Detached ciliary tufts mistaken for peritoneal parasites: a warning

Detached ciliary tufts of columnar epithelial cells from the female genital tract may be mistakenly identified as protozoa when examined in wet mounts of fluid specimens in the laboratory because of their appearance and motility, although they are generally identified correctly in fixed specimens prepared for cytologic examination. A case of such mistaken identity in specimens from a gynecologic patient was documented, and the literature on ciliary tufts was reviewed. Infectious disease and gynecology consultants should be alert to the potential confusion arising from the presence of ciliary tufts in body fluids.     

Brain metastases from papillary thyroid carcinomas

Brain metastasis from papillary thyroid carcinoma (PTC) is extremely rare and carries a poor prognosis. We report nine cases (five females and four males) of brain metastasis of PTC. The age of patients ranged from 46 to 87 years old. The patients presented with nonspecific symptoms such as headaches. Brain metastasis was the first clinical presentation in three of nine patients; two of which had the aggressive tall cell variant of PTC. Six patients had prior history of PTC (four classic, one oncocytic variant, and one columnar cell variant) for 2 to 17 years with a median of 12 years. Gross total resection of brain metastasis was achieved for eight of our patients. Eight patients were treated with radioactive iodine. The median follow-up time was 12 months, ranging from 1 month to 4 years. Three patients died of their disease in 6 months, 21 months and 4 years, respectively after their first presentation of brain metastasis. It seems that these rare aggressive variants of PTC, such as tall cell variant, not only have higher propensity to develop brain metastasis, but also more frequently present with brain metastasis as their first clinical presentation than classic PTC. Furthermore, patients with PTC can develop brain metastasis even after many years.     

Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-²H₂-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA_1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.     

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Adult stem cells are believed to be maintained by a specialized microenvironment, the niche, which provides short-range signals that either instruct stem cells to self-renew or inhibit execution of preprogrammed differentiation pathways. In Drosophila testes, somatic cyst stem cells (CySCs) and the apical hub form the niche for neighboring germline stem cells (GSCs), with CySCs as the proposed source of instructive self-renewal signals [Leatherman JL, Dinardo S (2010) Nat Cell Biol 12(8):806–811]. In contrast to this model, we show that early germ cells with GSC characteristics can be maintained over time after ablation of CySCs and their cyst cell progeny. Without CySCs and cyst cells, early germ cells away from the hub failed to initiate differentiation. Our results suggest that CySCs do not have a necessary instructive role in specifying GSC self-renewal and that the differentiated progeny of CySCs provide an environment necessary to trigger GSC differentiation. This work highlights the complex interaction between different stem cell populations in the same niche and how the state of one stem cell population can influence the fate of the other.The ability of a stem cell niche to maintain a population of stem cells ensures the continued availability of adult stem cells to replenish and repair specific tissues throughout the lifetime of an organism (1, 2). Failure of a niche to maintain its appropriate stem cell population may lead to degeneration, aging, or an inability to repair tissue damage (3). Conversely, failure of a niche to properly regulate differentiation versus proliferation may contribute to the genesis of cancer in adult stem cell lineages (4). A comprehensive understanding of how the local microenvironment of the stem cell niche functions suggests strategies for expansion of adult stem cell populations in vitro, facilitates design of artificial niches for transplantation, and provides ideas for increasing maintenance and functionality of endogenous adult stem cell populations used for regenerative medicine.The Drosophila testis stem cell niche, a key model for understanding how the microenvironment regulates stem cell behavior (5–7), supports two distinct adult stem cell populations—germline stem cells (GSCs) and cyst stem cells (CySCs)—both of which attach to a cluster of postmitotic somatic cells that form the apical hub (Fig. 1A). GSCs and CySCs normally divide with oriented spindles to produce daughters that remain next to the hub and self-renew and daughters displaced away from the hub that initiate differentiation (8, 9). GSCs give rise to gonialblasts (Gb) and CySCs give rise to postmitotic cyst cells (10), a pair of which encapsulates each Gb to form a cyst. The encapsulated Gb undergoes four rounds of synchronous transit-amplifying (TA) divisions before entering meiosis and terminal differentiation (Fig. 1A).Open in a separate windowFig. 1.Early germ cells can be maintained after ablation of CySCs and cyst cells. (A) Diagram of Drosophila spermatogenesis at the apical tip of the testis. (Red) fusomes; (green) Bam protein expression. (B–G) Immunofluorescence images of c587Gal4; UAS Grim; tubGal80^ts testes stained with anti-FasIII (white, hub), anti-Vasa (red, germ cells), and anti-Tj (green) nuclei of hub, CySCs, and cyst cells). (B) Newly eclosed flies before shift to 30 °C. (Arrowheads) CySCs; (arrows) cyst cells. (C) Flies shifted to 30 °C for 1 d. (D) Flies shifted to 30 °C for 1 d and back to 18 °C for 7 d. (E) Flies shifted to 30 °C for 1 d and back to 18 °C for 7 d. (F) Flies shifted to 30 °C for 1 d and back to 18 °C for 14 d. (G) Flies shifted to 30 °C for 1 d and back to 18 °C for 21 d. (H) Bar graph depicting phenotype distribution at different time points. (Blue bar) Testes with CySCs and/or cyst cells (incomplete ablation); (red bar) testes with early germ cells but lacked CySCs or cyst cells; (green bar) testes lacking early germ cells, CySCs, and cyst cells. No significant difference in phenotype distribution was observed among the 7-, 14-, and 21-d time points. (Scale bar: B–G, 10 μm.)Both the apical hub and the CySCs influence the GSC state. A cytokine-like signal from the hub activates the JAK-STAT signaling pathway in both GSCs and CySCs (11, 12). Although JAK-STAT signaling is required cell autonomously for CySC maintenance, it is not necessary to retain GSCs in their stem cell state. Rather, activity of Stat in the germline is essential for continued attachment of GSCs to the hub and retains GSCs in their niche (13). Several lines of evidence suggest that CySCs provide a niche for maintenance of GSCs (13–15). Consistent with this model, it has been proposed that self-renewal of GSCs is specified by instructive signal(s) from the CySCs, with a likely candidate being TGF-β signaling (13).Here we show that early germ cells can be maintained next to the hub in testes in which CySCs and cyst cells had been permanently ablated. We further show that the progeny of GSC-like cells displaced from the hub failed to initiate the TA program in the absence of CySCs and cyst cells, and instead continued to proliferate as undifferentiated cells. Our findings suggest that CySCs do not play a required instructive role in GSC self-renewal and that cyst cells, the differentiated progeny of CySCs, are required for proper onset of the germline differentiation.