Search PubMed⌕ Search

Biomedical subjects

B J Biller

Publications and source records attributed to B J Biller.

13 recordsLinked to original sources

Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer.

Regulatory T cells (Treg) are a distinct group of T lymphocytes with immunosuppressive properties that serve normally to prevent harmful autoimmune responses. However, Tregs can also interfere with beneficial immune responses such as anti-tumor and anti-viral immunity in humans and rodents. Given the overall importance of Tregs, it is likely that they play an important role in diseases of dogs as well. However, at present reagents required for identification of Tregs in dogs are not available. Therefore, we investigated whether expression of FoxP3, a transcription factor that is highly expressed in Tregs in humans and rodents could also be used to identify Tregs in dogs. We found that a cross-reactive FoxP3 antibody identified a subset of CD4(+) T cells in blood and lymph nodes of dogs. By flow cytometry the mean percentage of FoxP3(+)CD4(+) T cells in normal dogs was 4.3% in blood and 9.8% in the lymph nodes. In dogs with cancer, there was a significant increase in numbers of Treg in blood (7.5%) and tumor-draining lymph nodes (17.1%) compared to age-matched healthy control dogs. We also found that FoxP3(+)CD4(+) T cells in dogs could be significantly expanded in vitro by TCR activation together with addition of TGF-beta and IL-2. Treated cells also significantly increased expression of TGF-beta and IL-10mRNA. We conclude from these studies that a cross-reactive FoxP3 antibody can be used to identify Tregs in dogs and that this reagent may serve as a useful tool for investigating the role of Treg in a variety of diseases of dogs.

Animals↗

Telomerase activity as a marker for malignancy in feline tissues.

OBJECTIVE: To establish the diagnostic significance of the telomeric repeat amplification protocol (TRAP) assay in detecting feline malignancies. SAMPLE POPULATION: Solid tissue specimens collected from 33 client-owned cats undergoing diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital between July 1997 and September 1999 and an additional 20 tissue samples were collected from 3 clinically normal control cats euthanatized at the conclusion of an unrelated study. PROCEDURE: The TRAP assay was used for detection of telomerase activity. Each result was compared to its respective histopathologic diagnosis. RESULTS: Twenty-nine of 31 malignant and 1 of 22 benign or normal tissue samples had telomerase activity, indicating 94% sensitivity and 95% specificity of the TRAP assay in our laboratory. CONCLUSIONS AND CLINICAL RELEVANCE: The diagnostic significance of telomerase activity has been demonstrated in humans and recently in dogs by our laboratory. We tested feline samples to determine whether similar patterns of telomerase activity exist. On the basis of our results, the TRAP assay may be clinically useful in providing a rapid diagnosis of malignancy in cats. The telomerase enzyme may also serve as a therapeutic target in feline tumors.

Animals↗

Evaluation of an assay for detecting telomerase activity in neoplastic tissues of dogs.

OBJECTIVE: To determine feasibility of using the telomere repeat amplification protocol (TRAP) assay to detect telomerase activity in tumors of dogs. SAMPLE POPULATION: Samples of tumor or normal tissue were obtained from client-owned dogs that underwent surgical biopsy during the period of January 1996 through December 1997. PROCEDURE: The TRAP assay was used to detect telomerase activity in malignant or benign tumors of dogs. Telomerase status (positive or negative) was compared with results of histologic examination for each sample to estimate specificity and sensitivity of this assay for the diagnosis of malignancy. RESULTS: Of 26 malignant tumors, 24 were telomerase positive on TRAP assay, whereas 3 of 4 benign tumors and 3 of 3 normal tissues were telomerase negative. Analysis of these results indicated an estimated sensitivity of 92% and specificity of 86% for tumor analysis, using the TRAP assay. CONCLUSION: The TRAP assay can be used to measure telomerase activity in malignant tumors of dogs. CLINICAL RELEVANCE: Because telomerase activation may be required for indefinite longevity of cells, it may also serve as a tumor marker and therapeutic target. The TRAP assay can be used to detect telomerase in samples of fluid as well as tissues obtained from solid tumors. Therefore, it may have considerable clinical value in rapid and noninvasive diagnosis of neoplasia in dogs. Additional studies must be completed to more accurately determine sensitivity and specificity of the assay.

Animals↗

Long-term follow-up of transsphenoidal selective adenomectomy for prolactinoma.

Although transsphenoidal selective resection of prolactinoma has high cure rates and low morbidity, the frequency of late recurrence of adenoma is controversial. Long-term follow-up data were available on 29 of our patients having initial return to normal prolactin levels after microadenoma resection; in 24, prolactin levels remained normal at 50 +/- 3 months' (range, 11 to 81 months) follow-up. Five patients manifested hyperprolactinemia again after intervals of six to 16 months. In five patients with normal prolactin levels immediately after macroadenoma resection, who were available for long-term follow-up, prolactin levels remained normal in four at 41 +/- 3 months; one patient had a relapse 78 months after surgery. Testing of prolactin secretory dynamics six weeks postoperatively was not predictive of who would suffer relapse. It is not known whether these relapses are due to regrowth of tumor remnants or represent new tumor formation.

Adenoma↗

Surgical cure of prolactinoma reverses abnormal prolactin repsonse to carbidopa/L-dopa.

To determine whether the abnormalities in dopaminergic regulation of PRL secretion in patients with prolactinomas persist after resection of the adenoma, we evaluated PRL inhibitory responses to L-dopa alone and L-dopa given after pretreatment with the dopa decarboxylase inhibitor carbidopa before and after transsphenoidal selective resection of prolactinomas in 23 women. Eighteen women were cured by surgery (normal PRL, menses, no galactorrhea), while 5 women were not cured. Preoperatively, the PRL inhibitory responses to L-dopa cured, 4 .3 +/- 3.8%; uncured, 50.1 +/- 5.5% of baseline) was blunted by pretreatment with the decarboxylase inhibitor carbidopa (cured, 79.1 +/- 4.1%; uncured, 76.8 +/- 9.2%). Postoperatively, this blunting disappeared in the cured patients (L-dopa, 49.1 +/- 3.5%; carbidopa/L-dopa, 56.3 +/- 5.1%), but the blunting persisted in the uncured patients (L-dopa, 49.3 +/- 7.9%; carbidopa/L-dopa, 69.3 +/- 4.2%). The return to normal of the carbidopa/L-dopa test in cured prolactinoma patients after surgery is evidence that in these individuals, preoperative abnormalities of secretion are due to either intrinsic abnormalities of the tumor or alteration of hypothalamic function secondary to tumor secretion. In those patients not cured by surgery, dynamic tests of function remain abnormal, findings attributable to either incomplete tumor resection or the presence, in some patients, of underlying hypothalamic dysregulation.

Adenoma↗

Bromocriptine therapy in acromegaly: use in patients resistant to conventional therapy and effect on serum levels of somatomedin C.

Seven patients with clinically active acromegaly who had not responded completely to previous surgical or radiation therapy were treated with bromocriptine. Bromocriptine was well tolerated; only one of the seven patients discontinued treatment secondary to side effects. Six of the seven patients improved during bromocriptine therapy, although GH levels were normalized in only two patients. All patients had elevated levels of somatomedin C (Sm-C) before therapy even when basal levels of GH were less than 10 ng/ml. One patient normalized both GH and Sm-C during bromocriptine therapy and had an excellent clinical response. Five patients had moderately good clinical responses; four of these patients had substantial falls in GH levels, but Sm-C levels fell minimally if at all in four and actually increased in one patient. In one patient, there was no change in clinical status, GH levels, or Sm-C levels. Thus, the clinical response did not correlate well with changes in Sm-C in most patients. The patterns of response to provocative stimuli of GH secretion in acromegaly were maintained during bromocriptine therapy, as has been previously been reported. Based on our experience, bromocriptine appears to be a useful adjunct in the therapy of acromegaly, even in patients who have had prior ablative therapy.

Acromegaly↗

Galactorrhea, oligo/amenorrhea, and hyperprolactinemia in patients with craniopharyngiomas.

We report three patients with craniopharyngiomas who had galactorrhea, oligo/amenorrhea, and abnormal sellar tomograms, clinically suggesting the presence of a prolactinoma. One patient had an intrasellar craniopharyngioma (Rathke's cleft cyst) diagosed during surgical exploration of the pituitary fossa for removal of a suspected prolactinoma, and two had suprasellar caraniopharyngiomas whose presence was suspected on the basis of computed tomography. This finding emphasizes the importance of computed tomography in the evaluation of patients with the clinical presentation of a prolactinoma. In two patients, PRL levels were elevated before surgery and remained elevated after removal of the craniopharyngioma. In the third case, an initially normal serum PRL level became elevated after removal of the tumor.

Adult↗

Selective transsphenoidal adenomectomy in women with galactorrhea-amenorrhea.

Thirty women with prolactin (PRL)-secreting adenomas underwent selective adenomectomy via a transsphenoidal route. All had abnormal sella polytomes or visual fields, amenorrhea with low basal serum gonadotropin levels despite decreased serum estradiol concentrations, and elevated basal serum PRL levels with blunted PRL response to neuroendocrine stimulation tests )thyrotropin-releasing hormone, levodopa, chlorpromazine, and hypoglycemia). Of 17 patients with microadenomas, 14 (82.4%) were cured and three (17.6%) improved. None were unchanged or worse. Three (60%) of five patients with larger, but still intrasellar tumors, had normalization of PRL levels, return of menses, and resolution of galactorrhea. The patients with tumors extending out of the sella did not fare as well. Overall, 21 (70%) were cured, six (20%) improved, two (6.7%) were unchanged, and the condition of one (3.3%) became worse. All preoperative neurologic deficits resolved. Postoperative complications were minimal with no neurologic morbidity. When tumors are small, surgical results are excellent with minimal risk.

Adenoma↗

The value of computed tomography in evaluating patients with prolactinomas.

The use of computed tomography (CT) in 28 patients with surgically proved prolactinomas is described. The authors' experience suggests that in evaluating patients with galactorrhea-amenorrhea syndrome, CT in combination with pluridirectional tomography usually provides sufficient information to make further invasive studies unnecessary. In selected cases with low-density areas within the sella as seen on CT, pneumoencephalography is still advisable to distinguish between the empty sella and the necrotic tumor. Angiography is still necessary to exclude vascular causes for suprasellar and parasellar masses such as aneurysms and meningiomas.

Empty Sella Syndrome↗