Antigen preservation in infarcted lymphoid tissue. A novel approach to the infarcted lymph node using monoclonal antibodies effective in routinely processed tissues

We studied 11 cases of malignant lymphoma diagnosed concurrently with or following lymph node infarction. Cases included seven B-cell lymphomas, three T-cell lymphomas, and one case of Hodgkin's disease. Sections of viable and infarcted tissue were immunostained in parallel using a panel of antibodies effective in routinely processed, wax-embedded tissue. The panel included anti-leucocyte-common antigen (CD45), T-cell-associated antigens (UCHL1, MT1), B-cell-associated antigens (MB1, 4KB5 (CD45R), MT2, LN1), a B-cell-specific antigen (L26), C3D-1 (CD15), and BER-H2 (CD30). Antibodies to intermediate filament cytoskeletal proteins, epithelial membrane antigen, and Factor VIII-related antigen were also used. In eight cases, staining of the infarcted material gave evidence of a lymphoid proliferation of either T- or B-cell type; an in the case of Hodgkin's disease, the results supported this diagnosis. The immunophenotype derived in the infarcted tissue mirrored the findings in the viable material in these eight cases of non-Hodgkin's lymphoma. A case of testicular infarction with concurrent intraosseous lymphoma was also examined. Staining in this case provided evidence of infarcted lymphoma. Thus, immunostaining of infarcted lymphoid tissue with these novel antibodies provides valuable information that conventional light microscopy cannot offer.     

Fournier''s gangrene of the scrotum following day case vasectomy.

A case of Fournier's gangrene of the scrotum is reported in a 31-year old man who had outpatient vasectomy during an intercurrent diarrheal illness. The surgery was done through a midline incision, under local anesthesia of plain 2% lignocaine, with a preoperative chlorhexidine scrub. Although his scrotum was red and swollen within 3 hours, he did not have medical care until admission to hospital 48 hours later. At admission he had Fournier's gangrene of the scrotum and penis, Gram-negative septic shock, and acute renal failure. In the intensive care unit he was treated with continuous dialysis, parenteral metronidazole, benzylpenicillin, Ceftazidime and inotropes. He had a cardiorespiratory arrest after emergency radical debridement. After resuscitation he developed adult respiratory distress syndrome and disseminated intravascular coagulation. Pathological exam showed necrosis of the dermis and subcutaneous layers, thrombosis and beta-hemolytic streptococci. After adding gentamicin and vancomycin, 2 weeks of ventilator care, 4 more surgical debridements, a left orchidectomy, and a despite a grossly abnormal EEG recording, the man regained consciousness and recovered. His scrotal and penile skin re-epithelialized over 3 months. Patients requesting vasectomy should be assessed for local and systemic illness before performing the procedure.     

Regulation of fluid intake in dogs following water deprivation

Whereas water loss in land living animals occurs continuously, water intake takes place discontinuously. At the normal operating set point of plasma osmolality, urine is more concentrated than plasma due to secretion of vasopressin. Thus animals operate around a state of mild dehydration. As water loss occurs, the severity of dehydration and thirst increase in intensity and at some point water intake occurs. Sufficient water is consumed to return plasma osmolality to the normal operating set point. Food intake and water balance are interdependent as food provides the osmoles which determine obligatory renal solute excretion. When dry food with the same osmotic content was substituted for canned food (water content 74%), dogs increased water intake from 24.2 +/- 4.3 to 62.2 +/- 8.8 ml/kg. Urine output and urine osmolality were unchanged, as under conditions of normal hydration, near maximal urine concentration is achieved. Changing water intake is the only available variable to maintain water balance. During water deprivation, the major renal mechanism appears to be natriuresis. In rehydration, satiety mechanisms ensure appropriate water intake and renal sodium conservation restores sodium balance.     

Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.     

Immunophenotype predicts radiation resistance in T-lineage acute lymphoblastic leukemia and T-lineage non-Hodgkin's lymphoma.

In the preclinical arm of our study, the radiobiologic features of primary malignant cells from newly diagnosed and relapsed T-lineage acute lymphoblastic leukemia/non-Hodgkin's lymphoma patients were analyzed using clonogenic assays. A marked heterogeneity existed relative to the intrinsic radiation sensitivity of clonogenic T-lineage ALL/NHL cells from 42 patients. The mean SF2 (surviving fraction at 200 cGy) and alpha values (initial slope of the survival curve) were 0.36 +/- 0.04, and 0.558 +/- 0.079 Gy-1. Fourteen cases had SF2 values of > or = 0.50 and alpha values of < or = 0.2 Gy-1, consistent with a marked intrinsic radiation resistance at the level of clonogenic leukemia/lymphoma cells. Of these 14 radiation resistant cases, 12 were CD3+. Furthermore, the SF2 and D0 values of the 28 CD3+ cases were significantly higher than the SF2 and D0 values of the 14 CD3- cases (SF2: 0.441 +/- 0.048 versus 0.189 +/- 0.045, p = 0.002; D0: 189.6 +/- 26.3 cGy versus 108.7 +/- 18.2 cGy, p = 0.047) and CD3+ cases had smaller alpha values than CD3- cases (0.454 +/- 0.087 versus 0.765 +/- 0.152, p = 0.06). Thus, clonogenic cells from CD3+ T-lineage ALL/NHL patients were more resistant to radiation than clonogenic cells from CD3- T-lineage ALL/NHL patients. In the clinical arm of our study, 33 T-lineage ALL/NHL patients received autologous bone marrow transplants during remission. Pretransplant conditioning consisted of total body irradiation combined with high dose chemotherapy. The expression of CD3 antigen predicted the outcome of relapsed T-lineage ALL/NHL patients undergoing autologous bone marrow transplantation following total body irradiation plus high dose chemotherapy. Overall, the Kaplan-Meier estimate and standard error of the probability of remaining in remission at 3.5 years was 11 +/- 9% with a median relapse-free interval of 102 days. The disease-free survival at 3.5 years was 8 +/- 7% with a median disease-free survival time of 96 days. Notably, the expression of CD3 antigen on T-lineage ALL/NHL cells correlated with the probability of relapse after bone marrow transplantation. While 16 of 19 CD3+ patients relapsed after bone marrow transplantation, only 3 of 8 CD3- patients relapsed. The Kaplan-Meier estimates and standard errors of the probability of remaining in remission at 1 year after bone marrow transplantation were 7 +/- 6% (median relapse-free interval = 74 days) for CD3+ patients (n = 19) and 63 +/- 17% for CD3- patients (n = 8) (p = 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)