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Biomedical subjects

G A Khan

Publications and source records attributed to G A Khan.

At least 19 recordsLinked to original sources
PubMed2001

The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells.

Loss of the tumor suppressor gene NF1 in neurofibromatosis type 1 (NF1) contributes to the development of a variety of tumors, including malignant peripheral nerve sheath tumors (MPNST) and benign neurofibromas. Of the different cell types found in neurofibromas, Schwann cells usually provide between 40 and 80%, and are thought to be critical for tumor growth. Here we describe the identification of growth factors that are upregulated in NF1-/- mouse Schwann cells and are potential regulators of angiogenesis and cell growth. Basic fibroblast growth factor (FGF-2), platelet-derived growth factor (PDGF) and midkine (MK) were found to be induced by loss of neurofibromin and MK was further characterized. MK was induced in human neurofibromas, schwannomas, and various nervous system tumors associated with NF1 or NF2; midkine showed an expression pattern overlapping but distinct from its homolog pleiotrophin (PTN). Immunohistochemistry revealed expression of MK in S-100 positive Schwann cells of dermal and plexiform neurofibromas, and in endothelial cells of tumor blood vessels, but not in normal blood vessels. Furthermore, MK demonstrated potent mitogenic activity for human systemic and brain endothelial cells in vitro and stimulated proliferation and soft agar colony formation of human MPNST derived S100 positive cells and fibroblastoid cells derived from an NF1 neurofibroma. The data support a possible central role for MK as a mediator of angiogenesis and neurofibroma growth in NF1. Oncogene (2001) 20, 97 - 105.

Adult↗
PubMed2001

Therapeutic efficacy of G207 in a novel peripheral nerve sheath tumor model.

Nerve involvement poses a significant obstacle for the management of peripheral nervous system tumors, and nerve injury provides a frequent source of postoperative morbidity. The lack of suitable animal models for peripheral nerve tumors has impeded the development of alternative nerve-sparing therapies. To evaluate the effect of a multimutated replication-competent herpes simplex virus (G207) on the growth of peripheral nerve tumors and on nerve function, we developed a novel peripheral nerve sheath tumor model. Human neuroblastoma-derived cells injected into murine sciatic nerve consistently caused tumor development within the nerve sheath after 2 weeks followed by increasingly severe impairment of nerve function. Tumor treatment by a single intratumoral injection of G207 resulted in significant reduction of functional impairment, inhibition of tumor growth and prolonged survival. Direct injection of G207 viral particles into the healthy nerve sheath caused no obvious neurologic sequelae, whereas injections of wild-type virus resulted in uniform lethality. The results indicate that viral therapy might be considered as a safe alternative to surgical removal of tumors with peripheral nerve involvement.

Animals↗
PubMed1997

Beta 2-microglobulin amyloidosis presenting as esophageal perforation in a hemodialysis patient.

A 45-year-old male with hypertensive end-stage renal disease and on maintenance hemodialysis for 13 years is reported. He presented with life-threatening hematemesis, secondary to esophageal rupture. Immunohistological staining and electron microscopy examination of the esophageal perforation showed depositions of beta 2-microglobulin (beta 2-M) amyoloid. The unique aspect presented here is the localized esophageal involvement with beta 2-M amyloidosis. This is the first reported patient with esophageal perforation, due to the deposition and infiltration of the lower esophagus with beta 2-M which predisposed to its rupture.

Amyloidosis↗
PubMed1996

Recognizing Weber-Christian disease.

The eponym Weber-Christian Disease (WCD) defines a chronic disorder characterized by relapsing febrile episodes and panniculitis. Systemic manifestations due to visceral involvement may be present. WCD is associated with no identifiable cause, although chronic panniculitis may be due to definable underlying disorders. A variety of distinctive disease entities, such as systemic lupus erythematosus (SLE), pancreatic disease, alpha-I-antitrypsin disease, lymphoproliferative neoplasia, infections, or trauma are associated with chronic panniculitis. The accurate diagnosis of panniculitis requires an adequate deep skin biopsy showing inflammation of the subcutaneous layers. We describe a white woman with fever and recurrent episodes of painful nodules of the lower extremities, excisional biopsy of which confirmed panniculitis. The febrile episodes and skin lesions responded dramatically with the use of oral corticosteroids.

Adrenal Cortex Hormones↗
PubMed1995

Pulmonary haemorrhage following renal transplantation.

The case history is presented of a 32 year old black man who developed haemoptysis leading to pulmonary haemorrhage and bilateral pulmonary infiltrates. He was found to have Kaposi's sarcoma of the lung with no evidence of skin or endobronchial lesions.

Adult↗
PubMed1995

Interpretation of positive edrophonium (Tensilon) test in patients with end-stage renal disease.

Many patients with end-stage renal disease (ESRD) have signs and symptoms of easy fatigability, fluctuating weakness, apathy, dry mouth, and blurring of vision. These symptoms can be confused with disorders of neuromuscular transmission. When present, the physician may want to determine whether the patient has myasthenia gravis--the commonest of all neuromuscular disorders--and administer the edrophonium (Tensilon) test. An unequivocally positive response to the test must be interpreted with caution in ESRD. However, the exact mechanism of a positive response is unclear but may be explained by metabolic abnormalities related to end-stage renal disease, i.e., uremic toxins, disordered calcium metabolism, abnormal neuromuscular mechanism, associated neurological disorders, or myopathic processes in uremia, all of which can affect neuromuscular transmission.

Aged↗
PubMed1995

Fulminating systemic capillary leak syndrome with lymphocytosis and hypogammaglobulinemia.

We report a case of fulminating systemic capillary leak syndrome which temporarily responded to verapamil, a calcium channel blocker. We noted two features of the disease not previously reported: a rise in lymphocyte count 2-3 days prior to an attack, and hypogammaglobulinemia. These findings are discussed in relation to the possible etiology of this disease.

Agammaglobulinemia↗
PubMed1995

Recurrence of systemic lupus erythematosus in a hemodialysis patient presenting as a unilateral abducens nerve palsy.

A 45-year-old hemodialysis patient presenting with recurrence of SLE which manifested predominantly as a unilateral left abducens (VIth) nerve palsy is described. The signs and symptoms of the cranial nerve palsy resolved within two weeks of initiating corticosteroid therapy. This is the first reported case of an abducens nerve palsy occurring in a maintenance hemodialysis patient associated with recurrence of SLE.

Abducens Nerve↗
PubMed1994

Mechanism of vasoconstriction induced by chronic inhibition of nitric oxide in rats.

Either acute or chronic inhibition of nitric oxide synthesis by L-arginine analogues results in increases in mean arterial pressure and reductions in renal blood flow. The role of endogenous vasoconstrictors in mediating these effects is not entirely clear. In the present study, nitric oxide was inhibited in male Sprague-Dawley rats by oral administration of nitro-L-arginine for 3 weeks. At the end of this time, mean arterial pressure was 30 to 40 mm Hg higher than in normal controls, renal blood flow and glomerular filtration rate were 25% to 30% lower, and renal vascular resistance was markedly increased. Intravenous infusion of receptor antagonists for angiotensin II, thromboxane, epinephrine, and endothelin-1 had no significant effect on the hypertension. Inhibition of prostaglandin synthesis and furosemide-induced diuresis in the presence of angiotensin blockade also had no effect on blood pressure. Renal vascular resistance was also unaffected by these interventions, except that saralasin did reduce renal resistance in both control and nitric oxide-inhibited groups. However, the absolute level of renal vascular resistance remained higher in the latter group. Calcium channel blockade partially corrected blood pressure and renal resistance, but the levels remained significantly higher than in control animals. The findings are consistent with the view that the increase in vascular smooth muscle tone caused by inhibition of nitric oxide synthesis cannot be accounted for by overexpression of common endogenous vasoconstrictors. Rather, the generalized increase in vascular smooth muscle tone appears to be due to a direct effect of reduced nitric oxide availability, which may lead to an increase in intracellular calcium concentration or sensitivity.

Animals↗
PubMed1994

An adult patient with hyperimmunoglobulemia E (Job's) syndrome, end-stage renal disease and repeated episodes of peritonitis.

We report the first case of an adult patient with hyperimmunoglobulemia E (Job's) syndrome, end-stage renal disease and repeated episodes of Staphylococcus peritonitis. A 42-year-old black female with end-stage renal disease was treated with hemodialysis, and later switched to peritoneal dialysis because of severe vascular access problems. On CAPD, she had numerous (> 15) episodes of staphylococcal peritonitis. Past history included chronic atopic eczema and repeated sinopulmonary infections since childhood. She was found to have serum IgE levels greater than 10,000 units/ml. This combination of repeated infections, chronic skin condition and phenomenal elevation of IgE levels establish the diagnosis of hyperimmunoglobulemia E (Job's) syndrome. The cause of repeated episodes of Staphylococcal peritonitis are presumed to be related to impaired host defense mechanisms known to be present in patients with this disorder. As nephrologists, we should be aware that patients with impaired host defense mechanisms are highly susceptible to peritonitis in the presence of an indwelling peritoneal catheter.

Adult↗