Hartley Strain Guinea Pigs Research Articles

Role of Phagocytes in Antimicrobial Defence of the Middle Ear

The role of phagocytes in the antimicrobial defence of the middle ear was investigated in this experiment, using Hartley strain guinea pigs with an experimental otitis media. Otitis media was induced with an inoculation of Streptococcus pneumoniae into the tympanic cavity through the ear drum. For depletion of peripheral blood phagocyte population such as monocytes and polymorphonuclear neutrophils (PMNs), whole body irradiation (250 rad or 500 rad) was carried out on guinea pigs three days before S. pneumoniae inoculation into the middle ears. Carrageenan was also used for selective depletion of mononuclear cells, to distinguish their role from polymorphonuclear neutrophils. In control animals, otitis media was induced reproducibly with middle ear inoculation of more than 10(6) S. pneumoniae. In irradiated animals, which underwent 10(2) or 10(4) S. pneumoniae inoculation, the incidence of otitis media because of S. pneumoniae infection became higher in accordance with the dosage of irradiation. However, no significant difference was seen in the occurrence of otitis media and the number of viable bacteria recovered from bulla washings between controls and carrageenan-treated animals. These results suggest that phagocytes, particularly neutrophils, are essential for antimicrobial defense at the early phase of the middle ear infection with S. pneumoniae.

アセチルコリンおよびヒスタミン暴露に対する気道感受性を異にするモルモット二系統の選抜育種

We developed two lines of guinea pigs, one as model animals for bronchial asthma with bronchial hypersensitivity and the other with hyposensitivity as a control. In the last four years, the bronchial hypersensitive line (BHS) and hyposensitive line (BHR), both derived from Hartley strain guinea pigs, have been selected by using bronchial reactivity to acetylcholine and to histamine as parameters. Both lines have reached the F6 generation. The following results were obtained with the two lines: 1) Sib and cous in matings, and mating of selected consanguineous individuals were adopted in breeding BHS and BHR. The breeding started with six families, each, but in the F6 generation the number of families decreased to two in each line. 2) Appearance rates of hyper- or hyposensitivity to acetylcholine and histamine increased with successive generations in both lines, which had been completely separated by the F6 generation. 3) Coefficients of inbreeding in BHS and BHR in the F6 generation ranged from 42% to 45% in the former and 42% in the latter. 4) Heritabilities (h2) of BHS and BHR for the appearance rates of sensitivity to acetylcholine were presumed to be 0.54 in the former and 0.69 in the latter. 5) No difference in the body weight of 0, 20, and 40 day-old BHS was observed in any generation. On the other hand, the body weight of 20 and 40 day-old BHR tended to decrease with successive generations. 6) Mean litter sizes of BHS and BHR in each of the generations ranged from 2.24 to 3.47 animals in the former and from 2.63 to 3.38 animals in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Anionic Sites of the Basement Membrane of the Labyrinth

The presence of anionic sites in the labyrinth is demonstrated in this study, using polyethyleneimine as a cationic probe. Hartley-strain guinea pigs (200-300 g) with a normal Preyer's reflex were used. A 0.5% polyethyleneimine (PEI, MW 1,800) solution adjusted to pH 7.3 with HCl following Schurer's method was systemically administered through an axillary vein. In the cochlea, the presence of anionic sites was demonstrated on the basement membrane of the capillary wall in the stria vascularis. The presence of anionic sites was also confirmed on the basement membrane in Reissner's membrane but its density was much lower than that in the stria vascularis. In the ampulla and macula, the anionic sites were present on the basement membrane of the capillary wall and sensory epithelium.

Influence of Weight on Pulmonary Function in the Adult Guinea Pig

We examined a group of 63 adult female Hartley strain guinea pigs with weight ranging from 625 to 1,200 g in order to ascertain whether pulmonary function tests including lung volumes, pressure-volume curves, and flow-volume curves were affected by the weight of the animal. We found that there was a weight effect on total lung capacity, vital capacity, residual volume, and the forced expiratory flow between 25 and 75% of total lung capacity, although there was no effect on other parameters of airflow. Flow-volume curves for each animal could be accurately fitted to a mathematical equation, and this equation did not vary with the animals' weight. Pressure-volume curves were affected by animal weight, but could be accurately fitted to a weight-corrected equation. We conclude that when pulmonary function tests are performed on adult guinea pigs, lung volumes may be altered in proportion to the weight of the animal. When pressure-volume or flow-volume curves are being considered, although weight can either be corrected for or has no bearing on the shape of the curve, there is a large between-animal variation, and it may be necessary to use large experimental groups when it is impossible to use the same animal as its own control.

Comparable Sensitivity of Hairless and Hartley Strain Guinea Pigs to a Primary Irritant and a Sensitizer

AbstractA hairless mutant guinea pig (crl:IAF/HA[hr/hr]BR) has recently been developed that could be useful for the study and evaluation of primary irritants and contact sensitizers. The quality of responses in this new strain was therefore compared to the standard Hartley strain animal.Two standard procedures commonly utilized for risk assessment were selected. Dose-response experiments were designed to evaluate a full range of dermal responses. It was determined that the hairless guinea pig is more susceptible to both a primary irritant and a contact sensitizer as determined by use of the guinea pig immersion and Buehler methodologies.The results, in terms of risk evaluation, are discussed.

Localization of Trimetaphosphatase Activity in Epithelium of the Guinea Pig Cochlear Duct

The localization of trimetaphosphatase (TMPase) activity in the epithelium of the guinea pig cochlear duct was investigated cytochemically and compared with that of acid phosphatase (ACPase) activity and that of horseradish peroxidase (HRP) injected into the subarachnoid space. Cochlear from Hartley strain guinea pigs weighing 250300g, were fixed with 2% glutaraldehyde and decalcified with 10% EDTA. TMPase activity was detected by the methods of Doty et al. (J Histochem Cytochem 25 : 1381, 1977) and Kobayashi et al. (J Histochem Cytochem 36 : 959, 1988), and ACPase activity by the method of Robinson and Karnovsky (J Histochem Cytochem 31 : 1197, 1983). ACPase activity was observed in a small number of round lysosomes in the epithelial cells, and in short tubular lysosomes in the marginal cells of the stria vascularis and root cells. However, many round and tubular lysosomes showing TMPase activity were seen in the marginal cells of the stria vascularis, root cells and interdental cells. The re-action products of TMPase activity were electron-dense fine granules on the limiting membranes and in the lumens of the lysosomes. The localizing-pattern of TMPase activity in epithelium was very similar to that of HRP injected in the subarachnoid space. The lysosomal fraction was collected from guinea pig and rat kidney cortex, and TMPase was separated from ACPase by electrophoresis with 5% polyacrylamide gel and stained with 0.5% yellow ammonium sulfide after incubation in a cytochemical medium for enzyme localization.The present results show that TMPase is different from ACPase in its biochemical properties and its cytochemical localization in the lysosomal system. TMPase-positive lysosomes in the epithelium of guinea pig cochlear ducts seem to possess a function associated with pinocytosis, and might also be involved in the formation of endolymphatic hydrops.

抗原誘発後の鼻粘膜ＳＲＳ‐Ａ含有量の経時的変化

We evaluated the time course of production of SRS-A in the nasal mucosa after antigen challenge in the guinea pigs with nasal allergy and the effect of Ketotifen sprayed topically over the nasal mucosa on SRS-A production. Fifty-six Hartley strain guinea pigs were sensitized passively by intravenous injection of 0.4 ml of sera containing antiovaTbumin IgE and γ1 antibody (7 days' PCA titer, ×1664; 48 hours' RCA titer, ×5632). After 7 days, all animals received nasal challenge with 50 μl×2 of 1 % ovalbumin. Thirty-two animals were subdivided into 8 groups that were killed before the challenge and 15 min, 30 min, 1 hr, 3 hr and 12 hr after antigen challenge. The nasal mucosa was removed and the amount of LTC4, LTD4 and LTE4 in the nasal mucosa was measured using high-powered liquid chromatography combined with radioimmunoassay. In 12 animals, nasal spray of 0.1 mg Ketotifen dissolved in normal saline was given once a day for 6 days until the day of antigen challenge and another 12 animals were given nasal spray of normal saline as a control. Thirty minutes after nasal antigen challenge, the animals were killed and the nasal mucosa was removed to measure the amount of SRS-A. LTC4, LTD4 and LTE4 in the nasal mucosa increased significantly between 15 and 60 min after antigen challenge and then decreased markedly. Ketotifen sprayed topically over the nasal mucosa significantly inhibited production of LTC4, LTD4 and LTE4 by as much as 50%.

Contact Hypersensitivity Response To Glutaraldehyde in Guinea Pigs and Mice

Glutaraldehyde has a wide spectrum of uses which can result in dermal contact with the agent. The low number of reports of hypersensitive reactions to glutaraldehyde indicates a low incidence of sensitization. This paper describes the contact hypersensitivity response to glutaraldehyde in the guinea pig and the mouse. Female albino Hartley strain guinea pigs and female B6C3F1 mice were sensitized with 0.3, 1.0 and 3.0% glutaraldehyde and challenged with 10% glutaraldehyde. Doses of glutaraldehyde were selected from assays for primary irritancy. Guinea pigs received 100 microliters by direct dermal application, for 14 consecutive days, and mice received 20 microliters by direct dermal application, for 5 or 14 consecutive days, to sites prepared by shaving and dermabrading. Rest periods were 7 or 14 days for guinea pigs and 4 or 7 days for mice. Measurement of the contact hypersensitivity response in guinea pigs was both visual evaluation (scoring) at 24 and 48 hours following challenge and radioisotopic assay at 48 hours, and in mice by radioisotopic assay 48 hours after challenge. Both guinea pigs and mice demonstrated dose-dependent contact hypersensitivity responses to glutaraldehyde. The radioisotopic assay appeared to be more sensitive than visual evaluation in detecting contact allergic hypersensitivity to glutaraldehyde.

Developmental disturbances of the fetal brain in guinea-pigs caused by methylmercury.

Pregnant guinea-pigs of Hartley strain were orally administered methylmercuric chloride once at a dose of 7.5 mg Hg/animal (weighing 500-800 g) on one of days 21, 28, 35, 42 or 49 (3-7 weeks) of gestation. They were killed on day 63 (9 weeks) and their fetuses were removed. Both maternal and fetal blood, brain, liver and kidney, and fetal hair, urine, gastric content and amniotic fluid as well, were sampled for mercury analysis. The fetal brains were also examined pathologically. The maternal kidney contained mercury at a high concentration but the fetal kidney did not. The mercury concentration was strikingly high in the fetal hair, but fairly low in the urine, gastric contents and amniotic fluid. Mercury distributed unevenly in various brain regions of both dams and fetuses after treatment at 6 and 7 weeks of pregnancy (3 and 2 weeks before sampling). The concentration was high in the neopallium and archipallium, followed by the paleopallium, diencephalon and mesencephalon, but low in the rhombencephalon, including cerebellum. Mercury contents were relatively low and distributed almost evenly in various brain regions of both the dams and fetuses following treatment at 3, 4, and 5 weeks of pregnancy. Morphologically, the fetal brains were disturbed in the development following treatment at 3, 4 and 5 weeks of pregnancy. The cerebral cortex was thinned, the nucleus caudatus putamen and the hippocampal formation were reduced in size, and the lateral ventricles were dilated. However, the histological architecture of the cerebral cortex was not strikingly maldeveloped; only a slight disarrangement of the cellular alignment was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced survival to endotoxin in guinea pigs fed IV fish oil emulsion.

Improved survival to endotoxin has been demonstrated in rats pretreated with cyclooxygenase inhibitors or made essential fatty acid deficient, implying that excessive omega 6 fatty acids, possibly through their eicosanoid products, contribute to mortality. Following endotoxin administration, we also have shown improvement in survival with oral diets supplemented with fish oil. This study sought to explore whether parenteral fish oil ameliorates the adverse impact of endotoxin. Male Hartley-strain guinea pigs were obtained at a body weight of 500 g and fed a normal laboratory diet. Central venous lines through which the animals received either a 10% safflower oil emulsion (n = 11) or a 10% fish oil emulsion (n = 11) during two, 24-hr periods separated by two days were inserted. Two days after the second infusion, endotoxin (0.35 mg/100 g b.w.), was given intraperitoneally, and survival was noted. The animals received a total of 25.4 g of IV fat per kg b.w., including 5.3 g of eicosapentaenoic acid per kg b.w., for the fish oil group. From six hr after endotoxin through four days, there was better survival in the fish oil group (p less than .006). Final mortality showed 7/11 fish-fed vs 2/11 safflower-fed animals surviving. We conclude that the administration of parenteral fish oil, even for a brief time, can have a profound effect on subsequent survival to endotoxin.

Toxicity and evidence for metabolic alterations in 2,3,7,8-tetrachlorodibenzo- p-dioxin-treated guinea pigs fed by total parenteral nutrition

The effect of total parenteral nutrition (TPN) on the toxicity of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in male, Hartley-strain guinea pigs was determined. At a single dose of 2 μg TCDD/kg, TPN-fed guinea pigs maintained body weight at a level which was slightly, but consistently, below that of the TPN-fed control animals. However, despite the sustenance of body weight, TCDD-treated animals died or were sacrificed due to morbidity between Days 8 and 24 following treatment. Approximately 50% of this group demonstrated a profound loss of body weight within a few days prior to death or sacrifice. With the exception of the pattern of weight loss, the signs of toxicity in the TPN-fed, TCDD-treated animals were strikingly similar to those observed in TCDD-treated guinea pigs fed ad libitum. Although livers from TCDD-treated, TPN-fed animals demonstrated increased content of lipid and cytochrome P-450, this tissue appeared to be morphologically and functionally comparable to that from TPN-fed controls. Of the blood chemistry examined, only the serum concentrations of 3,5,3′-triiodothyronine were significantly decreased in the treated animals fed by TPN. Results were also compared to TCDD-treated guinea pigs fed ad libitum and respective pair-fed controls. Many of the physiological and biochemical responses observed in animals fed ad libitum following TCDD treatment could be explained by a decrease in food consumption. This study demonstrated that although food consumption clearly accounts for the major effect of TCDD on body weight loss in guinea pigs fed ad libitum, additional physiological and/or biochemical alterations occurred which also contribute to body weight loss, other signs of toxicity, and subsequent lethality.

Annulate lamellae in guinea pig sertoli cells

Unilateral torsion of the spermatic cord was surgically induced in 24 Hartley strain guinea pigs. Groups of six animals were sacrificed 4, 8, 12, and 16 months after the surgery and testes were excised. Nine animals had severely damaged testes. Extensive study on the Sertoli cells of each of these nine animals was carried out after testicular tissues were processed for electron microscopy following the usual procedure. The majority of the affected seminiferous tubules contained a single layer of Sertoli cells without any differentiating germ cells. The Sertoli cells were vacuolated and contained highly lobulated nuclei. Each nucleus contained a nucleolus. The Sertoli cells contained an elaborate annulate lamellae system. The membranous portion of the annulate lamellae was associated with the rough and smooth endoplasmic reticulum. Close association of the annulate lamellae with the lysosomes and lipid droplets was found to be a consistent feature. Although it was not possible for us to predict the functional significance of these annulate lamellae, the present investigation clearly established for the first time, the presence of an annulate lamellae system in the Sertoli cell of a rodent species.

Germ Cell Degeneration in the Contralateral Testis of the Guinea Pig with Unilateral Torsion of the Spermatic Cord Quantitative and Ultrastructural Studies

This study evaluated the long term effects of unilateral torsion of the spermatic cord on the contralateral testis of guinea pigs, employing both fine structural and quantitative studies. Young, adult Hartley strain guinea pigs were divided into six experimental groups (12 animals per group). The first three groups consisted of 36 animals in which unilateral torsion was surgically induced. In group I (torsion maintained), unilateral torsion of the spermatic cord was maintained until the day of sacrifice; in group II (torsion and untwist), torsion of the spermatic cord was maintained for 8 to 12 hours, then the spermatic cord was untwisted and the testis was retained until the day of sacrifice. In group III (torsion and orchiectomy), testes were removed after 8 to 12 hours of spermatic cord torsion. The second three groups consisted of 36 animals: group IV (unilateral orchiectomy), group V (unilateral sham operation), and group VI (pentobarbital injection alone), which served as controls. One half of the animals from each group were killed after 4 months and the other half were killed after 8 months. The most frequently observed histologic changes in the contralateral testes of the experimental animals were focal disorganization and exfoliation of immature germ cells into the lumen. Severe damage, with almost complete absence of germ cells, was noted only in an occasional tubule. Quantitative evaluation of the germ cells of the contralateral testis revealed significant loss of germ cells in groups I, II, and III after 4 months, and in groups I and II after 8 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide

Page 1630: C, Murlas and J. H. Roum, “Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide.” Page 1630: the first sentence of methods should read: Forty-seven male Hartley strain guinea pigs (550–750 g in weight) were used in the study. Page 1631, column 1, paragraph 1: next to last sentence should read: The remaining animals were divided into groups of four or more. Page 1634: Figs. 4B and 5B are derived from Ref. 21. Page 1635: Fig. 7 legend, fourth and fifth sentences should read: Values represent means ± SE for 4 animals at each time point except at 2 h for normal animals ( n = 7). Values for normal animals are indicated by open bars and are derived from Ref. 21. Page 1633, corrected Fig. 20 should be substituted: (See PDF)

The hemostatic derangement produced by T-2 toxin in guinea pigs

T-2 toxin produced significant coagulation abnormalities when administered parenterally to Hartley strain guinea pigs. The animals developed depressed activity of all coagulation factors except fibrinogen. Platelet aggregation in whole blood was depressed in response to ADP and collagen. The animals also exhibited an initial rise followed by a fall in hematocrit level, leukocytosis, and a decrease in platelet count. These changes were detectable within hours of toxin administration, reached a maximum at 24 hr, and returned to normal over the next 2 days. Pretreatment of animals with vitamin K 1 had no effect on the activity of coagulation factors. The activated partial thromboplastin time of dilutions of plasma from animals given T-2 toxin with plasma from control animals revealed a pattern which pointed to a deficiency of coagulation factors as the principal cause of prolonged clotting times in treated animals. The presence of a weak circulating anticoagulant could not be ruled out. The addition of T-2 to plasma and blood of normal animals in a concentration of 1 μg/ml had no effect on clotting times or platelet aggregation.

Cytotoxicity of leukocytes from normal and Shigella-susceptible (opium-treated) guinea pigs against virulent Shigella sonnei.

Intraepithelial lymphocytes were collected from the ileum of adult Hartley strain guinea pigs and used as effector cells in a 60-min bactericidal assay with virulent Shigella sonnei as target cells. Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) were measured and correlated with the resistance of the animals to infection by S. sonnei. Normal guinea pig intraepithelial lymphocytes exhibited mean NKC and ADCC values of 22.8 +/- 5.0 and 34.1 +/- 13.6, respectively. These animals were resistant to oral challenge with virulent S. sonnei. Intraepithelial lymphocytes from guinea pigs which were fasted for 4 days demonstrated NKC and ADCC values similar to those of normal animals (31.0 +/- 8.1 and 41.7 +/- 6.7, respectively). These animals also were resistant to oral challenge. Intraepithelial lymphocytes from guinea pigs which were given 1 ml of deodorized tincture of opium 2 h before cell collection demonstrated deficient NKC (4.7 +/- 4.2) and ADCC (5.3 +/- 4.9) values but remained resistant to infection by S. sonnei. When guinea pigs were fasted for 4 days and given opium, deficient NKC (2.0 +/- 2.0) and ADCC (1.3 +/- 1.3) values were demonstrated; this group of animals was susceptible to infection by S. sonnei (P less than 0.04). These experiments demonstrated that opium treatment depresses one form of gut immunity. When combined with starvation, opium treatment may increase susceptibility to infection by shigellae by modulation of immunity in addition to the effects on gut motility and bacterial flora.

Immune Rejection of Trichinella spiralis Infective Larvae in the Guinea Pig

Once infected with Trichinella spiralis, rats become refractory to the establishment of a secondary or challenge inoculum. Resistance to reinfection is expressed locally in the small intestine and is directed against infective (L,) stage larvae (stage designated according to Despommier, 1983. In Trichinella and Trichinosis, W. G. Campbell (ed.). Plenum Press, New York, p. 80). Striking features of this host response are the rapidity with which it is expressed and its efficacy. As early as 15 min after L1 larvae enter the small intestine, there is a dramatic reduction in the number of parasites successfully establishing in as compared with rats (Russell and Castro, 1979, J. Inf. Dis. 139: 304-312). Larvae that are prevented from establishing suffer no irreversible, detrimental effect and are expelled from the small intestine in a viable state (Hessel et al., 1982, J. Parasit. 68: 202-207). The rapid rejection reaction and a phenomenon termed rapid expulsion have been carefully defined in the rat (Russell and Castro, 1979, J. Inf. Dis. 139: 304-312; Bell and McGregor, 1979, Exp. Parasitol. 48: 42-50; Bell et al., 1982, Int. Arch. Allergy Appl. Immunol. 69: 73-80) and apparently represent a similar expression of resistance viewed at different time intervals, i.e., 15 min versus 4 to 24 hr, respectively, after a challenge inoculation. These phenomena appear to be characteristic of the species of Rattus norvegicus regardless of the strain (McCoy, 1940, Am. J. Hyg. 32: 105-116; Castro et al., 1976, J. Nutr. 106: 1484-1491; Love et al., 1976, Immunology 30: 7-15). In contrast, rapid expulsion in the mouse appears to be host strain specific (Wakelin and Lloyd, 1976, Parasitology, 72: 173182). During experimentation in our laboratory, inquiring into the physiological mechanism underlying the rapid rejection response, the guinea pig was considered as a host animal. Since no information is available on the capacity of this species to express rapid rejection, this report entails a description of experiments performed to clarify this point. Outbred, male, Hartley strain guinea pigs (Dutchland, Denver, PA) weighing 275-400 g at the time of primary infection, served as hosts. T. spiralis larvae used for inoculation of guinea pigs were obtained from the same species. The strain of T. spiralis was one maintained for more than 10 years in our laboratory by serial passage through mice. Larvae were recovered from skeletal muscle by established methods (Castro and Fairbairn, 1969, J. Parasit. 55: 51-58). Guinea pigs were immunized by inoculation with 2 x 103 larvae administered orally in saline. Counterparts from the same initial lots of animals, inoculated only with saline, served as nonimmunized controls. Challenge infection was with larvae administered orally or intraduodenally to guinea pigs 6 wk after the immunizing inoculation (Table I). Specific inoculation procedures are described below. Worms were recovered from the small intestine of challenged hosts by direct microscopic examination of mucosal scrapings cleared with NaOH. Three different experimental designs were employed in studies with guinea pigs. In the first experiment resistance to establishment of secondarily inoculated larvae was assessed by comparing intestinal worm burdens in immune and nonimmune animals 24 hr postchallenge with 5 x 103 larvae. Results presented in Table I revealed the presence of significantly fewer worms in the mucosa of previously infected hosts as compared with controls. The number of intestinal worms in immune guinea pigs was only 7.9% of that in nonimmune counterparts. Analogous studies in rats (Russell and Castro, 1979, J. Inf. Dis. 139: 304-312) produced an immune host: nonimmune host worm recovery mean ratio of approximately 19%.

Lymphoproliferative changes induced by infection with a lymphotropic herpesvirus of guinea pigs.

The effects of experimental infection with guinea-pig herpes-like virus (GPHLV) on hematologic and histopathologic parameters were studied in Hartley strain guinea pigs inoculated intraperitoneally with 10(3) or 10(6) 50% tissue culture infectious doses of GPHLV. The total leukocyte count, the percentage of cells that were mononuclear, the number of spontaneous rosette-forming cells, and hematocrit values were determined after various intervals. Cells from spleens, cervical lymph nodes, and bone marrow of animals killed at various times were assayed for infectious virus, and tissues were prepared for histological examination. Spleen-to-body weight ratios were also determined. GPHLV infection resulted in a mild, asymptomatic, transient lymphoid hyperplasia. The infected animals experienced a relative and absolute peripheral-blood lymphocytosis lasting for seven to eight weeks. The spleens showed evidence of immune stimulation for four to six weeks. Despite the transient nature of the histological and peripheral-blood changes, virus was recovered by cocultivation from the spleen, bone marrow, and lymph nodes for up to eight months (the time of the last test). Infectivity titers were highest in the B-lymphocyte subpopulation during latent infection. These findings of GPHLV persistence after a mild, acute mononucleosis-type syndrome were compared with observations during human Epstein-Barr viral infection.

Receptor-specific mediation by immunoglobulin E of antigen-induced contraction of tracheal and lung parenchymal strips isolated from the guinea pig.

The guinea pig is much like humans in the cells and mediators involved in immediate hypersensitivity reactions. However, the major anaphylactic antibody in this species is IgG1, not IgE. Recently, we have been successful in producing IgE antibody in guinea pigs. The current study examined whether guinea pig IgE antibody could mediate pulmonary smooth muscle contraction. IgE antibody to picryl and oxazolone determinants was induced by immunizing Hartley strain guinea pigs pretreated with cyclophosphamide. Hyperimmune serum from these animals was passed through a heavy chain-specific anti-IgG1 affinity column. The presence of IgE anti-hapten antibody in the filtrate fraction was verified by passive cutaneous anaphylaxis (PCA) testing with a 7-d period of local passive sensitization and by heat lability (56 degrees C X 4 h) of PCA activity. This IgE-rich fraction, and purified IgG1 anti-hapten antibody were transferred to normal guinea pigs. Both fractions sensitized trachea and pulmonary parenchyma for antigen-induced smooth muscle contraction. The IgG1-mediated antigen-induced contractile response was not affected by heat (56 degrees C X 4 h) and was inhibited in a dose-dependent fashion by IgG1 blocking antibody (anti-OA). The IgE-mediated antigen-induced contractile response was significantly decreased by heat and was not affected by the anti-OA blocking antibody even at a concentration of 100 mg/kg. Thus, two antigen-specific factors in guinea pig serum can mediate antigen-induced pulmonary smooth muscle contraction: IgG1 and IgE antibodies. Our data also suggests that these antibodies mediate the contractile response through separate receptors. The finding that guinea pig IgE can mediate pulmonary smooth muscle contraction suggests this species can be a model for IgE-mediated events in the lung.

Vaccination against transplacental cytomegalovirus transmission: vaccine reactivation and efficacy in guinea pigs.

The guinea-pig model of cytomegalovirus (CMV) infection was used in continuing studies of experimental CMV vaccines for prevention of congenital CMV infection. Low-passage guinea-pig cytomegalovirus (GPCMV) vaccine, which has been shown to be effective in preventing transplacental CMV transmission, was tested for reactivation during pregnancy. In Hartley strain guinea pigs intraperitoneally given 10(5.5) 50% tissue culture infective doses (TCID50) of low-passage vaccine, 27 (41%) of 66 throat swabs obtained during subsequent pregnancies showed CMV, in contrast to 28 (24%) of 115 throat swabs obtained from nonpregnant control animals. High-passage GPCMV vaccine (approximately 5 X 10(3) TCID50) did not cause acute viremia, detectable generalized infection, or GPCMV reactivation during subsequent pregnancies. Immune pregnant animals and their fetuses were protected against generalized CMV infection when challenged with virulent GPCMV. In contrast, nonimmune pregnant controls developed generalized maternal, placental, and fetal infection. Experimental low-dose, high-passage GPCMV vaccine can protect against transplacental CMV transmission without apparent vaccine reactivation during pregnancy.