Effect of the spleen extracts on primary immune response in mice]

Experiments were conducted on mice. Direct Jerne's test demonstrated a possibility of intensification of the primary immune response in the sexually mature mice under the effect of the splenic extracts. The significance of the extract dose and of the time of administration for the manifestation of the stimulating action was studied.     

Effect of long-term restraint stress on behavior of female C57BL/6J and CBA/Lac inbred mice. Dispersion and cluster analysis]

An augmented exploratory behaviour and motor activity and diminished anxiety after a restraint stress were found in CBA/Lac female mice [corrected] but not in C57BL/6J ones. In the Porsolt test the result was exactly opposite. A possibility of inherent anxiety-depressive pathological condition in the C57BL/6J mice [corrected] developing under the effect of repeated psychological stress, is assumed.     

The effect of naloxone administration on pregnancy-associated seizures

Pregnant mice are more susceptible to flurothyl-induced seizures than are non-pregnant controls. The possibility that the well-known increase in beta-endorphin concentration which accompanies pregnancy was involved in this effect was examined by testing whether naloxone administration could block the increased seizure susceptibility. Pregnant female, control female and male C3H mice were treated with 5-50 mg/kg naloxone 5 min before flurothyl seizure testing. Naloxone markedly increased clonic seizure susceptibility in all three groups at a dose of 50 mg/kg, but had little effect at lower doses. In contrast, naloxone had differential effects on myoclonic seizures in pregnant and control female mice, being anticonvulsant in the controls, but proconvulsant in the pregnant mice. A role for endogenous opiates is unlikely in mediating clonic seizures in pregnant mice, but may be involved in myoclonic seizures.     

Does weak local gamma irradiation modify the effect of CDDP on mouse mastocytoma?

The possibility that an irradiation with small doses of gamma rays given shortly before might enhance the cure effect of cis-diammine-dichloroplatinum (II) (CDDP) was tested in tumor bearing mice. Tumor cells of FMA3, a cloned cell line of murine mastocytoma, were transplanted in the muscle of a hind leg in one experiment and in the abdominal cavity in another experiment. In both cases, a single injection of CDDP at 4 mg/kg was effective to lengthen the mean survival time of mice. gamma rays at the dose of 1, 2 and 4 Gy given 3 hours before did not modify the effect of CDDP.     

Antinociceptive effect following dietary-induced thiamine deficiency in mice: involvement of substance P and somatostatin

We produced thiamine deficiency by treating mice with a thiamine deficient (TD) diet, but not with pyrithiamine, a thiamine antagonist. Twenty days after TD feeding, a significant antinociceptive effect was observed in the formalin test. A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19th day after TD feeding (on the late TD stage) failed to reverse the antinociceptive effect, the muricide effect, and impairment of avoidance learning induced by TD feeding, as compared to pair-fed controls. These results indicate the possibility that the TD-induced antinociceptive effect may result from irreversible changes in the spinal and/or brain neurons. To clarify the involvement of substance P (SP) and somatostatin (SST) systems in the spinal cord, we examined the effect of intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of pain threshold. I.t. injection of SP and SST elicited a behavioral response consisting of reciprocal hindlimb scratching, biting and/or licking of hindpaws. There was no significant difference in the behavioral response to SP between TD mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day after TD feeding the response to SP was significantly increased compared with PF mice. This phenomenon was also observed with SST on the 20th day after TD feeding. These results indicate the possibility that TD feeding may produce an increased behavioral response to SP and SST through an enhanced sensitivity of neurokinin-1 and SST receptors in the spinal cord. Taken together, the antinociceptive effect following TD feeding may result from a decrease in spinal SP and SST contents.     

Determination of bacterial endotoxin admixtures in inactivated influenza vaccines

The materials substantiating the possibility of using the method for the determination of the lethal effect of endotoxin on dactinomycin-treated mice are presented. This determination is made with a view to detecting the admixtures of endotoxins in whole-virion and subvirion inactivated influenza vaccines at different stages of their manufacture, as well as in the final product. The proposed test is highly sensitive, rather simple in its practical realization and can be used for evaluating the degree of the purification of influenza vaccines from endotoxins.     

Graft-versus-host reaction-like phenomenon induced by BCG in mice lethally irradiated and transferred with syngeneic bone marrow cells.

Heat-killed BCG in paraffin exerted a lethal effect on CS7BL/6 mice irradiated lethally and transferred with syngeneic bone marrow cells. Such an effect was not detectable when mice were subjected to adult thymectomy and used as the hosts. Lymphoid cells from such nonthymectomized mice exhibited cytotoxicity to syngeneic tumor cells but not to allogeneic tumor cells in an in vivo cytotoxicity test and induced splenomegaly in sublethally irradiated syngeneic recipients after systemic transfer. The cytotoxicity of such lymphoid cells was abolished by a treatment with anti-θ serum and complement. In the bone marrow of mice irradiated and transferred with bone marrow cells, the number of nucleated cells, the ratio of myeloid to erythroid cell series, and the percentage of lymphocytes were increasd by BCG injection. These results suggest the possibility that self-tolerance may be broken by BCG stimulation in the process of reconstitution of lymphoid cells in the irradiated mice.     

Schistosoma mansoni: reduced efficacy of chemotherapy in infected T-cell-deprived mice

The effect of host immunosuppression on the efficacy of schistosomicidal chemotherapy has been tested in T-cell-deprived CBA mice infected with Schistosoma mansoni. The drugs hycanthone, oxamniquine, and praziquantel were found to kill fewer adult S. mansoni worms in deprived mice than in comparably infected strain-, age-, and sex-matched, immunologically intact controls. Inconsistent results were obtained with niridazole, and amoscanate was as effective in deprived mice as in controls. The possibility that hycanthone, oxamniquine, praziquantel, and previously studied antimony act synergistically with immune effector mechanisms in killing adult schistosomes is discussed.     

Evidence that nitric oxide modulates food intake in mice

Nitric oxide (NO) may be an intercellular modulator within the central nervous system. L-arginine, which results in NO synthesis, increased food intake in mice while the inhibitor of NO synthesis, L-NG-nitro arginine (L-NO Arg) inhibited food intake in food deprived mice. L-arginine, but not D-arginine, partially reversed the inhibitory effect of L-NO Arg on food intake. These findings suggest the possibility that NO may be a physiological modulator of food intake and that the possibility of exploring the utility of L-NO arg in the treatment of obesity should be explored.     

Chromosome effect of cyclophosphamide in various strains of mice]

The chromosomes of four different mouse strains were examined after administration of a single dose of cyclophosphamide, 100 mg/kg. Chromosomal breaks and rearrangements were produced in C3H mice three to four times as frequently and in AKR mice twice as frequently as in C57 B1 and XLII Orl mice. This indicates that cytogenetic investigations in mutation research using mice as in vivo test systems may be variable depending on the mouse strain employed. Because the effect of the alkylating agent was not pronounced in the two strains having a high incidence of cancer and leukemia (C3H and AKR), the possibility of a relationship between chromosomal instability and cancer proneness is discussed.     

Relation between Enhanced Antibody Responses Elicited by Adjuvant Injection and Those Elicited by Secondary Antigenic Stimulation

An attempt was made to determine if there is any common mechanism in the enhanced antibody response caused either by injection of adjuvant, such as bacterial endotoxin (LPS) and complexed polynucleotides, or by secondary antigenic stimulation. LPS inoculated in mice 4 days before injection of sheep red blood cells (SRBC) and polyA:U invalidated the adjuvant effect of polyA:U injected together with SRBC, and the hemolysin plaque-forming cell (PFC) response of such mice was similar to that of the mice which received SRBC alone. When mice primed with SRBC 24 days in advance were injected with LPS and 4 days later re-stimulated with SRBC, their PFC response to the secondary stimulation was suppressed to less than one tenth of the normal secondary PFC response. The suppressive effect of LPS on the secondary antibody response was abolished if the serum collected from mice injected with LPS was given to the primed and LPS-injected mice at the time of the secondary antigenic stimulation. From these results we discussed the possibility that some common mediator might play a role in the enhanced antibody response elicited by either adjuvant injection or secondary injection of antigen.     

Response of CBA/N mice to human B cell activating factor.

The in vitro antibody responses of CBA mutant and normal mice were studied with respect to their relative abilities to respond to stimulation by purified B cell activating factor (BAF). It was found that mice carrying the X-linked inability to respond to T-independent antigens can respond to BAF. This result is discussed with respect to the possibility that BAF exerts its effect on a subset of B cells distinct from those cells responsive to non-mitogenic T-independent antigens.     

Resistance to IP leptin-induced adipose apoptosis caused by high-fat diet in mice

The objectives of this experiment were to determine whether leptin causes adipocyte apoptosis in mice, whether peripheral administration is an effective means of studying leptin-induced adipocyte apoptosis, and whether high-fat feeding results in reduced responsiveness to leptin-induced adipocyte apoptosis. Continuous 13-day intraperitoneal infusion of 10 microg/day leptin significantly increased adipocyte apoptosis in the epididymal/parametrial fat pads of male and female mice, but only male mice developed reduced responsiveness to leptin-induced adipocyte apoptosis after high-fat (45% fat) feeding for 5 or 15 weeks. There was a positive correlation between serum leptin concentration and percent apoptotic adipocytes. These findings demonstrate that leptin administered peripherally is effective in inducing adipocyte apoptosis in mice, thus extending the possibility of studying this effect of leptin in a wider variety of animal models. In addition, high-fat feeding has a gender-specific effect on development of reduced responsiveness to leptin-induced adipocyte apoptosis.     

Effect of hydrocortisone and methods of infection on the isolation of Brucella from the body of albino mice

It was experimentally revealed that subcutaneous method of albino mice infection in combination with hydrocortisone administration offered a possibility of decreasing the period of discharge of brucella to 7 days with a 100% culturing from the inguinal, paraaortal lymph nodes and the spleen. In intracerebral method of infection with a preliminary treatment with hydrocortisone the period of the culture isolation decreased to 14 days.     

Murine survival of lethal irradiation with the use of human umbilical cord blood.

We have found that human umbilical cord blood (HUCB) will routinely protect mice exposed to lethal levels of irradiation. At the end of 50 days, over seventy percent (70%) of mice injected with HUCB survived 900 cGy or irradiation, which produced 100% deaths in the uninjected control animals. Moreover, there was some evidence that human colony stimulating factors further improved survival. Anti-Natural Killer cell (NK) antibody was utilized along with HUCB in these studies, however, Anti-NK cell serum alone had no radioprotective effect in mice. The studies reported here suggest the possibility of utilizing HUCB for immediate protection of humans from lethal irradiation.     

Study of a mtDNA deletion in BALB/c mice exposed to ionizing radiation

A novel large mtDNA deletion of 5914 bp was detected in mice exposed to X-radiation. The regions flanking the deleted fragment were characterized by the method of sequencing. The possibility of using a minimum sample of the mouse auricle tissue for detecting mtDNA deletions in the same animals at different postradiation times is demonstrated.     

Highly sensitive histamine-sensitization test for residual activity of pertussis toxin in acellular pertussis vaccine

Histamine-sensitization test method based on histamine-sensitizing death is widely used for controlling residual activity of pertussis toxin in acellular pertussis vaccines. The test method evaluates the residual activity according to the death of mice injected with a test vaccine after histamine challenge and the test result, therefore, depends on the sensitivity of mice. A highly sensitive test method based on change in rectal temperature of mice has been used in Japan for many years but has limited feasibility in other countries. We examined the possibility of a test method using dermal temperature measured by infrared thermometer to reduce animal suffering instead of rectal temperature. The dermal temperature method was shown to be as sensitive as the rectal temperature method. Furthermore, the dermal as well as rectal temperature methods can evaluate the activity of a test vaccine in relative to a reference preparation so as to allow direct comparison of the test results among different laboratories. The activity by means of the dermal temperature method was also found to be well consistent with that by the rectal temperature method.     

The rejuvenating effect of pregnancy on muscle regeneration

Aging is characterized by reduced tissue regenerative capacity attributed to a diminished responsiveness of tissue‐specific stem cells. With increasing age, resident precursor cells in muscle tissues show a markedly impaired propensity to proliferate in response to damage. However, exposure to factors present in the serum of young mice restores the regenerative capacity of aged precursor cells. As pregnancy represents a unique biological model of a partially shared blood system between young and old organisms, we hypothesized that pregnancy in aged mice would have a rejuvenating effect on the mother. To test this hypothesis, we assessed muscle regeneration in response to injury in young and aged pregnant and nonpregnant mice. Muscle regeneration in the aged pregnant mice was improved relative to that in age‐matched nonpregnant mice. The beneficial effect of pregnancy was transient, lasting up to 2 months after delivery, and appeared to be attributable to activation of satellite cells via the Notch signaling pathway, thus supporting the possibility that pregnancy induces activation of aged dormant muscle progenitor cells.     

Comparative evaluation of anticonvulsant and anti-arrhythmic effects of phenazepam, a benzodiazepine receptor agonist

It was established on white mice that benzodiazepine receptor agonist phenazepam possessed a high anticonvulsant activity to antagonize bicuculline, corrasol, picrotoxin and thiosemicarbazide. It was also shown that phenazepam had a potent antiarrhythmic effect on ischemic and reperfusion cardiac arrhythmias in Wistar rats in situ. The effect was of a central nature since it was irreproducible in isolated heart. It seems to be due to the potentiating effect of phenazepam on the realization of GABA inhibitory control of centers of the heart regulation. The facts obtained evidence a possibility of using phenazepam not only as an anticonvulsant but also as an antiarrhythmic means.     

Use of immunomodulators isolated from marine invertebrates for reducing the toxic effects of thermostable toxin and lipopolysaccharides from Yersinia pseudotuberculosis on a macroorganism]

The possibility to use immunomodulators isolated from marine invertebrates for the lowering of the toxic effects caused by Yersinia pseudotuberculosis thermoresistant toxin and lipopolysaccharide was investigated. Effects were evaluated by the animals survival rate in per cent and mice average lifetime after toxin lethal dose injection. It was shown that polypeptide gangleen when compared to timalin as well as glycanes mitilane and strombus had dose-dependent protective effect. These substances increased animals survival rate to 15-17 per cent and prolonged life period for about two times when compared to control group. These results demonstrates the possibility to use investigated immunomodulators is clinical practice at the treatment of the patients with pseudotuberculosis.