inhalation↗

PubMed1998

Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma.

OBJECTIVE: To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to severe persistent asthma. STUDY DESIGN: In our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, a total of 404 children with asthma, who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy, were randomly assigned to receive either 100, 200, or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline, mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to 123.3%) of the predicted normal value. RESULTS: Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo. Improvements were evident within 2 weeks and were maintained throughout the 12 weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function, and the incidence of reported adverse events was similar in all treatment groups. CONCLUSION: Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children (6 to 18 years of age) with moderate to severe persistent asthma.

Administration, Inhalation↗

PubMed1998

Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma.

BACKGROUND: Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers. OBJECTIVE: We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients. RESULTS: Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P </=.026), reducing use of breakthrough medication (P </=.032), and improving morning peak expiratory flow (P </=.030). The number of dropouts because of worsening asthma was also significantly fewer in the budesonide groups (P </=.015). There were no differences between doses of budesonide. Adverse events and basal and adrenocorticotrophic hormone-stimulated cortisol responses were not different between budesonide and placebo groups. CONCLUSION: Budesonide inhalation suspension, 0.25 mg, 0.50 mg, and 1.0 mg twice daily, is an effective and safe treatment for young children with inhaled steroid-dependent, persistent asthma.

Administration, Inhalation↗

PubMed1998

Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension.

Oxidative stress and inflammation have recently been linked to endothelial damage in essential hypertension (EH). Activated peripheral polymorphonuclear leukocytes (PMN) damage surrounding tissue by releasing reactive oxygen species (ROS) and proteolytic enzymes before self-necrosis. PMN necrosis further exacerbates inflammation and promotes chemotaxis and PMN recruitment. The number and properties of PMN from untreated EH patients is the focus of the present study. Oxidative stress was assessed by measuring the rate of superoxide anion release from separated, phorbol ester-stimulated PMN and the redox state of plasma glutathione. Inflammation was estimated indirectly by determining PMN number and their in vitro survival. PMN from EH patients (n = 37) released superoxide anion faster (P < .0001) than those of normotensives (NC, n = 37), 17.7 +/- 1.14 v 9.54 +/- 0.51 nmol/10 min/10(6) cells. The redox state of glutathione was twofold higher in EH plasma (P < .02) indicating systemic oxidative stress. PMN survival in vitro correlates linearly with the rate of superoxide release (r2 = 0.60, P < .02) and PMN count of EH patients, although in the normal range, were significantly higher (P < .0001), indicating necrosis and recruitment. Hypertensive plasma significantly reduced NC PMN viability, whereas normal plasma significantly increased EH PMN viability. What our studies show is that EH is accompanied by a primed state PMN that does not correlate with the levels of blood pressure. PMN priming in EH patients reflects an in vivo exposure to a constant stimulus ending in oxidative stress, increased self-necrosis, and cell recruitment. Oxidative stress and inflammation will result in endothelial damage and atherosclerosis in the long run.

Adult↗

PubMed1997

Combined Fmoc-Alloc strategy for a general SPPS of phosphoserine peptides; preparation of phosphorylation-dependent tau antisera.

A block method for the solid phase synthesis (SPPS) of serine phosphopeptides has been developed using a combination of Fmoc and Alloc strategies. Alloc-Ser[PO(OCH2CH CH2)2] OH2, prepared in a one pot procedure from Alloc-Ser-OH, was introduced at the N-terminus of a sequence prepared by standard Fmoc-SPPS. Global cleavage of the allyl ester based protecting groups, followed by coupling of a tripeptide fragment, led to the tau phosphopeptide, 1. Using tau phosphopeptides a series of phosphorylation state-dependent antisera to human tau protein have been raised. These antisera are valuable tools for studying the tau protein which is found in an abnormal, hyperphosphorylated form in Alzheimer's disease brain.

Amino Acid Sequence↗