Cardiovascular and pupillary light reflexes in subjects with abnormal glucose tolerance

It is well known that in diabetes mellitus autonomic neuropathy frequently develops. This is usually determined by the cardiovascular reflex. Furthermore, even in borderline cases that have not become overt diabetes, we have already reported the presence of autonomic neuropathy as assessed by the pupillary light reflex. However, a relationship between the impairments of the cardiovascular and pupillary light reflexes is not clear, especially in people with abnormal glucose tolerance. In the present study diabetics were divided into three groups according to the results of their cardiac beat-to-beat variation (BBV) tests and Schellong tests; group I had no abnormality of these cardiovascular reflexes, group II had abnormal BBV scores and normal Schellong test scores, and group III had abnormal responses to both tests. People with borderline diabetes (B-DM) were free from any impairment of their cardiovascular reflexes. We examined their pupillary light reflexes. Age-matched non-diabetics were also studied as a control. The following results were obtained. (1) Compared to controls, (a) diabetics, but not borderline diabetics, had smaller pupils before photic stimulation (A1) and lower maximum dilatation velocities (VD). These illustrate sympathetic function; (b) diabetics and borderline diabetics had lower amplitudes of constriction (A3) and maximum constriction velocities (VC). These illustrate parasympathetic function; (c) borderline diabetics and those diabetics belonging to group III experienced a lower pupillary constriction rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination Treatment with Irritant and Recombinant Interleukin 2 in the Peritoneal Cavity for Evoking Effective Anti-tumor Activity: Generation of Lymphokine-activated Killer Cells and Tumor-specific Killer Cells

Meth A sarcoma, growing in the subcutaneous tissue of syngeneic BALB/c mice, regressed completely after an intraperitoneal (ip) injection of protease peptone (PP) (on day 6) followed by 2 ip administrations (on days 7 and 8) of human recombinant interleukin-2 (IL-2, 25 μg/day), whereas one such treatment alone had little effect on the tumor growth. While this combination treatment was effective in anti-asialo GM1 antibody-treated mice, no such effect was noted in T cell-depleted ATXFL (thymectomized, irradiated and fetal liver cell-reconstituted) mice. These results show that T cells are mainly responsible for this antitumor effect. Treatment with a combination of PP and IL-2, but not with either PP or IL-2 alone, resulted in a marked increase in the T cell population in the peritoneal cavity after the treatment. At an early stage after the combination treatment, both peritoneal exudate cells (PEC) and spleen cells exhibited killing activity with a promiscuous specificity. However, at a later stage, 7 days after the treatment, Meth A-specific killer activity was observed in both PEC and the spleen. Meth A rechallenge was rejected by the mice in which the tumor had regressed, but the antigenically different Meth 1 was accepted by them. A similar result was obtained in Winn's neutralization test. These results suggest that this combination treatment, which is effective in the generation of lymphokine-activated killer cells in the peritoneal cavity, finally resulted in the induction of tumor-specific killer cells in the periphery. These results clearly show the anti-tumor efficacy of combination treatment with PP and rIL-2.     

Platelet size and function in septic rats: changes in the adenylate pool

Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.     

The distribution of vasopressin- or oxytocin-neurons projecting to the posterior pituitary as revealed by a combination of retrograde transport of horseradish peroxidase and immunohistochemistry

The distribution of vasopressin (AVP)-containing or oxytocin (OXT)-containing neurons in the rat hypothalamus which project to the posterior pituitary was revealed by the combination of retrograde tracing of horseradish peroxidase (HRP) and immunohistochemistry. The majority of magnocellular neurons labeled with HRP were located in some of the hypothalamic nuclei, including the supraoptic nucleus and paraventricular nucleus. Many of these neurons were also immunostained by anti-AVP or anti-OXT. On the other hand, some of the immunostained neurons were not labeled with HRP in the dorso-medial and the most caudal parts of the paraventricular nucleus. These data confirmed previous reports concerning the distribution of AVP- or OXT-neurons projecting to the posterior pituitary, as a more direct visualization of both the neuropeptides and the retrogradely transported HRP in the same tissue section was attained. In addition, some of the HRP-labeled perikarya which seemed to have direct contact with the ventricular lumen were occasionally seen; its functional significance is discussed.     

Nicotinic acetylcholine receptors in the rat stomach: I. (-)-[3H]nicotine binding

The nicotinic acetylcholine receptors in the rat stomach were characterized by means of a radioligand binding assay with (-)-[3H]nicotine as ligand. Saturation binding studies on the gastric fundus membranes revealed the presence of two binding sites with dissociation constant (KD) values of 3.1 and 289 nM, and maximum binding capacity (Bmax) values of 3.6 and 76 fmol/mg protein, respectively. The Bmax of the high affinity binding site was greatest in the cardia, followed by fundal mucosa, fundal muscle, and, finally antrum. The IC50 values of cholinergic drugs to inhibit (-)-[3H]nicotine binding in fundus membranes were as follows: (-)nicotine, 0.12 nM; cytosine, 9.3 nM; acetylcholine, 17.7 nM; carbachol, 700 nM; hexamethonium, 2270 nM. The IC50 values of alpha-bungarotoxin, d-tubocurarine and atropine were greater than 100 microM. The muscarinic acetylcholine receptors were also characterized with [3H]quinuclidinyl benzilate and the choline acetyltransferase activity was measured. These results suggest that nicotinic acetylcholine receptors as well as muscarinic acetylcholine receptors are present in the rat stomach and that the regional distribution of these receptors is uneven.