Immunohistochemical renin study of DES-induced renal tumor in the Syrian hamster

Diethylstilbestrol (DES) treatment of a male Syrian hamster resulted in the development of a renal tumor and its widely scattered scrosal metastases. Cells in both the primary tumor and metastatic nodules contained secretory granules. The tumors were transplanted serially into DES-supported and non-DES-supported host hamsters until DES-independent tumors developed. Rabbit antiserum to mouse salivary renin and rabbit antiserum to rat kidney resin were reacted with sections of the primary tumor, metastatic nodules, and all transport tumors. The sections were stained by the PAP and Vector-ABC-AP procedures. Renin-positive material was observed in all tumors. Plasma renin activity (PRA) was determined for the host hamsters carrying the renal tumor transplants and compared to the PRA values that had been determined for normal non-DES-treated male and female hamsters. It was found that the average PRA values of host hamsters carrying the tumor transplants were significantly higher than the normal PRA ralues.     

Sensory inputs from the oral region to the cerebral cortex in behaving rats: an analysis of unit responses in cortical somatosensory and taste areas during ingestive behavior

1. The responses of 90 cortical neurons in the somatosensory and gustatory areas were recorded with chronically implanted fine wires in freely moving Wistar rats. The responses were analyzed mainly while the animals were freely licking solutions and eating dry pellets. Cortical neurons were classified into several groups according to their response properties. 2. "Mechanosensitive" neurons (n = 20) showed rhythmic phasic activity in different phases of the licking cycle, depending on the location of their receptive field in the peripheral orofacial region. 3. "Movement-related" neurons (n = 27) changed their activities tonically during licking, chewing, or grooming behavior. The responses were either excitatory or inhibitory. Receptive fields and adequate stimuli could not be identified. These neurons might receive somatosensory (except light tactile) inputs from wide or deep areas of intra- or perioral regions, or might be related to orofacial active movement. 4. "Taste" neurons (n = 35) increased or decreased their discharge rates during licking of particular taste solutions. Some taste neurons received convergence from somatosensory inputs. 5. "Temperature" neurons (n = 2) responded exclusively to water of temperatures lower or higher than room temperature. The responses were opposite in direction between cold and warm stimuli. 6. "Anticipation" neurons (n = 4) increased their impulse discharges before the start of licking in the situation in which the animal expected access to the drinking tube. 7. "Attention" neurons (n = 2) responded to arousal stimulation such as sound, a flash of light, and body touch. These neurons showed only a slightly increasing response during ingestive behavior. 8. The locations of 56 of 90 units were histologically identified. Mechanosensitive neurons were located in the appropriate parts of the somatotopic pattern within the primary somatic sensory area in the granular cortex. Taste neurons were found evenly in the dysgranular cortex and the agranular insular cortex. Other types of neurons were located mainly in the dysgranular cortex between the granular cortex and agranular insular cortex, and some were intermingled with taste neurons in the agranular insular cortex. 9. The present study has shown that cortical neurons in the orolingual somatosensory and taste areas have different response characteristics related to each aspect of ingestive behavior.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in human colonic epithelia and exert an antimicrobial effect

The hypotensive and vasorelaxing peptides adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), were found to be distributed on the surface of the colonic mucosa. AM and PAMP showed dose-dependent antimicrobial activity against E. coli. The results suggest that the novel vasoactive peptides AM and PAMP play an important role in mucosal defence.     

Atypical Glomus Tumor in the Mediastinum: A Case Report with Immunohistochemical and Ultrastructural Studies

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small “glo-moid” cells arranged in organoid and hemangiopericytoma-like patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

C3-independent immune haemolysis: mechanism of membrane attack complex formation

The isolated active complex of C5 and C6, C56, was found to bind to EAC142 in the absence of C3 or C7, and to form a unique intermediate, EAC14256, which is susceptible to lysis by the addition of C7, C8 and C9. Further studies revealed that C56 alone could bind to EAC142 but not to E, EA, EAC1 or EAC4, nor to EAC14 in the absence of C7, that the C56 binding to EAC142 was highly dependent on temperature and on the ionic strength of the buffer, and that the degree of EAC14256 formation from EAC142 and C56 depended on the amount of C2 on EAC142 and on the amount of added C56. These findings suggest that C2 or C42 on EAC142 may be an acceptor for C56. In addition, C56 appears to bind to EAC142 much more efficiently than to unsensitized erythrocytes, even in the presence of C7. Thus, binding of C56 to EAC142 is likely to be an initial step of membrane attack complex formation in C3-independent immune haemolysis.     

Effect of intracellular dialysis of ATP on the hyperpolarization-activated cation current in rat dorsal root ganglion neurons

The mechanism of the effect of intracellular ATP on the hyperpolarization-activated non-selective cation current (Ih) in rat dorsal root ganglion neurons was investigated using a whole cell voltage-clamp technique. Under voltage-clamp conditions, Ih was activated by hyperpolarizing pulses raised to a voltage of between -70 and -130 mV. The activation curve of Ih in rat dorsal root ganglion (DRG) neurons shifted by about 15 mV in the positive direction with an intracellular solution containing 1 mM cAMP. When ATP (2 mM) was applied intracellularly, the half-maximal activation voltage (Vhalf) of Ih shifted from -97.4 +/- 1.9 to -86.8 +/- 1.6 mV, resulting in an increase in the current amplitude of Ih by the pulse to between -80 and -90 mV. In the presence of an adenylate cyclase inhibitor, SQ-22536 (100 microM), the intracellular dialysis of ATP also produced a shift in the voltage-dependence of Ih in rat DRG neurons, indicating that the effect of ATP was not caused by cAMP converted by adenylate cyclase. Intracellular dialysis of a nonhydrolysable ATP analog, AMP-PNP or ATP-gamma-S, also produced a positive shift in the voltage-dependence of Ih activation, suggesting that the effect of ATP results from its direct action on the channel protein. These results indicate that cytosolic ATP directly regulates the voltage dependence of Ih activation as an intracellular modulating factor.     

Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpoint

Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1-F-box). It forms an adapter bridge between Cullin-1 and the substrate-determining component, the F-box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3-D structure of human Skp1 suggested that the mutants would be compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope-tagged, and co-immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1(ts) suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3Delta and skp1(ts), implicating a novel role for Skp1 in the checkpoint-signalling cascade.     

Interaction between poly(L-lysine) and sulfated poly(vinyl alcohol)

Ionic polymer-polymer interaction was studied in aqueous solution for poly(L -lysine) (PLL) and sulfated poly(vinyl alcohol) (PVS) as functions of pH, the degree of sulfation, the functional unit mole ratio of the two polymers and temperature by means of circular dichroism and viscosity measurements. In all the cases studied, strong inter-polymer complexes were formed at the functional unit mole ratio (VS)/(LL) higher than 1. Although PLL itself is well known to take the α-helical conformation at such a high pH as 11, the PLL conformation in the PLL/PVS complexes did not depend on pH but on the degree of sulfation: at room temperature, PLL took random coil conformation in PLL/PVS-25 (25: degree of sulfation in mole-%) and PLL/PVS-30, and the α-helical conformation (helicity of 70%) in PLL/PVS-46 and PLL/PVS-95. Models for the complex structures are postulated. Methanesulfonic acid did not influence the conformational transition of PLL, supporting that a polymer effect took place in the complex formation between PLL and PVS. Thermal effect on the PLL conformation in the complex is also discussed.