Intracerebroventricular passive immunization with anti-Abeta antibody in Tg2576.

Current Alzheimer's disease (AD) research has established the fact that excessive genesis of Abeta derived from amyloidogenic processing of beta-amyloid (Abeta) precursor protein is fundamental to AD pathogenesis. There has been considerable interest in using immunization strategies for clearing excessive Abeta. Studies in animal models of AD have shown that active immunizations or systemic passive immunizations reduced cerebral plaque load and improved behavioral deficits.

Membrane dynamics, cholesterol homeostasis, and Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid (A beta) plaques derived from the amyloidogenic processing; of a transmembrane protein called beta-amyloid precursor protein (APP). In addition to the known genetic/sporadic factors that promote the formation of A beta, the composition and structural dynamics of the membrane are also thought to play a significant role in the amyloidogenic processing of APP that promotes seeding of A beta. This minireview reinforces the roles played by membrane dynamics, membrane microdomains, and cholesterol homeostasis in relation to amyloidogenesis, and reviews current strategies of lowering cholesterol in treating AD.

Regulation of myeloma cell growth through Akt/Gsk3/forkhead signaling pathway.

The interleukin-6 (IL-6) signaling pathway contributes to myeloma cell growth and viability through activation of the PI3/Akt kinase pathway. To understand the downstream signaling elements in the PI3/Akt kinase pathway that are involved in the regulation of myeloma cell growth, we determined the role played by glycogen synthase kinase 3 (Gsk3) and forkhead transcription factors (FH) in the RPMI-8226 myeloma cell line. We demonstrate that both Gsk3 and FH transcription factors FKHRL1 (FOX3a), FKHR (FOXO1a), and AFX (FOXO4) are phosphorylated (inactivated) by IL-6.

Infection by bacterial pathogens expressing type III secretion decreases luciferase activity: ramifications for reporter gene studies.

Pathogenic microbes influence gene regulation in eukaryotic hosts. Reporter gene studies can define the roles of promoter regulatory sequences. The effect of pathogenic bacteria on reporter genes has not been examined.

Phase II trial of aminocamptothecin (9-AC/DMA) in patients with advanced squamous cell head and neck cancer.

Fourteen patients with squamous cell carcinoma of the head and neck received 9-AC/DMA infusions of 850 mg/M2/day over 72 hours. Eligibility criteria included good performance status, advanced disease incurable by conventional means, no prior treatment of metastatic disease, and measurable lesions for objective response assessment. The infusions were repeated at 21 day intervals until progression or prohibitive toxicity occurred.

New anti-inflammatory treatment strategy in Alzheimer's disease.

Numerous reports have indicated that patients suffering from inflammatory diseases (e.g., arthritis) who take anti-inflammatory medication have a reduced risk of developing Alzheimer's disease (AD).

Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery.

Setting: In vitro and in vivo study of an isoniazid (INH) drug delivery system.

Objective: To develop a system for the treatment of tuberculosis using a subcutaneous polymer implant with a large drug load released slowly over a long period. INH delivery by biodegradable poly-(alpha-hydroxy acid) polymers was evaluated using ground polymer and compression molded implants.

End-diastolic pressure-volume relationship in sepsis: relative contributions of compliance and equilibrium chamber volume differ.

Background: Compliance is a complex parameter to measure both clinically and in the laboratory. Investigations in recent years have interpreted changes in the end-diastolic pressure-volume relationship (EDPVR) as changes in compliance. However, without considering the equilibrium chamber volume (LV volume when transmural pressure = 0), changes in the EDPVR may not reflect changes in left ventricular chamber compliance.

Psychological assessment (MMPI-2) of male African-American substance-abusing patients with and without histories of childhood physical abuse.

Twenty-nine drug addicted patients in a VA substance abuse program with a history of childhood physical abuse were compared to 29 drug addicted patients without a history of childhood abuse, using the MMPI-2 as a measure of personality traits and functioning. Drug addicted patients with an abuse history showed psychological maladjustment on almost all measures and at greater levels of intensity and severity than the nonabused group. We conclude that drug addicted patients who have been abused represent a unique subset of the drug addicted population and may require targeted psychological treatment for residual problems associated with childhood abuse.

Factor structure of the MCMI-III.

The factor structure of the Millon Clinical Multiaxial Inventory (Millon, 1994; MCMI-III) was assessed among 444 African American inpatient substance abusers and constitutes the first factor analysis of the MCMI-III. We found 3 main factors: General Maladjustment, Paranoid Behavior/Thinking With Detached Emotionality, and Antisocial Acting Out. These factors were essentially similar to previous findings of factor studies with the MCMI and MCMI-II across diverse populations.

Regulation of renal Na-HCO3 cotransporter: VIII. Mechanism Of stimulatory effect of respiratory acidosis.

We examined the effect of respiratory acidosis on the Na-HCO3 cotransporter activity in primary cultures of the proximal tubule of the rabbit exposed to 10% CO2 for 5 min, 2, 4, 24 and 48 hr. Cells exposed to 10% CO2 showed a significant increase in Na-HCO3 cotransporter activity (expressed as % of control levels, 5 min: 142 +/- 6, 2 hr: 144 +/- 13, 4 hr: 145 +/- 11, 24 hr: 150 +/- 15, 48 hr: 162 +/- 24). The increase in activity was reversible after 48 hr.

MCMI-III-derived typological analysis of cocaine and heroin addicts.

A sample of 441 African American men who were either inpatient heroin or cocaine addicts, or both; were assessed with the MCMI-III. The modal codetype showed primary elevations on the Antisocial Personality Disorder Scale (6A), consistent with previous research using the MCMI-I and MCMI-II with substance abusers. The data were subjected to 3 independent clustering procedures that resulted in general consistency among procedures.

Assessing PTSD with the Millon Clinical Multiaxial Inventory-III.

We studied the utility of the Millon Clinical Multiaxial Inventory-III (MCMI-III) in assessing substance-abusing (n = 228), combat-related PTSD patients (n = 32). The MCMI-III produced a code type (16A) that was quite different from MCMI-I and MCMI-II code types (8A2) among similar populations. The PTSD Scale (R) successfully differentiated between a PTSD and non-PTSD substance-abusing group using mean Base Rate scores, was the best predictor of PTSD in a multiple regression equation, and the scale's sensitivity and specificity in detecting and/or ruling out the disorder was above that provided by chance alone and higher than the values reported in the test manual for that scale.

The renal cortical Na+/HCO3- cotransporter VI: the effect of chemical modification in cotransporter activity.

The Na+/HCO3- cotransporter is the main system that mediates bicarbonate removal out of the proximal tubule cell into the blood. We have previously partially purified this protein and showed that chemical modification of the alpha-amino groups by fluorescein isothiocyanate (FITC) inhibited the activity of the Na+/HCO3- cotransporter. The inhibition was prevented by the presence of Na and bicarbonate suggesting that this compound binds at or near the substrate transport sites of the cotransporter.

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on the bactericidal functions of neutrophils.

The hematopoietic growth factors granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) not only regulate the numbers of circulating neutrophils but also modulate the function of mature cells. Additionally, newly developed neutrophils subsequently released from the bone marrow in response to colony-stimulating factors (CSFs) also have enhanced function. A variety of different functions are affected, including changes in adherence, movement, phagocytosis, priming and stimulation of the respiratory burst, secretion, and degranulation.

Apoptosis and Its Role in Neutrophil Dysfunction in AIDS.

Apoptosis, or programmed cell death, is a mechanism of cell death in many biological processes, including growth and development, normal cell turnover, and tissue remodeling. Apoptosis is also very important in the regulation of immune responses. Apoptosis of B cells and T cells is key in regulating humoral and cell-mediated immune responses.

Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome.

Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers.

Parathyroid hormone-related protein expression in the human colon: immunohistochemical evaluation.

Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. In addition to its hypercalcemic action, PTHrP has been implicated as an autocrine modulator of growth and differentiation, as well as an early response gene in some tissues. Several different types of tumors have been evaluated for the presence of PTHrP immunoreactivity.

Psychological screening of impotence with Finney's MMPI-derived Impotence Scale.

Three groups of patients in treatment were assessed for impotence, using MMPI-derived Impotence Scale. Group I were 46 patients who had been screened and scheduled for a penile prosthesis when the impotence resulted from known organic causes (biogenic). Group II were 198 patients in a sexual dysfunction clinic, for whom biogenic causes had been ruled out (psychogenic).

Formalizing written communication by decentralized pharmacists with prescribers.

The development of a standardized drug information system is explained. The development of such a system provides increased communication, documentation, and quality assurance information. The pharmacist is now able to effectively and consistently communicate with the medical staff regarding pertinent patient information.

Neutrophil Priming Mechanisms of Sulfolipid-I and N-Formyl-Methionyl-Leucyl-Phenylalanine.

The principal sulfatide of virulent Mycobacterium tuberculosis, sulfolipid-I (SL-I), both directly stimulates neutrophil superoxide (O(-)(2)) release and, at substimulatory concentrations, primes these cells for markedly enhanced oxidative responsiveness to other stimuli. The present study was undertaken to clarify the priming mechanisms by comparing cellular events following priming doses of SL-I with those following priming with N-formyl-methionyl-leucylphenylalanine (FMLP). We compared the involvement of the calcium cation (Ca(2+)), as well as membrane protein kinase C (PKC) activity and the translocation of NADPH oxidase-cytosolic cofactor effected by priming levels of the two agonists.

Effects of endurance exercise on bone histomorphometric parameters in intact and ovariectomized rats.

Physical activity is important for maintenance of bone mass. The effects of exercise on bone histomorphometry were studied in 9-month-old intact (INT) and ovariectomized (OVX) rats. The rats were either kept sedentary (SED) or were exercised (EX) on a treadmill at 21 m/min for 1 h/day 5 days/week for 3 months.