Peter O. Kohler

Giant Invasive Prolactinomas

Two of the largest prolactinomas ever documented that have been followed for nine and 10 years, respectively, demonstrate how aggressive prolactinomas may become and how difficult invasive prolactinomas are to treat. One of these prolactinomas invaded both internal auditory canals and simultaneously grew inferiorly, reducing the bony support of the skull and necessitating the patient to utilize both hands to hold his head up. The second patients prolactinoma invaded the sphenoidal, ethmoidal, and cavernous sinuses. Both of these patients had neurosurgical debulking of their tumors followed by radiation therapy. Neither patients prolactin levels decreased significantly during their first five years post-surgically, at which time bromocriptine was added. Since then, there has been a gradual lowering of serum prolactin levels and a decrease in the size of these tumors. These cases demonstrate that prolonged treatment and very large doses of bromocriptine may be necessary for tumor reduction in patients with invasive prolactinomas.

Glucocorticoid induction of β-adrenergic receptors in the DDT1 MF-2 smooth muscle cell line involves synthesis of new receptor

We have shown that glucocorticoids induce the appearance of β2-adrenergic receptors in membranes of the ductus deferens smooth muscle cell line (DDT1 MF-2). A concomitant increase in isoproterenol stimulated adenylate cyclase activity in the absence of exogenously applied GTP was observed as was a significantly increased (p < 0.05) sensitivity of the adenylate cyclase system to exogenously applied GTP. However, no significant difference in the maximal velocity of adenylate cyclase between control and steroid treatment was measurable in the presence of sodium fluoride. Induction of β2-adrenergic receptors in DDT1 MF-2 cells is correlated with the presence of steroid receptors (androgen and glucocorticoid) in the cells since estrogens and progesterones had no effect on receptor levels. Finally, utilizing dense amino acid labeling of cells to measure old versus newly synthesized receptor sites by a density shift method, we have documented that glucocorticoid induction of β2-adrenergic receptors involves synthesis of new receptor protein.

Community-Driven Research Agenda to Reduce Health Disparities.

This paper describes how a new regional campus of an academic health center engaged in a community‐based participatory research (CBPR) process to set a community‐driven research agenda to address health disparities. The campus is situated among growing Marshallese and Hispanic populations that face significant health disparities. In 2013, with support from the Translational Research Institute, the University of Arkansas for Medical Sciences Northwest began building its research capacity in the region with the goal of developing a community‐driven research agenda for the campus. While many researchers engage in some form of community‐engaged research, using a CBPR process to set the research agenda for an entire campus is unique. Utilizing multiple levels of engagement, three research areas were chosen by the community: (1) chronic disease management and prevention; (2) obesity and physical activity; and (3) access to culturally appropriate healthcare. In only 18 months, the CBPR collaboration had dramatic results. Ten grants and five scholarly articles were collaboratively written and 25 community publications and presentations were disseminated. Nine research projects and health programs were initiated. In addition, many interprofessional educational and service learning objectives were aligned with the community‐driven agenda resulting in practical action to address the needs identified.

Autocrine regulation of growth: II. Glucocorticoids inhibit transcription of c-sis oncogene-specific RNA transcripts

The ductus deferens smooth muscle tumor cell line (DDT1MF-2) expresses c-sis proto-oncogene poly A+ RNA transcripts which are thought to encode at least one subunit of the potent mitogen platelet derived growth factor (PDGF). We have previously demonstrated that glucocorticoids block DDT1MF-2 cells in G0/G1 stage of the cell cycle, and that exogenously applied PDGF reinitiates cell cycle progression. In this paper we document that glucocorticoids act to inhibit cell cycle progression by inhibiting the expression of c-sis poly A+ transcripts, which we suggest are encoding a PDGF-like molecule for DDT1MF-2 cells.

Family Model of Diabetes Education With a Pacific Islander Community

Purpose The purpose of the study was to use a community-based participatory research approach to pilot-test a family model of diabetes education conducted in participants’ homes with extended family members. Methods The pilot test included 6 families (27 participants) who took part in a family model of diabetes self-management education (DSME) using an intervention-driven pre- and posttest design with the aim of improving glycemic control as measured by A1C. Questionnaires and additional biometric data were also collected. Researchers systematically documented elements of feasibility using participant observations and research field reports. Results More than three-fourths (78%) of participants were retained in the study. Posttest results indicated a 5% reduction in A1C across all participants and a 7% reduction among those with type 2 diabetes. Feasibility of an in-home model with extended family members was documented, along with observations and recommendations for further DSME adaptations related to blood glucose monitoring, physical activity, nutrition, and medication adherence. Conclusions The information gained from this pilot helps to bridge the gap between knowledge of an evidence-based intervention and its actual implementation within a unique minority population with especially high rates of type 2 diabetes and significant health disparities. Building on the emerging literature of family models of DSME, this study shows that the family model delivered in the home had high acceptance and that the intervention was more accessible for this hard-to-reach population.

Health Beliefs of Marshallese Regarding Type 2 Diabetes.

OBJECTIVES The Marshallese population suffers from disproportionate rates of type 2 diabetes. This study identifies the underlying beliefs and perceptions that affect diabetes self-management behavior in the US Marshallese population living in Arkansas. METHODS The study employs focus groups with a semi-structured interview guide developed using a community-based participatory research (CBPR) approach and the Health Belief Model. Data were collected from 41 participants; bilingual community co-investigators provided translation as needed. RESULTS The results show high-perceived threat, with most participants describing diabetes as inevitable and a death sentence. Participants are generally unaware of the benefits of diabetes self-management behaviors, and the Marshallese population faces significant policy, environmental, and systems barriers to diabetes self-management. The primary cue to action is a diagnosis of diabetes, and there are varying levels of self-efficacy. CONCLUSIONS The research grounded in the Health Belief Model provides important contributions that can help advance diabetes self-management efforts within Pacific Islander communities.

Glucocorticoids induce a 29 000 Mr protein in DDT1 MF-2 smooth muscle cells but not in the DDT1 MF-2 GR glucocorticoid resistant variant

We have demonstrated that glucocorticoids induce in DDT1 MF-2 cells by a glucocorticoid mediated mechanism the synthesis of a methionine-cysteine rich protein of 29 000 Mr (p29). Induction of p29 is not observed in DDT1 MF-2 GR glucocorticoid resistant variants which have only 7% of glucocorticoid receptor site per cell compared to wild type cells. Increased synthesis of p29 is specific to glucocorticoids since neither androgens, estrogens, progesterone nor the glucocorticoid antagonist dexamethasone mesylate are effective inducers. Stimulation of p29 synthesis in wild type cells is observed at 10−10 M triamcinolone acetonide, reaching a maximum at a concentration of 1 × 10−8 M. The induction of p29 is not a function of glucocorticoid arrest of DDT1 MF-2 cells since DDT1 MF-2 cells promoted to re-enter the cell cycle by 50 ng/ml platelet derived growth factor (PDGF) continue synthesis of p29. Finally, increased levels of p29 translation products are observed in cell free translation assays carried out utilizing poly A− RNA transcripts isolated from glucocorticoid treated cells. These data suggest that the glucocorticoid stimulation of p29 synthesis is a transcriptional and/or RNA processing event controlled by glucocorticoid receptor complexes.

Familial ovarian dysgenesis in 46,XX females

Three phenotypic female sisters in a sibship of four sisters and one brother were found to have pure ovarian dysgenesis, which was confirmed by the finding of streak gonads at laparotomy in two of the three sisters who presented with amenorrhea and lack of secondary sexual characteristics. No evidence of any other congenital anomaly was found in any of these sisters. Pure gonadal dysgenesis syndrome distinguishes a group of women with primary gonadal failure with amenorrhea whose heights are over 152 cm and who are without either webbed necks or any of the other somatic anomalies that are characteristic of Turners syndrome. Cytogenetic studies revealed a normal female (46,XX) karyotype in all the affected members. Endocrine studies indicated that the affected sisters had elevated FSH and LH values with decreased plasma estradiol and urinary estrogen determinations. This is the second report of a family with 46, XX karyotype that meets all the criteria for the pure gonadal dysgenesis syndrome. The multiple affected sibs suggests an autosomal recessive mode of inheritance.

Hyperalimentation as cause of markedly worsened metabolic control in a patient with autoantibodies to the insulin receptor

Patients with type B insulin resistance and acanthosis nigricans have autoantibodies to their insulin receptors and usually have signs and symptoms of other autoimmune diseases. The first case demonstrating that hyperalimentation markedly disturbs blood glucose control in type B insulin-resistant patients is described. Neither prednisone, insulin (up to 240 units per hour), nor tolbutamide appeared to help this patients metabolic control. After the addition of cyclophosphamide for one week, the anti-insulin receptor autoantibody titer dropped from greater than 1:1,000 to 1:1. Six months later, the patient had a complete remission, which is rare, with only three other reported remissions in these patients with type B insulin resistance.

Separation of glucocorticoid receptors by phosphocellulose chromatography at pH 6.8

Abstract A high molecular weight glucocorticoid receptor partially purified at pH 7.4 from DDT, MF-2 cytosol in the presence of sodium molybdate can be shown to elute from DEAE-cellulose at 0.20 M KCl. This receptor fails to bind to phosphocellulose. However, if the receptor is partially purified at pH 6.8 it now binds to phosphocellulose eluting at 0.14 M KCl. A smaller fraction of receptor obtained at pH 6.8 elutes from phosphocellulose at 0.21 M KC1 and from DEAE-cellulose at 0.09 M KCl. Neither of the two receptor forms binds to DNA-cellulose unless a heating step (30° for 15 min) in the absence of sodium molybdate is performed. Under these conditions the form eluting at 0.09 M (DEAE) or 0.21 M KCl (phosphocellulose) is transformed to a DNA-binding form. Concomitant with transformation is a shift in sedimentation velocity from 8.8S to 3.9S.