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Biomedical subjects

A D Smith

Publications and source records attributed to A D Smith.

At least 73 records · Page 4Linked to original sources

Effect of gold(I) compounds on the virulence of an amyocarditic strain of coxsackievirus B3.

Coxsackieviruses, especially B strains (CVB), are known etiological agents of myocarditis. Both amyocardititc and myocarditic strains exist and at least one amyocarditic strain, CVB3/0, can convert to virulence when passaged through selenium or vitamin E-deficient mice. Gold(I)-containing compounds, such as aurothiomalate (ATM) and aurothioglucose (ATG), can act as selenium antagonists. In this study, we examined the effect of intraperitoneal administration of equal doses of ATM or ATG on the virulence of CVB3/0. ATM but not ATG increased mortality in CVB3/0-infected mice. CVB3/0-infected mice treated with ATM had total necrosis of the pancreatic exocrine tissue. Heart damage also occurred in ATM-treated mice but did not correlate with mortality. Increased viral titers and persistence were observed in ATM-treated mice and, to a lesser extent, in ATG-treated mice. Thus, under our conditions, only ATM increased the virulence of CVB3/0, whereas ATG did not. On the other hand, both ATG and ATM inhibited thioredoxin reductase activity in heart and pancreas, but neither affected glutathione peroxidase activity. In contrast, dietary selenium deficiency reduces both enzyme activities. Thus, it is unlikely that these compounds affect virulence by acting as selenium antagonists.

Animals↗

Ureteral reconstruction: small intestine submucosa for the management of strictures and defects of the upper third of the ureter.

PURPOSE: We evaluated the effectiveness of small intestine submucosa in ureteral reconstruction. MATERIALS AND METHODS: We report an experimental study in 6 female pigs weighing between 50 and 60 pounds. The animals were anesthetized, midline laparotomy was performed and two-thirds of the diameter of the upper third of the left ureter were incised parallel to the ureteral axis, leaving intact only a third of the ureteral wall for a segment of 7 cm. A 5Fr double-J*; stent was positioned to secure patency at all times. The created gap was then bridged with an small intestine submucosa patch in a cylindrical format, which was subsequently sutured to the proximal and distal ureteral segment. The right ureter served as our control and simple intubated Davis ureterotomy was performed. RESULTS: All animals survived the whole followup of 7 weeks. Histologically there was evidence of epithelial regeneration along the segments reconstructed with small intestine submucosa, supported by a well vascularized collagen and smooth muscle background. There was no evidence of foreign body reaction to the graft material. In vivo patency was confirmed by retrograde pyelography in the bridged ureters 7 weeks after the initial procedure. All the ureters without an small intestine submucosa bridge had ureteral stenosis without evidence of epithelial regeneration. CONCLUSIONS: The use of small intestine submucosa is a novel, effective material for the scaffolding of ureteral defects and/or strictures of the upper ureteral segment in the pig model.

Animals↗

Serum total testosterone is lower in men with Alzheimer's disease.

OBJECTIVES: The purpose of this study was to determine whether the level of serum total testosterone (TT) was different in cases of Dementia of the Alzheimer's Type (DAT) than in controls. SETTING AND DESIGN: We included 83 referred DAT cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford Project To Investigate Memory and Ageing. METHODS: Information was obtained about potential confounds in the relation of DAT with testosterone, including age, gender, education, body mass index, smoking, (ab)use of alcohol, diabetes mellitus, endocrine therapy, and having undergone hysterectomy. TT was measured in non-fasting serum obtained between 10 and 12 a.m. using a competitive enzyme immunoassay. RESULTS: Men with DAT (n=39) had lower levels (p =0.005) of total serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L). Lower TT was more likely in men with DAT, independent of potential confounds (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT levels between cases (n=44) and controls (n=62). MAIN FINDINGS: Our results suggested that low TT may be a co-morbid feature of DAT in men. However, low TT levels could also exacerbate the disease. CONCLUSIONS: Prospective longitudinal studies should investigate whether low TT levels precede or follow the onset of DAT (209 words).

Aged↗

Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia.

Low blood folate levels result in hyperhomocysteinemia, which has been associated with increased risk for cardiovascular disease, neural tube defects and cognitive deficits. Intake of dietary folates is the chief determinant of blood folate levels. Molecular defects in the intestinal absorption of dietary folates that precipitate low blood folate levels and hyperhomocysteinemia have not been investigated previously. Dietary folates are a mixture of polyglutamylated folates which are digested to monoglutamyl folates by the action of folylpoly-gamma-glutamate carboxypeptidase (FGCP), an enzyme that is anchored to the intestinal brush border membrane and is expressed by the glutamate carboxypepidase II (GCPII) gene. We cloned GCPII cDNA from human intestine and identified both a full-length transcript and a 93 bp shorter transcript lacking exon 18, consistent with the presence of a splice variant. In addition, we identified an H475Y polymorphism in GCPII in DNA samples from a healthy Caucasian population (n = 75). We found that membranes of transfected COS-7 cells expressing the H475Y variant GCPII cDNA had 53% less FGCP activity than did cells expressing wild-type GCPII. The presence of the H475Y GCPII allele was significantly associated with lower folate and higher homocysteine levels in this population. These data suggest that the presence of the H475Y GCPII allele impairs the intestinal absorption of dietary folates, resulting in relatively low blood folate levels and consequent hyperhomocysteinemia.

Aged↗

Luminometric quantitation of photinus pyralis firefly luciferase and Escherichia coli beta-galactosidase in blood-contaminated organ lysates.

Firefly luciferase and Escherichia coli beta-galactosidase chemiluminescent reporter gene assays are rapid and sensitive means of detecting reporter enzyme activities in cell lysates of both eukaryotic and prokaryotic systems. In these assays, expression vectors containing the luciferase or beta-galactosidase genes are transferred to cells in culture or animal tissues in vivo. Crude cell or organ lysates are then prepared and submitted to enzyme assays. The level of enzyme activity is proportional to the efficiency of gene delivery and expression. When used with modified substrates that emit light when cleaved by the appropriate enzyme, luciferase and beta-galactosidase activity can be detected luminometrically. Attempts to apply these assays to cell lysates contaminated with blood, as from any whole organ lysate, have had questionable results thus far because of light absorption by hemoglobin in the ranges of light emission by both of these assays. We have made several adjustments to standard chemiluminescent reporter gene assay protocols to minimize errors in quantitation contributed by hemoglobin. To this end, we have developed a method for quantitating the protein due to blood and due to the organ itself in a blood-contaminated organ lysate. We have also found that the use of a colorimetric protein assay that is unaffected by hemoglobin absorbance is preferred for protein quantitation. In conclusion, luciferase and beta-galactosidase assays can be applied to blood-contaminated organ lysates; however, the luciferase assay proved to be superior due to minimal endogenous activity and lower absorption by hemoglobin of light emitted by the enzyme product.

Animals↗

Chronic expansion of the renal pelvis: a new method for reconstruction of upper ureteral defects.

OBJECTIVES: To evaluate whether the dilated renal pelvis can be used as an autologous source for the surgical reconstruction of upper ureteral defects or strictures. METHODS: In 7 female pigs, the renal pelvis was expanded by a percutaneously placed Council balloon catheter. Every other day for 4 weeks, the renal pelvis was progressively dilated with a bolus injection of saline and contrast medium, which allowed expansion of the renal pelvis to 70 to 75 mL. Four to six weeks after the initial intervention, 5 to 7 cm of the proximal ureter was resected in an open operation and replaced with a tubularized spiral flap made from the expanded renal pelvis. Three weeks later, the animals were killed, and the area of manipulation was resected for pathologic evaluation. RESULTS: All animals reached the desired expansion of the renal pelvis, and in all cases, the spiral flap was fashioned and anastomosed to the distal ureteral segment, bridging the initial defect (mean length 7 cm). Two animals died from sepsis, 4 and 6 days after the spiral flap reconstruction. A viable ureteral lumen with a patent anastomosis and a functioning pelvocaliceal unit was observed on intravenous urography in all animals. The main histologic findings were a chronic inflammatory process with concomitant mucinous metaplasia and reactive atypia of the tubules. CONCLUSIONS: The use of a balloon expander in the renal pelvis is a safe and effective technique for producing native tissue for the reconstruction of defects or strictures of the upper ureteral segment.

Anastomosis, Surgical↗

Stone recurrence after endopyelotomy.

OBJECTIVES: The purpose of this study was to evaluate whether repair of the ureteropelvic junction (UPJ) obstruction reduces the incidence of stones in stone-forming patients with concurrent UPJ obstruction. METHODS: We performed a retrospective study evaluating 90 patients with UPJ obstruction who underwent endopyelotomy and simultaneous stone extraction (group A) and 80 patients without UPJ obstruction who underwent only stone extraction (group B). Group A consisted of 52 men and 38 women with an average age of 54.4 years (range 15 to 82), and group B of 46 men and 34 women with an average age of 53.5 years (range 8 to 94). Metabolic evaluation was available in 47 patients of group A and 42 patients of group B. RESULTS: We achieved a stone-free state in all patients of both groups. Stone recurrence was observed in 7 patients (8%) in group A and in 32 patients (40%) in group B. Nine of 47 patients (19%) in group A showed metabolic abnormalities. In group B we found 30 of 42 patients (71.4%) with metabolic abnormalities. CONCLUSIONS: Our results suggest that correction of the anatomic obstruction facilitates the drainage of the previously entrapped urine, and thus decreases the incidence of recurrent urinary stone formation.

Adolescent↗

Percutaneous endopyelotomy.

OBJECTIVES: During the past 10 years, numerous reports around the world have documented the safety and success rate of antegrade endopyelotomy. We describe the classic endopyelotomy in conjunction with some new alternatives for making the incision. TECHNICAL CONSIDERATIONS: Antegrade endopyelotomy is performed through the 0.5-in. incision of the percutaneous nephrostomy created by way of an upper or middle calix. Using the hook-shaped cold knife, an endopyelotome is positioned, and the entire procedure can be performed under direct vision, which determines the exact position, depth, and extent of the incision. The ureteropelvic junction (UPJ) obstruction is incised in a posterolateral position, and the hook is withdrawn from the proximal ureter. Using nephroscopic scissors, a small full-thickness puncture is made into the renal pelvis and then the scissors is opened, under constant visual control, until it reaches the peripelvic space. The section of the pelvic wall is completed with the scissors running through the UPJ, without any interchange of the nephroscope. A holmium laser has been also used, with the 365-microm fiber introduced through a stent-pusher. Under direct vision, the UPJ is incised with fiber, permitting observation and coagulation of bleeding from small vessels. After the procedure, either a 14-8.2F endopyelotomy stent or a 14-7F tapered endoureterotomy stent is placed over the guidewire. CONCLUSIONS: Percutaneous antegrade endopyelotomy is a safe and effective treatment of UPJ obstruction for most patients, regardless of the method used to perform the incision.

Humans↗

Ontogeny of orientation flight in the honeybee revealed by harmonic radar.

Cognitive ethology focuses on the study of animals under natural conditions to reveal ecologically adapted modes of learning. But biologists can more easily study what an animal learns than how it learns. For example, honeybees take repeated 'orientation' flights before becoming foragers at about three weeks of age. These flights are a prerequisite for successful homing. Little is known about these flights because orienting bees rapidly fly out of the range of human observation. Using harmonic radar, we show for the first time a striking ontogeny to honeybee orientation flights. With increased experience, bees hold trip duration constant but fly faster, so later trips cover a larger area than earlier trips. In addition, each flight is typically restricted to a narrow sector around the hive. Orientation flights provide honeybees with repeated opportunities to view the hive and landscape features from different viewpoints, suggesting that bees learn the local landscape in a progressive fashion. We also show that these changes in orientation flight are related to the number of previous flights taken instead of chronological age, suggesting a learning process adapted to changes in weather conditions, flower availability and the needs of bee colonies.

Animal Communication↗

Differential effects of dopamine receptor subtype blockade on performance of rats in a reaction-time paradigm.

RATIONALE: Pharmacological manipulation of the dopaminergic system with antipsychotic agents disrupts motor behavior. Although most antipsychotic drugs have high affinity for D2 receptors, they also interact with other dopamine receptor subtypes. Therefore, the role of each of these receptor subtypes on motor performance is unclear. OBJECTIVE: The present study sought to investigate the relative importance of D1, D2, and D3 receptors on performance in a conditioned reaction-time task known to be extremely sensitive to dysfunction of the dopaminergic nigrostriatal pathway. METHODS: Rats were trained to release a lever in response to a visual cue within a reaction-time limit to receive a reinforcer (45mg food pellet). After the behavior of the rats had stabilized, the effects of a D1 (A69024), D2 (eticlopride), and D3 (nafadotride) receptor antagonists were assessed. RESULTS: A-69024 had no effect on performance at any dose tested (0.3, 0.6, and 1.3 mg/kg s.c.). Nafadotride (0.1, 0.3, and 1 mg/kg s.c.) produced only a mild deficit in performance at the highest dose. This deficit was characterized by an increase in the number of delayed responses with a non-significant decrease in the number of premature responses indicative of non-specific sedative effects. In contrast, the D2 receptor antagonist eticlopride (0.005, 0.01, and 0.02 mg/kg s.c.) produced profound deficits in performance as evidenced by a dose-dependent decrease in the number of correct responses. This decrease was accompanied by an increase in the number of delayed responses and a lengthening of the reaction time at the highest doses. CONCLUSIONS: These results provide further evidence that the execution of the reaction-time task is dependent preferentially upon the activation of D2 receptors, but not D1 or D3 receptors.

Animals↗

Association of butyrylcholinesterase K variant with cholinesterase-positive neuritic plaques in the temporal cortex in late-onset Alzheimer's disease.

In confirmed late-onset (>65 years) Alzheimer's disease, we found a greater load, both of overall neuritic plaques and of cholinesterase-positive neuritic plaques, in the temporal cortex of carriers of the butyrylcholinesterase K variant (BCHE-K) aged <80 years than of all other patients. The differences were most striking in the case of cholinesterase-positive neuritic plaques. Among BCHE-K carriers, densities of such plaques were over six times higher in patients <80 years at death than in those >80 years (P=0.01). Furthermore, in subjects <80 years, BCHE-K carriers had nearly six-fold greater densities of these plaques than non-carriers (P=0.009). We consider three potential explanations for these findings: that the K variant binds more readily to plaque constituents, that it promotes fibril formation or that it induces aberrant neurite growth.

Age of Onset↗

Modular organization and identification of a mononuclear iron-binding site within the NifU protein.

The NifS and NifU nitrogen fixation-specific gene products are required for the full activation of both the Fe-protein and MoFe-protein of nitrogenase from Azotobacter vinelandii. Because the two nitrogenase component proteins both require the assembly of [Fe-S]-containing clusters for their activation, it has been suggested that NifS and NifU could have complementary functions in the mobilization of sulfur and iron necessary for nitrogenase-specific [Fe-S] cluster assembly. The NifS protein has been shown to have cysteine desulfurase activity and can be used to supply sulfide for the in vitro catalytic formation of [Fe-S] clusters. The NifU protein was previously purified and shown to be a homodimer with a [2Fe-2S] cluster in each subunit. In the present work, primary sequence comparisons, amino acid substitution experiments, and optical and resonance Raman spectroscopic characterization of recombinantly produced NifU and NifU fragments are used to show that NifU has a modular structure. One module is contained in approximately the N-terminal third of NifU and is shown to provide a labile rubredoxin-like ferric-binding site. Cysteine residues Cys35, Cys62, and Cys106 are necessary for binding iron in the rubredoxin-like mode and visible extinction coefficients indicate that up to one ferric ion can be bound per NifU monomer. The second module is contained in approximately the C-terminal half of NifU and provides the [2Fe-2S] cluster-binding site. Cysteine residues Cys137, Cys139, Cys172, and Cys175 provide ligands to the [2Fe-2S] cluster. The cysteines involved in ligating the mononuclear Fe in the rubredoxin-like site and those that provide the [2Fe-2S] cluster ligands are all required for the full physiological function of NifU. The only two other cysteines contained within NifU, Cys272 and Cys275, are not necessary for iron binding at either site, nor are they required for the full physiological function of NifU. The results provide the basis for a model where iron bound in labile rubredoxin-like sites within NifU is used for [Fe-S] cluster formation. The [2Fe-2S] clusters contained within NifU are proposed to have a redox function involving the release of Fe from bacterioferritin and/or the release of Fe or an [Fe-S] cluster precursor from the rubredoxin-like binding site.

Amino Acid Sequence↗

Primary percutaneous approach to upper urinary tract transitional cell carcinoma.

The optimal approach to upper tract TCC remains to be redefined. A routine nephroureterectomy for every filling defect in the upper urinary system, even in the case of a normal contralateral kidney, constitutes an unnecessary mutilation in more than two thirds of the cases. Nephroureterectomy does not reduce the need for a long-term cystoscopic follow-up because of the high rate of bladder tumor recurrence that may happen years later after nephroureterectomy. Relying solely on radiography and cytology, lacking sensitivity and specificity, to recommend a nephroureterectomy is against the principles of oncologic surgery, especially now that preoperative histologic proof is easy to obtain endoscopically without compromising cancer control. Ureteroscopy, rigid and flexible, provides a complete assessment of the upper urinary system. Biopsy specimens taken with ureteroscopy may be sufficient for grading but less adequate for staging of the tumor. The authors reserve ureteroscopy for ureteral tumors and small (< 1.5 cm) single tumors of the renal pelvis. They approach large or multiple tumors of the renal pelvis percutaneously, in which a full histologic assessment is possible along with a complete resection of the tumor. The decision on the therapeutic approach is made only after the final pathologic report is reviewed. Grade I and grade II superficial disease (Ta, T1) can be treated endoscopically with minimal morbidity and with an efficiency comparable with the standard more invasive nephroureterectomy (Table 5). The indications for endourologic treatment in these cases can be extended safely beyond a solitary kidney or a high surgical risk to include any healthy individual with a normal contralateral kidney who is willing to commit to a rigorous lifelong follow-up. Patients with grade II T1 lesions require a more vigilant follow-up. For grade III Ta disease, more caution should be exercised in selecting these patients for elective endourologic management. When criteria of good prognosis are found, such as absence of carcinoma in situ, presence of diploidy, low p53 expression and a single-tumor, endoscopic management can be offered [table: see text] with a closer follow-up and resorting always to immediate nephroureterectomy at the first evidence of upstaging. Because of the high incidence of recurrence and progression, elective endourologic management for grade III T1 tumors is not recommended. Endoscopic conservative surgery still can be offered in the cases of a solitary kidney or chronic renal insufficiency or for poor surgical candidates. Patients with localized stages (T2, T3) TCC should be offered immediate nephroureterectomy. The authors do not expect adequate endoscopic extirpation with muscle invasive tumors. Although the tissue removed may include deep layers, deep resection is precluded by the thin renal pelvic wall and the associated risk for perforation. Patients with more extensive disease (T3, T4) have a bad prognosis regardless of the form of therapy. Achieving local control percutaneously while preserving as many nephrons as possible for the future chemotherapy can be a reasonable option.

Carcinoma, Transitional Cell↗

Chemolysis of urinary calculi.

Irrigant chemolysis was developed to collaborate with open surgery, removing the residual fragments. With the worldwide diffusion of the procedures performed by the endourologist in the early 1980s and the present availability of ESWL, however, direct irrigation of stones has a reduced field of influence even as an adjunctive measure. Urologists have applied economic analysis to their clinical practices, and the findings related to irrigant chemolysis made this technique an unusual procedure. The cost to the providers of medical care, the burden on the patient in terms of suffering and loss of productivity, and the amount of time required to liberate the patient even partially from the stones make irrigant chemolysis an inauspicious scenario. In this era of cost containment and decreasing length of stay, it is increasingly difficult to justify hospital admissions for this form of therapy. Being simultaneously more expensive and less effective than the existing alternatives, local chemolysis should be discarded, except for special situations, such as patients at high risk for any surgical procedure. Oral chemolysis preserves reduced indications, for example as an adjuvant to an endourologic operation or ESWL in special situations. As long as urinary stones continue to afflict humans, chemolysis is likely to retain a limited but important role in their management.

Calcium Oxalate↗

The young skater.

Figure skating is one of the best lifetime sports. Participants may skate alone or with a group, recreationally or competitively, at all ages and at all skill levels. As a sport that improves physical fitness, skating builds strength, flexibility, and cardiopulmonary endurance. As a weight-bearing or high-impact activity, it is one of the best sports for increasing bone mineral density and perhaps for preventing osteoporosis. At least half of all competitive figure skating injuries appear preventable. Boots should be as flexible as the skater can control and should be carefully fitted. Normal flexibility of lower extremity muscles, especially in the growing athlete, markedly decreases the incidence of overuse symptoms of the knee. Core body strength is critical for controlling high-impact jump landings and decreasing injuries to the spine, pelvis, and hip girdle. Adequate shoulder strength is required for pair skaters and ice dancers. A well-designed off-ice training program decreases injury incidence and enhances performance. Assisting these dedicated athletes is truly rewarding as they train and compete at their highest potential, with passion for their sport.

Adolescent↗

The use of vertical-looking radar to continuously monitor the insect fauna flying at altitude over southern England.

The continuous automatic monitoring of the aerial density, biomass and relative diversity of high-flying insect faunas has been made practicable by a new, vertical-looking radar. This inexpensive radar system, with its novel signal analysis capability, represents a major advance over earlier vertical-beam radars because it provides estimates of the body mass of individual overflying insects, as well as measurements of their direction and speed of movement. This paper summarizes data collected over a three-month period by the new radar in the height range from 150 m to c.1 km, over agricultural land in Worcestershire, England. The day-to-day variation in the numbers of insects and their altitudinal and diurnal patterns of flight activity are presented. Examples are also given of distributions of mass, displacement speed and direction, and orientation direction. The potential of the new radar for various research and operational monitoring tasks is briefly discussed.

Altitude↗

Increased production of IL-4 by gut T-cell lines from patients with dermatitis herpetiformis compared to patients with isolated gluten-sensitive enteropathy.

Dermatitis herpetiformis (DH) and isolated gluten-sensitive enteropathy (GSE) are gluten-sensitive diseases in which ingestion of dietary gluten results in the development of clinical disease. Patients with DH develop cutaneous IgA deposits and a severe skin disease, but rarely develop gastrointestinal symptoms. Patients with isolated GSE develop clinically significant gastrointestinal symptoms, but not skin disease or cutaneous IgA deposits. The aim of this study was to investigate the mechanism by which a mucosal immune response to the same dietary antigen can result in two distinct clinical phenotypes. T-cell lines were derived from activated T-cells in the small bowel mucosa of five patients with DH and 14 patients with isolated GSE and analyzed for T-cell markers and cytokine production in vitro. T-cell lines from DH and isolated GSE patients produced IFN-gamma after stimulation (mean: DH = 2,619 pg/ml; isolated GSE = 1,993 pg/ml; NS). T-cell lines from patients with DH, however, produced significantly more IL-4 than the T-cell lines from patients with isolated GSE (IL-4: DH = 2,010 pg/ml; isolated GSE = 235 pg/ml; P < 0.05). Analysis of intracytoplasmic cytokine production by the T-cell lines showed that T-cell lines from patients with DH were CD4+ predominant, with a greater proportion of CD4+/IL4+ cells than CD4+/IFN-gamma+ cells. In contrast, isolated GSE T-cell lines were predominantly CD8+, with an equal proportion of IL-4- and IFN-gamma-positive cells. These studies demonstrate that T cell lines from patients with DH produce significantly more IL-4 than T-cell lines from patients with isolated GSE, while producing similar amounts of IFN-gamma. This difference in cytokine pattern may play an important role in the different clinical manifestations of these two forms of gluten sensitivity.

Adult↗

Hydrophobic protein that copurifies with human brain acetylcholinesterase: amino acid sequence, genomic organization, and chromosomal localization.

The mechanism of attachment of acetylcholinesterase (AChE) to neuronal membranes in interneuronal synapses is poorly understood. We have isolated, sequenced, and cloned a hydrophobic protein that copurifies with AChE from human caudate nucleus and that we propose forms a part of a complex of membrane proteins attached to this enzyme. It is a short protein of 136 amino acids and has a molecular mass of 18 kDa. The sequence contains stretches of both hydrophobic and hydrophilic amino acids and two cysteine residues. Analysis of the genomic sequence reveals that the coding region is divided among five short exons. Fluorescence in situ hybridization localizes the gene to chromosome 6p21.32-p21.2. Northern blot analysis shows that this gene is widely expressed in the brain with an expression pattern that parallels that of AChE.

Acetylcholinesterase↗