Hypoxia-inducible lentiviral gene expression in engineered human macrophages.

Background: Human immune cells, including monocyte-derived macrophages, can be engineered to deliver proinflammatory cytokines, bispecific antibodies, and chimeric antigen receptors to support immune responses in different disease settings. When gene expression is regulated by constitutively active promoters, lentiviral payload gene expression is unregulated, and can result in potentially toxic quantities of proteins. Regulated delivery of lentivirally encoded proteins may allow localized or conditional therapeutic protein expression to support safe delivery of adoptively transferred, genetically modified cells with reduced capacity for systemic toxicities.

Human macrophages engineered to secrete a bispecific T cell engager support antigen-dependent T cell responses to glioblastoma.

Background: Targeted and effective treatment options are needed for solid tumors, including glioblastoma (GBM), where survival rates with standard treatments are typically less than 2 years from diagnosis. Solid tumors pose many barriers to immunotherapies, including therapy half-life and persistence, tumor penetrance, and targeting. Therapeutics delivered systemically may not traffic to the tumor site.

Genetically engineered macrophages persist in solid tumors and locally deliver therapeutic proteins to activate immune responses.

Background: Though currently approved immunotherapies, including chimeric antigen receptor T cells and checkpoint blockade antibodies, have been successfully used to treat hematological and some solid tumor cancers, many solid tumors remain resistant to these modes of treatment. In solid tumors, the development of effective antitumor immune responses is hampered by restricted immune cell infiltration and an immunosuppressive tumor microenvironment (TME). An immunotherapy that infiltrates and persists in the solid TME, while providing local, stable levels of therapeutic to activate or reinvigorate antitumor immunity could overcome these challenges faced by current immunotherapies.

An Uncoupling of Canonical Phenotypic Markers and Functional Potency of -Expanded Natural Killer Cells.

Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches.

NKG2D ligand expression in pediatric brain tumors.

Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between tumor cells and immune cells in pediatric brain tumor patients is not as well-defined. In this study, we sought to determine whether the model of immune escape observed in adult brain tumors is reflected in patients with pediatric brain tumors by evaluating NKG2D ligand expression on tissue microarrays created from patients with a variety of childhood brain tumor diagnoses, and infiltration of Natural Killer and myeloid cells.

Genetically Engineered Macrophages: A Potential Platform for Cancer Immunotherapy.

In spite of their successes against hematologic malignancies, immunotherapeutic interventions for the treatment of patients with glioblastoma (GBM) have thus far been unsuccessful. This is in part due to the presence of a tumor microenvironment that fosters neoplastic growth and protects the tumor from destruction by the immune system. A novel genetically engineered macrophage-based platform has been developed with the potential to minimize the effects of the suppressive tumor microenvironment and improve innate and adaptive antitumor immune responses.

Management of locally advanced renal cell carcinoma with invasion of the duodenum.

Renal cell carcinoma (RCC) is rare but aggressive, with greater than 20% of patients presenting with stage III or IV, disease. Surgical resection of the primary tumor regardless of stage is the treatment of choice, and en bloc resection of involved organs provides the only potential chance for cure. This case report describes a patient with metastatic right-sided RCC with invasion of the inferior vena cava and duodenum managed by en block resection and pancreaticoduodenectomy.

Oral histoplasmosis in HIV-infected patients. A report of two cases.

Histoplasmosis is a fungal infection caused by the organism Histoplasma capsulatum. Disseminated disease usually occurs in immunosuppressed patients or in patients with chronic illnesses. Although relatively uncommon, histoplasmosis has been reported in patients with AIDS, and oral lesions have been noted on multiple sites and in various clinical presentations.

25 years of kidney transplantation in Hawaii.

The first kidney transplant in Hawaii was performed in August 1969. In the following 25 years, more than 433 kidney transplants were performed. The most common etiology leading to transplantation was chronic glomerulonephritis.

The clinical biomechanics award paper 1993 Posture and the compressive strength of the lumbar spine.

The effect of posture on spinal compressive strength was examined in a series of three experiments on cadaveric material. Lumbar 'motion segments', consisting of two vertebrae and the intervening disc and ligaments, were compressed while positioned in various angles of flexion and extension. In the first experiment load sharing between the disc, the apophyseal joint surfaces, and the intervertebral ligaments was inferred from measurements of intradiscal pressure (IDP).

Oral Kaposi's sarcoma: a 10-year retrospective histopathologic study.

Microscopic diagnosis of early Kaposi's sarcoma continues to be a challenge to the pathologist, as does the identification of bacillary angiomatosis (BA) which may have a similar appearance. 120 oral Kaposi's sarcoma (KS) biopsies submitted to the UCSF oral pathology service from 1981-1991 were reviewed in order to describe the clinical-pathologic spectrum of these lesions and to search for unrecognized cases of BA. Also, histopathologic features of oral KS were compared to 30 oral pyogenic granulomas, and immunohistochemical stains for endothelium-associated CD34 antigen were done.

Clinical characteristics and management outcome in the burning mouth syndrome. An open study of 130 patients.

Clinical characteristics and treatment responses were studied in 130 patients with burning mouth syndrome (BMS). Most patients were postmenopausal women, and the tongue was the most frequently afflicted site. Although 39% of the patients complained of dry mouth, no causative factors were evident.

Blunt urinary tract trauma: identifying those patients who require radiological diagnostic studies.

We evaluated prospectively 506 consecutive patients who presented with a history of blunt trauma and hematuria. All patients initially underwent excretory urography and cystography. Of the 506 patients 25 had detectable urinary tract injuries that were confirmed either by the initial studies or by computerized tomography, angiography or direct intraoperative inspection.

The role of transabdominal ultrasound in the preoperative evaluation of patients with benign prostatic hypertrophy.

We evaluated 59 consecutive patients for obstructive voiding symptoms with physical examination, excretory urography, urethrocystoscopy, post-voiding residual volumes, uroflowmetry and transabdominal ultrasound of the prostate. Of the patients 53 underwent transurethral resection of the prostate and 6 underwent open prostatectomy. Followup uroflowmetry was done 4 weeks postoperatively.

History and current status of infant formulas.

Formulas that approximate the composition of human milk are widely used as the sole source of nutrients for infants during the first months of life. Such formulas contain milk, soy, or meal proteins, or protein hydrolysates together with those forms of fat carbohydrate, vitamins, and minerals shown to be bioavailable to the infant. Legislation concerning nutrient composition and quality assurance of products labeled as infant formulas has been enacted by Congress.

Synthesis and identification of a third component of the San Jose scale sex pheromone.

Two components of the San Jose scale sex pheromone had previously been identified as 7-methyl-3-methylene-7-octen-1-yl propanoate (I) and (Z)-3,7-dimethyl-2,7-octadien-1-yl propanoate (II). An isomer and various homologs have subsequently been synthesized and tested in a greenhouse bioassay. TheE isomer of II (XI) was found to be attractive to male scales.