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Biomedical subjects

Y Kohno

Publications and source records attributed to Y Kohno.

At least 289 records · Page 16Linked to original sources

A unidirectional carrier effect.

A surprising unidirectional carrier effect has been observed in the antibody response to myoglobin-ferritin conjugate. This conjugate serves as a hapten-carrier complex for myoglobin-specific T cells to help ferritin-specific B cells make anti-ferritin antibodies, but it does not function for ferritin-specific T cells to help myoglobin-specific B cells to make anti-myoglobin. Therefore, myoglobin-ferritin does not bypass the Ir gene defect of low responders to myoglobin. In contrast, myoglobin-fowl gamma-globulin does induce anti-myoglobin antibodies in low responder mice and thus bypasses the Ir gene defect. Both complexes are covalently coupled. Since the myoglobin-ferritin conjugate serves for myoglobin-specific T cells to help myoglobin-specific B cells, the myoglobin in the conjugate is not altered in a way that would prevent recognition by myoglobin-specific B cells. Similarly, the conjugate serves for ferritin-specific helper T cells to help ferritin-specific B cells, so it can be recognized functionally by ferritin-specific T helper cells. Explanations such as unidirectional induction of or sensitivity to bystander help, or T-cell suppression, have been excluded. While the explanation for this unexpected observation is not yet certain, several possibilities are discussed to explain this novel phenomenon, which is believed to be the first example of such a unidirectional carrier effect between two proteins.

Animals↗

Correlation of intrathymic tolerance with intrathymic chimerism in neonatally tolerized mice.

T cell tolerance to alloantigens can be induced in neonatal mice by the injection of semiallogeneic adult spleen cells. The thymus of neonatally injected mice rapidly becomes specifically unresponsive to the alloantigens expressed by the injected cells, even though the level of chimerism in the thymus of such mice is reportedly marginal compared with that of the periphery. In this report, we have studied the immune reactivity and degree of chimerism in the thymuses of 24 neonatally injected mice. In 13 older mice, the proliferative response of the thymocytes from individual mice to the injected alloantigen varied from strong reactivity to complete tolerance. Interestingly, analysis by flow microfluorometry of the same thymocytes for the presence of the inoculated alloantigen revealed an inverse correlation. That is, the thymuses which had a greater degree of chimerism were tolerant and those with fewer or no detectable cells were partially or totally reactive. The thymuses of 11 younger neonatally injected mice were invariably tolerant to both the MHC and Mls alloantigens of the F1 inocula. Analysis by flow microfluorometry of the thymocytes of these mice revealed that significant numbers of F1 cells reside in the thymuses of mice injected as neonates with semiallogeneic cells. These cells represent a possible source of specific tolerogen for thymocytes during their intrathymic differentiation.

Aging↗

Monoclonal antibodies to thyroglobulin elucidate differences in protein structure of thyroglobulin in healthy individuals and those with papillary adenocarcinoma.

Monoclonal antibodies specific for human thyroglobulin (Tg) from normal subjects were prepared by the hybridoma technique. Antibodies from three clones (clones B2F, C6E, and C6G) were found to produce linear Scatchard plots, as predicted for homogeneous antibodies. Based on different patterns of cross-reactivity with Tg from various species, these monoclonal antibodies recognized different determinants on the Tg molecule. Moreover, antibodies from clone B2F bound simultaneously with clone C6E or C6G to Tg. Therefore, antibody from clone B2F must bind to a site on Tg distant from those recognized by clone C6E or C6G. The monoclonal antibodies C6G and C6E bound almost equally to normal Tg and Tg from patients with Graves' disease, adenoma, follicular carcinoma, and papillary adenocarcinoma. In contrast, whereas clone B2F bound equally well to normal Tg and Tg from patients with Graves' disease, adenoma, and follicular carcinoma, this clone bound poorly to Tg from patients with papillary adenocarcinoma. Since the binding activity of clone B2F for unfolded or degenerated Tg was remarkably decreased, these differences in binding activities to native Tg may reflect changes in conformation of the Tg molecule. Thus, the results indicate there may be conformational changes in Tg from patients with different thyroid diseases.

Adenocarcinoma, Papillary↗

[Dopamine-induced up-regulation of alpha 2-adrenoceptors in crude synaptic membranes of rat brain].

After cerebral cortical membranes were incubated with 0.1-100 microM of dopamine (DA) in 50 mM Tris-HCl buffer (pH 7.7) at 37 degrees C for 30 min, [3H] clonidine binding to alpha 2-receptors was increased in a concentration-dependent manner without changing [3H] WB4101 and [3H] DHA binding to alpha 1- and beta-receptors, respectively. Scatchard analysis of [3H] clonidine binding to cortical membranes showed that DA increased the Bmax in both high- and low-affinity components. The increasing effect of DA on [3H] clonidine was dependent on incubation time and temperature, and it was antagonized by pimozide and cis-flupenthixol. The addition of GTP produced a reduction in DA-induced elevation in [3H] clonidine binding, while that of cyclic AMP did not affect the effect of DA. DA and Mn2+, though both of them increased [3H] clonidine binding, appeared to act at a different site in the membrane. Furthermore, the DA-induced increase in [3H] clonidine was found uniformly in membranes prepared from 7 other regions of the rat brain. These results suggested that DA regulates specifically alpha 2-receptor density by stimulating D1-receptors and/or via other mechanism(s).

Animals↗

Interspecies cross-reactive determinants of thyroglobulin recognized by autoantibodies.

In this study, we have attempted to characterize the epitopes of thyroglobulin (Tg) recognized by autoantibodies. Anti-autologous Tg from the serum reacted with other Tg from whales, pigs, cows, chickens and rats as well as with human Tg, thereby indicating that human Tg share epitopes recognized by autoantibodies with Tg from various animal species.

Adolescent↗

A major anti-myoglobin idiotype. Influence of H-2-linked Ir genes on idiotype expression.

A rabbit antiidiotypic antiserum raised against an A.SW IgG1K monoclonal anti-sperm whale myoglobin (Mb) antibody, HAL19, and extensively absorbed with normal mouse immunoglobulin and MOPC 21 (IgG1K), was found to detect a common or major anti-Mb idiotype expressed by some but not all anti-Mb monoclonal antibodies, regardless of immunoglobulin G (IgG) subclass, and by 40-50% of the anti-Mb antibodies in immune serum from five high responder strains of mice representing five different Igh allotypes. It did not inhibit antibodies to three unrelated protein antigens. The fraction of antibodies expressing this idiotype, denoted IdHAL19, was regulated by H-2-linked genes that correlated exactly in four independent haplotypes and an F1 with the known Mb immune response (Ir) genes and may be identical to these. Whereas less than 50% of antibodies from high responder mice were inhibitable by anti-IdHAL19, greater than 80% of antibodies from low responder mice, tested at comparable final antibody concentration, were inhibitable. This result was true for both low responder haplotypes, H-2b (B10) and H-2k (B10.BR). The idiotype was found to be present on antibodies that bound to native Mb but not fragments 1-55 or 132-153 of Mb or a denatured form, S-methyl Mb. This specificity for native Mb paralleled that of the monoclonal idiotype HAL19 itself. Therefore, the production of antibodies specific for native in contrast to denatured Mb was studied in H-2-congenic high and low responder strains. Strikingly, low responders produced antibodies that reacted almost exclusively with the native conformation, whereas a larger proportion of antibodies from high responder mice also reacted with the denatured form, S-methyl Mb. Bypassing of the Ir gene defect by immunization with Mb attached to a carrier, F gamma G, resulted in low responder antisera resembling higher responder sera in both idiotype expression and conformational specificity. The simplest explanation of these results is that H-2-linked Ir genes control antibody fine specificity, which is reflected in the idiotypes of the variable regions expressed. We suggest that low responder mice produce a more limited repertoire of antibodies consisting primarily of IdHAL19-positive antibodies specific for the native conformation of Mb. High responder mice produce a greater diversity of antibodies to Mb, so that the IdHAL19-positive, conformation-specific population represents a smaller proportion of the total. Similarly, the use of carrier-specific helper T cells in low responder mice results in a greater diversity of antibodies, which dilutes out the IdHAL19 subset.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Recovery of stress-induced increases in noradrenaline turnover is delayed in specific brain regions of old rats.

Male Wistar rats at 2 and 12 months of age were sacrificed before, immediately following, and at 6 and 24 hours after a 3-hour immobilization stress period. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in eight brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases of MHPG-SO4 levels in all brain regions examined and significant elevations in plasma corticosterone levels in both 2 and 12 month old rats. In 2 month old rats, the MHPG-SO4 levels in all brain regions returned to control levels within 6 hours after release from the stress. However, in 12 month old rats, the metabolite levels in the hypothalamus, amygdala, pons plus medulla oblongata (pons+med. obl .) and midbrain still remained at significantly increased levels at 6 and 24 hours after the stress. Moreover, in the amygdala of older rats, stress-induced decreases in NA levels persisted even 6 hours after stress. Plasma corticosterone levels also showed significant elevations at 6 and 24 hours after the stress only in 12 month old rats. These results suggest that brain NA metabolism during recovery periods from an acute exposure to a stressful situation is altered by the aging process in such a manner that NA neurons in the hypothalamus, amygdala, pons+med. obl . and midbrain in older rats remain activated by stressful stimuli for prolonged periods of time following release from stress.

Aging↗

[A case of portal hypertension with massive gastrointestinal bleeding from ileal varices].

A rare case of massive gastrointestinal bleeding from ileal varices was reported. On December 28, 1982, a 49-year-old male was admitted to Kurashiki Central Hospital because of massive gastrointestinal bleeding. Eleven years ago, the patient underwent an emergency operation for rupture of esophageal varices. The venous phase of selective superior mesenteric and celiac angiography showed mesenteric varices, but no definite bleeding point was noted. Endoscopy revealed esophageal varices, but no area of bleeding was encountered. Because of frequently repeated hemorrhages, laparotomy was performed. A large vein was found on the surface of the ileal wall, through an adhesion to the lateral pelvic wall. Partial resection of ileum was performed. Histological examination of the resected small bowel demonstrated ruptured submucosal varices. The postoperative course was uneventful and he was discharged on the 40th postoperative day. It is stressed that this disease should be considered as a differential diagnosis for a patient with lower gastrointestinal bleeding and portal hypertension.

Gastrointestinal Hemorrhage↗

Arrhythmia during insulin-induced hypoglycemia in a diabetic patient.

The temporal relationship between the level of blood glucose and the frequency of ventricular premature contractions (VPCs) during 24 hours was examined in a 45-year-old man with diabetes mellitus who was treated with a regular insulin injection. The number of VPCs increased sharply when the blood glucose level fell to about 50 mg/dL while the patient was awake. There was a minimal increase in VPCs during sleep, despite a decrease to 21 mg/dL in the blood glucose level. The insulin tolerance test produced frequent VPCs during hypoglycemia, which was suppressed by glucose administration. Changes in the level of plasma epinephrine correlated well with changes in the frequency of VPCs. These data suggest that increased levels of plasma epinephrine may have played a role in the genesis of VPCs that occurred during insulin-induced hypoglycemia.

Arrhythmias, Cardiac↗

Serotonergic-catecholaminergic interactions and foot shock-induced jumping behavior in rats.

The role of serotonergic neurons in foot shock-induced jumping behavior was evaluated by studying the effects of serotonin agonists and depletors under conditions of increasing activity of catecholaminergic neurons by combining different shock intensities with methamphetamine or clonidine pretreatment. Low shock (40 V) jumping was suppressed by three different kinds of serotonergic agonists: 5-hydroxytryptophan (50 and 100 mg/kg), 5-methoxydimethyltryptamine (1 and 5 mg/kg) and clomipramine (5 mg/kg) but these drugs did not suppress high shock (60 V) jumping. A depletor of brain serotonin, p-chlorophenylalanine (200 mg/kg), failed to affect the jumping induced by both shock intensities. The inhibitory effect of serotonergic agonists on low shock jumping was abolished by pretreatment with methamphetamine (1 mg/kg) or clonidine (100 micrograms/kg). Furthermore, 5-methoxydimethyltryptamine (5 mg/kg), a serotonergic postsynaptic receptor stimulant, potentiated high shock jumping in rats pretreated with methamphetamine (3 and 5 mg/kg). The results indicated that activation of serotonergic neurons has a differential effect on jumping behavior ranging from inhibitory to facilitatory, depending upon the increasing activity of catecholaminergic neurons.

Animals↗

Differential effects of morphine on noradrenaline release in brain regions of stressed and non-stressed rats.

Effects of morphine on noradrenaline (NA) turnover in the 8 brain regions were investigated in non-stressed and stressed rats. Morphine at 3 mg/kg and 6 mg/kg caused dose-dependent increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of brain NA, in the hypothalamus, amygdala, thalamus, hippocampus and midbrain and decreases in NA levels in the first 4 of these regions. In contrast to these enhancing effects of morphine on NA release in non-stressed rats, pretreatment with morphine at 6 mg/kg significantly attenuated immobilization-stress-induced increases in MHPG-SO4 levels in the above regions. The morphine effects in both states, non-stressed and stressed, were reversed by naloxone at 0.5 mg/kg and 5 mg/kg in the hypothalamus, amygdala and thalamus. These neurochemical changes are apparently related to the distress-evoked hyperemotionality. Behavioral changes observed during the restraint stress such as struggling, vocalization and defecation were attenuated by morphine at 6 mg/kg and enhanced by naloxone at 5 mg/kg, and this action of morphine was also reversed by naloxone at 5 mg/kg. These results suggest that morphine acts to attenuate stress-induced increases in NA release in the hypothalamus, amygdala and thalamus via opiate receptors, although the drug facilitates NA release in these regions in non-stressed rats. Together with previous findings that naloxone enhances stress-induced increases in NA release selectively in these regions, it is further suggested that endogenous opioids released during stress might act to inhibit NA release in these specific brain areas and that these decreased noradrenergic activities might be closely related to the relief of the distress-evoked hyperemotionality in animals.

Animals↗

Differential modification by opioid agents of acutely enhanced noradrenaline release in discrete brain regions.

Although immobilization stress-induced increases in MHPG-SO4 level in the hypothalamus, amygdala and thalamus were enhanced by naloxone and attenuated by morphine, both agents failed to exert significant effects upon regional MHPG-SO4 levels in methamphetamine-treated rats. The results indicate that there is a differential modification by opioid agents of acutely enhanced noradrenaline release induced by physiological and by pharmacological manipulations.

Animals↗

Differential effects of clonidine on alpha 1- and alpha 2-adrenoceptors in footshock-induced jumping behavior.

The effects of clonidine (0.01-100 micrograms/kg i.p.) on jumping behavior in rats were investigated using different shock conditions (low shock: 40 V or high shock: 60 V). Under the low shock condition, 0.01-0.05 micrograms/kg doses of clonidine reduced jumping frequency and the effect was antagonized by yohimbine (1 micrograms/kg i.p.) or tolazoline (1 mg/kg i.p.) indicating alpha 2-adrenoceptor involvement. Under the high shock condition, 10-100 micrograms/kg doses of clonidine increased jumping frequency and the effect was antagonized by phenoxybenzamine (20 mg/kg i.p.), indicating alpha 1-adrenoceptor involvement.

Animals↗