Diphenylhydantoin-induced pure red cell aplasia

The pathogenesis of diphenylhydantoin-induced pure red cell aplasia was investigated in the case of a 32-year-old man who developed pure red cell aplasia while he was under treatment with diphenylhydantoin. The patient's serum IgG purified from serum drawn at the time of diagnosis suppressed normal allogeneic marrow colony-forming (CFU-E) and burst- forming (BFU-E) and autologous blood BFU-E growth in vitro only in the presence of diphenylhydantoin. This IgG-diphenylhydantoin complex had no effect on CFU-GM growth in vitro. Normal IgG or patient's IgG purified from serum drawn after the remission of red cell aplasia had no effect on erythroid colony formation in vitro in the presence of diphenylhydantoin. The IgG-diphenylhydantoin complex exerted no direct cytotoxic effect on normal marrow erythroblasts, CFU-E, and BFU-E, nor did it interfere with the action of erythropoietin on marrow erythroblasts. These studies suggest that diphenylhydantoin-induced red cell aplasia is immunologically mediated through an IgG inhibitor, which requires the presence of the drug to suppress erythroid colony formation in vitro. This inhibitor seems to exert its effect on erythroid progenitors at or beyond the stage of differentiation of CFU- E, but not on erythroblasts.     

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

CGA-7 and HHF, two monoclonal antibodies that recognize muscle actin and react with adherent cells in human long-term bone marrow cultures

The CGA-7, a monoclonal antibody that reacts with smooth muscle cell actin but not with endothelial cell or fibroblast actin, and HHF, a monoclonal antibody that reacts with smooth muscle, skeletal muscle, and cardiac muscle actin, both recognize microfilaments present within adherent cells from actively hematopoietic human long-term marrow cultures. Macrophages, monocytes, and cultured marrow fibroblasts do not react with either antibody. These data suggest that the anti-actin antibodies may serve as useful markers for in vitro microenvironmental cells and lend support to the hypothesis that stromal cells from long- term marrow cultures are different from marrow fibroblasts and may constitute a unique cell lineage.     

The interaction of androgen and thyroid hormones in the submandibular gland of the genetically hypothyroid (hyt/hyt) mouse

The development and maintenance of granular convoluted tubule cells in the mouse submandibular gland (SMG) and the production of renin-1, renin-2, and epidermal growth factor (EGF) by these cells are under complex hormonal control. Hypophysectomy causes profound involution and loss of renin activity in this gland. We have shown previously that T4 acts synergistically with 5 alpha-dihydrotestosterone (DHT) to restore SMG morphology and renin-2 activity in hypophysectomized female mice. Investigating the mechanism of T4 and DHT interaction in the hypophysectomized mouse proved impractical, and in the present study we have used genetically hypothyroid (hyt/hyt) mice that carry the structural gene for renin-1 but not for renin-2. Levels of SMG renin-1 and EGF in hyt/hyt mice were less than 4% of those in euthyroid (hyt/+) littermates. Administration of a pharmacological dose of T4 (2.5 micrograms/g BW X day, ip) to male hyt/hyt mice for 18 days restored SMG renin-1 and EGF to near-normal levels. The weights of SMG, seminal vesicle, and epididymis were also lower in hypothyroid mice and increased in response to T4. The effect on SMG renin-1 and EGF of either DHT (150 micrograms/g BW every other day, sc) or T4 (0.025-2.5 micrograms/g BW.day, ip) was blunted in female hyt/hyt mice. A combination of DHT and T4 (0.1 microgram/g BW.day) that restored total circulating T4 and T3 to physiological levels acted synergistically to increase SMG renin-1 and EGF. The administration of 2.5 micrograms T4/g BW.day plus DHT for 7 days increased the specific activity of SMG renin-1 and EGF to levels approaching those in euthyroid littermates given the same treatment. T4 (0.1 microgram/g BW.day) did not alter the quantity or sedimentation characteristics of high affinity androgen-binding protein in SMG from female hyt/hyt mice and induced SMG renin-1 in Tfm/Y mice. Thus, T4 does not appear to exert its effect via the androgen receptor. The administration of DHT and T4 to female hyt/hyt mice produced lower circulating levels of both T3 and T4 than the same dose of T4 given alone, suggesting that DHT does not act by enhancing the conversion of T4 to T3. This study demonstrates that the interaction of T4 and DHT is not a pharmacological phenomenon, but occurs at doses of T4 that restore serum T3 and T4 in female hyt/hyt mice to normal or near-normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

TPA induces differentiation of purified human myeloblasts in the absence of proliferation

Normal granulocyte-monocyte progenitor cells have an absolute requirement for colony-stimulating factor (CSF) for proliferation and differentiation in vitro. In contrast, cells derived from acute myeloblastic leukemia patients are often defective in their response to CSF, but can be induced to undergo terminal differentiation by exposure to 12-o-tetradecanoyl phorbol-13-acetate (TPA) by a process that does not require cell proliferation. To investigate the relationship between TPA-induced leukemic cell differentiation and CSF-induced myeloid cell differentiation we investigated the effects of TPA on myeloblasts highly enriched from normal bone marrow and stable-phase chronic myeloid leukemia peripheral blood. TPA (10(-6)-10(-9) M) induced the rapid appearance of macrophage characteristics in the majority of myeloblasts in the absence of proliferation. The mechanisms of TPA- and CSF-induced myeloblast differentiation were compared by examining the requirement for DNA synthesis. Exposure of myeloblasts to CSF induced increased triatiated thymidine (3H-TdR) incorporation within a few hours, while TPA did not induce 3H-TdR incorporation by itself and was inhibitory to CSF-induced 3H-TdR uptake. This requirement for DNA synthesis was further investigated by reversibly inhibiting DNA synthesis by depleting intracellular polyamines with difluoromethylorinithine (DFMO). DFMO inhibited both CSF-induced proliferation and differentiation of myeloblasts, but had no effect on TPA-induced differentiation. These results demonstrate that the process of differentiation of myeloblasts induced by TPA is distinct from CSF-induced differentiation.     

Entrainment of vastus medialis complex activity differs between genders

Introduction: That the vastus medialis oblique (VMO) is a functional unit of the vastus medialis (VM) is disputed. Delayed VMO activation predicts patellofemoral pain, which has higher rates in women. Methods: Single MUs and surface electromyogram (EMG) were collected from the VMO and VM of 9 men and 9 women. Men were tested once; women were tested during 5 menstrual phases. Coherence was assessed for motor unit (MU) firings within and between the VM and VMO using multilevel logistic models to determine statistical significance. Results: Compared with women, men have 741% (MU pairs) and 256% (MU‐EMG pairs) greater odds of common drive (0–5 Hz ) coherent oscillations. MU pairs from the VMO and the dual VM/VMO complex have 228% and 212% greater odds of coherent oscillations in the beta band (15–35 Hz ) compared with VM pairs. Conclusions: The VM and VMO are neurologically different muscles; control of the VM complex is sexually dimorphic. Muscle Nerve 53 : 633–640, 2016     

Should peritoneal dialysis catheters be removed at the time of kidney transplantation?

Background:

Delayed graft function (DGF) following transplantation necessitates support in the form of hemodialyis (HD) or peritoneal dialysis (PD). However, post-transplant PD-related complication and failure rates are unknown.

Methods:

We studies patients who were on PD at the time of kidney transplantation over a 4-year period at two separate institutions.

Results:

Of the 137 PD patients, 19 had their catheters removed at the time of transplant. Of the remaining 118 patients, 89% had immediate graft function. PD-related complications in this group included peritonitis (n=5), catheter-related infections (n=2) and emergency laparotomy (n=1). Of the 15 patients requiring post-transplant PD, 33% developed peritonitis and 20% had fluid-leaks necessitating HD. Overall, leaving a PD catheter in situ post- transplantation is associated with 7% rate of peritonitis versus 0% if removed (p < 0.05).

Conclusions:

PD catheter removal should be considered at the time of renal transplantation, as postoperative PD-related failure/complication rates are high.     

Intra-aneurysm pressure measurements in successfully excluded abdominal aortic aneurysm after endovascular repair

PURPOSE: This study was performed to determine intra-aneurysm sac pressure of abdominal aortic aneurysm after endovascular aneurysm repair in patients considered successfully treated with aneurysm shrinkage and absence of endovascular leakage. METHODS: In 10 patients with median aneurysm shrinkage of 12 mm (range, 7 to 22 mm) and median follow-up of 19 months (range, 14-43 months), a percutaneous translumbar intra-aneurysm pressure measurement was made with a 0.014-inch guide wire-mounted pressure sensor and compared with intra-aortic pressure. RESULTS: Median intra-aneurysm systolic/diastolic/mean pressure was 19/18/19 (range, 17-35/13-33/17-31) compared with median intra-aortic pressure of 135/75/99 (range, 126-199/60-95/84-129). Mean intra-aneurysm pressure was 20% of mean intra-aortic pressure (range, 13%-33%). Pulsatility was negligible. CONCLUSION: Successful endovascular aneurysm repair of abdominal aortic aneurysm results in considerable pressure reduction in the aneurysm sac. The ability to monitor intra-aneurysm pressure provides hemodynamic information within the sac, which can be used in conjunction with imaging to determine whether a secondary intervention is warranted.