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B K Kinder

Publications and source records attributed to B K Kinder.

At least 19 recordsLinked to original sources
PubMed1999

Inhibition of protein phosphatase 1 decreases PTH secretion from isolated dispersed parathyroid cells.

To investigate the regulation of parathyroid hormone secretion by phosphatases we examined the effect of okadaic acid, a selective inhibitor of protein phosphatases (PP)-1 and -2A, on isolated, dispersed parathyroid cells. Okadaic acid inhibited secretion from intact bovine, intact human and streptolysin-O permeabilized bovine cells. Approximately 10(-6) M okadaic acid resulted in a 50% decrease in parathyroid hormone (PTH) secretion from both intact and permeabilized cells, consistent with PP-1 being the target of inhibition. Upon subcellular fractionation, PP-1 overlapped but was not identical to either PTH, a marker of the secretory granule, or Na+/K+-ATPase, a plasma membrane marker. In summary, PP-1 activity is involved in Ca2+-dependent but not basal PTH secretion.

Animals↗
PubMed1998

Genetic and biochemical screening for endocrine disease: II. Ethical issues.

The ability to test for specific genes conferring susceptibility to a variety of diseases has profound ethical implications for the way in which we care for patients. Legislators and health care insurers are scrambling to address the aspects of genetic screening that they believe fall within their purview. Critical to the development of appropriate societal regulations regarding genetic screening is a fundamental understanding of the ethical issues involved. A review of those concerns and the areas in which they interface with legal and insurance issues is the topic of this paper.

Anonymous Testing↗
PubMed1997

Reconstitution of calcium-regulated parathyroid hormone secretion from streptolysin-O-permeabilized parathyroid cells by guanosine 5'-O-(thio)triphosphate.

Intracellular Ca2+ levels determine the amount of PTH secretion from parathyroid cells. Dissociated calf parathyroid cells were permeabilized with streptolysin-O (SLO) to provide an in vitro model system to examine Ca(2+)-dependent regulation of hormone secretion. PTH release from these cells was energy dependent and increased by cytosolic cofactors. Guanosine 5'-O-(thio)triphosphate (GTP gamma S) increased PTH secretion from SLO-permeabilized cells in a dose-dependent manner from 0.1-100 microM. In the absence of GTP gamma S there was no relationship between the ambient Ca2+ concentration and the rate of PTH secretion. However, in the presence of GTP gamma S, intracellular Ca2+ inhibited PTH secretion with an EC50 of approximately 0.1 microM, corresponding to physiological intracellular Ca2+ levels. Thus, the addition of GTP gamma S to SLO-permeabilized parathyroid cells reconstituted the inverse relationship between extracellular Ca2+ and PTH secretion that is observed in vivo and in intact cells. The data indicate that this effect is mediated at least in part by heterotrimeric guanosine triphosphatases. In addition, calcium/calmodulin-dependent protein kinase II appears to mediate low Ca(2+)-dependent PTH secretion from these cells.

Animals↗
PubMed1996

Mechanism of technetium 99m sestamibi parathyroid imaging and the possible role of p-glycoprotein.

BACKGROUND: Localization of parathyroid glands is critical in the treatment of recurrent or persistent hyperparathyroidism. Technetium sestamibi imaging may improve localization; however, the mechanism of visualization of parathyroid tissue remains unclear. On the basis of the chemical structure of sestamibi it has been suggested that p-glycoprotein is involved in the transport of sestamibi across cell membranes. This study was designed to examine sestamibi uptake and retention and p-glycoprotein expression in normal and abnormal parathyroid tissue. METHODS: Thirty-two consecutive patients underwent 2-methoxy-isobutyl-isonitrile imaging immediately before parathyroid exploration. Tissue was obtained from normal and abnormal parathyroids and from the thyroid gland. Touch preparations gave rapid confirmation of tissue origin. Specimens were trimmed and weighed, and gamma-emission was counted. Percentage injected dose per gram of tissue was calculated. Immunohistochemistry was obtained with a battery of monoclonal antibodies to identify p-glycoprotein in parathyroid tissue submitted for permanent histologic examination. Slides were graded by a pathologist familiar with immunohistochemistry. RESULTS: Abnormal parathyroid tissue had a higher mean retention of injected dose per gram than did normal thyroid and parathyroid tissue. Immunohistochemistry revealed that abnormal parathyroid tissue expresses less p-glycoprotein. CONCLUSIONS: These results suggest that size is not the single determinant of parathyroid visualization and that p-glycoprotein expression may be involved in the mechanism of parathyroid imaging.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

DARPP-32 (dopamine and cAMP-regulated phosphoprotein, M(r) 32,000) is a membrane protein in the bovine parathyroid.

A distinct form of DARPP-32, a protein phosphatase-1 inhibitor, has been identified in bovine calf parathyroid glands. Immunoblot analysis of parathyroid tissue revealed a 32 kDa protein present predominantly in a particulate fraction; it remained particulate after treatment with 1.0 M NaCl or 0.1 M Na2CO3. Metabolic labeling of parathyroid cells with mevalonolactone demonstrated that DARPP-32 is isoprenylated. Immunocytochemical localization studies demonstrated that DARPP-32 is present in vesicles throughout the cytoplasm of parathyroid cells, and that protein phosphatase-1 gamma is concentrated in the region of the plasma membrane. Thus, in contrast to the predominately soluble form of DARPP-32 that has been characterized in selected areas of the central nervous system, the parathyroid form is tightly associated with intracellular membranes.

Animals↗
PubMed1995

Localization studies in patients with hyperparathyroidism.

Patients with hyperparathyroidism who have not had previous neck surgery do not require preoperative localization because of the high success rate of cervical exploration (95%) and the limited sensitivity and specificity of all imaging modalities currently in use. Successful parathyroid exploration requires knowledge of the normal and frequently encountered variations in parathyroid anatomy (Fig. 4). Experience permits recognition of often subtle multiple gland disease. In skilled surgical hands, results are excellent with minimal morbidity. When recurrent or persistent disease or previously operated patients are encountered, confirmation of the diagnosis and attempts at localization should precede operation. Technetium sestamibi SPECT imaging and ultrasonography with FNA of suspicious glands are complementary tests that are readily available, inexpensive, and well tolerated by patients. If these tests are unsuccessful, MRI, CT, and invasive procedures should be pursued until the gland is localized.

Biopsy, Needle↗
PubMed1994

Antibodies to an epitope on synapsin I detect a protein associated with the endocytic compartment in non-neuronal cells.

To detect potential substrate proteins for Ca2+/calmodulin-dependent protein kinase II outside the central nervous system, antibodies were made to a synthetic peptide corresponding to a sequence within synapsin I which is phosphorylated by this enzyme. In neural tissues, this antibody (212) identified an 86/80 kDa doublet corresponding to synapsin I. In rat liver, intestinal enterocytes and the clone 9 cell line this antibody identified two proteins of 170 and 85 kDa. These proteins were present in the particulate fraction of liver postnuclear supernatant, and were released into the soluble fraction when extracted with 100 mM NaCl. In liver, enterocytes, and clone 9 cells, these antigens were localized by immunocytochemical techniques to small intracellular vesicles. The endocytic compartment of clone 9 cells was labeled by continuous uptake of horseradish peroxidase; antibody 212-labeled vesicles exhibited overlap with the compartment. To confirm the identity of this compartment as endosomal, rat liver endosomes were labeled in vivo by intravenous injection of horseradish peroxidase. Horseradish peroxidase-containing endosomes of approximately 80 nm were recognized by antibody 212. Occasionally, larger endosomes (approximately 300-500 nm) were also labeled. In clone 9 cells, partial overlap was observed between the 212 antigen and a transferrin receptor-positive, brefeldin A-sensitive compartment. In clone 9 cells double-labeled with anti-tubulin and antibody 212, then imaged using confocal microscopy, these vesicles appeared to be associated with microtubules. This antigen has properties similar to that of CLIP-170, a membrane-associated endosomal phosphoprotein. These findings demonstrate that a 170/85 kDa antigen containing an epitope for the Ca2+/calmodulin-dependent protein kinase II phosphorylation sequence is associated with an endocytic compartment.

Animals↗
PubMed1993

Histologic, flow cytometric, and genetic criteria in endocrine surgery.

Differential diagnosis of endocrine neoplasms as benign or malignant is frequently extremely difficult. Similarly, assessing prognosis in cases of malignancy is problematic. Traditionally, histologic criteria, including grade of the tumor, architectural features, and cytologic appearance, have been used to predict biologic behavior. In addition, clinical scoring systems may be useful in assigning prognosis in individual cases. Examination of the DNA profile of individual cells by flow cytometry may correlate with the aggressiveness of the tumor. Recent developments in molecular genetics have yielded genetic markers that may be useful in diagnosis and prognosis as well as illuminating the pathogenesis of endocrine neoplasia. This review summarizes the status of traditional and newer methods of pathologic interpretation of endocrine neoplasms. In general, the most accurate assessment of these tumors is derived from consideration of a collage of the clinical and pathologic criteria discussed herein.

Adrenal Gland Neoplasms↗
PubMed1993

Parathyroid carcinoma: the relationship of nuclear DNA content to clinical outcome.

This article reports the use of flow cytometry to determine tumor nuclear DNA content and its correlations with clinical outcome in a series of patients with parathyroid carcinoma. Information concerning nine patients with parathyroid cancer (aged 25 to 88 years) was reviewed. Paraffin-embedded, formalin-fixed archival tissue was used to determine tumor DNA content flow cytometrically. Twenty-five operative procedures were performed in nine patients, including 11 parathyroidectomies, two wide local excisions, six central neck dissections, and four median sternotomies for resection of metastases. With flow cytometry used to determine a tumor DNA index, five patients had evidence of tumor aneuploidy; in two patients two aneuploid peaks were evident. The DNA index ranged from 0.7 (hypodiploid) to 1.92 (mean, 1.31). Follow-up ranged from 1 to 18 years. Four patients died. Five were alive 1 to 13 years after diagnosis of parathyroid disease. Four of the five patients with evidence of tumor aneuploidy had metastatic disease and died, and the fifth has had three local recurrences. The four patients with diploid tumors were alive and free of disease 1, 3, 4, and 8 years after the initial operation. It is concluded that in patients with clinically or pathologically demonstrated parathyroid cancer, flow cytometry may help differentiate those whose cancers are likely to behave indolently (diploid tumors) from those with tumors (aneuploid) more likely to behave aggressively by recurring locally or metastasizing.

Adult↗
PubMed1992

P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma.

BACKGROUND: The response of adrenocortical carcinoma (ACC) to adjuvant chemotherapy has been disappointing with no significant impact on survival. The normal adrenal cortex has very high levels of P-glycoprotein, an energy-dependent efflux pump of a variety of structurally unrelated chemotherapeutic agents. P-glycoprotein has been implicated as a cause of multidrug resistance in a variety of neoplasms. The purpose of this study was to evaluate P-glycoprotein expression in ACC. METHODS: Eleven patients with ACC had paraffin-embedded tumor evaluated for P-glycoprotein expression. These were analyzed by immunohistochemistry assay with a battery of four anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2, MDR). RESULTS: All eleven cases showed intense, predominantly membrane immunoreactivity for P-glycoprotein. In 10 of the cases, most tumor cells were immunoreactive with at least three antibodies, and six of 11 cases were positive for all four antibodies. In this small series no correlation existed between P-glycoprotein expression and tumor grade, stage of disease, or survival. CONCLUSIONS: All 11 cases of ACC studied showed P-glycoprotein expression, which was similar to the normal adrenal cortex. This possible mechanism of multidrug resistance may help explain the significant chemoresistance seen in ACC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Advances in the diagnosis and treatment of pheochromocytoma.

Diagnosis and management of pheochromocytoma, once dangerous and uncertain, have been dramatically altered in recent years by advances in imaging, assays, and pharmaceuticals. During the past ten years we have treated 18 patients who had pheochromocytoma. Biochemical diagnosis was made in all patients by measurement of 24-hour urinary total catecholamine excretion or by epinephrine-norepinephrine fractionation. Determination of epinephrine-norepinephrine ratios was instrumental in making the diagnosis of pheochromocytoma in two patients in whom total catecholamine levels were normal. Localization of the pheochromocytoma in the most recently treated cases was accomplished by ultrasound, computed tomography, or iodine I 131 iobenguane (iodine I 131 metaiodobenzylguanidine) scanning. Nine patients in the series were prepared for surgery with phenoxybenzamine hydrochloride and six with prazosin hydrochloride. Preoperative total alpha-adrenergic blockade with phenoxybenzamine offered no advantage over selective blockade with prazosin in terms of perioperative fluid requirements or intraoperative hemodynamic stability.

Adrenal Gland Neoplasms↗
PubMed1988

Poorly differentiated ("insular") carcinoma of the thyroid gland: an aggressive subset of differentiated thyroid neoplasms.

Four patients with a histologically distinctive thyroid carcinoma--which recently has been referred to as poorly differentiated ("insular") carcinoma--are reported. This study confirms the previous conclusions that patients with this neoplasm often experience an aggressive clinical course, with focal recurrences and distant metastases common, which results in death in the majority of patients. Such aggressive behavior may occur even when the insular component accounts for only a small percentage of an otherwise well-differentiated carcinoma, as seen in one of our patients. After subtotal or total thyroidectomy, three of the four patients have experienced local recurrence (1) and metastases to lung (3), mediastinum (1), and bone (1). All three of these patients died within 2 years of the diagnosis of insular carcinoma. The remaining patient is alive without evidence of disease 1 year after total thyroidectomy. Histologically, this neoplasm is characterized by well-defined nests (insulae) that are composed of relatively small, uniform cells and sometimes associated with small, thyroglobulin-containing follicles. Tumor necrosis is often present. Insular carcinoma may comprise the entire neoplasm (2 patients) or be associated with well-differentiated follicular (1 patient) or papillary (1 patient) carcinoma. The rapid and often fatal course associated with insular carcinoma warrants aggressive treatment at the time of initial diagnosis, including total thyroidectomy and node dissection (if involved), as well as possible iodine-131, external beam irradiation and chemotherapy.

Adult↗