Pulmonary metastases in guinea pigs as a consequence of dermal implantation of line-10 tumor cells

Summary Metastases to the lungs of guinea pigs occurred at high frequency as a consequence of intradermal implantation of tumor cells derived from the syngeneic hepatocellular carcinoma line-10. Surgery had a major influence on the proportion of guinea pigs found to have pulmonary metastases at necropsy. Without surgery all guinea pigs died with extensive lymph node metastases; macroscopic pulmonary metastases were present in a minority of the animals. Animals treated by excision of dermal tumors survived longer than untreated animals, and macroscopic pulmonary metastases were present in the majority of the animals. Animals treated by excision of dermal tumor and regional lymph nodes were rendered tumor-free. The data suggest that lymph node metastases were the most likely source of the tumor cells that spread to the lungs in animals from whom the dermal tumor transplant had been removed.     

A Mouse Tumor Model of Surgical Stress to Explore the Mechanisms of Postoperative Immunosuppression and Evaluate Novel Perioperative Immunotherapies

Surgical resection is an essential treatment for most cancer patients, but surgery induces dysfunction in the immune system and this has been linked to the development of metastatic disease in animal models and in cancer patients. Preclinical work from our group and others has demonstrated a profound suppression of innate immune function, specifically NK cells in the postoperative period and this plays a major role in the enhanced development of metastases following surgery. Relatively few animal studies and clinical trials have focused on characterizing and reversing the detrimental effects of cancer surgery. Using a rigorous animal model of spontaneously metastasizing tumors and surgical stress, the enhancement of cancer surgery on the development of lung metastases was demonstrated. In this model, 4T1 breast cancer cells are implanted in the mouse mammary fat pad. At day 14 post tumor implantation, a complete resection of the primary mammary tumor is performed in all animals. A subset of animals receives additional surgical stress in the form of an abdominal nephrectomy. At day 28, lung tumor nodules are quantified. When immunotherapy was given immediately preoperatively, a profound activation of immune cells which prevented the development of metastases following surgery was detected. While the 4T1 breast tumor surgery model allows for the simulation of the effects of abdominal surgical stress on tumor metastases, its applicability to other tumor types needs to be tested. The current challenge is to identify safe and promising immunotherapies in preclinical mouse models and to translate them into viable perioperative therapies to be given to cancer surgery patients to prevent the recurrence of metastatic disease.     

Animal Protection Measures in Taiwan: Taiwanese Attitudes Toward the Animal Protection Law and Animal Shelters

This study used a questionnaire, self-administered by 387 Taiwanese citizens, to assess Taiwanese perception and knowledge of the Animal Protection Law and perception and use of animal shelters. Most respondents (87%) knew that Taiwan has legal protection for animals. A –5 to 5 summary score measured knowledge of companion animal dog-related legal requirements. The median score was 3, indicating that almost all respondents had inadequate knowledge about these requirements. Although more dog caregivers had adequate knowledge of the law than did nondog caregivers (prevalence ratio = 1.9, 95% confidence interval: 1.1, 3.2), only 19% had adequate knowledge. Although most respondents (81%) knew Taiwan has animal shelters, only 19 (5%) reported visiting or participating in shelter activities. Only 6 (32%) of shelter visitors or users had a "good or better" impression of services received. Despite low usage of animal shelters, most respondents thought shelters should accept (87%) and relocate (90%) unwanted animals, capture strays (64%), assist in finding lost pets (79%), and educate the public about responsible ownership (85%). More than half (52%) thought shelters should perform euthanasia.     

Animal protection measures in Taiwan: Taiwanese attitudes toward the animal protection law and animal shelters

This study used a questionnaire, self-administered by 387 Taiwanese citizens, to assess Taiwanese perception and knowledge of the Animal Protection Law and perception and use of animal shelters. Most respondents (87%) knew that Taiwan has legal protection for animals. A -5 to 5 summary score measured knowledge of companion animal dog-related legal requirements. The median score was 3, indicating that almost all respondents had inadequate knowledge about these requirements. Although more dog caregivers had adequate knowledge of the law than did nondog caregivers (prevalence ratio = 1.9, 95% confidence interval: 1.1, 3.2), only 19% had adequate knowledge. Although most respondents (81%) knew Taiwan has animal shelters, only 19 (5%) reported visiting or participating in shelter activities. Only 6 (32%) of shelter visitors or users had a “good or better ”impression of services received. Despite low usage of animal shelters, most respondents thought shelters should accept (87%) and relocate (90%) unwanted animals, capture strays (64%), assist in finding lost pets (79%), and educate the public about responsible ownership (85%). More than half (52%) thought shelters should perform euthanasia.     

Isolation and characterization of chemically transformed pancreatic acinar cell lines from young and old mice

Summary To evaluate the role of animal age in chemically induced transformation, pancreatic cells were grown in culture 6 to 8 wk after injecting mice at either 6 or 22 mo. of age with a single dose ofN-methyl-N-nitrosourea (NMU). The cell type and the frequency with which lines were obtained from aged animals paralleled the frequency and pattern of tumor induction by NMU in vivo. Outgrowth of pancreatic explants from young animals required the presence of the tumor promoter 12-o-tetradecanoyl-phorbol-13-acetate to establish continuously growing cell lines. Whereas NMU alone produced lines from aged mice, the promoter did not increase the frequency with which continuous lines were recovered from the aged animals. Of eight cloned cell lines (four young and four old), all had characteristics of transformed mouse pancreatic acinar cells when tested for lectin binding, lactate dehydrogenase isozyme pattern, chromosome number, and anchorage-independent growth. Cell lines derived from aged animals were slower growing and had higher chromosome numbers than lines derived from their younger counterparts.     

Effects of passive stretch on growth and regression of muscle from chickens of various ages

A non-invasive procedure was used to determine the effect of animal age on the growth response of muscle to passive stretch. Stretch increased patagialis muscle weight 61% in 6-week-old chicks and 34% in 10-month-old chicks, 28-month-old animals had an 18% loss of muscle mass during passive stretch. Removal of the stretch stimulus was followed by a rapid return of patagialis weight to control values in 6-week and 10-month animals, while muscle size of 28-month-old animals had not returned to control levels by 22 days, following removal of the stretch. The stretch-induced changes in muscle wet weight could, in part, be attributed to changes in muscle protein. Total muscle DNA content increased during rapid growth in 6-week- and 10-month-old chickens, and returned to control levels during muscle regression. Muscle hydroxyproline content increased in parallel with increases in muscle mass but did not return to control levels during muscle regression in 6-week-old animals. Results of the present study indicate that there was an effect of animal age on stretch-induced hypertrophy and regression of the patagialis muscle.     

A rat model for hyperkalemia

It is often necessary to have a small animal model for hyperkalemia for use in electrolyte and acid base experiments. In reviewing the literature, we found a paucity of such animal models, especially for acute hyperkalemia. We have had difficulty in inducing acute hyperkalemia in rats using potassium chloride alone either intravenously or intraperitoneally and felt the need for an easily reproducible small animal model for hyperkalemia. We gave experimental animals a combination of intraperitoneal amiloride 3 mg/kg and potassium chloride 2 meq/kg in two divided doses while control animals received only the potassium chloride. Initial serum potassiums were similar but at 2 hr, the experimental group had significantly higher serum potassium levels which were sustained throughout the 8 hr of the experiment. Arterial blood gas revealed no significant difference in blood pH values at all time points during the experiment. We conclude that the combination of amiloride and potassium chloride is useful to produce acute hyperkalemia in rats and that this hyperkalemia is sustained beyond 6 hr. This model is convenient for use in metabolic experiments requiring the use of acutely hyperkalemic rats.     

Immunotherapy of bovine ocular squamous cell carcinoma by repeated intralesional injections of live bacillus Calmette-Guérin (BCG) or BCG cell walls

Summary Thirty cows of the Dutch Friesian and the Maas-Rijn-Ijssel breed with histologically confirmed ocular squamous cell carcinoma were treated by repeated intralesional injection of live bacillus Calmette-Guérin (BCG) (n = 14) or a BCG cell-wall vaccine (n = 16). Complete regression of the primary tumour was observed in 64% and 57% of the animals respectively. In the 2-year follow-up period there was no recurrence of primary tumours. This sharply contrasts with the recurrence frequency (40%–50%) after complete remission induced by a single intralesional injection with BCG, observed in an earlier study. In 1 animal a new primary tumour developed. At necropsy metastases were present in 33% of the treated animals: in 3 of 17 animals that showed complete regression of the primary tumour and in 7 of 13 animals with partial regression or progressive disease. This did not differ significantly from results obtained after a single treatment (27%). Delayed-type hypersensitivity toM. bovis purified protein derivative (PPD) was more persistent in animals showing regression of the primary tumour than in non-responding animals. Of the animals with a positive PPD response 6 months after treatment, 79% showed tumour regression. Regression was observed in only 28% of the animals not responding to PPD after the same period of time. In conclusion: (a) recurrence of the primary tumour was not observed after repeated BCG treatment; (b) the frequency of metastases was not decreased compared to results obtained with a single treatment; (c) regression was correlated with a positive delayed-type hypersensitivity reaction to PPD (P <0.05) 6 months after treatment; (d) no significant differences were observed when the clinical results of treatment with live BCG and the BCG cell wall vaccine were compared.     

On Hans,Zou and the others: wonder animals and the question of animal intelligence in early twentieth-century France

During the second half of the nineteenth century, the advent of widespread pet ownership was accompanied by claims of heightened animal abilities. Psychical researchers investigated many of these claims, including animal telepathy and ghostly apparitions. By the beginning of the twentieth century, news of horses and dogs with the ability to read and calculate fascinated the French public and scientists alike. Amidst questions about the justification of animal cruelty in laboratory experiments, wonder animals came to represent some extraordinary possibilities associated with their kind. Psychologists speculated on the feats of wonder animals. They considered the possibility that these animals shared consciousness and intelligence with humans, and that—if confirmed—their alleged amazing abilities could lead to a new understanding of cognition for all animals. This article focuses on the few years during which claims of wonder animals occupied a significant place in French psychology and psychical research. It argues that as explanations involving deception or unconscious cues gained increased acceptance, the interest in wonder animals soon led to a backlash in comparative psychology that had repercussions for all animals, particularly those used in experimentation, in that it contributed to the decline of research addressing cognitive abilities in non-human species.     

Belief in Animal Mind among Spanish Primary School Children

Beliefs concerning the mental experiences of nonhuman animals have been related to how people treat, see, and take care of nonhuman animals. Whereas this issue has been the subject of several studies on adults, few have been conducted with children. Taking advantage of a recently published scale, the Child-BAM questionnaire, we aimed to explore the beliefs in animal minds of Spanish primary school children. The study also considered the effects of a child's age, school year group, gender, and pet ownership on their beliefs in animal mind. The Child-BAM questionnaire, concerning the mental capabilities of eight different species (human, chimpanzee, dog, cow, otter, sparrow, frog, and fish), was distributed at a primary school sited in Cordoba, Spain. A total of 416 participants were included aged between 6 and 13 years. Each child provided scores for animals’ ability to have intelligence, experience pain, fear, happiness, and sadness, and total scores for the eight species were calculated. The results showed that children's beliefs about animal minds differed depending on the type of animal, and that children were more likely to believe in the emotional capacities of animals rather than their cognitive capabilities. Dogs achieved similar scores to humans regarding all capabilities, and higher than any other species, while the cow, fish, and frog generally scored the lowest. Age, school year group, and having a companion animal at home affected beliefs in animal minds, whereas gender had no effect. This study highlights cultural similarities in children's beliefs about animal minds and the potential importance of this variable for future research in child–animal interactions.     

Glutathione transferases in aquatic and terrestrial animals from nine phyla

Glutathione transferase (GST) was present in 71 of 72 animal species/stages representing nine phyla when measured with 1-chloro-2,4-dinitrobenzene (CDNB). Our hypothesis that all animals have GST was not falsified. Transferase activity towards ethacrynic acid (ETHA) was present in species from all phyla investigated, but some animals seem to be without this activity. Activity towards 1,2-dichloro-4-nitrobenzene (DCNB) was less developed in aquatic animals than in terrestrial ones. The amount of protein binding to GSH-affinity gel matrix was rather uniform, ranging between 0.3 and 0.7% of soluble protein in homogenates of widely diverse animal species, thus being less variable than the enzyme activity. Transferases active towards DCNB did not bind at all or were less firmly bound to the GSH-affinity gel than the activity towards CDNB or ETHA. Fractionation was obtained by using a gradient of GSH. With SDS-electrophoresis it was demonstrated that the proteins with affinity to GSH had monomers in the MW-range 21.500-29.000. Hydra attenuata had one band (MW = 25,000); all other sources gave a complex pattern with up to six bands. It is concluded that GSTs are characteristic major constituents of animal cells, probably with some common basic function. Mutant forms able to aid detoxication are retained in the phylogenesis when they increase the fitness of the animal.     

The effect of kupffer cell stimulation or depression on the development of liver metastases in the rat

Summary Tumour cells from a squamous carcinoma (approximately 2.5×10⁵) were injected intraportally into a syngeneic strain of rats to produce liver metastases 14 days later. Kupffer cells were stimulated by Corynebacterium parvum (7 mg or 1 mg i.v.) and zymosan (10 mg intraportally). Kupffer cell activity was depressed by the administration of silica, gadolinium chloride or human red cells. The animals in each group were sacrificed at 14 days, the livers removed and the number of visible surface metastases counted and compared. (Mann-Whitney U-test).Kupffer cell stimulation significantly reduced the number of surface liver metastases in all animals (P0.0048). In contrast depression of Kupfer cell activity significantly increased the number of metastases in all animals (P0.0045), suggesting that the activity of these cells has an important effect on the development of liver metastases.     

“He’s so Fluffy I’m Gonna Die!” Cute Responses by Hikers to Autonomous Animals on the Appalachian Trail

The Appalachian Trail is a more than 2,000-mile-long wilderness trail in the Eastern United States. Every year, aspiring long-distance hikers travel from across the US and abroad, intending to hike the entire length of the trail, which takes around 6 months to complete. Numerous species of wildlife dwell on and around the trail. The aim of this study was to explore how long-distance hikers perceived the nonhuman animals that they encountered on their trek, and how they described navigating these encounters. Due to a thriving online community of hikers who blogged about their experiences on the trail, it was possible to retrieve a substantial amount of rich data detailing first hand encounters between hikers and animals on the trail. It was found that just under a third of all hiker narratives mentioning wild animals on the trail indicated that the author had responded to the animal as being cute. Despite cuteness frequently being perceived as trivial or banal, this paper argues that a hiker’s perception of an animal as cute is more complex and meaningful to their overall experience of the animal than might initially be assumed. Both the aesthetic of cuteness and the effect of cuteness on an observer are considered in light of existing research on the subject. Some specific accounts of a hiker perceiving and responding to cuteness in animals on the trail are then explored, which leads on to a consideration of why so many animals on the trail might have been perceived as being cute. Finally, the paper discusses what being seen as cute meant for the animal involved, as hikers stared at, approached, followed, and frequently made attempts at touching or feeding animals that they found cute. The paper concludes that, far from being inconsequential, the perception of cuteness in an animal was meaningful for the human observer, as well as having consequences for the animal in question.     

Metastases of human tumor cells in immunosuppressed newborn rats

The metastatic ability of human tumour cells can easily be evaluated by using as an experimental model the production of metastases in newborn rats immunosuppressed by an optimal dose of anti-thymocyte serum. Thus, following sub-cutaneous injection of 10(6) cells, a human melanoma cell line, tumorigenic but non metastatic in nude mice, produces within 3 weeks tumours in all inoculated rats and lymph node and pulmonary metastases in 50% of the animals. The cloning of this cell line in semi-solid agar shows its heterogeneity and demonstrates that it contains poorly tumorigenic but highly metastatic cells.     

Hereditary melanoblastoma in miniature pigs and its successful therapy by devitalization technique.

Applying selective breeding for 10 years we established the MeLiM (Melanoblastoma-bearing Libechov Minipigs) strain. Melanoblastoma (MB) in this strain shows a hereditary occurrence. Cutaneous tumours are usually nodular, multiple and distributed on various parts of body. They appear in darkly pigmented animals already at the birth or during two months thereafter (57% of all animals). Numerous organ metastases mainly into the spleen, lymph nodes and lungs are regularly ascertained in animals with cutaneous MB. Tumour cells were surprisingly found also in the inner organs of phenotypically healthy minipigs in which no cutaneous MBs were observed visually (27% of all animals). About 34% of all affected piglets die during the first 2 months of age. These features document a malignancy of this tumour in the MeLiM strain. Original surgical technique was applied in more than 40 affected minipigs at 1-2 months of age. It consists in a devitalization (ischemization) of one of cutaneous tumours by the mattress sutures conducted around the tumour base without any excision of tumour tissue. This simple procedure causes a total destruction of MB cells in all cutaneous tumours as well as in all organ metastases during 4-6 months. Animals treated by this technique were fully healed of tumour cells and no relapses were observed. This technique could bring similar positive results also in therapy of human MB.     

SARS动物模型的研究

利用分离的SARS CoV毒株BJ 0 1,经滴鼻等途径感染大鼠、豚鼠、黑线仓鼠、白化仓鼠和雏鸡等 5个种属的动物 ,筛选对SARS易感的小动物。在此基础上 ,选择食蟹猴和恒河猴进行SARS的人工感染实验 ,评价其作为SARS动物模型的可能性。结果表明 ,大鼠、豚鼠、黑线仓鼠、白化仓鼠和雏鸡等动物对SARS均不易感 ,感染后未观察到任何的临床及病理学改变 ,不过从感染 2周后的大鼠和豚鼠的肺和咽等组织样本中检测到了的特异的核酸 ,提示SARS CoV能够在这两种动物的体内复制。从感染猴子的分泌物和脏器中分离出了病毒 ,证明SARS CoV也能够在猴子体内复制。临床和病理组织学检查结果显示 ,SARS病毒接种食蟹猴和恒河猴后 ,可以引起所有实验猴发生间质性肺炎 ,其病理学改变与人类感染SARS病毒后肺部病变近似 ,但病变的严重程度比较人类的轻得多 ,除此之外无任何其它的明显的临床表现及组织病理学改变 ,按照动物模型的指标判断食蟹猴和恒河猴并不是SARS的理想动物模型 ,不过在目前尚没有更理想的动物模型情况下 ,以间质性肺炎为病理学检查指标 ,恒河猴和食蟹猴可以作为评价抗SARS药物和疫苗的模型动物     

The question of animal immortality: changing attitudes

Abstract

Christian teaching has long held that only humans possess an immortal soul and it is commonly thought that this has had the effect of downgrading animal status. One item in each of two separate questionnaires investigated current attitudes to human and animal immortality. The first Survey (A), consisted of a 21-section questionnaire which focussed on the changing status of animals across three family-related generations. One hundred and one students, one of their parents and one of their grandparents were asked whether they believed in an afterlife for (a) humans and (b) all animals or (c) some animals (n = 303). The second survey (B) was a separate enquiry. It was sent both to principals of Christian ministerial courses (n = 22) and to those running university departments of philosophy. An extra item, asked of ministerial courses only, enquired what was the current teaching as to whether animals had the possibility of a life beyond this. Both questionnaires found that attitudes to animal immortality are changing.     

The effect of long-term administration of low oral doses of chlormadinone acetate on heat cycles and ovarian functions in beef heifers

Chlormadinone acetate (CAP) was given orally for 42 days to four groups of 15 regularly cycling Hereford heifers in Central Mexico (19°N, altitude 2200 m). The CAP doses (0.625; 1.25 and 2.5 mg/day per animal) represent 1/16th, 1/8th and 1/4th, respectively, of the cycle synchronizing dose of 10 mg. Heat was observed for 1 hour at 06.00, 12.00 and 18.00 h and animals in heat were rectally palpated at 6 h intervals until ovulation had occurred. Observations continued for the duration of the treatment period and 26 days thereafter. CAP treatment had significant effects. With 2.5 mg, occurrence of the next heat was delayed in 8 and inhibited in 6 animals; nine animals had synchronized heat after CAP withdrawal; five animals did not ovulate but developed luteinized follicles; animals not cycling had prolonged periods of vulvar swelling. With 1.25 mg CAP, most animals continued cycling, but estrous intervals were prolonged and 3 animals developed luteinized follicles. With 0.625 mg CAP, only a slight prolongation in estrous intervals and of the heat periods was observed.Individual differences in response to CAP were marked in all treatment groups. CAP at the higher doses interfered with mechanisms of ovulation and was partially effective in preventing heat and follicular development.In cycling animals the length of the cycle, the duration of heat and the daily variations of the onset of heat were within reported limits. The interval between disappearance of heat symptoms and ovulations (21.23 h) was about twice that reported in the literature. Ovulations followed a daily rhythm with a major peak between 24.00 and 0.600 h and a minor elevation between 12.00 and 18.00 h.     

Adaptation of skeletal muscle fibers to endurance training, confinement or selection for body weight and physical endurance of laboratory mice

By the help of histological methods the changes in skeletal muscle of laboratory mice, which had different levels of exercise during postweaning period (training, confinement) or had been selected for body weight and endurance fitness (Du-6+LB), were investigated. The animal groups with the better endurance fitness (Du-6+LB, trained) had a higher total number of muscle fibres. An increased aerobic capacity of metabolism for the trained and selected animals, a decreased one for the confined animals resulted, indicated by the composition of muscle fibre types of M. rectus femoris. The appearance of stress-induced pathological changes of muscle fibres was observed, with the highest extent in the confined group with decreased endurance fitness. Similar correlations between structure of muscle and fitness in domestic animals are to be expected.     

Spontaneous ovarian tumors in twelve baboons: a review of ovarian neoplasms in non-human primates

Twelve spontaneous ovarian tumors were found in the Southwest Foundation for Biomedical Research baboon colony. These included four granulosa cell tumors, three teratomas, two endometrioid carcinomas, one seromucinous cystadenofibroma, a cystic papillary adenocarcinoma, and an ovarian carcinoma. Age was a pre-disposing factor. With one exception, the tumors of surface epithelial- and sex cordstromal origin occurred in baboons over 17 years of age. The exceptional animal was 7 years of age when a malignant granulosa cell tumor with Sertoli cell differentiation was identified. The two endometrioid tumors, which were found in 17- and 30-year-old animals, were both associated with endometriosis. In contrast, the teratomas, which are tumors of germ cell origin, were found in younger animals, i.e. 17 years of age or younger. One case of an ovarian carcinoma with metastases was observed in a 6-month-old infant. Cases of spontaneous ovarian tumors from the literature are reviewed.