Biomedical subjects
Publications and source records attributed to C J Cohen.
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Tetrodotoxin (TTX) block of cardiac sodium channels was studied in rabbit Purkinje fibers using a two-microelectrode voltage clamp to measure sodium current. INa decreases with TTX as if one toxin molecule blocks one channel with a dissociation constant KD approximately equal to 1 microM. KD remains unchanged when INa is partially inactivated by steady depolarization. Thus, TTX binding and channel inactivation are independent at equilibrium. Interactions between toxin binding and gating were revealed, however, by kinetic behavior that depends on rates of equilibration. For example, frequent suprathreshold pulses produce extra use-dependent block beyond the tonic block seen with widely spaced stimuli. Such lingering aftereffects of depolarization were characterized by double-pulse experiments. The extra block decays slowly enough (tau approximately equal to 5 s) to be easily separated from normal recovery from inactivation (tau less than 0.2 s at 18 degrees C). The amount of extra block increases to a saturating level with conditioning depolarizations that produce inactivation without detectable activation. Stronger depolarizations that clearly open channels give the same final level of extra block, but its development includes a fast phase whose voltage- and time-dependence resemble channel activation. Thus, TTX block and channel gating are not independent, as believed for nerve. Kinetically, TTX resembles local anesthetics, but its affinity remains unchanged during maintained depolarization. On this last point, comparison of our INa results and earlier upstroke velocity (Vmax) measurements illustrates how much these approaches can differ.
The relationship between membrane potential (Em) and the potassium equilibrium potential (EK) was investigated in hypoxic guinea pig papillary muscle. After more than 8 hours of hypoxia, cells with near normal Em (-86.2 +/- 0.9 mV) and action potentials were observed. However, the intracellular potassium concentration ([K+]i) based on chemical analysis and the assumption that potassium was homogeneously distributed was 41.8 +/- 4.3 mM; the apparent EK was -55.7 +/- 2.9 mV, significantly positive to Em. Measurements with potassium ion-selective microelectrodes revealed that prolonged hypoxia results in at least two populations of cells with different characteristics. The first population had an intracellular potassium activity (aiK) of 101.5 +/- 1.9 mM, and EK was 4.7 mV negative to Em. In contrast, EK was 33.4 +/- 1.3 mV negative to Em in the second population. These cells also exhibited a reduced sensitivity to changes in bath potassium, and calculations suggest aiK was about 18 mM. The existence of cell populations with a near normal and very low aiK can explain the intermediate value of [K+]i calculated assuming a homogenous potassium distribution. Cells with near normal Em and action potentials represent the population with near normal aiK. Hypoxia may also cause non-uniform changes in other cellular characteristics.
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An unusual case of brochial carcinoid tumor with skin and bilateral metastases is presented. Histochemical stains and electronmicroscopic findings confirmed the diagnosis. The peculiar pathologic features and unique clinical characteristics are described.
Leukocyte migration studies with amniotic fluid (AF) were performed in 47 pregnant women and 24 control patients. Previous reports about the enhancing effect of AF on leukocyte migration during pregnancy were confirmed (p less than 0.003). No enhancing effect was observed with first-trimester leukocytes. Maximal enhancement occurred during the second trimester (p less than 0.0001). It decreased during the third trimester (p less than 0.01) and lost significance in the postpartum period (p less than 0.072). Fifteen pregnant and control patients were investigated with autologous plasma. Leukocyte migration enhancement (LME) was significant with pregnancy plasma (PL) (p less than 0.03). Again LME was the largest during the second trimester (p less than 0.006). It is concluded that an immunologically active factor is present in AF and PL which in term induces the enhancing activity of a predetermined effector cell subgroup. This process is absent in conjunction with male leukocytes and is lacking in the majority of patients with toxemia of pregnancy.
Leukocyte migration enhancement (LME), a common denominator of pregnancy and malignancy, was investigated in order to determine the immunologic factors and processes involved in this in vitro assay. Reproducibility of results was confirmed by parallel investigations of single patients in an independent laboratory. Preliminary evidence also suggests that the phenomenon of LME is observable not only with the leukocyte migration assay, as performed in the present study, but also with the "indirect" migration inhibitory factor (MIF) assay. Highly significant correlation between results obtained with plasma (PL) and amniotic fluid (AF) was observed (p less than 0.00089). No significant correlation between LME and IgG concentrations as well as complement (C3) concentrations in AF and PL could be detected. C3 concentrations correlated significantly to gravity (p less than 0.007) and parity (p less than 0.003). No immune complexes were detected in either AF or PL samples. An unspecific protein effect as the cause of LME was ruled out in showing no significant correlation between LME and protein concentrations of AF and PL. A highly significant correlation between antigen concentration in PL and migration area was demonstrated (p less than 0.00001). It is suggested that leukocyte migration inhibition (LMI) represents a state of antigen excess, while LME represents antibody excess. Through selective removal of the IgG immunoglobulins LME could be converted into LMI, indicating an IgG subfraction as the responsible immunoglobulin in the phenomenon of LME.
Two patients with measurable recurrent endometrial adenocarcinoma achieved complete remission proven by second-look operation. Both patients were treated with a combination of melphalan, 5-fluorouracil and medroxyprogesterone acetate.
The pseudo-Meigs syndrome is clinically important because it resembles metastatic pelvic cancer. However, the prognosis is much more favorable when the syndrome is associated with a benign tumor. The authors point out that a woman with this condition can expect full recovery after surgery.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Two patients with advanced adenocarcinoma of the fallopian tube were treated with cis-diamminedichloroplatinum, adriamycin, and progestins. Cyclophosphamide was added to the treatment of 1 patient. Both regimens achieved surgically proved complete remission. No severe drug-related toxicity occurred.
A dysgerminoma of the left gonad exhibiting malignant features was diagnosed at laparotomy in a 33-year-old virginal phenotypic female who had a normal menstrual history. Pathologic examination of the contralateral (right) gonad revealed an ovotestis. The nonaffected residual portion of the tumor-bearing left gonad exhibited only ovarian stroma. The ovotestis was characterized by a nodule of testicular parenchyma composed of partly hyalinized seminiferous tubules without evident spermatogenesis. The ovotestis was contiguous to normal ovarian elements, including a cystic corpus luteum and primordial follicles. Proliferative endometrium was found lining the small uterus. The findings are indicative of true hermaphroditism. The occurrence of dysgerminoma and other tumors in association with various forms of gonadl dysgenesis is discussed. To the authors' knowledge, this is the first reported case of dysgerminoma occurring in a phenotypic female hermaphrodite.
Three patients with advanced endometrial adenocarcinoma achieved prolonged clinical remission by treatment with hormonal and cytotoxic chemotherapy. Second-look surgery was employed to determine complete remission. Our preliminary experience with this procedure in patients with endometrial carcinoma is described.
Amniotic fluid was found to cause significant leukocyte migration enhancement during the second and third trimester of pregnancy and in the early postpartum period when compared to the migration area obtained with an ovarian tumor homogenate antigen (p less than 0.01), choriocarcinoma spent medium (p less than 0.01), and placental pool homogenate (p less than 0.01). Only borderline significance (p less than 0.1) was obtained when migration enhancement with AF was compared between pregnant and nonpregnant female control patients, indicating minimal unspecific activity of AF. Migration enhancement with autologous amniotic fluid was slightly larger than with homologous amniotic fluid, but the difference did not reach significance (p less than 0.4). None of the control antigens caused migration enhancement; placental pool homogenate in concentrations above 4 mg. per cent caused migration inhibition but did not in lower concentrations. The enhancing effect of AF could be abolished by dilution but not by addition of excessive antibody to estrogen of HCG. It is suggested that a blocking factor is present in AF preventing recognition of fetoplacental antigen by the maternal immune system. Thus in vitro leukocyte migration enhancement may correlate to in vivo graft enhancement.