Dhrs3a regulates retinoic acid biosynthesis through a feedback inhibition mechanism.

Retinoic acid (RA) is an important developmental signaling molecule responsible for the patterning of multiple vertebrate tissues. RA is also a potent teratogen, causing multi-organ birth defects in humans. Endogenous RA levels must therefore be tightly controlled in the developing embryo. We used a microarray approach to identify genes that function as negative feedback regulators of retinoic acid signaling. We screened for genes expressed in early somite-stage embryos that respond oppositely to treatment with RA versus RA antagonists and validated them by RNA in situ hybridization. Focusing on genes known to be involved in RA metabolism, we determined that dhrs3a, which encodes a member of the short-chain dehydrogenase/reductase protein family, is both RA dependent and strongly RA inducible. Dhrs3a is known to catalyze the reduction of the RA precursor all-trans retinaldehyde to vitamin A; however, a developmental function has not been demonstrated. Using morpholino knockdown and mRNA over-expression, we demonstrate that Dhrs3a is required to limit RA levels in the embryo, primarily within the central nervous system. Dhrs3a is thus an RA-induced feedback inhibitor of RA biosynthesis. We conclude that retinaldehyde availability is an important level at which RA biosynthesis is regulated in vertebrate embryos.

Zebrafish wnt8 encodes two wnt8 proteins on a bicistronic transcript and is required for mesoderm and neurectoderm patterning.

In vertebrates, wnt8 has been implicated in the early patterning of the mesoderm. To determine directly the embryonic requirements for wnt8, we generated a chromosomal deficiency in zebrafish that removes the bicistronic wnt8 locus. We report that homozygous mutants exhibit pronounced defects in dorso-ventral mesoderm patterning and in the antero-posterior neural pattern. Despite differences in their signaling activities, either coding region of the bicistronic RNA can rescue the deficiency phenotype. Specific interference of wnt8 translation by morpholino antisense oligomers phenocopies the deficiency, and interference with wnt8 translation in ntl and spt mutants produces embryos lacking trunk and tail. These data demonstrate that the zebrafish wnt8 locus is required during gastrulation to pattern both the mesoderm and the neural ectoderm properly.

Renal angiomyolipoma associated with neurofibromatosis and primary carcinoid of mesentery.

A patient with von Recklinghausen's disease manifested by dermal neurofibromatosis and cafe-au-lait spots presented with complaints of malaise, weight loss, lower extremity weakness, and a palpable left lower abdominal quadrant mass. Evaluation revealed a lumbar neurofibroma, a localized primary carcinoid tumor of the mesentery, and a left renal angiomyolipoma. Although an association between neurofibromatosis and carcinoid has been previously reported, we believe this is the first report documenting the association of all three entities.

Eosinophilic granuloma of the cavernous sinus and orbital apex in an HIV-positive patient.

A 35-year-old HIV-positive woman with painful ophthalmoplegia, sensory loss extending to all branches of the trigeminal nerve, and progressive optic neuropathy was found to have eosinophilic granuloma of the cavernous sinus, superior orbital fissure, and orbital apex. There was no radiologic evidence of a lytic bone lesion within the skull or orbit and clinical evidence suggested a primary intracranial origin for this lesion. This is the first case of a cavernous sinus syndrome caused by eosinophilic granuloma and the first time HIV infection is reported in association with histiocytosis-X.

Diffuse neurofibroma of the pylorus: a cause of gastric outlet obstruction.

We describe a benign diffuse neurofibroma of the pylorus, unassociated with von Recklinghausen's neurofibromatosis, which was a cause of pyloric stenosis; epigastric discomfort, vomiting, and weight loss of 60 lb were the most prominent symptoms. Partial gastrectomy resulted in a cure. The literature on nerve-sheath tumors of the stomach is reviewed.

Bilateral ureteral necrosis and obliteration secondary to pancreatic pseudocyst.

We report an unusual case of bilateral distal ureteral necrosis and obliteration associated with a pancreatic pseudocyst. After cyst drainage bilateral ureteral obstruction developed, requiring surgical correction. While it is known that a pancreatic pseudocyst can cause extensive damage to contiguous organs, to our knowledge this case represents the first report of ureteral necrosis and obliteration resulting from pancreatic enzyme damage to the ureters.

Benign symmetrical lipomatosis.

Benign symmetrical lipomatosis is an unusual disorder of fat metabolism that results in a characteristic accumulation of adipose tissue around the head and neck. Surgical extirpation is the only known effective therapy. Physical examination does not provide a comprehensive delineation of tumor extent. We present the first reported use of CT scanning to investigate the anatomic limits of BSL and to plan the operative approach.

Acute myelogenous leukemia following complete remission of small cell carcinoma of the lung.

The treatment of patients with small cell carcinoma of the lung (SCCL) with combination chemotherapy and radiation has dramatically improved survival in the past decade. With this increased survival, long term complications of therapy are becoming apparent. We report a patient who died of acute myelogenous leukemia (AML) while in complete remission from SCCL. Review of the literature indicates that there may be an increased incidence of AML following successful induction of complete remission in patients with SCCL.

Association of lymphocytic neoplasia and mesothelioma.

Two lymphocytic neoplasms, chronic lymphocytic leukemia and poorly differentiated lymphoma, were detected in two patients who had nonoccupational exposure to asbestos. Both had a pleural mesothelioma subsequent to their initial presentation with lymphocytic neoplasm. Recent reports have suggested a possible association between asbestos exposure and lymphoproliferative neoplasms. Chronic antigenic stimulation by asbestos could predispose one to the immunoproliferative disorders seen in these patients. The possible significance of this relationship is discussed for future consideration.

Fatal hemorrhage from rectal varices. Report of two cases.

We report two cirrhotic patients who succumbed to massive rectal bleeding. The source of this hemorrhage remained undiscovered clinically despite endoscopy, a bleeding scan, and celiac angiogram in one patient. Autopsy revealed that the source of the bleeding was rectal varices in both cases.

Heterologous malignant mixed Müllerian tumor of the cervical stump.

A 76-year-old woman presented with vaginal bleeding 37 years following supracervical hysterectomy for a benign disease. Extensive malignant mixed Müllerian tumor was found in the remaining uterine cervix. This appears to be the first documented case of the malignant mixed Müllerian tumor arising in a cervical stump. Possibility of derivation of this tumor from endometriosis notwithstanding, the cervical Müllerian neoplastic potential parallels that of the endometrium because of the developmental kinship of the two. This potential has been fully retained and expressed as a tumor in the cervical stump in this case.

Malignant fibrous histiocytoma of the colon associated with diverticulitis.

We report the second case of a malignant fibrous histiocytoma of the large bowel. The neoplasm constituted an incidental finding during the diagnostic work-up for diverticulitis of the sigmoid colon. There was a massive abdominal recurrence of the tumor four months after colectomy, and the patient died nine months after the initial operation. The literature on fibroblastic sarcomas of the colon is also reviewed.