Lipid-tagged single domain antibodies for improved enzyme-linked immunosorbent assays.

Anti-Staphylococcal Enterotoxin B single domain antibodies were engineered to include the N-terminal peptide sequence of the major outer membrane lipoprotein from Escherichia coli, which directs the N-terminal addition of lipid to the single domain antibody. We produced and purified two different single domain antibodies as well as a variant and dimer construct of one of the two, all with and without the added lipid. Their ability to function as the capture antibody in standard enzyme-linked immunosorbent assays were evaluated, finding that coating polystyrene microtiter plates with the lipid-tagged single domain antibodies gave a 3-fold improvement in the observed limit of detection. This increase was likely due to an increased amount of single domain antibody adsorbed to the microtiter plate, which translated to improved limits of detection of Staphylococcal Enterotoxin B over using the same single domain antibody sans lipid-tag. However, improved orientation may also play a role. Regardless of the mechanism, the biosynthetic lipid-tagging of single domain antibodies represent a facile modality that can enhance their ability to be utilized as immunoassay capture reagent as well as facilitate their incorporation into liposome targeting applications in the future.

Dose escalation study of carboplatin-pemetrexed followed by maintenance pemetrexed for elderly patients with advanced nonsquamous nonsmall-cell lung cancer.

BACKGROUND: This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed. RESULTS: The combination of carboplatin at an area under the concentration-time curve (AUC) of 5, and 500 mg/m(2) pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68-216 days) and the median overall survival time was 461 days (95% CI 168-754 days). CONCLUSIONS: This combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m(2)) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC.

Effect of topotecan as second-line chemotherapy for small cell lung cancer patients with interstitial lung disease.

Small cell lung cancer with interstitial lung disease (ILD-SCLC) is difficult to treat because of the risk of fatal pneumonitis. Our study aims to evaluate the validity of topotecan (TOP) as chemotherapy for patients with relapsed ILD-SCLC. Overall survival was compared between TOP and other drugs as second-line treatments for ILD-SCLC patients. Forty-seven patients began chemotherapy and second-line treatment was administered in 48.5% of relapsed cases. The response rate of TOP for second-line therapy was 16.7%. Hematologic toxicities were grade 4 anemia, grade 3 neutropenia and grade 3 thrombocytopenia. Mild pulmonary toxicity was observed in 1 case. Patients receiving TOP as second-line treatment showed no significant difference in survival when compared to patients who underwent other regimens (median survival time 179 vs. 76 days; p =0.76). TOP is a well tolerated drug and is a viable candidate for second-line treatment of ILD-SCLC patients.

[A case of pituitary adenoma presenting binasal inferior quadrants hemianopsia].

Visual field defect due to pituitary adenoma ordinarily shows bitemporal hemianopsia. But we experienced a case presenting binasal inferior quadrants hemianopsia. A 60-year-old woman was admitted to our hospital complaining of headache and blurred vision. At ophthalmologic examination, the visual acuity on the right was 0.02 and on the left 0.3. Visual field showed a loss of bilateral inferior nasal quadrants. There was neither pallor nor edema of either of the optic disks. A computerized tomography (CT) scan showed an enhancing mass in the intra- and suprasellar region. But despite remarkable suprasellar expansion of the tumor, the straight view of bilateral carotid angiograms revealed no elevation of the first part of the anterior cerebral arteries (ACA). On the lateral view, the terminal portion of the precommunicating part of the left ACA showed rather marked anteroinferior displacement. 2 mm thin sliced CT scans at the suprasellar region revealed that the left internal carotid artery had been touching the lateral portion of the tumor and the ACA had been displaced anteriorly by the tumor. Two weeks after admission, transsphenoidal tumor resection was carried out. Total removal was achieved and histological examination showed that the tumor was nonfunctioning chromophobe adenoma. The postoperative course was uneventful except for transient diabetes insipidus. The patient's visual acuity rapidly improved to 0.8 on the right and 0.5 on the left two weeks after operation. Although there was still a tendency for left inferior nasal field defect, remarkable improvement was obtained subjectively and objectively. According to the findings of CT scans and cerebral angiograms, binasal hemianopsia may have been produced by the mechanism as follows.(ABSTRACT TRUNCATED AT 250 WORDS)

Generalized epilepsy in a patient with hypokalemic periodic paralysis and cardiac arrhythmia.

A 17-year-old female who had Hypokalemic periodic paralysis with arrhythmia developed syncopal attacks. Although syncope in this rare disorder has been attributed to ventricular tachycardia or ventricular fibrillation, the clinical manifestation, electroencephalogram, serum electrolytes and blood sugar at the attack, and the results of lumbar puncture indicated that idiopathic generalized epilepsy was the cause of the syncopal attacks in the present case. To our knowledge, this is the first case report of the association of epilepsy with periodic paralysis and arrhythmia in the literature.