In chloralose-urethane anesthetized spinal rats, electrical stimulation of systematically chosen points over the entire caudal brain stem area was carried out to explore the site(s) responsible for vagally mediated bradycardia. A dorsomedial locus including the nucleus dorsalis and the adjacent structures, the nucleus tractus solitarius, the nucleus commissuralis and the area postrema, and a ventrolateral locus around the nucleus ambiguus were found to elicit bradycardia with low threshold and high responsiveness. In another series of experiments, horseradish peroxidase (HRP) was iontophoretically administered through a glass capillary microelectrode into the identified cardiac branch of the vagus nerve of rats in order to localize more precisely the cells of origin of vagal cardioinhibitory fibers within the brain stem. Distribution of the HRP-labeled cells was not confined to one area, but these cells were found within the nucleus dorsalis, the reticular formation surrounding the nucleus ambiguus and an intermediary zone between the two nuclei. Such a pattern of distribution of vagal cardioinhibitory preganglionic cells is discussed in relation to phylogenetic and ontogenetic development of the vagal motor nuclei.

In chloralose- and urethan-anesthetized rats, the cardiac branch (CB) of the vagus nerve was electrically stimulated, and antidromic responses of medullary cells were recorded. The cells identified as the vagal cardiac preganglionic neurons (VCPN) were localized in the dorsal motor nucleus (ND group, 8 cells), a region in and around the nucleus ambiguus (NA group, 7 cells) and an intermediary zone (IM group, 2 cells) lying in between. Latencies of the antidromic responses were distinctly different among the three groups, and calculated conduction velocities indicated that the VCPN of the ND group possess C-fiber axons whereas those of the NA group and probably of the IM group, B-fiber axons. In another series of experiments, the right carotid sinus nerve (CSN) or the left cervical vagus nerve was stimulated, and efferent fiber group(s) mediating reflexly evoked discharges to the CB was determined by means of two-point recordings. Among reflex discharges evoked by stimulation of the CSN the shortest latency reflex was proved to be mediated by B-efferent fibers. In contrast, among reflex discharges evoked by stimulation of the vagus nerve, the greatest reflex component was found to be conveyed by C-efferent fibers. It was concluded that the VCPN consist of two types of cells, each located in a different region of the medulla oblongata and contributing to vagal cardiac reflex mechanisms in a different manner.

In chloralose-urethane anesthetized rats, compound spike potentials provoked in the cervical vagus nerve with electrical stimulation of the central cut end were found to consist of three major groups, A, delta-B and C. A remarkable cardioinhibition was observed on repetitive stimulation of the vagus nerve with an intensity which gave rise to the delta-B spike potential group. However, when the stimulus intensity was increased further beyond the level where the delta-B potential group had reached the maximum, the potency of cardioinhibition continued to be reinforced with the development of the C potential group. Selective activation of C fibers by anodal block of conductions along A and delta-B fibers was still associated with a considerable degree of cardioinhibition. These findings indicate that activities of both C fibers and delta-B fibers contribute to vagal cardioinhibition in rats and the view that the vagal cardioinhibition is mediated by B fibers, although valid in cats, can not be held applicable to all species of mammalians.

The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)

1. Anatomical pathways and natures of reflex as well as spontaneous activities of cardiac sympathetic nerves (CNs) were investigated in rats. 2. Anatomically, the stellate CNs on both sides provide a major sympathetic supply to the rat heart with additional contribution of the thoracic CNs on the left side. 3. Functions of these CNs were studied in chloralose-urethane anesthetized and artificially ventilated rats. Electrical stimulation of these CNs produced an increase in heart rate and a rise in blood pressure. The increase in heart rate was more potent on the right-side stimulation, while the rise in blood pressure was greater on the left-side stimulation. 4. Stimulation of the aortic depressor nerve (ADN) inhibited spontaneous discharges of the CN for a longer period as compared with those of the cervical postganglionic sympathetic nerve (CSN). On the other hand, stimulation of the sural nerve produced a longer lasting reflex increase in discharges of the CN as compared with that of the CSN. These findings suggest that cardioregulatory sympathetic outflow is more affected by visceral and somatosensory input than is the other sympathetic outflows. 5. Spontaneous discharges of both nerves showed a rhythmicity associated with heart beats. Although the magnitude of this rhythmicity was not clearly different between these two nerves, the time from bottom to peak firing level of the phasic discharges of the CN was significantly longer than that of the CSN. This finding is consistent with the longer lasting effect of the ADN stimulation on the CN discharges.Since the cardiac nerve (CN) innervates the heart, including the conduction systems, myocardium and coronary arteries, its function can be regarded as purely circulatory and may differ from functions by the other sympathetic nerves. This assumption stems from the view that the activities of different sympathetic nerves show a non-uniform pattern NINOMIYA et al., 1970NINOMIYA et al., , 1971