Bronchial asthma is a chronic and heterogeneous inflammatory disorder of the conducting airways with immune and non-immune etiologies. Although the underlying molecular basis of asthma is not completely understood, inflammation is a key pathological feature of bronchial asthma. The increasing prevalence in Western countries (approximately 15% of children and 8% of adults) supports the vast resources deployed to find treatments and drugs that act upon pathways not targeted in current therapies are of particular interest. (more...)

Treating blood loss with cell free oxygen carrier (artificial blood) is essential to maintain oxygen supply to the patient as well as prevent the collapse of capillaries. Effective substitution by artificial blood hinges on oxygen delivery, blood-gas and pH balance, and carbon dioxide removal. Therefore it is important to monitor the efficacy of the artificial blood or compare the efficacy of different types of them. (more...)

The current gold standard for disease monitoring in the clinical treatment of asthma are flow rate and lung volumes readings, which are combined in spirometer. When another important biochemical indicator fluctuates significantly, this indicates inflammation of the airways.  While these disease monitoring data points can currently be obtained in a clinical setting on a one-off basis, it would be very useful if they were available on an ongoing basis, and ideally also in a home setting.  If spirometry and specific biochemical levels could be monitored in tandem on an ongoing basis, this would provide predictability of an asthma attack.   In response to this challenge, investigators at University of California at Berkeley have developed an inhaler based asthma attack predicting spirometer-biochemical sensor.   This innovation combines these two key clinical indicators on an inhaler, which is used regularly and frequently by asthma patients.  The asthma attack predicting sensor has an inlet for spirometry measurements where the air flows into one chamber.  Here, biochemical levels and airflow are quantified. The asthma attack predicting sensor also has a pressure sensor and signal transducer for the flow rate measurements.  All information can be transmitted wirelessly to the clinician.  An outlet for the inhaler medication to be released is also provided, just as in a regular inhaler.  The first commercial use of the asthma attack predicting sensor will be to monitor the severity in the occurrence of an asthma attack in children ages 8-12 with severe asthma.  The broader usages will be to provide information to clinicians for the personalization and predictability of an asthma attack in all asthma patients. Potentially, anyone with asthma, regardless of the severity and age of the user, would find the device beneficial in tracking medical information for personal reasons or to provide the information to their clinician. (more...)

Although significant efforts have been devoted to bridging the gap between synthetic nanomaterials and viable biologics, development of a bio-mimetic delivery vehicle has remained elusive. Challenges include the limited ability to reproduce a cell’s complex membrane makeup on a nanoscale substrate and the fact that most bioconjugation techniques lead to protein denaturation. Efforts to extend nanoparticle residence time in vivo have inspired a variety of strategies to bypass macrophage uptake and systemic clearance. However, none of these have been able to recapitulate what nature has already evolved as its’ own long-circulating delivery vehicles—the red blood cell (RBC). (more...)

Human skin is exposed to a multitude of chemicals on a daily basis, many of which can be hazardous or induce an irritant reaction.  While there is strict government regulation in regards to screening of these chemicals, this testing has typically relied on the use of animal models.  However, in recent years the use of in vitro screening methods has become more prominent, with reconstructed human epidermis models being a preferred technique.  Unfortunately, this approach is both time-comsuming and expensive, as well as being difficult to develop as a high throughput screen. (more...)

There are approximately 20-40 million people in the United States with sleep apnea. Obstructive sleep apnea has been recognized as a very common disorder and an important cause of morbidity and mortality. Obstructive sleep apnea is characterized by repetitive interruptions of breathing during sleep due to the collapse of the upper airway. Sleep apnea can lead to severe health complications including hypertension, heart failure, memory impairment, motor vehicle and work accidents, decreased work productivity, and increased risk of death. The development of a novel, simple, rapid, minimally invasive method for the diagnosis and optimization of treatment of patients with obstructive sleep apnea would be a tremendous advance for these millions of patients. Optical coherence tomography (OCT) is an imaging modality that can perform cross section views of tissue. OCT is analogous to ultrasound except that imaging is performed with light instead of acoustic waves. OCT is non invasive and non ionizing allowing study over lengthy periods during both sleep and wakefulness. Conventional OCT which is based on time domain technique has very limited imaging speed which precludes its use in real-time, dynamic monitoring and large volume detection. Researchers at the University of California have developed a technique including the step of combining a narrow line-width sweptsource based Fourier domain OCT (FDOCT) system with an endoscopic probe to enable an ideal upper airway imaging technology which is low-cost, compact, noninvasive, non-ionizing, dynamic (to visualize apneic events), suitable for supine position study, and capable of high resolution three dimensional images. This technology provides a mechanism for dynamic evaluation of obstructive sleep apnea. (more...)

Background: In 2009, 300 million people worldwide suffered from asthma and the incidence continues to increase. Current therapies lead to global suppression of the immune system rather than specifically treating asthma symptoms and could result in unwanted side effects. Beta agonists are the most widely used clinical treatment to reverse airway narrowing and shortness of breath caused by smooth muscle dysfunction. However, there is conflicting evidence as to the long-term safety of their use, with some reports of increased mortality in patients who rely heavily on their use. Therefore, innovative therapies are needed that specifically target and reverse airway constriction and rapidly alleviate shortness of breath resulting from acute asthma exacerbations without leading to adverse effects. Technology Description: Researchers at UCSF have identified a novel protein that could be used as a therapy to reduce shortness of breath in asthma. The protein has been shown to target a molecular pathway that controls smooth muscle contraction and thereby affects airway constriction. In both short-term and chronic allergen challenge models, mice deficient in this protein developed more severe asthma as shown by increased airway hyperresponsiveness. The therapeutic effects of the protein on airway smooth muscle contraction are evident in a mouse model of allergic asthma where after in vivo induction of asthma, tracheal rings are isolated from mice to measure their contractile response to agonists in vitro. The administration of this protein to tracheal rings reduces the force of contraction and the degree of airway narrowing. Addition of the protein also specifically acts to reduce asthmatic symptoms only after asthma induction, thus reducing the risk of potentially hazardous adverse effects. Thus, this protein holds promise as a novel and safe quick-relief therapeutic for asthma sufferers. Current and future studies are focused on validating these results by therapeutically administering the protein in in vivo mouse models, mapping the protein domain responsible for therapeutic action, screening for small peptides that reproduce the effects of the whole protein, identifying the molecular target of the protein, and testing the combined effect of the protein with beta agonists. The identification of a peptide with specific action could decrease any potential side effects that are present in the whole protein. Closely related proteins will also be studied for their action in asthma models. After validation in mouse models, the efficacy of the protein therapeutic will be evaluated in human subjects with asthma. (more...)

UCSF researchers have identified a set of biomarkers that can be used to diagnose sarcoidosis in whole blood samples. Currently, there are no routinely used non-invasive tests for diagnosing sarcoidosis, therefore these biomarkers are promising for the development of rapid and standardized diagnostic tests that can be widely implemented in the clinics. (more...)

A smart conserver that responds with each breath, automatically metering out O2 as needed to meet changing patient demand. (more...)

Scripps Institution of Oceanography (SIO) at UC San Diego is one of the oldest, largest, and most important centers for global science research and education in the world. With the oceans covering 70 percent of the earth's surface, it is no surprise that approximately two-thirds of the world's animal phyla are found in marine environments and many are exclusively marine. SIO scientists were among the first to explore the natural product chemistry of marine organisms and this research helped to develop the field of marine natural products chemistry and the realization that the oceans harbor myriad new organic molecules with utility for the development of pharmaceuticals and other products. This research led to the discovery of hundreds of new compositions of matter for new products—some of which are already well progressed into commercial development. Two compounds are now entering phase II clinical trials. One of these, Salinosporamide A, is a potent proteasome inhibitor. The second compound, which is derived from the fungal metabolite halimide, acts as a vascular disrupting agent. (more...)

Treatment for tuberculosis infection involves multiple drug therapy using combinations of rifampin, isoniazid, pyrazinamide, and ethambutol. However, rifampin is a highly toxic antibiotic that induces hepatitis, thrombocytopenia, bullous skin rashes and other injury. Drug toxicity is caused by free rifampin in the blood stream that failed to bind human serum albumin (HSA) to which it binds non-specifically . (more...)

The only currently available TB vaccine, an attenuated Mycobacterium bovis strain Bacille Calmette-Guerin (BCG), is of variable efficacy. A large carefully conducted meta-analysis has estimated the potency of BCG to be approximately 50%. UCLA researchers developed and reported in the last several years a recombinant BCG expressing the Mycobacterium tuberculosis 30 kDa major secretory protein (r30). This vaccine, named rBCG30, induces greater protection than BCG against aerosol challenge with a highly virulent strain of M. tuberculosis. (more...)

Quantification of pulmonary blood flow (PBF) is essential for the assessment of efficient gas exchange. The ability to quantitatively evaluate changes in regional PBF (rPBF) can enhance our understanding of the relationship between lung structure and function in both health and disease. Aerial spin labeling (ASL) is a powerful MRI technique for noninvasive perfusion imaging of organs. It uses arterial blood water as the endogenous contrast agent without the exposure of ionizing radiation, the limitation of spatial or temporal resolution, or the need for an exogenous contrast agent, making possible for this non-invasive procedure to be widely available at relatively low cost. Pulsed ASL techniques have been validated for cerebral blood flow; however, because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain. (more...)

Although algorithms and chemistries for developing new therapeutic entities are constantly evolving, none can replicate the path and novelty of natural selection over eons of time. Inventors at the Scripps Institution of Oceanography have engaged their fleet of research ships to cull the oceans for marine organisms from which new compositions are isolated.  Using a variety of culture systems, selective fractionation and bioassays, two, distinct classes of compounds, isolated from actinomycetes, have demonstrated potent anti-tumor activity and considerable selectivity toward some cancers. One class of compounds, the ammosamides, are unique molecules that target a previously untargeted intracellular pathway. It is anticipated that proprietary methods and naturally evolved compositions may yield therapeutics that are significantly differentiated from those developed by limited iteration of pre-defined platforms. (more...)

A series of novel lipid derivatives of phosphonate compounds has been synthesized. These novel compounds have been shown to promote oral uptake and increase delivery of the conjugate to the lung in animal models when compared with the parent compounds. A similar derivatization strategy can also be applied to non-phosphonate compounds making this approach applicable to a variety of existing drugs. Drugs that have been modified in this way will very likely be more effective against diseases of the lung and this approach has the potential to improve the efficacy of drugs that are directed against pulmonary infections, such as influenza, or lung diseases, such as cancer. (more...)

Human lung surfactant is a complex mixture of lipids and proteins that reduces surface tension in the lung, enabling normal breathing. Lack of effective surfactant results in Respiratory Distress Syndrome (RDS), a potentially fatal condition seen in premature infants and in adults with lung infection or trauma. While replacement lung surfactant (RLS) therapy has revolutionized neonatal RDS treatment, it is relatively ineffective in adults. Even with neonatal RDS, up to 30% of infants do not respond to RLS therapy. This failure in RLS therapy has been attributed, at least in part, to inactivation of the replacement lung surfactant in distressed lungs.Researchers at the University of California, San Francisco, have discovered that inactivation of surfactants by endogenous substances present in the lung can be significantly reduced by administration of either ionic or nonionic polymers. Ionic polymers are particularly effective, and have the advantage that lung epithelial cells produce them endogenously. The polymers may therefore be useful in the design of second-generation surfactants for use in RLS. (more...)

Mycobacteria are a significant cause of morbidity and mortality, particularly among immunocompromised or elderly individuals and in countries with limited medical resources. Ninety-five percent of human infections are caused by seven species: Mycobacterium tuberculosis, M. avium (also known as the mycobacterium avium complex or M. avium-intracellulare), M. leprae, M. kansasii, M. fortuitum, M. chelonae, and M. absecessus. The most common mycobacterial infections in the United States are pulmonary infections by M. tuberculosis or M. avium. Such mycobacterial infections have been of increasing concern over the past decade, particularly in light of the increasing incidence of multi-drug resistant strains.   Mycobacterium tuberculosis is the causative agent of the disease tuberculosis in humans. Estimates indicate that one-third of the world's population, including 10 million in the U.S., are infected with M. tuberculosis, with 8 million new cases and 3 million deaths reported world wide each year. Although incidence of tuberculosis steadily decreased since the early 1900s, this trend changed in 1984 with increased immigration from endemic countries and increased infection among homeless individuals, drug and alcohol abusers, prisoners, and HIV-infected individuals. The increasing occurrence of drug-resistant strains requires continued research into new and more effective treatments. SUMMARY OF THE INVENTION Novel mycobacterial sulfation pathway proteins and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway protein. The present invention further provides genetically modified mycobacteria having a defect in a sulfation pathway enzyme gene; and immunogenic compositions that include such genetically modified mycobacteria. ABSTRACT Novel mycobacterial sulfation pathway enzymes and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting growth and/or virulence of a pathogenic mycobacterium, and methods of treating disease conditions associated with a pathogenic mycobacterium, particularly by administering an inhibitor of a mycobacterial sulfation pathway enzyme. Normal.dotm 0 0 1 85 489 UC Berkeley 4 1 600 12.0 0 false 18 pt 18 pt 0 0 false false false /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} (more...)