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Biomedical subjects

I Nasser

Publications and source records attributed to I Nasser.

At least 19 recordsLinked to original sources

Hepatic colon cancer metastases in mice: dynamic in vivo correlation with hypoechoic rims visible at US.

PURPOSE: To use videomicroscopy of tumor-bearing livers of live mice to depict tumors directly to determine the exact nature of rims seen on corresponding ultrasonographic (US) scans. MATERIALS AND METHODS: Seventy-six hepatic colorectal cancer metastases were studied in exteriorized livers of 18 mice by using intravital microscopy, US, and histologic examination of the same tumors. RESULTS: Hypoechoic rims correlated with distended sinusoidal spaces in vivo. These spaces surrounded only locally invasive tumors (mean diameter, 0.85 mm) that had obstructed the supplying terminal portal venules. These spaces, containing adherent leukocytes and tumor cells, gave rise to new tumor vasculature. Results of histologic examination of rims (portal inflammation, congested or compressed sinusoids, cell atrophy) correlated with leukocyte endothelial adherence, occluded sinusoids, and new vessel formation in vivo. CONCLUSION: Unlike results from previous studies, dynamic in vivo observations of peritumoral rims demonstrated distended sinusoidal spaces giving rise to new tumor-penetrating vessels. These sinusoids arose around locally invasive tumors and were associated with more advanced intrahepatic disease. These dynamic observations provide a pathophysiologic explanation for previous histologic correlates of peritumoral rims.

Analysis of Variance↗

Detection of concurrent/recurrent non-Hodgkin's lymphoma in effusions by PCR.

A subset of patients with non-Hodgkin's lymphoma (NHL), present with or subsequently develop lymphocytic effusions. Differential diagnosis between reactive lymphocytosis and recurrent low-grade NHL is difficult by cytology alone. We studied the use of polymerase chain reaction (PCR)-based techniques to detect concurrent/recurrent NHL. Both primary tumors and atypical lymphocytic effusions of 12 low-grade B-NHL patients and 4 T-NHL patients were studied. Six pleural effusions (reactive/carcinomatous), in patients with no history of NHL, were included. Samples were amplified by PCR, using Fr3, Fr2, LJH, and VLJH primers specific for the immunoglobulin heavy chain (IgH) gene and Vgamma-8, Vgamma9, Vgamma10, Vgamma11 and Jgamma1/Jgamma2 consensus primers specific for the T-cell receptor gamma (TCR-gamma) gene. IgH gene PCR products were analyzed by polyacrylamide gel electrophoresis (PAGE). TCR-gamma gene PCR products were analyzed using a novel nonradioactive single-strand conformational polymorphism (SSCP) procedure. IgH gene rearrangement analysis demonstrated monoclonality in 11/12 primary low-grade B-NHLs. Identical monoclonal bands were found in both primary tumor and effusion in 9 patients. TCR-gamma gene rearrangement analysis demonstrated monoclonality in 4 of 4 primary T-NHLs. Identical monoclonal banded patterns were found in both primary tumor and effusion in 3 patients. Our results strongly support the diagnosis of concurrent/recurrent NHL in 13 of 16 (81%) cases of atypical lymphocytic effusions. IgH/PAGE and TCR-gamma/SSCP analyses are useful tools in the diagnoses of lymphocytic effusions in patients with NHL.

Diagnosis, Differential↗

Several noncontiguous domains of CDK4 are involved in binding to the P16 tumor suppressor protein.

Cyclin-dependent kinase 4 (CDK4) is a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point. Its activity is specifically regulated by p16 (also known as p16/CDKN2A, p16(INK4a), and MTS1), a tumor suppressor frequently altered in human cancers. A specific mutation in CDK4 codon 24 (Arginine to Cysteine) prevents p16 binding and thus inhibition by p16. This mutated CDK4 acts as a dominant oncogene and has been found in both sporadic and familial melanoma. To study the effects of other mutations in CDK4, we generated a panel of 18 CDK4 mutants using Charged-to-Alanine scanning mutagenesis, and investigated the p16-binding capacity of these mutants to identify novel sites involved in p16 binding. The mutant CDK4 proteins were generated by direct coupled transcription-translation in vitro and tested for binding to p16 using a p16-GST fusion protein. Several mutants demonstrated loss of p16 binding. In addition to the previously identified codon 24 mutants, alterations in and around codon 22, 25, 97, and 281 all showed loss of p16 binding capacity. These results indicate that several noncontiguous amino acid sequences on CDK4 are required for binding to p16, which suggests the existence of multiple sites of interaction with p16. Since p16-binding deficient CDK4 has oncogenic potential, these mutations may be present in melanomas or other human neoplasms.

Arginine↗

Malignancy-related hydrocephalus: clinical features and results of ventricular peritoneal shunt procedure in three patients.

Three patients with hydrocephalus secondary to central nervous system (CNS) metastases from lung or breast cancer are reviewed representing less than 5% of patients with CNS metastases seen at The Cancer Center of Boston over a 10-year period. The clinical picture is characterized by ataxia and mental confusion with dilated ventriculi on computed tomography (CT) scan of the brain. Computerized tomography of the brain and microscopic analysis of the cerebrospinal fluid are complementary in establishing the diagnosis of meningeal carcinomatosis. Surgical management by ventricular peritoneal shunt is an important component to multimodality therapy. The clinical course and extended survival in three patients provides a basis for recommending palliative surgical bypass as a therapeutic intervention with or without intrathecal chemotherapy, radiation, or both.

Aged↗

Increased spasticity in a chronic spinal cord injury patient after scabies infestation: a case report.

Spasticity is a common feature of spinal cord injury (SCI). Spasticity exacerbation is commonly encountered with nociceptive and exteroceptive stimuli including bladder and bowel dysfunction, pressure sores, contracture, tight-fitting leg bags and clothing, and ingrown toenail. This report describes a patient with chronic SCI (T4 level) who complained of increasing spasticity of bilateral lower extremities for 5 weeks. He also had skin lesions on different parts of his body, accompanied by itching above the spinal cord lesion level. A clinical diagnosis of scabies was made and pharmacologic treatment was initiated. Following treatment, spasticity was significantly reduced and the skin rash with itching faded out. This report is the first of scabies skin infestation lesions triggering exacerbation of spasticity in an SCI patient.

Adult↗

Liver metastases from colorectal cancer: drug delivery with liposome-encapsulated doxorubicin.

PURPOSE: To evaluate the intratumoral distribution of liposome-encapsulated doxorubicin. MATERIALS AND METHODS: Tumor-bearing livers of 24 mice were studied with in vivo fluorescence and electron microscopy after injection of liposomal doxorubicin in the hepatic artery, portal vein, or tail vein. Distribution and uptake of liposomes and doxorubicin in tumors were compared at 5, 30, and 60 minutes after injection. In vitro evaluation of uptake of doxorubicin in Kupffer cells and in human colorectal cancer cells incubated under normoxic and hypoxic conditions for 5, 30, and 60 minutes was performed with fluorescence microscopy. RESULTS: Doxorubicin autofluorescence was seen in tumors 30 minutes after intraarterial and intraportal injection and was statistically significantly greater at 60 minutes (P < .001). Liposomes were observed in small tumors (diameter < 300 microns) and were trapped in Kupffer cells around larger, hypovascular tumors. Electron microscopy findings confirmed intracytoplasmic, perinuclear uptake of liposomes in tumor cells. In vitro, a higher proportion of doxorubicin was seen in cancer cells (92%) than in Kupffer cells (75%) after 60 minutes incubation. CONCLUSION: Liposomal doxorubicin can be reliably delivered to liver metastases via the hepatic artery, eliminating need for tumor embolization. Further evaluation is warranted, and the drug may be useful for treating patients with unresectable liver metastases.

Animals↗

Terminal duct carcinoma. Recognition of a low-grade salivary adenocarcinoma.

We describe six cases of terminal duct carcinoma of the minor salivary glands. All were localized to the oral cavity, without regional nodal or distant metastases. Histologically, five were originally mistaken for adenoid cystic carcinoma; one was interpreted as monomorphic adenoma with areas of adenoid cystic carcinoma. Treatment consisted of wide resection with or without radiation therapy, with no incidence of recurrence or metastasis. The characteristics of this recently described pathologic entity are reviewed. The less aggressive behavior of this tumor compared with adenoid cystic carcinoma should call for less radical therapy, with a favorable prognosis in most cases. Recognition of this tumor as a distinct clinical and pathologic entity is therefore important.

Adenocarcinoma↗

Pulmonary hemorrhage. An uncommon cause of pulmonary infiltrates in patients with AIDS.

We describe two patients with AIDS who developed new diffuse pulmonary infiltrates during the course of their hospitalization. In both cases, the infiltrates were attributed to pulmonary hemorrhage complicating an existing condition rather than representing a new pulmonary process. Identification of pulmonary hemorrhage in these patients allowed for discontinuation of treatment with empiric medications and continued appropriate supportive care.

Acquired Immunodeficiency Syndrome↗