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D H Davis

Publications and source records attributed to D H Davis.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pancreastatin secretion by pituitary adenomas and regulation of chromogranin B mRNA expression.

Pancreastatin, a carboxyl-terminal amidated peptide derived from chromogranin (Cg)A, inhibits secretion of insulin and parathyroid hormone. Our recent studies found significant amounts of immunoreactive pancreastatin in all pituitary adenomas except prolactin adenomas. To analyze the effects of pancreastatin on pituitary cell function, 17 cultured pituitary adenomas were examined for immunoreactive pancreastatin and pancreastatin secretion by the tumors. The effects of pancreastatin on pituitary hormone secretion and on pituitary hormone (follicle-stimulating hormone and prolactin), CgA, and CgB mRNA levels were also examined. Immunoreactive pancreastatin and CgA were present diffusely in gonadotroph and null cell adenomas, but only a few prolactin adenoma cells expressed pancreastatin or CgA. When cells were treated with hypothalamic peptides, gonadotroph adenomas were the only group that released increased amounts of pancreastatin in response to gonadotropin-releasing hormone (10(-7) mol/L). Pancreastatin (10(-7) mol/L) treatment did not stimulate pituitary hormone secretion significantly. In situ hybridization analyses showed that gonadotropin-releasing hormone and pancreastatin treatment led to significant increases in CgB and follicle-stimulating hormone mRNAs in gonadotroph adenomas, whereas CgA mRNA levels did not change significantly. These results show that there is a differential distribution of pancreastatin secretion in pituitary adenomas and that the hypothalamic hormone gonadotropin-releasing hormone and the CgA-derived peptide pancreastatin can regulate CgB mRNA in gonadotroph adenomas, suggesting an autocrine effect of pancreastatin on pituitary tumor function.

Adenoma↗
PubMed1995

Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT).

Sixteen novel potential prodrugs derived from phenol or aniline mustards and their 16 corresponding drugs with ring substitution and/or different alkylating functionalities were designed. The [[[4-]bis(2-bromoethyl)-(1a), [[[4-[bis(2-iodoethyl)-(1b), and [[[4-[(2-chloroethyl)-[2-(mesyloxy)ethyl]amino]phenyl]oxy] carbonyl]-L-glutamic acids (1c), their [[[2- and 3-substituted-4-[bis(2-chloroethyl)amino]phenyl]oxy]carbonyl]-L- glutamic acids (1e-1), and the [[3-substituted-4-[bis(2-chloroethyl)amino]phenyl]carbamoyl]-L- glutamic acids (1o-r) were synthesized. They are bifunctional alkylating agents in which the activating effect of the phenolic hydroxyl or amino function is masked through an oxycarbonyl or a carbamoyl bond to a glutamic acid. These prodrugs were designed to be activated to their corresponding phenol and aniline nitrogen mustard drugs at a tumor site by prior administration of a monoclonal antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2) in antibody-directed enzyme prodrug therapy (ADEPT). The synthesis of the analogous novel parent drugs (2a-r) is also described. The viability of a colorectal cell line (LoVo) was monitored with the potential prodrugs and the parent drugs. The differential in the cytotoxicity between the potential prodrugs and their corresponding active drugs ranged between 12 and > 195 fold. Compounds 1b-d,f,o exhibited substantial prodrug activity, since a cytotoxicity differential of > 100 was achieved compared to 2b-d,f,o respectively. The ability of the potential prodrugs to act as substrates for CPG2 was determined (kinetic parameters KM and kcat), and the chemical stability was measured for all the compounds. The unsubstituted phenols with different alkylating functionalities (1a-c) proved to have the highest ratio of the substrates kcat:KM. From these studies [[[4-[bis(2-iodoethyl)amino]phenyl]oxy]carbonyl]-L-glutamic acid (1b) emerges as a new ADEPT clinical trial candidate due to its physicochemical and biological characteristics.

Antibodies, Monoclonal↗
PubMed1995

Papillary craniopharyngioma: a clinicopathological study of 48 cases.

Two distinct clinicopathological variants of craniopharyngioma exist: the classic adamantinomatous type and a recently described papillary form that predominates in adults and reportedly behaves in a less aggressive manner. The present study describes the clinicopathological features of 48 patients with papillary craniopharyngioma treated at the Mayo Clinic between 1910 and 1994. An additional four tumors were found to have histological features of both adamantinomatous and papillary craniopharyngioma. Whereas adamantinomatous tumors typically occur in adolescent patients, the mean age of the 48 patients (23 males and 25 females) with papillary craniopharyngioma was 44.7 years (range 10 to 74 years). Presenting clinical features included visual impairment (84%), headache (68%), and pituitary insufficiency (anterior 42%; posterior 27%). Preoperative computerized tomography (CT) and magnetic resonance (MR) imaging in 17 patients typically revealed a noncalcified, partially cystic mass that enhanced peripherally and contained mural nodules (67%). Many (41%) of the lesions involved or extended into the third ventricle on imaging. At first surgery, gross total tumor removal was achieved in 17 patients (36%) and subtotal resection in 30 patients (64%) in whom tumor resection was attempted. Tumor recurrence was noted in two patients who underwent gross total removal. Tumor-free survival rates of 100% and 78% were obtained in patients who underwent gross total and subtotal resection at initial surgery, respectively. Postoperative radiation therapy was beneficial to patients having undergone a subtotal resection, with an increase in tumor-free survival from 26% to 86%. Aside from well-documented morphological distinctions, papillary craniopharyngiomas differ from adamantinomatous tumors in several important respects. These include the almost exclusive occurrence of papillary tumors in adulthood and their more uniform appearance on both CT and MR imaging. However, a preliminary analysis of our data suggests there are no significant differences between the two lesions with respect to resectability, efficacy of radiation therapy, and overall survival.

Adolescent↗
PubMed1995

False-positive inferior petrosal sinus sampling in the diagnosis of Cushing's disease. Report of two cases.

Inferior petrosal sinus sampling (IPSS) for adrenocorticotropic hormone (ACTH) levels in patients with Cushing's syndrome has become a useful method to distinguish ACTH-secreting pituitary tumors (Cushing's disease) from other causes of the syndrome, principally ectopic adrenocorticotropin secretion by an occult tumor. Although the test is generally regarded as highly specific, the authors recently encountered two patients whose IPSS measurements were false-positive for Cushing's disease. The results of IPSS suggested a pituitary origin of ACTH secretion in both patients, but transsphenoidal surgery failed to disclose a pituitary adenoma or to improve postoperative plasma cortisol levels. Both patients subsequently were found to have an ACTH-secreting carcinoid tumor of the lung. The false-positive IPSS studies were due to periodic hormonogenesis. The patients must be hypercortisolemic at the time IPSS is performed for the study to be valid.

Adrenocorticotropic Hormone↗
PubMed1995

Analysis of the chromogranin A post-translational cleavage product pancreastatin and the prohormone convertases PC2 and PC3 in normal and neoplastic human pituitaries.

Several members of the chromogranin/secretogranin (Cg/Sg) family are post-translationally processed in neuroendocrine cells and tumors to smaller peptides, some of which are biologically active. For example, CgA is processed to pancreastatin, parastatin, and other peptides. We analyzed the distribution of pancreastatin and CgA proteins in normal and neoplastic pituitaries as well as the prohormone convertases PC2 and PC3/1 (PC3), the putative processing enzymes for the Cg/Sg family, in 35 pituitary adenomas and 4 non-neoplastic pituitaries by immunohistochemistry and immunoblotting with highly specific antisera. CgA and CgB mRNAs were also examined. Pancreastatin was present in all subtypes of pituitary tumors, although prolactin-secreting adenomas expressed this peptide less frequently than did other tumor types. CgA protein and CgA mRNA expression were also restricted in prolactin adenomas and in normal prolactin cells, as shown by combined in situ hybridization and immunostaining. The prohormone convertases PC2 and PC3 were present in pituitary tumors and in non-neoplastic pituitaries. Immunoblot analysis and immunostaining showed a principal approximately 69-kd PC3 band and a approximately 68-kd PC2 band. Adrenocorticotrophic hormone-secreting adenomas expressed mainly PC3 as determined by immunoblotting and immunohistochemistry, whereas all other adenoma groups expressed predominantly PC2. These results indicate that the enzymes capable of processing CgA and other members of the Cg/Sg family to peptides with biological activity such as pancreastatin are widely expressed in human pituitary adenomas and in non-neoplastic pituitaries, with adrenocorticotrophic hormone tumors expressing predominantly PC3 and other adenomas expressing mainly PC2. The infrequent expression of CgA protein and pancreastatin peptides in normal and neoplastic prolactin cells suggests a unique role of CgA in these tumors.

Adult↗
PubMed1994

Mixed oligoastrocytomas: a survival and prognostic factor analysis.

Seventy-one patients with supratentorial mixed oligoastrocytomas underwent surgery only (5 patients) or surgery with postoperative radiation therapy (66 patients) between 1960 and 1982. The median survival for these 71 patients was 5.8 years and the 5-, 10-, and 15-year survival rates were 55, 29, and 17%, respectively--values significantly different from those of an age- and sex-matched normal reference population. Uni- and multivariate survival analyses were applied to 14 possible prognostic factors, including the following: patient factors--age, sex, and seizures; tumor factors--site, size, side, computed tomographic enhancement, and calcification; pathological factors--tumor grade and dominant cellular component; and treatment factors--extent of surgical resection, lobectomy, and radiation dose and field. Of these factors, tumor grade, as determined by the Kernohan method, was the most strongly associated with survival. The 60 patients with Grades 1 and 2 tumors had a median survival of approximately 6.3 years and 5- and 10-year survival rates of 58% and 32%, respectively, compared with 2.8 years (36 and 9%, respectively) for the 11 patients with Grades 3 and 4 tumors. Age < 37 years, gross total resection, partial brain radiation, and radiation dose > or = 5000 cGy were other factors significantly associated with improved survival in both uni- and multivariate models. Three of five patients not receiving postoperative radiation therapy experienced tumor recurrence and died. Seven of eight patients from whom tissue was obtained at the time of tumor progression demonstrated anaplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Pituitary adenomas in childhood and adolescence. Results of transsphenoidal surgery.

Pituitary adenomas are uncommon in childhood. Between 1975 and 1988, 36 patients underwent transsphenoidal resection at the Mayo Clinic before their 17th birthday. Fifteen (41.7%) had prolactin (PRL)-secreting tumors, 16 (44.4%) had adrenocorticotropic hormone (ACTH)-secreting tumors (including two patients with Nelson-Salassa syndrome), and three (8.3%) had tumors secreting growth hormone (GH); two patients (5.6%) had clinically nonfunctioning tumors. Of the 36 patients, 21 (58.3%) were girls, and girls predominated in every group except that with ACTH-secreting tumors, where they accounted for only 37.5% of the patients. The average age at the time of surgery was 14.7 +/- 2.2 years, the youngest patient being 7.3 years old. The ACTH-secreting tumors were associated with an earlier onset of symptoms than the other tumor types: six (37.5%) of 16 patients became symptomatic before 10 years of age, compared with two (10.0%) of the 20 other patients. Presenting symptoms primarily reflected endocrine dysfunction, with neurological presentation (visual field deficits) occurring in only two patients. There were no deaths in this patient group. Significant operative morbidity included steroid-induced psychosis in one patient and diabetes insipidus in three, which resolved in two. Plurihormonal tumors, broadly defined as tumors producing more than one hormone, were common, comprising five (36%) of 14 PRL-secreting tumors, all three GH-secreting tumors, and one of two clinically nonfunctioning tumors, or 25.7% overall. Macroadenomas accounted for 89% of plurihormonal tumors. Long-term follow-up review (median > 5 years) revealed good control of PRL-secreting tumors (although five of 15 patients had received postoperative radiotherapy), contrasted with a 25% late recurrence rate for ACTH-secreting tumors, which had an 80% initial remission rate. The majority of patients had good endocrine function, including reproductive function. It is concluded that: 1) although pediatric pituitary adenomas occur primarily in adolescence, Cushing's disease is found at any age; 2) transsphenoidal surgery is feasible and safe in this age group; 3) plurihormonal tumors occur more frequently in the pediatric age group than in adults; and 4) long-term control rates in PRL- and ACTH-secreting tumors are probably similar to those seen in adults.

Adenoma↗
PubMed1993

A retrospective analysis of pituitary apoplexy.

Thirty-seven patients with pituitary apoplexy were analyzed with an emphasis on clinical presentation and visual outcome. Their mean age was 56.6 years, with a male to female ratio of 2:1. Presenting symptoms included headache (95%), vomiting (69%), ocular paresis (78%), and reduction in visual fields (64%) or acuities (52%). Computed tomographic scanning correctly identified pituitary hemorrhage in only 46% of those scanned. Thirty-six patients underwent transsphenoidal decompression. By immunostaining criteria, null-cell adenomas were the most frequent tumor type (50%). Long-term steroid or thyroid hormone replacement therapy was necessary in 82% and 89% of patients, respectively. Long-term desmopressin therapy was required in 11%, and 64% of the male patients required testosterone replacement therapy. Surgery resulted in improvement in visual acuity deficits in 88%, visual field deficits in 95%, and ocular paresis in 100%. Analysis of the degree of improvement in preoperative visual deficits with the timing of the surgery demonstrated that those who underwent surgery within a week of apoplexy had significant recovery in their visual acuities. In the stable, conscious patient with residual vision in each eye, surgical decompression should be performed as soon as possible, because delays beyond 1 week may retard the return of visual function.

Adenoma↗
PubMed1993

Results of surgical treatment for growth hormone-secreting pituitary adenomas.

The results of surgical therapy for acromegaly were reviewed in a series of 175 patients treated between 1972 and 1983. Patients with prior surgery or radiation therapy were excluded from the study. Postoperative radiation therapy was given to 54 patients. The criterion of achieving a postoperative basal or glucose-suppressed growth hormone level of 2 ng/ml or less was used to indicate remission. Utilizing the most recently available growth hormone determinations, 90 (51.7%) of 174 patients were in remission. The actuarial probability of remission at 1 and 5 years after surgery was 48.8% and 62.7%, respectively. Tumor size and the preoperative basal growth hormone level were correlated with outcome. Surgical excision of a pituitary adenoma is the most effective therapy currently available for acromegaly.

Adenoma↗
PubMed1992

Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.

PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion, characterized by elevated serum free thyroxine and triiodothyronine levels in association with measurable serum TSH concentrations, remains an uncommon cause of hyperthyroidism that is being recognized with increasing frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH secretion or selective pituitary resistance to thyroid hormone. In an effort to better understand this rare cause of hyperthyroidism, we undertook a retrospective analysis of our institution's experience with this condition. PATIENTS: We reviewed our cumulative experience (10 patients) with hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS: Six patients were diagnosed with TSH-secreting pituitary adenomas and four were found to have selective pituitary resistance to thyroid hormone. One patient with tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully treated with transsphenoidal adenomectomy with or without pituitary radiotherapy. All four patients with pituitary resistance had thyroid ablation or resection prior to their correct diagnosis. Therefore, therapy for this group of patients involved thyroid hormone replacement and efforts to suppress TSH hypersecretion. All 10 patients have done well clinically, with follow-up ranging from 2 weeks to 13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery and, if necessary, adjuvant pituitary radiotherapy. The results are generally good if the tumor is diagnosed and treated at an early stage. Primary therapy for hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed at suppression of pituitary TSH hypersecretion. The evaluation of any patient with hyperthyroidism must be thorough and, in some cases, should include measurement of TSH to determine the presence of inappropriate secretion. Eliminating this diagnosis will help avoid improper and potentially harmful treatment of hyperthyroid patients.

Adenoma↗
PubMed1992

Oligodendrogliomas: the Mayo Clinic experience.

Eighty-one patients with pure supratentorial oligodendrogliomas underwent surgery alone (19 patients) or surgery plus postoperative radiation therapy (63 patients) between the years 1960 and 1982. The median survival time and the 5-, 10-, and 15-year survival rates for these 82 patients were 7.1 years, 54%, 34%, and 24%, respectively; these values were significantly different from those for an age- and sex-matched normal reference population. Univariate and multivariate survival analyses were performed on 13 possible prognostic factors including: patient age and sex; presence of seizures; site, size, side, computerized tomography (CT) enhancement, grade, and calcification of the tumor; and treatment (extent of surgical resection, lobectomy, radiation dose, and radiation field). Of these factors, tumor grade as classified by the Kernohan and St. Anne-Mayo methods was most strongly associated with survival. Patients with Grade 1 or 2 tumors by either grading method had a median survival time and 5- and 10-year survival rates of approximately 9.8 years. 75%, and 46%, respectively, compared to 3.9 years, 41%, and 20% for those with Grade 3 or 4 tumors. The extent of surgical resection was also associated with survival. The 19 patients who underwent gross total resection of their tumor had a median survival time and 5- and 10-year survival rates of 12.6 years, 74%, and 59%, compared to 4.9 years, 46%, and 23%, respectively, for the 63 who had subtotal resection. When comparing the 19 patients who underwent surgery alone with the 63 who had surgery plus postoperative radiation therapy, there did not appear to be a survival benefit to be gained from the addition of postoperative radiation therapy. However, the patients who had surgery alone tended to have gross total resections and lower tumor grades. Analysis of the subset of 63 patients who underwent subtotal resection alone or with radiation therapy showed that the median survival time and 5- and 10-year survival rates were: 2 years, 25%, and 25% for the eight patients with subtotal resection alone; 4.5 years, 39%, and 20% for the 26 patients with surgery and low-dose (less than 5000 cGy) radiation therapy; and 7.9 years, 62%, and 31% for the 29 patients receiving surgery and high-dose radiation therapy (greater than or equal to 5000 cGy), respectively.

Adolescent↗
PubMed1991

Preservation of natural endothelial cytopathogenicity of cytomegalovirus by propagation in endothelial cells.

Cytomegalovirus (CMV) is a source of major complications in immunosuppressed individuals, and endothelial involvement in CMV infection is well documented. Traditionally the virus has been propagated in fibroblasts, however this process may alter CMV's characteristics, thereby limiting the fibroblast model's utility as a research tool. In our efforts to develop a more accurate in vitro model of CMV/endothelial cell interaction, we have propagated a recent isolate (CMV VHL) through multiple passages in human umbilical vein endothelial cells (HUVE) and, collaterally in neonatal human dermal fibroblasts (NHDF). Infection of HUVE inoculated with either sub-strain of the virus was confirmed by CMV-specific in situ hybridization and by immunocytochemical staining for CMV antigens. Whereas infection of HUVE by substrain VHL/E (endothelial-raised) was accompanied by dramatic cytopathology resembling that observed clinically, the endothelial cytopathic potential of VHL/F (fibroblast-raised) was lost by its 20th passage in NHDF. Similarly, the ability of VHL/F to initiate sustained productive infection in HUVE was severely attenuated; plaque assay of culture supernatants and infected cell fractions, as well as virus-specific DNA polymerase assay of cell lysates, demonstrated progressive viral reproductive activity in VHL/E-inoculated HUVE, whereas VHL/F reproduction was barely detectable. Since properties of VHL/F bear strong resemblance to those of the fibroblast-raised AD169, these studies suggest that while the fibroblast adaptation process commonly employed in the propagation of CMV restricts the host range of the virus and attenuates its spectrum of cytopathic potential, endothelial-based propagation preserves the natural endothelial cytopathogenicity of the original isolate.

Antigens, Viral↗
PubMed1991

Selective peripheral denervation for torticollis: preliminary results.

Herein we report the preliminary results in nine patients who have undergone selective peripheral denervation for spasmodic torticollis and have been followed up for at least 13 months. All patients had improvement immediately after surgical intervention, and the results have been maintained in five patients. In one patient who had recurrent torticollis, a second procedure in conjunction with injection of botulinum toxin has produced substantial improvement; however, follow-up was brief (6 months). No surgical complications occurred. We believe that selective peripheral denervation is safe and that it can benefit patients with torticollis who have not responded to other types of therapy. These favorable results confirm other published reports on the efficacy of selective peripheral denervation. Long-term follow-up, however, is necessary for determining the role of this procedure in the management of torticollis.

Adult↗
PubMed1991

Expression of IgG Fc receptor antigens in placenta and on endothelial cells in humans. An immunohistochemical study.

Expression of leukocyte IgG Fc receptor (Fc gamma R) antigens by placenta, endothelial cells (EC) of normal tissues, and ECs of kidney and skin from subjects with immune complex diseases was studied immunohistochemically using anti-Fc gamma R monoclonal antibodies (MAb). Monoclonal antibodies against all three leukocyte Fc gamma R classes stained placental villous macrophages. Placental villous trophoblasts were stained intensely by anti-Fc gamma RIII MAb 3G8, while both anti-Fc gamma RI (MAb 32) and anti-Fc gamma RII MAbs IV3, KU79, CIKM5, 2E1, KB61, and 41H16) antibodies did not react with these cells. Anti-Fc gamma RII MAbs IV3, KU79, CIKM5, 2E1, KB61, and 41H16 immunostained placental villous capillary EC, in contrast to anti-Fc gamma RI MAb 32 and anti-Fc gamma RIII MAb 3G8, CLB-Granl, and B73.1, which did not bind. Anti-Fc gamma RI MAb 32, anti-Fc gamma RII MAb IV3 and CIKM5, and anti-Fc gamma RIII MAb 3G8 did not react with the ECs of tonsil, liver, kidney, spleen, intestine, lung, or uterus. Similarly no EC staining was seen with these four MAbs in 14 skin and 14 kidney biopsies from subjects with immune-complex diseases. Fc gamma R antigens are expressed constitutively only by placental villous ECs and are not induced on nonplacental ECs by immune-complex-mediated diseases.

Antibodies, Monoclonal↗
PubMed1990

Selected neurologic complications of pregnancy.

Many neurologic disorders, such as eclampsia, pseudotumor cerebri, stroke, obstetric nerve palsies, subarachnoid hemorrhage, pituitary tumors, and choriocarcinoma, can develop in the pregnant patient. Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion. Pseudotumor cerebri can be associated with serious visual complications; thus, the therapeutic goal is to prevent loss of vision. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The major causes of stroke in pregnant patients are arterial occlusion and cerebral venous thrombosis. Lumbar disk prolapse is common in pregnant patients, and lumbosacral plexus injuries can occur during labor or delivery. In addition, peripheral nerve compression or entrapment syndromes are thought to be caused by the retention of fluid during pregnancy. The incidence of subarachnoid hemorrhage during pregnancy is 1 in every 10,000 patients, a rate 5 times higher than in nonpregnant women. Because of a proliferation of prolactin-secreting cells, the pituitary gland can enlarge dramatically during pregnancy, a change that can disclose a previously unknown tumor or cause a known pituitary tumor to become symptomatic. The incidence of choriocarcinoma is 1 in 50,000 full-term pregnancies but 1 in 30 molar pregnancies. This malignant tumor has a high rate of cerebral metastatic lesions. In addition to these disorders that develop during pregnancy, the pregnant state can affect numerous preexisting neurologic conditions, including epilepsy, headaches, multiple sclerosis, myasthenia gravis, spinal cord injury, and brain tumors. We discuss advice for patients with such conditions who wish to become pregnant, recommendations for medical and surgical management, and surgical considerations for neurologic complications during pregnancy.

Female↗
PubMed1990

Inability of cytomegalovirus infection of cultured endothelial cells to induce HLA class II antigen expression.

Cytomegalovirus infection in the renal allograft recipient has been associated with the initiation of acute rejection. The mechanism of this induction is unknown. It may be related to renal tubular epithelial and endothelial expression of HLA class II antigens or a CMV immediate-early antigen that exhibits immunologic crossreactivity with HLA DR. In this study the ability of CMV to both infect and subsequently induce class II antigen expression on cultured human umbilical-vein endothelial cells (HUVEs), in the absence of cytokines, particularly gamma interferon, was tested. Individual HUVE cell lines were first proven to express HLA class II antigens in the presence of 10, 100, and 200 units of recombinant IFN-gamma as early as 24 hr postincubation by an immunohistochemical technique and by flow cytometry. These cell lines were successfully infected with CMV strains AD169 and CMV3 as determined by the presence of early and late viral antigens and CMV DNA. The degree of infection was dose and incubation-time dependent. Infection of HUVEs with these CMV strains and a nonattenuated clinical isolate failed to induce HLA DR, DP, or DQw1 expression in the absence of IFN-gamma. These findings support the hypothesis that endothelial cells in vivo may serve as reservoirs of CMV infection. They do not support the hypothesis that CMV produces an immediate-early antigen that has immunologic cross-reactivity with HLA DR. Furthermore, there is no support for the hypothesis that CMV independently induces HLA class II antigens in the absence of IFN-gamma.

Cells, Cultured↗