Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 469 records · Page 26Linked to original sources

PubMed1996

Induction of IL-6 production by bone marrow stromal cells on the adhesion of IL-6-dependent hematopoietic cells.

Cellular interactions between hematopoietic cells and stromal cells play crucial roles in the proliferation and differentiation of the hematopoietic cells. Interleukin-6 (IL-6)-dependent 7TD1 cells markedly proliferated without IL-6 when they were co-cultured with hematopoietic-supportive bone marrow stromal cells, HESS-5 cells and HESS-1 CL.3 cells, which can support long-term hematopoiesis in vitro with but not without direct cell contact, cell contact being prevented with a microporous membrane. The production of IL-6 and the amount of IL-6 mRNA in hematopoietic-supportive stromal cells but not 7TD1 cells significantly increased only when the stromal cells were co-cultured in direct contact with 7TD1 cells. Furthermore, the amount of IL-6 mRNA increased according to the number of 7TD1 cells co-cultured. These inductions were not observed on co-culture with a murine myeloid cell line, M1 cells, or on the addition of the co-culture supernatant. These results suggest that 7TD1 cells transmit the signal to stromal cells that enhances IL-6 production by stromal cells via direct cell contact. A certain specific molecule for transduction of the signals may exist on the surface membrane of stromal cells and hematopoietic cells.

Animals↗

PubMed1996

Rapid killing of murine lymph node T blasts by intestinal intraepithelial lymphocytes in vitro.

We examined the effect of murine intestinal intraepithelial lymphocytes (IEL) on the proliferation of murine lymph node T cells (LN-T) in vitro. An IEL fraction prevented the proliferation of LN-T stimulated with antigen and X-irradiated spleen cells, or with anti-CD3 monoclonal antibodies (mAb). Concanavalin A-activated LN-T were less sensitive. Such an inhibitory activity was recovered from a CD8-depleted population by panning of bulk IEL using anti-CD8 alpha mAb. This population of BALB/c IEL showed less granzyme A activity, and its surface markers were positive for CD8 (4%), CD3 (80-90%), CD4 (2-6%), alpha-beta TcR (45-70%), and gamma-delta TcR (4-9%). Asialo-GM1 and Thy1.2 were variably expressed, but interleukin-2 (IL-2) receptor-alpha and Fc gamma receptor were not. By contrast, no cytotoxicity against YAC-1 was detected in a CD8-depleted IEL population by a 6-h 51Cr-release assay. Although IEL from severe-combined immunodeficient mice lacking CD4, CD8 and TcR, but expressing IL-2 receptor, showed cytotoxicity against YAC-1, their inhibitory activity against LN-T was almost the same as that by IEL from BALB/c mice. When LN-T blasts (greater than 75% CD4+) activated with anti-CD3 were treated with CD8-depleted IEL, intact cellular DNA of the T blasts disappeared within 1 h with increased amounts of small-sized DNA. These results suggest that CD8- IEL directly and nonspecifically kill lymph node CD4+ T blasts and possibly down-regulate TcR-mediated proliferation of peripheral T cells in the gut epithelium.

Animals↗

PubMed1996

Immunohistochemical study of proteoglycans in D-galactosamine-induced acute liver injury in rats.

In this study, we carried out an immunohistochemical investigation of time-dependent alterations in the distribution of proteoglycans, and the proliferation profiles of hepatocytes and fat-storing cells (FSCs) in the livers of rats intoxicated with D-galactosamine (GalN). The proliferative cells were analyzed by proliferative cell nuclear antigen (PCNA) staining. In untreated rats, heparan sulfate, dermatan sulfate, and chondroitin/chondroitin sulfate were detected within the portal spaces and the central veins, and, with the exception of chondroitin, also within the reticular fibers. After administration of GalN, the number of PCNA-positive cells (FSCs and hepatocytes) and FSCs increased, reaching maximal on the 2nd and 3rd days, respectively. Heparan sulfate showed complicated changes. Dermatan sulfate decreased in portal spaces from the 2nd to the 3rd day, and in reticular fibers from 12 h to the 6th day. Chondroitin/chondroitin sulfate staining was observed from 2 h to the 6th day in the sinusoidal endothelia, which suggests that the sinusoidal endothelia may produce chondroitin/chondroitin sulfate transiently during liver damage as part of the mechanism of regeneration. Heparan sulfate and chondroitin/chondroitin sulfate were detected in necrotic regions, but dermatan sulfate was not. These observations suggest that heparan sulfate and chondroitin/chondroitin sulfate are involved in cell proliferation or morphogenesis and that the dermatan sulfate plays a role in the differentiation or functional maintenance of cells in liver regeneration.

Alanine Transaminase↗

PubMed1996

Effect of ketanserin on 5-hydroxytryptamine-induced constriction in isolated, perfused canine basilar arteries exposed to blood.

The blocking effect of ketanserin, a 5-hydroxytryptamine (5-HT)2 receptor antagonist, was examined on responses to intra-luminal 5-HT or potassium chloride (KCl) in isolated and perfused canine basilar arteries before and after extraluminal whole blood by means of the stainless-steel cannula inserting method. Four hours after the application of blood, the constriction to 5-HT was significantly enhanced, while that to KCl was significantly attenuated. The absolute value in the decrease of perfusion pressure for the 5-HT-induced constriction sensitive to ketanserin was much greater after the blood application than that before the application. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage immediately after subarachnoid haemorrhage (SAH) might be mediated by 5-HT2 receptors at least in part. This early constrictor mechanism may be implicated in the aetiology of the following late stage of cerebral vasospasm after SAH.

Animals↗

PubMed1996

Effect of clot removal on cerebrovascular contraction after subarachnoid hemorrhage in the monkey: pharmacological study.

Clot removal at early surgery has been reported to be clinically effective for the prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm. We examined the most efficacious timing of mechanical clot removal on pharmacological responses in a monkey SAH model. Cynomolgus monkeys (Macaca fascicularis) were randomized into five groups: sham-operated, clot removal in which the clot was removed 48, 72, or 96 h after SAH, and clot groups. An autologous blood clot was placed around the bilateral major cerebral arteries after craniectomy to mimic the hemorrhage. Seven days after the SAH, proximal and successively distal parts of the middle cerebral arteries were cut into rings for isometric tension measurement. The contractile responses to potassium chloride, 5-hydroxytryptamine, norepinephrine, adenosine triphosphate, prostaglandin F20, and hemoglobin were greater in the proximal parts than in the distal parts in each group. Compared with the sham-operated group, the responses of the clot-removal and clot groups to the drugs were progressively attenuated. The maximum responses to 5-hydroxytryptamine in the proximal parts and to adenosine triphosphate in the distal parts started to decrease, significantly, in the clot-removal group 48 h after SAH, while most of the responses to the other agonists began to decrease in the clot-removal groups later than 72 h after SAH. These results suggest that the attenuation of cerebrovascular contractile responses 7 days after SAH is pharmacologically inevitable, even if the clot is removed as early as 48 h after the SAH. Clot removal may thus be recommended within 48h after SAH to ameliorate the severity of cerebral vasospasm following SAH.

Adenosine Triphosphate↗

PubMed1996

Potentiation of antitumor and antimetastatic activities of adriamycin by a novel N-alkylated dihydropyridine, AC394, and its enantiomers in colon cancer-bearing mice.

PURPOSE: We have previously shown that a series of N-alkylated 1,4-dihydropyridines potentiate the therapeutic efficacy of vincristine in vincristine-resistant P388 leukemia. The purpose of this study was to investigate the ability of one of the compounds, AC394, and its enantiomers to potentiate the antitumor activity of adriamycin against colon cancer cells in vitro and in vivo. METHODS: The effects of AC394 on potentiation of adriamycin cytotoxicity and enhancement of its accumulation were evaluated using colon 26, HCT-15 and MCF-7 cells. Furthermore, the activities of AC394 and its enantiomers were compared. We also studied the combined effects of (+)-AC394 and adriamycin on subcutaneously (s.c.)-implanted and liver metastasis tumor models. RESULTS: AC394 potentiated the cytotoxicity of adriamycin and enhanced its accumulation in colon cancer cells (colon 26 and HCT-15), which are known to express P-GP (P-glycoprotein) intrinsically. Enhancement of adriamycin accumulation by AC394 was found in s.c.-implanted colon 26 cells in vivo. Although both enantiomers of AC394 showed equal activity in vitro, (+)-AC394 was more effective than (-)-AC394 given orally. (-)-AC394 was found to be cleared more rapidly from the plasma than (+)-AC394. Thus, (+)-AC394 was evaluated for further study. Administration of (+)-AC394 significantly potentiated the antitumor activities of adriamycin in human colon cancer HCT-15 cells implanted s.c. Furthermore, in the liver metastasis model using colon 26 cells, a model completely resistant to adriamycin, the combination therapy of adriamycin with (+)-AC394 produced superior antitumor effects over adriamycin alone. CONCLUSIONS: A newly synthesized N-alkylated 1,4-dihydropyridine derivative, (+)-AC394, showed superior effects on the potentiation of adriamycin antitumor and antimetastatic activities in vivo. These results suggest that this combination may have therapeutic efficacy not only against primary colon cancers but also against metastatic liver cancer.

Animals↗

PubMed1996

Immunogenicity of Leucocytozoon caulleryi sporozoites and their reactivity with specific immune sera.

The immunogenicity of Leucocytozoon caulleryi sporozoites for chickens and their reactivity in vitro with specific immune sera were studied. Almost all of the chickens that had been immunized with the sporozoite antigens survived the sporozoite challenge. The degree of parasitemia observed in the immunized chickens was significantly lower than that found in the nonimmunized chickens. Specific antibodies against sporozoites were tested by the circumsporozoite precipitation (CSP) reaction. Antibodies were demonstrated in the sera of chickens that had been immunized with the sporozoite antigens or chickens that had recovered from a primary infection with L. caulleryi sporozoites. When viable mature sporozoites were incubated in vitro with serum from immune chickens, agglutination and a long, thread-like precipitate at one end of the sporozoite could be seen within a few minutes under a phase-contrast microscope. The effects of specific immune serum on the infectivity of sporozoites were examined by the sporozoite neutralization activity (SNA) test. Sporozoites that had been incubated in vitro with serum from immune chickens lost their infectivity to chickens. The CSP reaction and the SNA test in L. caulleryi infection were stage- and species-specific.

Animals↗

PubMed1996

Elevated plasma superoxide dismutase activity in patients with systemic sclerosis.

Injury to vessel walls, especially microvascular damage due to free radicals, has been a focus of interest concerning the pathogenesis of systemic sclerosis. Excess reactive oxygen species may induce antioxidant defenses. We therefore measured plasma superoxide dismutase (SOD) activity in patients with systemic sclerosis and found average SOD activity of plasma in 16 patients with systemic sclerosis (5.00 +/- 3.10 U/ml) to be significantly (P < 0.001) higher than those in 89 healthy volunteers (1.56 +/- 0.234 U/ml). Patients with Raynaud's phenomenon and/or skin sclerosis had particularly high SOD activity. These findings suggest that plasma SOD activity may serve as a useful parameter for assessment of sclerotic progression and the presence of Raynaud's phenomenon.

Adult↗

PubMed1996

Increased expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of the samples from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells began at five days after injection of anti-Thy 1.1 antibody and peaked at the tenth day. On the other hand, the expression of the proliferating cell nuclear antigen in the mesangial cells was induced at two days after injection of anti-Thy 1.1 antibody and was maximal at the fourth day. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.

Adolescent↗

PubMed1996

Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC).

The third component of complement (C3) is central to both the classical and alternative pathways in complement activation. In this study, involvement of C3 activation in the mucosal injury of UC was investigated. We examined the distribution of activated (C3b) and degraded fragments (iC3b/C3dg) of C3, terminal complement complex (TCC), and complement regulatory proteins in normal and diseased colonic mucosa including UC and other types of colitis using immunohistochemical techniques at the level of light and electron microscopy. While C3b and iC3b/C3dg staining was negligible in the normal mucosa, iC3b/C3dg and, to a lesser extent, C3b were deposited in UC mucosa along the epithelial basement membrane. The deposition was enhanced in relation to the severity of mucosal inflammation (C3b, P less than 0.05; iC3b/C3dg, P less than 0.01). Epithelial deposition of TCC was not observed in most UC mucosa. Immunoelectron microscopy showed that C3b and iC3b/C3dg were distributed mainly along the epithelial basement membrane and the underlying connective tissue in a granular, studded manner, and weakly present along the basolateral surface of epithelial cells. These C3 fragments were also deposited in inflammatory control mucosa such as ischaemic and infectious colitis. Our findings suggest that deposition of the C3 fragments occurs in inflamed colonic mucosa of diverse etiologies, including UC, but to define a role of the deposition in the development of mucosal injury in UC awaits direct study.

Adult↗

PubMed1996

Cellular distribution of transcripts for tissue inhibitor of metalloproteinases 1 and 2 in human hepatocellular carcinomas.

The cellular distribution of tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 was studied by using in situ hybridization in surgically removed human hepatocellular carcinomas (HCCs) and cholangiocellular carcinomas (CCCs). The purpose of this study was to characterize the protein involvement of TIMPs in the development of HCCs and CCCs. All HCCs and CCCs expressed TIMPs. The distribution of transcripts for TIMPs in the tumors was mostly homogeneous. Expression of TIMP in cancer cells was more intense than that in the surrounding noncancerous liver (either, cirrhosis, chronic hepatitis, or normal), and expression of TIMP-1 was stronger than that of TIMP-2. Expression of TIMPs varied among HCC nodules, but there was no obvious association between the expression level of TIMPs and differentiation stages or invasiveness of the HCCs. Transcripts for TIMPs were clearly demonstrated in the metastatic HCC nodules in the lung. Expression of TIMP-1 CCC was strong, and small nodules of CCC were recognized in the liver. Immunohistochemical study for TIMP-1 revealed a consistent staining of the TIMP protein with the transcripts. In the peritumoral histologically normal liver, which was not infected with either hepatitis B or C virus, expression of TIMP-1 was found in various cell types, but that of TIMP-2 was weak. Expression of TIMP-1 in hepatocytes revealed clear zonal distribution. These results suggest that TIMPs may act on modulating the matrix/tumor interaction and may play an important role in growth and invasion of HCCs and CCCs. Expression of TIMP-1 can be a marker of HCC metastasis to the lung, and also that of the extent of CCC invasion. Furthermore, the consistent expression of TIMPs in many cell types of the noncancerous liver suggests some unknown functional role that must be clarified.

Aged↗

PubMed1996

Enzyme-linked immunoassay for midkine, and its application to evaluation of midkine levels in developing mouse brain and sera from patients with hepatocellular carcinomas.

Midkine (MK) is a growth factor that promotes neurite outgrowth and survival of neurons, and enhances the plasminogen activator in endothelial cells. A highly sensitive enzyme-linked immunoassay for MK was developed, involving affinity-purified anti-MK antibodies, their biotinylated form, and avidin-beta-galactosidase. The amount of bound avidin-beta-galactosidase was determined using a fluorogenic substrate, 4-methylumbelliferyl-beta-D-galactoside. This method allowed the detection of human and mouse MK in the range of 50 pg-10 ng. Pleiotrophin, which is related to MK in its amino acid sequence, did not show any cross reactivity. Employing this method, the MK levels in the developing mouse brain were determined. The MK level was 2 micrograms/g of wet tissue on the 12th day of gestation, and then steadily decreased during embryogenesis and postnatal development to 30 ng/g two months after birth. The assay method can also be applied to serum samples. Although the MK levels in the sera of normal human subjects were low or undetectable, 0.6-8 ng/ml of MK was detected in samples in the majority of cases of hepatocellular carcinomas.

Animals↗

PubMed1996

Epithelial cell proliferation during colonic chemical carcinogenesis in the rat.

To define the significance of alterations in epithelial cell proliferation as a marker of high risk mucosa for colorectal cancer, we examined cell proliferative events in the colonic mucosa during chemical carcinogenesis using in vitro bromodeoxyuridine labelling and by analysing serial colonoscopic biopsy specimens from dimethylhydrazine (DMH)-treated rats. In both the rectum and flexure of the colon, an increased labelling index of colonic epithelial cells, an upward extension of the proliferating zone and an upward shift of the major area of DNA synthesis of epithelial cells were observed during DMH-induced colonic carcinogenesis in rats. These changes preceded the development of the colonic tumour and were observed in endoscopically normal rectal mucosa where the tumour was absent. We confirmed the altered cell proliferative events preceding the development of the tumour by examining serial colonoscopic biopsies. The results suggest that these alterations are features that identify premalignant colonic mucosa in DMH-treated rats.

Animals↗

PubMed1996

Transient elevation of nerve growth factor content in the rat hippocampus and frontal cortex by chronic ethanol treatment.

The nerve growth factor (NGF) content in the hippocampus and frontal cortex of chronic ethanol-treated rats was measured and compared with that of control rats, using a two-site enzyme immunoassay (EIA) system. The different time periods of chronic ethanol treatment caused transient elevation of the NGF content in both the hippocampus and frontal cortex. The NGF content in the hippocampus was significantly elevated in rats undergoing ethanol treatment of 2 weeks and 1 month. Nerve growth factor content of the 1 month treatment was higher than that of the 2 week treatment. However, a 3 month administration of ethanol reduced the NGF content to the control level. The NGF content in the frontal cortex increased significantly in the 2 week administration, but decreased to the control level in the 1 month administration. The increase of NGF may be caused by the proliferation of glial cells or the enhancement of neuronal production of NGF.

Animals↗

PubMed1996

Chondroid syringoma: an immunohistochemical study using antibodies to Ca 15-3, KA-93, Ca 19-9, CD44 and BM-1.

The expression of Ca 15-3, KA-93, Ca 19-9, CD44 and BM-1 in normal skin and chondroid syringoma was investigated immunohistochemically using antibodies to these antigens. In the normal skin, the eccrine ducts and/or secretory elements were positive for all these antigens. On the other hand, the apocrine ducts and/or secretory elements were positive for the antibodies to Ca 15-3, KA-93 and CD44. In chondroid syringoma, the luminal cells of tubuloglandular structures were positive for the antibodies to Ca 15-3 and BM-1, and partly positive for those to KA-93 and Ca 19-9. The basal cells of the tubular structures and solid nests were positive only for the antibody to CD44. Stromal cells in the myxoid area were positive for the antibodies to KA-93 and CD44, and the chondroid matrix was positive for the antibody to BM-1. It is suggested that chondroid syringoma might originate from, or differentiate into the ducts and/or secretory elements of the eccrine sweat glands. In addition, the significance of the expression of BM-1 in the chondroid matrix is discussed.

Adenoma, Pleomorphic↗

PubMed1996

Apoptosis and proliferation of human hepatocellular carcinoma.

To investigate the contribution of apoptosis, a major mechanism of cell death, in the growth of hepatocellular carcinoma, we analyzed both apoptosis and cell proliferation in human hepatocellular carcinoma. We used the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method and proliferative cell nuclear antigen staining, respectively. Among 21 hepatocellular carcinoma specimens examined, four were well, ten were moderately, and seven were poorly differentiated hepatocellular carcinoma. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells in hepatocellular carcinoma were scattered individually or were sometimes clustered in the tumors. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling indices were 0.35 +/- 0.09, 0.81 +/- 0.29, and 1.9 +/- 0.94 in well, moderately, and poorly differentiated hepatocellular carcinoma, respectively. The proliferative cell nuclear antigen labeling indices were 6.6 +/- 0.9, 13.1 +/- 3.5, and 26.7 +/- 6.3 in hepatocellular carcinoma in the same respective order of differentiation. The differences in both terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling indices and proliferative cell nuclear antigen labeling indices (p < 0.05) were significant between well, moderately and poorly differentiated hepatocellular carcinoma. There was a positive correlation between the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and proliferative cell nuclear antigen labeling indices in hepatocellular carcinoma (r = 0.84, p < 0.001). This study showed that the proliferation rate and the incidence of apoptosis increased as the differentiation grade of hepatocellular carcinoma was lowered, suggesting a rapid turnover of cancer cells in the lower differentiation grades. Apoptosis may thus play an important role in the growth of hepatocellular carcinoma.

Apoptosis↗

PubMed1996

Telomere length in human liver diseases.

To determine the role of telomere-mediated gene stability in hepatocarcinogenesis, we examined the telomere length of human liver with or without chronic liver diseases and hepatocellular carcinomas (HCC). The mean telomere restriction fragment (TRF) length of normal liver (n = 13), chronic hepatitis (n = 11), liver cirrhosis (n = 24) and HCC (n = 24) was 7.8 +/- 0.2, 7.1 +/- 0.3, 6.4 +/- 0.2 and 5.2 +/- 0.2 kb, respectively (mean +/- standard error). TRF length decreased with a progression of chronic liver diseases and that in HCC was significantly shorter than that in other chronic liver diseases (p < 0.05). The ratios of TRF length of HCC to that of corresponding surrounding liver of well differentiated (n = 7), moderately differentiated (n = 10) and poorly differentiated (n = 4) HCCs were 0.83 +/- 0.06, 0.75 +/- 0.05 and 0.98 +/- 0.09, respectively. The ratio of poorly differentiated HCC was significantly higher than that of moderately differentiated HCC (p < 0.05). A comparison between the size and telomere length ratio of moderately differentiated HCCs revealed a decrease of the ratio with size until it reached 50 mm in diameter. In contrast, the ratio increased as the size enlarged over 50 mm. These findings suggest that the gene stability of the liver cells mediated by the telomere is reduced as chronic liver disease progresses and that telomerase is activated in poorly differentiated HCC and moderately differentiated HCC over 50 mm in diameter.

Adolescent↗

PubMed1996

A classical strain of Vibrio cholerae with diminished ability to process the proteolytically sensitive site in the A subunit of cholera toxin.

Vibrio cholerae O1, No. 31, a strain isolated from a patient with mild diarrhea, produced mainly the unnicked cholera toxin. The amount of toxin that had accumulated in the cells was approximately 200 times lower than that secreted into the culture medium. When the unnicked toxin was purified by three successive column chromatographies and then extracted from the polyacrylamide gel, the unnicked toxin showed two bands corresponding to the A and B subunits by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the A1 fragment was detected by trypsinization. Biological and enzymatic activities of the purified toxin with trypsinization were identical to those of cholera toxin from V. cholerae 569B as seen in the rabbit skin permeability test and the NAD:agmatine ADP-ribosyltransferase assay. DNA sequences of the A and B subunits were identical to those of the A- and B-subunit genes from the El Tor 2125 and classical 0395 strains, respectively. These data suggest that the wild V. cholerae strain, No. 31, produces a toxin identical to toxins previously reported in the literature and secretes it without accumulation in the cell, as is the case with other strains. However, strain No. 31's ability to nick the toxin is diminished compared with such abilities of other strains.

Animals↗