Modulatory synaptic actions of an identified histaminergic neuron on the serotonergic metacerebral cell of Aplysia

Possible sources of excitatory synaptic input to the serotonergic metacerebral cell (MCC) were determined by stimulating various neurons in the cerebral ganglion. Firing of the previously identified histaminergic neuron C2 was found to produce synaptic input to the MCC. The synaptic input consists of fast excitatory-inhibitory synaptic potentials on a background of a slow EPSP. The slow EPSP appears to be monosynaptic and chemically mediated since it persists in a solution of high divalent cations; broadening of the presynaptic spike enhances the EPSP; the size of the EPSP is a function of the Mg2+ and Ca2+ concentrations of the bathing solution; and the EPSP can be mimicked by application of histamine to the MCC. The slow EPSP, in addition to firing the MCC, can increase the excitability of the cell, even under conditions in which C2 is fired at a rate too slow to produce a measurable EPSP when the MCC is at rest potential. This property appears to be due to the fact that the slow EPSP results from an apparent decrease of membrane conductance so that the size of the EPSP increases markedly as the cell is depolarized, and the EPSP appears to be highly voltage-dependent so that it is small or absent close to the rest potential of the MCC. When the MCC is voltage-clamped, application of histamine to the bath results in an inward current that disappears when the MCC is hyperpolarized. The potential at which the histamine-induced current reverses or disappears is dependent on the concentration of external potassium, suggesting that, at least in part, the slow EPSP is due to a decrease of potassium conductance. The data on C2 are consistent with its being an element of the neuronal system that mediates a state of food arousal in Aplysia.     

First-year results of routine alpha-fetoprotein testing on prenatal patients in a family practice

For one year all pregnant women presenting to a family practice clinic for prenatal care were routinely tested for maternal serum alpha-fetoprotein levels (MSAFP). Unexpectedly, 14 (15.7 percent) of 89 tested patients had low MSAFP levels. All 14 pregnant women underwent appropriate diagnostic workups because of the low MSAFP level and were subsequently followed until delivery. Although the literature reports that low MSAFP levels are associated with chromosomal anomalies, none of the 14 women were delivered of infants with anomalies. Reasons for the unexpectedly high rate of abnormal MSAFP levels were investigated. Investigation revealed that normal values for MSAFP tests had been derived from testing performed on high-risk pregnant women who had an inherently higher rate of abnormal pregnancies and, apparently, a different range for normal MSAFP levels than a population of unselected family practice patients. The results of this study demonstrate that it may not be appropriate to apply diagnostic algorithms based on data derived in high-risk subspecialty clinics to unselected patients in a family practice.     

Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation.

Synovial sarcoma demonstrates epithelial differentiation, either by light microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural methods only (monophasic) and poorly differentiated synovial sarcoma. Although the glands of synovial sarcoma are known to have tight junction-like structures, far less is known about junction formation in the spindled component of synovial sarcomas. Additionally, it is unknown whether the tight junctions of synovial sarcoma are normally constituted. The tight junction is a multiprotein complex consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using commercially available antibodies, heat-induced epitope retrieval and standard avidin-biotin technique. When available, corresponding electron micrographs were reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT-SSX2 (two cases) gene fusion was known. Positive cases showed particulate membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1 (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal glandular epithelia, at the apical portion of the lateral membrane. The spindle cells of biphasic synovial sarcomas showed abnormal circumferential membranous expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8). By electron microscopy, recognizable tight junctions were seen only in glands. No correlation was seen between histologic subtype or fusion type and expression of tight junction proteins. We conclude that the glands of biphasic synovial sarcomas show well-organized, true epithelial tight junctions. In contrast, the spindled cells of all synovial sarcomas show significant abnormalities in the expression and localization of tight junction proteins, suggesting partial and/or aberrant epithelial differentiation.     

Hypersensitivity reactions.

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity.