Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers.

Arginylation is an emerging post-translational modification mediated by arginyltransferase (ATE1) that is essential for mammalian embryogenesis and regulation of the cytoskeleton. Here, we discovered that Ate1-knockout (KO) embryonic fibroblasts exhibit tumorigenic properties, including abnormally rapid contact-independent growth, reduced ability to form cell-cell contacts and chromosomal aberrations. Ate1-KO fibroblasts can form large colonies in Matrigel and exhibit invasive behavior, unlike wild-type fibroblasts. Furthermore, Ate1-KO cells form tumors in subcutaneous xenograft assays in immunocompromised mice. Abnormal growth in these cells can be partially rescued by reintroduction of stably expressed specific Ate1 isoforms, which also reduce the ability of these cells to form tumors. Tumor array studies and bioinformatics analysis show that Ate1 is downregulated in several types of human cancer samples at the protein level, and that its transcription level inversely correlates with metastatic progression and patient survival. We conclude that Ate1-KO results in carcinogenic transformation of cultured fibroblasts, suggesting that in addition to its previously known activities Ate1 gene is essential for tumor suppression and also likely participates in suppression of metastatic growth.

Late onset adrenocortical hydroxylase deficiencies associated with menstrual dysfunction.

Forty-eight women with menstrual dysfunction and clinical evidence of excess androgen production were subjected to an adrenocorticotropic hormone stimulation test that demonstrated the presence of a late-onset 11- or 21-adrenocortical hydroxylase deficiency. Adrenocortical suppression therapy with prednisone was then instituted. Eighty-three percent of the women improved and either conceived, established normal regular menstrual cycles, or noted a significant increase in menstrual regularity. In patients desiring fertility, there was an overall pregnancy rate of 64% and a corrected pregnancy rate of 93%. Some of these patients were given clomiphene in addition to the prednisone. The present study has demonstrated that an adrenocortical abnormality, characterized by a partial deficiency of either 11-hydroxylase or 21-hydroxylase, plays a significant role in many women with clinical evidence of hyperandrogenism and menstrual abnormalities. In such women, adrenocortical suppression is indicated and often results in a significant improvement of the menstrual disturbance.

Complications of laparoscopic sterilisation.

PIP: In their review of female sterilization procedures, Dr. Mumford and colleagues indicate a high complication rate for laparoscopy. In my extensive experience of laparoscopy, I occasionally create emphysema of the abdominal wall and even of the omentum. Abdominal wall emphysema is totally innocuous, and the same can be said for omental emphysema. To call these situations "complications" significantly distorts the true meaning of the word and skews the figures in a biased fashion. Eliminating the 20% of laparoscopic complications attributed to abdominal wall emphysema would reduce the rate to a level more comparable with that of other procedures reviewed. Many occurrences during surgery cause the patient little harm or discomfort. To list these events as complications compromises the meaning of the term and provides further grist for the legal mill. Care is needed with terminology, particularly as it pertains to surgical complications. The problem is that those who write the papers do not get sued, but those who read them do.^ieng

Androgen abnormalities in acne vulgaris.

Thirty-six women with acne vulgaris who consulted gynecologist with complaints of hirsutism, infertility, menorrhagia, or oligomenorrhea were evaluated for an androgen abnormality with assays for testosterone (T), androstenedione (A), and dehydro-epi-androsterone (DHEA). Forty-eight percent of the DHEA measurements were elevated and 61% of the patients had elevation of one or more of the three measurements. The frequency of abnormal androgen levels remained relatively constant regardless of the severity of the presenting signs and symptoms. This study calls attention to the high frequency of an androgen abnormality in acne patients who also have evidence of hirsutism, menstrual irregularity, and/or infertility. Consideration should be given to assaying DHEA, T, and A levels in an effort to discover those patients who have a systemic endocrine disorder, of which acne manifests as a sign.

The partial adrenocortical hydroxylase deficiency syndrome in infertile women.

Eighteen infertile women desiring conception were selected for additional diagnostic studies on the basis of clinical evidence of hyperandrogenism characterized by acne and/or facial hirsutism. These 18 patients underwent stimulation tests with adrenocorticotropic hormone which demonstrated the presence of partial adrenocortical hydroxylase deficiences. All patients were then placed on glucocorticoid suppression therapy. Ten patients conceived and, of these, six required no therapy other than prednisone. Four conceived using a combination of prednisone and clomiphene therapy. Of othe eight patients who did not conceive, seven had other significant infertility factors. Therefore, of the patients without other significant fertility factors, 91% conceived. This study demonstrates that partial adrenocortical enzyme defects play a significant role in some women with clinical evidence of hyperandrogenism, and, in such women, either glococorticoid therapy alone or in combination with clomiphene is indicated.

Therapy of adrenocortical hydroxylase deficiencies in acne vulgaris.

Twenty women with acne vulgaris who presented to a gynecologist's office with the complaints of hirsutism, infertility, menorrhagia, or oligomenorrhea were subjected to a 24-hour cosyntropin (ACTH) infusion to detect partial 11- or 21-adrenocortical hydroxylase deficiencies. All patients demonstrated enzymatic defects and were placed on prednisone therapy. The six patients with moderate acne either showed improvement of their acne or conceived. Of the 14 patients with mild acne, seven showed improvement of their acne or conceived; whereas, the remainder showed no improvement. Patients with acne and gynecologic signs and symptoms should be evaluated for the presence of 11- or 21-adrenocortical hydroxylase deficiencies.