IN VITRO ANALYSIS OF τ PHOSPHORYLATION SITES AND ITS BIOLOGICAL ACTIVITY

INTRODUCTIONThemicrotubule－associatedprotein蚲ishyperphos－phorylatedandglycosylatedinAlzheimerdisease（AD），andtheseabnormalmodificationsformedthebasisofprogressivelyretrogradeneurofibrillarydegenerationseeninADbrainandtherebythedementia（１，２）．ADab－normallyphosphorylated蚲notonlyismicrotubuleas－semblyincompetent，butalsoinhibitsassemblyanddis－assemblesthepreassembledmicrotubulesinvitro（３）．Inthetangle－bearingneuronsinADbrain，thenormalcytoskeletonisdisruptedandreplacedwi…     

Goldenhar’s Syndrome associated with congenital cyanotic heart disease

A case of Goldenhar’s Syndrome in a 10 year old girl is reported. The unusual features are the absence of epibulbar dermoid which is one of the major hallmarks of the Syndrome and the presence of an associated Cyanotic Heart disease.     

Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.     

Granulocytic sarcoma: An atypical presentation in the oral cavity

Acute myelogenous leukemia (AMU is a hematologic disorder that is characterized by an abnormal proliferation of immature myeloid cells. Granulocytic sarcomas are clusters of leukemic myeloid cells that may develop as a result of AML. Oral manifestations of AML are common and often involve enlargements of the gingiva and/or mucosal tissue from direct leukemia cell infiltration. We describe the case history of a 50-year-old man who had an ulcera-tive lesion of the oral mucosa that was determined to be a granulocytic sarcoma of AML-M0 subtype. The combination of both the subtype and clinical presentation of the leukemia makes this presentation unusual, and to the best of our knowledge, of a type that has not been previously reported in the literature.     

Geriatric diabetic nephropathy: an analysis of renal referral in patients age 60 or older

We report a series of 33 consecutive hospitalized geriatric diabetic patients who were referred for evaluation of diabetic nephropathy, defined as proteinuria greater than or equal to 1 g/d (1,000 mg/24 h) or a serum creatinine concentration greater than or equal to 177 mumol/d (greater than or equal to 2 mg/dL). The study population was 60 years old or older (mean age, 68 +/- 6 years), was comprised mainly of women (24 of 33, 72.7%), and was predominantly black (25 of 33, 75.8%). All patients had type II diabetes. A family history of diabetes in parent or sibling was elicited in 24 (72.7%) patients. There were eight patients undergoing maintenance hemodialysis and 25 with less severe nephropathy (mean proteinuria, 2.7 g/d [2,700 mg/24 h]; mean creatinine clearance, 0.57 mL-s [34 mL/min]). Cardiac disorders were noted in the majority of patients: congestive failure in 20 (60.6%), myocardial infarction in eight (24.2%), and active angina in five (15.2%). Other comorbid diseases were present in both hemodialysis patients and the subset of nondialyzed azotemic-proteinuric patients, and consisted of peripheral neuropathy in 31 (93.9%), gastroparesis in 16 (48.5%), retinopathy in 28 (84.8%), and legal blindness in 11 (33%). We conclude that geriatric diabetic nephropathy in type II diabetes is similar in presentation and severity of comorbid extrarenal complications to the syndrome described in younger adults. This inference must be tempered by both the small size and the limitation imposed by the demographics of the study population, which is predominantly composed of black patients receiving treatment at inner city hospitals.     

Pharmacokinetics of aditoprim and trimethoprim in buffalo calves

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.     

Gastric carcinoma--a study of 100 cases in northern Pakistan.

We describe 100 consecutive patients with histologically proven gastric carcinoma who were admitted to various hospitals in Northern Pakistan. Twenty-six per cent of patients were under 40 years of age. In a majority of patients the tumour was of a morphological type associated with poor prognosis. In most cases the disease was already at an advanced stage at the time of diagnosis, and most patients died within one year.