Characterization of a folate receptor in parotid gland and a folate binding protein in saliva from humans. Epitope relatedness to human milk folate binding protein.

The present study was performed to establish the antigenic identity and origin of the folate binding protein in human saliva. We identified a folate receptor in human parotid and submandibular gland which immunoreacted with antibodies against human milk folate binding protein, as evidenced by ELISA and immunostaining of ductal epithelium and secretory glandular material. The receptor concentration was 0.4-1.4 nmol 3H-folate bound/g protein. Ligand binding was of a high-affinity (K=10(10) M(-1)) type, exhibited positive cooperativity, a slow radioligand dissociation at pH 7.4, and inhibition by folate analogues. The concentration of immunoreactive folate binding protein in saliva as determined by ELISA with antibodies against human milk folate binding protein was several fold higher than that determined by radioligand binding (nil - 1 nM). This indicates that a major fraction of the immunoreactive material does not bind 3H-folate, and could represent a precursor form of the protein. In conclusion, the folate binding protein in human saliva seems to be a secretory product of the salivary glands. The protein is also epitope-related to folate binding proteins in other human mucosal secretions.

Cancer-associated retinopathy.

Patients with systemic cancer may have a variety of ocular complaints. Most commonly these are metastases or adverse effects of therapy. Paraneoplastic syndromes, like cancer-associated retinopathy, rarely cause ophthalmic symptoms. We describe a patient with a malignant mixed mullerian tumor and cancer-associated retinopathy who had circulating serum antibodies to recoverin and cells positive for recoverin in the tumor. We discuss the typical clinical symptoms as well as the pathophysiology of this uncommon disorder.

Characterization of a high-affinity folate receptor in normal and malignant human testicular tissue.

We have characterized the folate receptor in normal and malignant tissue from male gonads. Radioligand binding displayed characteristics typical of other folate receptors. Those included a high-affinity type of binding (K = 10(10M-1)), apparent positive cooperativity changing into non-cooperativity at low receptor concentrations, a tendency to increased binding affinity with decreasing receptor concentrations, a slow dissociation at pH 7.4 becoming rapid at pH 3.5 and inhibition by folates, in particular oxidized forms. The gel filtration profile of Triton X-100 solubilized tissue contained a 25 and 100 kDa peak of radioligand-receptor. The latter peak could represent receptor equipped with a hydrophobic membrane anchor that inserts into Triton X-100 micelles. The concentration of radiolabelled receptor ranged from 0.41 nmol/g protein to 1.68 nmol/g protein in specimens of normal testicular tissue from patients with prostatic carcinomas and from 1.54 nmol/g protein to 3.82 nmol/g protein in testicular tissue from young individuals. Compared to normal testicular tissue the concentration of receptor in seminoma tissue was low (0.38-1.27 nmol/g protein) but showed a higher degree of immunoreactivity in the presence of antibodies against human milk folate binding protein as evidenced by ELISA and immunohistochemistry data. Hence a folate receptor isoform homologous to human milk folate binding protein is apparently expressed in seminomas where the total expression of receptor, however, seems to be lower than in normal testicles.

Folate receptors in malignant and benign tissues of human female genital tract.

We have characterized the folate receptor in malignant and benign tissues of human female genital tract (Fallopian tube and benign and malignant tissues of uterus). Radioligand binding displayed characteristics similar to those of other folate binding proteins. Those include a high-affinity type of binding (K = 10(10)M-1), apparent positive cooperativity, a slow dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition of binding by folate analogues. The gel filtration profile of Triton X-100 solubilized tissue contained two large peaks of 3H-folate labelled protein (> = 130 and 100 kDa) as well as a 25 kDa peak. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The large molecular size forms on gel filtration appear to represent folate receptors having a hydrophobic membrane anchor inserted into Triton X-100 micelles. The folate receptor of female genital tract showed cross-reactivity in ELISA and positive immunostaining with rabbit antibodies against human milk folate binding protein. Variations in the ratio of immunoresponse to total high affinity folic acid binding suggests the presence of multiple isoforms of the receptor in different types of malignant and benign tissues.

Characterization of the folate receptor in human molar placenta.

We have characterized a high-affinity folate receptor in human molar placenta tissue. Radioligand binding exhibited characteristics typical of other high-affinity folate binding proteins. Those included, positive cooperativity, a tendency to increased binding affinity with decreasing receptor concentration, a slow ligand dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition by folate analogues. The folate receptor cross-reacted with antibodies against human milk folate binding protein, e.g. the syncytothrophoblastic layer of molar placenta tissue sections showed strongly positive immunostaining. The gel filtration profile contained two radioligand-bound peaks (25 and 100 kDa), however, with considerable overlap. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The folate receptor in placental tissue may play a crucial role in the transfer of folate from maternal circulation to the fetus.

Visual loss in cytomegalovirus retinitis caused by cystoid macular edema in patients without the acquired immune deficiency syndrome.

PURPOSE: Although serous macular exudation has been described in patients with the acquired immune deficiency syndrome (AIDS) with active cytomegalovirus (CMV) retinitis, cystoid macular edema (CME) is not encountered in this clinical setting. In contrast to these findings, we describe vision loss due to CME occurring in immunosuppressed patients without AIDS treated for CMV retinitis. METHODS: Three patients (four eyes) with systemic immunodeficiency presenting with vision loss underwent ophthalmologic examination, including fundus photography and fluorescein angiography. Systemic evaluation was performed to establish the etiology of immunodeficiency and to rule out human immunodeficiency virus infection. Patients were treated with topical corticosteroid and nonsteroidal anti-inflammatory medications for CME. RESULTS: All patients had severe generalized immune deficiency, related either to drug-induced immunosuppression or primary immunodeficiency. Laboratory studies confirmed the presence of systemic CMV infection. Affected eyes had mild reduction of central vision (range, 20/40 to 20/60). Three of four affected eyes had resolving CMV retinitis outside the posterior pole with mild panuveitis. These eyes showed CME on clinical examination and fluorescein angiography. The CMV lesions regressed after reduction of immunosuppressive agents or after systemic antiviral treatment. Response of CME to topical anti-inflammatory medication was variable. CONCLUSIONS: Cystoid macular edema can occur in the setting of resolving CMV retinitis in patients with immunodeficiency other than AIDS. This entity is distinct from serous macular exudation, which can occur in patients with AIDS with active CMV retinitis involving the posterior pole. The disparity between patients with and without AIDS in the development of CME may be important in understanding the pathogenesis of CME.

Mycobacterium avium complex infection, rifabutin, and uveitis--is there a connection?

Rifabutin, an antimycobacterial agent, has been recommended by the U.S. Public Health Service as prophylaxis against infection due to Mycobacterium avium complex (MAC) in patients with AIDS. When rifabutin is administered as prophylaxis, uveitis has been reported only rarely. However, uveitis has been reported in two studies in which rifabutin was administered at higher doses in combination with an azole, a macrolide, or both for treatment of disseminated MAC infection. The uveitis that has been reported has been predominantly anterior and mild-to-moderate in nature, although severe hypopyon uveitis has occasionally been reported. No etiologic infectious agent has been isolated from any of these patients, and treatment with topical steroids and cycloplegics usually leads to rapid resolution of the uveitis. It is necessary to discontinue prophylaxis or therapy with rifabutin only in cases of uveitis that are refractory to treatment or when the uveitis recurs. Immunologic factors, rather than direct drug toxicity, appear to be the most likely explanation for the occurrence of uveitis in patients receiving rifabutin; however, further study is required to elucidate the mechanisms involved.

Evidence of active cytomegalovirus infection in clinically stable HIV-infected individuals with CD4+ lymphocyte counts below 100/microliters of blood: features and relation to risk of subsequent CMV retinitis.

To determine the frequency and significance of cytomegalovirus (CMV) viremia and viruria in HIV-positive subjects with low CD4+ lymphocyte counts but with no clinical indications for culture, we studied 100 consecutive clinically stable subjects with CD4+ cells < or = 100/microliters of blood who agreed to culture of blood and urine. Serum was tested for CMV antibody, p24 antigen, neopterin, and liver enzyme concentrations, and patients were offered funduscopic examination. Subjects' records were reviewed an average of 9.1 months after enrollment for evidence of subsequent CMV retinitis. Three of the original cohort proved ineligible because of CD4+ count > 100/microliters; CMV antibody was present in 96% of the remainder. Isolation of CMV from blood was uncommon (2 of 93 seropositive subjects) whereas viruria occurred in 51.6%; likelihood of having a positive urine culture was significantly related to the subject's absolute CD4+ lymphocyte count: 60% for those with CD4+ < or = 50/microliters, vs. 26.1% for those with CD4+ 51-100/microliters. Neither serum p24 antigen nor neopterin was predictive of CMV in urine or blood. No subjects submitting to ophthalmologic exam had unsuspected CMV retinitis. Subsequent development of retinitis correlated with CMV viruria on entry: 13.5% if urine-positive, 1.9% if negative (p = 0.029; Fisher exact test).

Orbital ischemia, ophthalmoparesis, and carotid dissection.

We report a patient who developed an acute loss of vision in the left eye associated with proptosis, ophthalmoparesis, conjunctival injection, and chemosis. Funduscopy revealed optic disc swelling, and retinal whitening consistent with an ophthalmic artery occlusion. Angiography disclosed bilateral carotid dissections presumably resulting from head trauma 11 days earlier. An orbital ischemic syndrome may be a delayed manifestation of traumatic carotid dissection and precede cerebral hypoperfusion.

Conjugal temporal arteritis.

We report the simultaneous occurrence of biopsy-proven temporal arteritis in husband and wife. Serologic and viral studies were negative, including viral culture of the wife's temporal artery. The concurrent incidence of giant cell arteritis in a married couple would suggest a common exogenous exposure.

Rhinocerebral mucormycosis: management and survival after carotid occlusion.

Rhinocerebral mucormycosis is a rare but often fatal fungal infection. We present 2 patients with mucormycosis complicated by internal carotid artery thrombosis. Magnetic resonance imaging was superior to computed tomography in localizing the pathological process. Subtotal resection of devitalized tissue and intravenous amphotericin B therapy resulted in a successful outcome for both patients. Prompt recognition of this disorder by using modern diagnostic and therapeutic modalities promises to improve survival rates.

Bilateral ocular disease as the initial presentation of malignant lymphoma.

Malignant lymphocytic lymphoma rarely involves the eye. In two patients we found ocular signs and symptoms as the initial presentation of systemic disease. In the first patient periorbital swelling and ptosis of one year's duration ultimately proved to be the result of malignant lymphoma. After resolution of swelling and ptosis with chemotherapy, the patient returned with diffuse iris involvement and uveitis with a hypopyon. In the second patient an acute change of refractive error proved to be the result of a lymphomatous deposit in the choroid. In both instances common symptoms were the initial manifestations of a diffuse malignant disease.

Intralesional triamcinolone for cutaneous palpebral sarcoidosis.

Cosmetically disfiguring bilateral palpebral sarcoid dermatitis in a 32-year-old woman was treated with intradermal triamcinolone. There was rapid and complete resolution of lesions and there was no evidence of recurrence or hypopigmentation at a one-year follow-up examination. Thus, intradermal corticosteroid therapy can be useful for skin lesions in patients with sarcoidosis who do not require systemic therapy.