Biomedical subjects

C C Miller

Publications and source records attributed to C C Miller.

At least 91 records · Page 5Linked to original sources

PubMed1997

Impact of a problem-based learning conference on surgery residents' in training exam (ABSITE) scores. American Board of Surgery in Training Exam.

The impact of problem-based learning on surgery residents' education is unknown. In this study we measured the impact of a weekly structured problem-based learning conference on surgery residents' ABSITE scores and compared it to traditional clinical conferences and self-studying. A questionnaire was designed to determine the perceived quality of the basic (PQCB), and the clinical (PQCC) conferences as well as self-studying (PQCS). The Pearson correlation between PQCB, PQCC, PQCS, and attendance at the basic science conference and each of the ABSITE total score (ABSITE), basic science (BS) and clinical science (CS) component scores were calculated. PQCS (4.2) was significantly higher than PQCB (2.9) and PQCC (2.5) (P = 0.0002). PQCS and PQCB correlated highly with each of ABSITE, CS, and BS while PQCc did not show any correlation. A high correlation was also observed between attendance at basic science and each of ABSITE, CS, and BS but narrowly missed significance. It was also observed that BS scores highly correlated to the CS scores at all postgraduate levels (P = 0.0001). We conclude that performance on all components of the ABSITE is mostly dependent on individual residents. This individual factor is boosted by self-studying which can be motivated by instituting a problem-based learning technique within the program. Traditional conferences even if popular among residents have no impact on measurement tests.

Educational Measurement↗

PubMed1997

Impact of retrograde cerebral perfusion on ascending aortic and arch aneurysm repair.

PURPOSE: The effect of retrograde cerebral perfusion on the incidence of stroke and death among patients undergoing repair of aneurysms of the ascending aorta and transverse arch was determined. MATERIALS AND METHODS: Between January 1991 and March 1995, 161 patients were operated on for aneurysms of the ascending aorta and transverse arch. Thirty-three of the patients (20%) had an aneurysm of the ascending aorta only and 128 (80%) had aneurysms of both the ascending aorta and the transverse arch. All the patients underwent cardiopulmonary bypass, profound hypothermia, and circulatory arrest, and 120 (74%) also underwent retrograde cerebral perfusion. Median pump time was 143 minutes (range, 21 to 461 minutes). Median circulatory arrest time was 42 minutes (range, 8 to 111 minutes), and median myocardial ischemic time was 71 minutes (range, 14 to 306 minutes). RESULTS: The overall 30-day mortality rate was 6% (9 patients) and the incidence of stroke was 4% (7 patients). The use of retrograde cerebral perfusion demonstrated a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%; odds ratio, 0.24; confidence interval, 0.06 to 0.99; p < 0.049). This was most significant in patients more than 70 years of age; none of the 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p < 0.003). Only pump time was associated with an increased risk of stroke (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.005). Pump time also was associated with increased mortality (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.008). CONCLUSION: Retrograde cerebral perfusion decreased the incidence of stroke in patients undergoing repair of aneurysms of the ascending aorta and transverse arch.

Adult↗

PubMed1997

Improved survival with multiple left-sided bilateral internal thoracic artery grafts.

BACKGROUND: Although conceptually sound, the use of multiple internal thoracic artery (ITA) bypass grafts to improve long-term clinical results remains controversial. This operation typically involves grafting the left ITA to the anterior descending artery and the right ITA to the right coronary artery. Past clinical studies of bilateral ITA operations have not examined comparative results associated with which coronary arteries received the ITA bypass grafts. Because grafting a superior conduit to an artery of lesser physiologic importance might reduce the clinical benefits, we compared the outcomes of patients receiving different configurations of bilateral ITA operations. METHODS: The study group was 498 consecutive bilateral ITA operations, constituting the 10-year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3 years), and was 94.2% complete. These patients were divided into two groups, 311 patients (group I) who underwent the traditional operation (left ITA to the left anterior descending artery, right ITA to the right coronary artery), and 187 patients (group II) who received revascularization of branches of the left coronary artery (left ITA to the circumflex system and right ITA to the left anterior descending artery). RESULTS: The study groups were similar in age, severity of disease, number of bypassed arteries, ejection fraction, diabetes, hypertension, and duration of operation. There were more male patients in group II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA bypass grafts influenced survival independent of gender (p = 0.0288). Operative morbidity and mortality were similar between groups. Ninety-three patients had repeat angiography with equivalent patency rates of the ITA conduits (91.7% versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate demonstrated a significant improvement in survival of patients in group II who received both ITA bypass grafts to left-sided arteries (p = 0.021), with the survival curves diverging at 6 years. More patients in group II were in New York Heart Association class I or II, but the difference was not statistically significant (94.6% versus 91.6%). Only 2 patients required reoperation. CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA operations is achieved by grafting the ITA conduits to coronary arteries that supply more left ventricular muscle.

Coronary Angiography↗

PubMed1997

Observations on delayed neurologic deficit after thoracoabdominal aortic aneurysm repair.

PURPOSE: To describe the phenomenon of delayed-onset neurologic deficit after thoraco-abdominal aortic aneurysm repair and to discuss management of this type of deficit in a case series. METHODS: Since September 1992 we have used cerebrospinal fluid drainage and distal aortic perfusion routinely to reduce the risk of neurologic deficit in thoracoabdominal aortic aneurysm patients. All patent intercostal arteries were reattached when this was technically feasible. Delayed neurologic complications occurred in eight patients who underwent operation for thoracoabdominal aortic aneurysm between September 1992 and March 1997, between 1 and 14 days after awakening from anesthesia. All patients had immediate cerebrospinal fluid drainage on recognition of their symptoms. RESULTS: Patients were evaluated by an independent neurologist and were classified by a modified Tarlov score between 0 and 5. All eight patients improved at least two points by discharge. The mean change in Tarlov score from onset to discharge was 2.4 +/- 1.1 (p = 0.008). CONCLUSIONS: Cerebrospinal fluid drainage significantly improved late-onset neurologic deficit that occurred between 1 day and 2 weeks after operation in our series. Immediate drainage should be considered when signs of neurologic deficit first begin to appear.

Adult↗

PubMed1997

Cerebral spinal fluid drainage and distal aortic perfusion decrease the incidence of neurological deficit: the results of 343 descending and thoracoabdominal aortic aneurysm repairs.

OBJECTIVE: We reviewed our experience of 343 descending and thoracoabdominal aortic aneurysm repairs to determine the impact of the adjuncts distal aortic perfusion and cerebral spinal fluid drainage on neurological deficit and death. MATERIALS AND METHODS: Between January 1991 and March 1996, 104 (30%) patients were operated for thoracoabdominal aortic aneurysm type I, 118 (34%) for type II, 68 (20%) for type III or type IV, and 53 (15%) for descending thoracic type. Before September 1992, simple cross-clamp was used for 94 (27%) patients. After September 1992, adjuncts were used for 186 (54%) patients. RESULTS: Overall neurological deficit was 33/343 (10%). Neurological deficit for simple cross-clamp patients compared to adjunct patients was 15/94 (16%) vs. 12/186 (7%) (O.R. 0.36, p < 0.01). For types I and II the incidence was 11/52 (21%) vs. 12/141 (9%) (O.R. 0.35, p < 0.02) and for type II, nine out of 22 (41%) vs. 11/85 (13%) (O.R. 0.21, p < 0.003). Overall 30-day mortality was 43/343 (13%), including patients presenting with rupture. Excluding these patients, overall 30-day mortality was 33/322 (10%). CONCLUSION: Cerebral spinal fluid drainage and distal aortic perfusion decreased the incidence of neurological deficit and were particularly effective for patients at highest risk with type II thoracoabdominal aortic aneurysm.

Adolescent↗

PubMed1997

Normotensive blood pressure in mice with a disrupted renin Ren-1d gene.

Renin is an aspartyl protease that is involved in the conversion of angiotensinogen to angitensin II and hence participates in the regulation of blood pressure. Mice are polymorphic for the number of renin genes with some strains harbouring two renin genes, Ren-1d and Ren-2. To study the role of renin Ren-1d in regulating cardiovascular homeostasis, mice with a disrupted Ren-1d gene were created. Analyses of kidney renin mRNA expression in Ren-1d-/-/Ren-2+/+ mice demonstrated that only Ren-2 transcripts were present. Mean arterial blood pressures of Ren-1d+/+/Ren-2+/+, Ren-1d+/-/Ren-2+/+ and Ren-1d-/-/Ren-2+/+ mice showed no significant differences. These observations demonstrate that the Ren-1d gene product is not essential for normal blood pressure maintenance under normal physiological conditions.

Animals↗

PubMed1997

Phosphorylation of neurofilament heavy-chain side-arm fragments by cyclin-dependent kinase-5 and glycogen synthase kinase-3alpha in transfected cells.

The side-arm domain of neurofilament heavy-chain (NF-H) is heavily phosphorylated in axons. Much of this phosphate is located within a multiphosphorylation repeat (MPR) domain situated toward the carboxy terminus of the molecule. The MPR domain contains the repeat motif KSP of which there are two broad categories, KSPXX and KSPXK. In mouse NF-H, the KSPXK repeats are situated toward the latter part of the MPR domain. We have expressed in mammalian cells fragments of mouse NF-H side-arm containing all of the MPR domain, the latter part of the MPR domain containing the KSPXK repeats, and the complementary amino-terminal part of the MPR domain, which contains the KSPXX repeats. By cotransfecting these fragments with the neurofilament kinases cyclin-dependent kinase-5 (cdk-5)/p35 and glycogen synthase kinase-3alpha (GSK-3alpha), we show that cdk-5 induces cellular phosphorylation of the KSPXK-containing fragment of NF-H. Using the transfected fragments, we also map the epitopes for several commonly utilised NF-H monoclonal antibodies and describe the effects that phosphorylation by cdk-5 and GSK-3alpha have on their reactivities.

Amino Acid Sequence↗

PubMed1997

Staged repair of extensive aortic aneurysm: improved neurologic outcome.

OBJECTIVE: We reviewed the adjuncts for brain and spinal cord protection and modifications of operative techniques. SUMMARY BACKGROUND DATA: Two-staged repair--the "elephant trunk" technique--has provided the means for successful repair of massive aortic aneurysms, although historically morbidity has been high. METHODS: Between February 1991 and February 1996, we operated on 512 patients for thoracic aortic aneurysm. Preoperative, intraoperative, or postoperative predictors of morbid outcomes were studied in 63 patients treated with the elephant trunk technique. Data were analyzed by contingency table methods. RESULTS: After stage 1, there were no strokes among patients who received retrograde cerebral perfusion (0 of 53), two strokes occurred among patients who did not receive retrograde cerebral perfusion (2 of 10 [20%]), and early mortality occurred in 4 of the 63 patients (6%). Interval mortality occurred in 6 of 59 patients (10%); 3 (50%) of these 6 deaths were due to distal aortic aneurysm rupture. Thirty-eight patients have undergone stage two repair thus far. There was no incidence of neurologic deficit after stage 2, and early mortality occurred in 1 of the 38 patients (3%). CONCLUSIONS: Extensive aortic aneurysm can be successfully treated using the elephant trunk technique. In this group of patients, retrograde cerebral perfusion eliminated neurologic complications.

Adult↗

PubMed1996

The intracellular cytoplasmic domain of the Alzheimer's disease amyloid precursor protein interacts with phosphotyrosine-binding domain proteins in the yeast two-hybrid system.

We have used the yeast two-hybrid system to screen for proteins that interact with the carboxy-terminal domain of APP. Six different clones were isolated and sequence analyses revealed that they encoded domains of a previously described neuronal protein Fe65, a homologue of Fe65 and a homologue of protein X11. All of these proteins contain one or more phosphotyrosine binding (PTB) domains. PTB domain proteins bind to the sequence Asn-Pro-X-Tyr when the Tyr is phosphorylated and are believed to function in signal transduction. APP contains such a motif. These results are consistent with a role for APP in signal transduction mechanisms.

Adaptor Proteins, Signal Transducing↗

PubMed1996

Cellular phosphorylation of neurofilament heavy-chain by cyclin-dependent kinase-5 masks the epitope for monoclonal antibody N52.

N52 is a widely used monoclonal antibody reported to recognise both phosphorylated and non-phosphorylated forms of neurofilament (NF)-H. N52 is therefore classified as a phosphorylation-independent-type antibody. N52 is strongly reactive with NF-H in COS cells transfected with NF-H alone but co-transfection of NF-H with the neurofilament kinase cdk-5 and one of its activators p35, induced phosphorylation of NF-H that abolished this reactivity. Treatment of the cdk-5 phosphorylated NF-H with alkaline phosphatase so as to remove phosphate restored N52 reactivity. A fragment of NF-H containing the consensus cdk-5 sites was reactive with N52 but following co-transfection with cdk-5/p35 a slower migrating fragment species generated by cdk-5 was not labelled by N52. These results demonstrate that N52 is not a truly phosphorylation-independent-type NF-H antibody and suggest that the N52 epitope contains sites targeted for phosphorylation by cdk-5.

Animals↗

PubMed1996

Predictive factors for acute renal failure in thoracic and thoracoabdominal aortic aneurysm surgery.

PURPOSE: The purpose of this study was to analyze the factors associated with acute renal failure in total descending thoracic and thoracoabdominal aortic aneurysm surgery. METHODS: A total of 234 patients underwent thoracoabdominal aortic aneurysm or total descending thoracic aneurysm repair between January 1991 and January 1994. Eighty-five women and 149 men were evaluated. The median age was 67 years (range 8 to 88 years). Seventy-seven patients had type I thoracoabdominal aortic aneurysm, 99 had type II, 51 had type III or IV, and 7 had total descending thoracic aneurysm. Factors such as age, sex, aneurysm type, and visceral and distal aortic perfusion were examined with univariate fourfold table and multivariate logistic regression analysis. RESULTS: Acute renal failure, defined as an increase in serum creatinine by 1 mg/dl per day for two consecutive days after surgery, occurred in 41 (17.5%) of 234 patients. Thirty-six (15%) of 234 patients required dialysis. Twenty (49%) of 41 patients with acute renal failure died. Of the 21 survivors with renal failure, renal failure resolved in 18 (86%) within 30 days of surgery. The univariate odds ratio of death, given acute renal failure, was 6.7 (95% confidence interval [CI] 3.2 to 14.2, p < 0.0001). No significant association was found between the probability of acute renal failure and age, sex, hypertension, right renal artery reattachment, or renal bypass. Factors associated with increased risk of acute renal failure in multivariate analysis were visceral perfusion (odds ratio [OR] = 3.6 95%, CI 1.2 to 11.0, p < 0.02), left renal artery reattachment (OR = 4.4 95%, CI 1.6 to 11.9, p < 0.004), preoperative creatinine > or = 2.8 mg/dl (OR = 10.3, 95% CI 12.0 to 411.8, p < 0.0001), and simple clamp technique (OR = 3.4 95%, CI 1.07 to 10.76, p < 0.04). Direct univariate correlation was seen between preoperative creatinine and acute renal failure (OR = 3.2 per mg/dl increase, 95% CI 2.7 to 10.1, p < 0.0001). CONCLUSION: Postoperative acute renal failure after thoracoabdominal and total descending thoracic aortic aneurysm surgery is associated with preoperative creatinine level, visceral perfusion, left renal artery reattachment, and simple cross-clamp technique.

Acute Kidney Injury↗

PubMed1996

Assembly properties of neurofilament light chain Ser55 mutants in transfected mammalian cells.

Ser55 within the head domain of neurofilament light chain (NF-L) is transiently phosphorylated by protein kinase A, and phosphorylation of this residue is thought to regulate assembly of neurofilaments. To understand how Ser55 phosphorylation influences NF-L assembly, wild-type and mutant NF-L genes in which Ser55 was mutated to alanine, so as to prevent phosphorylation, or to aspartate, so as to mimic permanent phosphorylation, were transfected into mammalian cells that contain or do not contain an endogenous intermediate filament network. Wild-type and mutant NF-Ls localised to the Triton X-100-insoluble fraction, which suggests that phosphorylation of Ser55 does not inhibit assembly of NF-L and NF-L/ vimentin polymers at or below the tetrameric stage. Immunofluorescence microscopy of transfected cells demonstrated that the wild-type and mutant NF-Ls all colocalised with vimentin to produce similar filamentous arrays. However, in cells lacking an endogenous intermediate filament network, the aspartate mutant produced a pattern of staining different from that of the wild-type or alanine mutant. These results suggest that phosphorylation of NF-L Ser55 is not a mechanism that precludes assembly of neurofilaments from monomers into intermediate filament structures but that phosphorylation/dephosphorylation of this residue might confer more subtle characteristics on neurofilament assembly properties and architecture.

Amino Acid Sequence↗

PubMed1996

Differential cellular phosphorylation of neurofilament heavy side-arms by glycogen synthase kinase-3 and cyclin-dependent kinase-5.

To investigate the cellular mechanisms regulating neurofilament-heavy subunit (NF-H) side-arm phosphorylation, we studied the ability of three putative neurofilament kinases, glycogen synthase kinase-3 (GSK-3)alpha, GSK-3 beta, and cyclin-dependent kinase-5 (cdk-5), to phosphorylate NF-H in transfected cells. We analysed NF-H phosphorylation by using a panel of phosphorylation-dependent antibodies and also by monitoring the electrophoretic mobility of the transfected NF-H on sodium dodecyl sulphate-polyacrylamide gel electrophoresis because this is known to be affected by side-arm phosphorylation. Our results demonstrate that whereas GSK-3 alpha, GSK-3 beta, and cdk-5 will all phosphorylate NF-H, they generate different antibody reactivity profiles. GSK-3 alpha and GSK-3 beta induce a partial retardation of a proportion of the transfected NF-H, but only cdk-5 alters the rate of electrophoretic migration to that of NF-H from brain. We conclude that cdk-5 and GSK-3 phosphorylate different residues or sets of residues within NF-H sidearm in cells. We further show that cdk-5 is active in both the CNS and the PNS but that this activity is not dependent on expression of its activator, p35. This suggests that there are other activators of cdk-5.

Animals↗

PubMed1996

Nitric oxide effects on shortening velocity and power production in the rat diaphragm.

The present experiments tested nitric oxide (NO) effects on shortening velocity and power production in maximally activated rat diaphragm. Diaphragm fiber bundles (n = 10/group) were incubated at 37 degrees C in Krebs-Ringer solution containing no added drug (control), the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA; 10 mM), the NO donor sodium nitroprusside (SNP; 1 mM), or a combination (L-NNA + SNP) Loaded shortening velocity was measured via the load-clamp technique over a range of afterloads. Force-velocity data were fitted to the Hill equation to determine maximum velocity of shortening (Vmax). Unloaded shortening velocity was measured in control and L-NNA-treated bundles (n = 12/group) by using the slack test. Maximal isometric force and unloaded shortening velocity were not altered by L-NNA. In contrast, L-NNA decreased maximum velocity of shortening (P < 0.05), loaded shortening velocity (P < 0.0001), and power production (P < 0.0001). All L-NNA effects were prevented by coincubating fiber bundles with L-NNA + SNP. SNP alone had no effect on any variable. These data indicate that endogenous NO is essential for optimal myofilament function during active shortening.

Animals↗

PubMed1996

Dimensions of the sinus tympani and its surgical access via a retrofacial approach.

The sinus tympani (ST) is a critical anatomic region of the temporal bone. It lies medial to the facial nerve, between the ponticulus and the subiculum, and therefore is not easily visualized by routine surgical approaches to the middle ear and mastoid. This limited access makes the ST a site that is notorious for residual cholesteatoma. An extensive evaluation of the anatomic dimensions of the ST was made from human temporal bones. Three hundred twenty-seven bones were examined at four standardized levels to describe the dimensions and anatomic relationships of the ST with other structures of the temporal bone. The region of the stapedial tendon was found to be the most limited anatomic substructure in the vicinity of the ST. This study demonstrates the feasibility of a retrofacial approach to the ST as an aid in eradication of otherwise hidden disease.

Cholesteatoma, Middle Ear↗

PubMed1996

Cellular phosphorylation of tau by GSK-3 beta influences tau binding to microtubules and microtubule organisation.

Tau is a neuronal microtubule-associated protein that appears to function in the formation and maintenance of axons by influencing microtubule organisation. Tau is a phosphoprotein and is more heavily phosphorylated in fetal than in adult brain, and is also hyperphosphorylated in Alzheimer's disease where it forms the major component of paired helical filaments (PHFs). Tau phosphorylation probably modulates microtubule dynamics since in vitro, phosphorylated tau has a reduced affinity for microtubules and is less potent at promoting microtubule assembly. In order to understand how phosphorylation effects cellular microtubule organisation, we studied 3T3 and CHO cells transfected with tau and the tau kinase GSK-3 beta. Tau transfected cells displayed prominent bundles of microtubules that did not appear to be nucleated by a microtubule-organising centre. Co-transfection of tau with GSK-3 beta led to increased phosphorylation of tau and also to a reduction in microtubule bundling such that the microtubule network in many of the tau/GSK-3 beta transfected cells appeared similar to non-transfected interphase cells. Transfection of a mutant tau, in which five of the known GSK-3 beta targeted phosphorylation sites were mutated to alanine so as to preclude phosphorylation, also induced microtubule bundling. However, co-transfection of this mutant with GSK-3 beta did not diminish the bundling effect. Biochemical analyses of microtubule and cytosolic fractions from the transfected cells demonstrated that GSK-3 beta-mediated phosphorylation of tau reduced its affinity for microtubules. These results suggest that phosphorylation of tau by GSK-3 beta modulates its ability to organise microtubules into ordered arrays such as are found in axons.

3T3 Cells↗

PubMed1995

The phosphorylation state of the microtubule-associated protein tau as affected by glutamate, colchicine and beta-amyloid in primary rat cortical neuronal cultures.

The effects of the excitatory amino acid glutamate, the microtubule destabilizing agent colchicine, and beta 25-35-amyloid peptide on the phosphorylation state of tau were studied in rat cortical neurons in primary culture. Using immunocytochemistry and Western-blot analysis, we demonstrated that a proportion of tau in these cultures is normally highly phosphorylated, but most of this tau fraction is dephosphorylated after treatment of the cultures with glutamate or colchicine, but not with beta-amyloid; the glutamate- and colchicine-induced changes in tau phosphorylation commenced before cell death, as assessed by release of lactate dehydrogenase. Dephosphorylation of tau was readily revealed by using the monoclonal antibodies Tau.1 and AT8, which have phosphate-sensitive epitopes that both centre around serine-199 and -202 (numbering of the largest tau isoform). On Western blots and by immunocytochemistry, AT8 labelling strongly decreased after glutamate and colchicine treatments, whereas Tau.1 staining was more intense. Neurofilament monoclonal antibodies, including RT97, 8D8, SMI31 and SMI310, all additionally known to recognize tau in a phosphorylation-dependent manner, also demonstrated that glutamate and colchicine treatments of the cultures induced a dephosphorylation of tau. We also showed immunocytochemically that there is an increase in tau immunoreactivity in neuronal perikarya in response to glutamate and colchicine treatment, and this occurs concomitantly with the dephosphorylation of tau. Treatment of the primary rat cortical neuronal cultures with beta 25-35-amyloid peptide, under conditions which induce neuronal degeneration, did not induce a change in tau phosphorylation, and failed to act synergistically with glutamate to produce an increase in dephosphorylation of tau over that produced by glutamate treatment alone. These findings demonstrate that glutamate and colchicine induce tau dephosphorylation, as opposed to increased tau phosphorylation, which would be more indicative of Alzheimer-type neurodegeneration.

Amyloid beta-Peptides↗

PubMed1995

Stimulation of MAP kinase by v-raf transformation of fibroblasts fails to induce hyperphosphorylation of transfected tau.

A proportion of the microtubule-associated protein, tau, is in an elevated state of phosphorylation in foetal and adult brain whereas all of the tau in paired helical filaments, which are characteristic of Alzheimer's disease is hyperphosphorylated; it is important therefore to elucidate the mechanisms that regulate tau phosphorylation. Here we describe results that show that although MAP kinase can hyperphosphorylate tau in vitro, activation of MAP kinase in transformed fibroblasts does not result in hyperphosphorylation of transfected tau, whereas glycogen synthase kinase-3 beta (GSK-3 beta) when co-transfected with tau does result in tau hyperphosphorylation. The findings imply that GSK-3 beta may be a stronger candidate than MAP kinase for inducing tau hyperphosphorylation in vivo.

3T3 Cells↗