Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 109 records · Page 6Linked to original sources

PubMed1999

Human glutathione S-transferase P1 polymorphism and susceptibility to smoking related epithelial cancer; oral, lung, gastric, colorectal and urothelial cancer.

The A/G polymorphism at nucleotide 313 in the glutathione S-transferase P1-1 (GSTP1) gene was examined in patients with different types of smoking-related cancers (oral, lung, gastric, colorectal and urothelial cancers) and healthy control individuals. This polymorphism results in an amino acid substitution from isoleucine to valine at residue 105, which reduces catalytic activity of the enzyme. In control individuals, 23.8% of individuals had GSTP1 AG or GG genotype. This rose to 37.3% [n = 83, odds ratio = 1.93 (1.05-3.58), P = 0.035] in oral cancer patients. No increase in the frequency of the GSTP1 AG or GG genotype was obtained in lung, gastric, colorectal or urothelial cancers in this Japanese population. After grouping by smoking status, no consistent difference was observed between smoking patients and corresponding control individuals for the frequency of the GSTP1 A/G polymorphism for any cancer. However, a moderate risk (odds ratio = 2.78; 95% confidence interval 1.06-7.51) was associated with this polymorphism in the non-smoking group of oral cancer patients. The results suggest the GSTP1 polymorphism at nucleotide 313 may be associated with susceptibility to oral squamous cell carcinoma in the Japanese population.

Base Sequence↗

PubMed1999

[Chemoradiation therapy for advanced esophageal cancers--report of 3 cases].

Three cases of prominent-type advanced esophageal cancer were treated with chemoradiation therapy using a 5-FU analog and low dose CDDP. All cases showed a complete response after the treatment. Only mild bone marrow suppression was found in one case. This protocol will be applied for patients with prominent-type advanced esophageal cancers, especially high risk patients.

Aged↗

PubMed1999

[p-Nitrophenol].

Explore the source record for details and available documents.

Environmental Monitoring↗

PubMed1998

Effects of glutathione S-transferase (GST) M1 and GSTT1 genotypes on urothelial cancer risk.

The M1 member of the mu class of the glutathione S-transferase (GSTM1) gene is present in about 50% of individuals. GSTT1, a member of the theta class, which has been recently shown to be polymorphic, is expressed in 35-90% of individuals. In this study, 145 Japanese patients with urothelial transitional cell carcinoma and 145 healthy controls, frequency-matched for age and gender, were compared for frequencies of GSTM1 and GSTT1 genotypes. The urothelial cancer risk increased due to the GSTM1 null genotype (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.05-2.79). On the other hand, the OR tended to decrease due to the GSTT1 null genotype, although not significantly. Among individuals of the GSTM1 null genotype, those of the GSTT1-positive genotype had a two-fold risk (OR 2.62, 95% CI 1.36-5.05) compared with the GSTT1 null genotype (OR 1.25, 95% CI 0.62-2.51). A significant interaction between the GSTM1 genotype and smoking status was found; the GSTM1 null genotype was associated with an increased risk of urothelial cancer among smokers (OR 1.98, 95% CI 1.10-3.57).

Aged↗

PubMed1998

Expression of membrane-bound transferrin-like protein p97 on the cell surface of chondrocytes.

A concanavalin-A-binding protein of 76 kDa was purified from the plasma membrane fraction of rabbit chondrocyte cultures. Amino acid sequencing of the N-terminal region and of tryptic peptides of the protein, in addition to sequencing of its cDNA revealed that this protein is highly similar to the tumour-associated antigen p97. Hence, it was concluded that this protein is the rabbit form of p97. Western blotting, Northern blotting and reverse-transcription PCR analyses indicated that rabbit p97 is expressed at high levels in cartilage and chondrocytes, but is barely detectable in the bone, liver, kidney, small intestine, eye, pancreas, heart, testis, skeletal muscle, spleen and fibroblasts. Immunocytochemical and immunohistochemical analyses demonstrated that p97 is expressed in the plasma membrane of chondrocytes. p97 transcript was detected in all zones of the cartilage but the level was relatively low in the hypertrophic zone. These findings suggest that p97 is involved in maintaining the cell surface characteristics of chondrocytes.

Amino Acid Sequence↗

PubMed1998

[Trends of the biological monitoring measurements from 1991 to 1995].

Partial amendments to the Japanese Regulation on the Prevention of Lead Poisoning and that of Organic Solvent Poisoning were made in 1989. As a result, the measurement of blood lead and urinary delta-aminolevulinic acid (delta-ALA) became indispensable items of the occupational health examination for workers who handle lead. Also, the measurement of urinary metabolites of workers who handle eight kinds of organic solvents (xylene, N,N-dimethylformamide, styrene, tetrachloroethylene, 1,1,1-trichloroethane, trichloroethylene, toluene, and normal-hexane) became mandatory. The results of the biological monitoring mentioned above are classified into one of three categories, that is, distribution 1, 2 and 3, according to the concentration of the determinants. In this paper, the incidence of distribution 1, 2 and 3 of each determinant is reported and its change from 1991 to 1995 is discussed. The incidence of distribution 3 was 0.1-5.0% in each determinant. Although the ratio of distribution 1, 2 and 3 seems to have been almost the same for 5 years some determinants decreased their percentage of distribution 3. It is important to utilize the biological monitoring results for the improvement of working environments and working styles, and health management.

Aminolevulinic Acid↗

PubMed1998

Pancreatic carcinoma: correlation between E-cadherin and alpha-catenin expression status and liver metastasis.

BACKGROUND: Dysfunction of the E-cadherin/catenin-mediated cell-cell adhesion system has been associated with invasiveness and poor differentiation of human carcinomas. However, its importance in the genesis of liver metastasis has not been examined sufficiently. METHODS: A series of 26 primary pancreatic carcinomas and the concomitant liver metastases from 15 of them, obtained at autopsy, were analyzed for E-cadherin and alpha-catenin protein expression by immunohistochemistry. RESULTS: Both E-cadherin and alpha-catenin expression were preserved in 15 (58%) and reduced in 11 (32%) of the 26 primary pancreatic carcinomas. In the former 15 primaries, carcinoma cells were attached to each other tightly, whereas the latter 11 primaries showed isolated or loosely connected attachments. The metastatic ratio was higher in tumors exhibiting tight adhesion than in those with loose adhesion: 73% and 36%, respectively (P = 0.059). E-cadherin and alpha-catenin expression patterns in liver metastases basically followed those in the corresponding primaries (P < 0.01). CONCLUSIONS: Reduced E-cadherin and alpha-catenin expression in primary pancreatic carcinoma has no significant predictive value regarding the presence of liver metastasis. Rather, there is a greater tendency for liver metastasis in cases in which the integrity of the E-cadherin/catenin-mediated cell-cell adhesion system is intact.

Adult↗

PubMed1998

Role of chondroitin sulfate-hyaluronan interactions in the viscoelastic properties of extracellular matrices and fluids.

The purpose of this study was to investigate the role of chondroitin sulfate-hyaluronan interactions in the viscoelastic properties of tissues and fluids, using capillary and cone-on-plate viscometers. Chondroitin sulfate markedly increased the viscosity of hyaluronan solutions at a wide range of hyaluronan mass (50-1900 kDa) under physiological conditions of pH, temperature, ionic strength and glycosaminoglycan concentration (0.5-40 mg/ml), although the viscosity of the chondroitin sulfate solutions themselves was very low. In the assay using a cone-on-plate viscometer, chondroitin sulfate increased the viscosity of hyaluronan solutions at various shear rates. At low shear rates, the viscosity of a chondroitin sulfate (5 mg/ml)-hyaluronan (0.5 mg/ml) mixture was about 40% of that of an aggrecan (5 mg/ml)-hyaluronan (0.5 mg/ml) mixture, and at 2.8-fold higher concentrations, chondroitin sulfate elicited the same effect on the viscosity of hyaluronan solutions (5 mg/ml) as an aggrecan monomer. In the presence of oscillatory motion, the addition of aggrecan increased the elasticity (storage) modulus G' and the viscosity (loss) modulus G" of hyaluronan solutions and markedly decreased the loss tangent G"/G' at frequencies corresponding to normal joint movements. In contrast, chondroitin sulfate had only a marginal effect on the loss tangent G"/G', although it increased G' and G". These findings demonstrated that chondroitin sulfate, as well as aggrecan, increases the viscosity of hyaluronan solutions, although chondroitin sulfate has less effect on the elasticity of hyaluronan solutions than that of aggrecan, and suggest that chondroitin sulfate may play an important physiological role in determining the viscoelastic properties of extracellular matrices and fluids.

Aggrecans↗

PubMed1998

Structural and phylogenetic analyses of RGD-CAP/beta ig-h3, a fasciclin-like adhesion protein expressed in chick chondrocytes.

A cDNA for RGD-CAP/beta ig-h3 was cloned from a chick embryo chondrocyte cDNA library. The deduced amino acid sequence showed that the chick RGD-CAP/beta ig-h3 is 76-77% identical with human, mouse and pig forms of the protein, and 43% identical with human and mouse osteoblast specific factor 2 (OSF2). RGD-CAP/beta ig-h3 contained four internal repeat domains and two highly conserved sequences (H1 and H2) in each repeat. Chick RGD-CAP/beta ig-h3, as well as the mammalian RGD-CAP/beta ig-h3, contained an RGD sequence, which may serve as a recognition sequence for integrins, in the fourth repeat. Database searches revealed that the H1 and H2 sequences are conserved in some secreted or membrane proteins of several species including mammals, insects, sea urchins, plants, yeast and bacteria. Phylogenetic analysis showed that a portion of the common ancestor gene for RGD-CAP/beta ig-h3 and OSF2 was duplicated to form four repeat domains before the separation of the genes followed by the divergence of vertebrate species.

Amino Acid Sequence↗

PubMed1998

Differential effects of various growth factors and cytokines on the syntheses of DNA, type I collagen, laminin, fibronectin, osteonectin/secreted protein, acidic and rich in cysteine (SPARC), and alkaline phosphatase by human pulp cells in culture.

The purpose of this study is to differentiate roles of several growth factors and cytokines in proliferation and differentiation of pulp cells during development and repair. In human pulp cell cultures, laminin and type I collagen levels per cell remained almost constant during the whole culture period (22 days). On the other hand, secreted protein, acidic and rich in cysteine (SPARC/osteonectin) and alkaline phosphatase (ALPase) levels markedly increased after the cultures reached confluence. Laminin and type I collagen, as well as fibronectin, stimulated the spreading of pulp cells within 1 h. Adding transforming growth factor-beta (TGF-beta) decreased laminin and ALPase levels, whereas it increased SPARC and fibronectin levels 3- to 10-fold. Western and Northern blots showed that TGF-beta enhanced SPARC synthesis at the protein and mRNA levels. Basic fibroblast growth factor (bFGF) decreased type I collagen, laminin, SPARC, and ALPase levels without changing the fibronectin level. Platelet-derived growth factor (PDGF) selectively decreased laminin, SPARC, and ALPase levels. Epidermal growth factor (EGF) also decreased SPARC and ALPase levels. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) decreased type I collagen and laminin levels, and abolished SPARC and ALPase syntheses. Of these peptides, bFGF and PDGF showed the greatest stimulation of [3H]thymidine incorporation into DNA. TGF-beta, EGF, and TNF-alpha had less effect on DNA synthesis, whereas IL-1beta inhibited DNA synthesis. These findings demonstrated that TGF-beta, bFGF, EGF, PDGF, TNF-alpha, and IL-1beta have characteristically different patterns of actions on DNA, laminin, type I collagen, fibronectin, ALPase, and SPARC syntheses by pulp cells.

Alkaline Phosphatase↗

PubMed1998

Elevation of serum human hepatocyte growth factor (HGF) level in patients with pneumonectomy during a perioperative period.

OBJECTIVE: Proliferation of alveolar type II cells is thought to be critical for the restoration of lung function after diffuse alveolar damage or pneumonectomy. However, the factors that regulate alveolar type II cell proliferation, and the mechanism that brings about compensatory lung growth are not well understood. Hepatocyte growth factor (HGF) has been shown to have hepatotrophic and nephrotrophic functions for regeneration of the liver and kidney. We have attempted to investigate the involvement of HGF in lung regeneration after lung resection. DESIGN: A prospective, controlled study. SETTING: Adult surgical patients in a university hospital. PATIENTS AND MEASUREMENTS: We measured serum HGF levels in eight patients undergoing major lung resection, and in five patients undergoing mastectomy as controls, by using radioimmunoassay and an enzyme-linked immunosorbent assay. RESULTS: In all cases of pneumonectomy, the serum HGF levels increased 3- to 5-fold at 1-3 days (with a peak at 3 days) after operation, and then decreased to nearly basal levels in 2 weeks. However, these levels in patients undergoing mastectomy did not change much over the first 2 weeks, postoperatively. CONCLUSIONS: Serum HGF levels increased in patients after major lung resection, which suggests that HGF might play an important role in lung regeneration or compensatory lung growth in humans.

Analysis of Variance↗

PubMed1998

Doubly entrapped baker's yeast survives during the long-term stereoselective reduction of ethyl 3-oxobutanoate in an organic solvent.

To attain long-term bioreaction in organic solvents with living microorganisms, we tried to protect the microorganisms from the toxicity of the solvent by immobilization. In this study, baker's yeast, which is not tolerant to organic solvents such as isooctane, was selected as a model microorganism and the immobilized living yeast cells were examined for activity in the steroselective reduction of ethyl 3-oxobutanoate to ethyl (S)-3-hydroxybutanoate in isooctane; an activity that correlated well with the viability of the yeast cells. It was found that double entrapment, that is, further entrapment of calcium-alginate-gel-entrapped cells with a urethane prepolymer, made it possible for the yeast to remain viable in isooctane, although other conventional immobilization methods, such as single entrapment using polysaccharide or synthetic resin prepolymers, were insufficient for its protection. Furthermore, doubly entrapped living yeast cells could carry out the stereoselective reduction in isooctane repeatedly for a long period (more than 1200 h) with occasional cultivation. Thus, double entrapment enabled a microorganism sensitive to organic solvents to survive over long-term bioreaction in an organic solvent.

Acetoacetates↗

PubMed1998

Immunocytochemical localization of annexin 5, a calcium-dependent phospholipid-binding protein, in rat endocrine organs.

Annexin 5, a unique calcium- and phospholipid-binding protein, has been investigated for its specific distribution in rat endocrine organs by immunocytochemistry with a specific antiserum to recombinant rat annexin 5. Follicular epithelial cells and parafollicular cells of the thyroid gland, adrenocortical cells of the zona fasciculata and zona reticularis, luteal cells, testicular interstitial cells, and Sertoli cells were shown to contain annexin 5. To examine whether the synthesis of annexin 5 would be affected by a change in humoral signal, the distribution of annexin 5 in the anterior pituitary was examined three weeks after ovariectomy. The withdrawal of ovarian hormones induced huge castration cells in the anterior pituitary gland, which contained abundant annexin 5. Annexin 5 was not detected in the pineal gland, the parathyroid gland, the islet of Langerhans, the adrenal medulla, zona glomerulosa cells, and granulosa cells. Since annexin 5 was shown to exist in many of the endocrine tissues examined, to be localized in specific cell types, and to be abundant in castration cells, it is suggested that annexin 5 contributes to secretory cell functions, which may be common to endocrine cells secreting chemically different hormones.

Animals↗

PubMed1998

SKW 6.4 cell differentiation induced by interleukin 6 is stimulated by butyrate.

We investigated if sodium butyrate (NaBu), an inhibitor of histone deacetylase, and its analogs modulate cytokine-induced differentiation of the human B cell line SKW 6.4 transformed by the Epstein-Barr virus. NaBu markedly enhanced interleukin (IL)-6-induced IgM production with an accompanying increase in the level of histone H4 acetylation and augmented IgM production induced by IL-4 and phorbol 12-myristate 13-acetate. From both the enhancing effect of cell differentiation and the effect of inducing histone hyperacetylation in SKW 6.4 cells, other histone deacetylase inhibitors and NaBu analogs were divided into three groups: those that increased both IL-6-induced antibody production and histone acetylation, those that caused histone hyperacetylation, but failed to induce the differentiation, and those that were ineffective at inducing either activity. No agent that enhanced IgM production without inducing histone hyperacetylation was found among the inhibitors and analogs we tested. These results suggest that the increase in the histone acetylation is necessary, but it is insufficient to augment differentiation of SKW 6.4 cells. Thus another activity of NaBu in addition to the inhibition of histone deacetylase may be involved in promoting IL-6-induced differentiation. Our results also suggest that fatty acids that have a straight chain of four carbon atoms or are branched with four and five carbon atoms, which contain no hydrophilic substituents, or those with similar structures, show this other activity.

Acetylation↗

PubMed1998

Flow dynamics of angiographically no-flow patent internal mammary artery grafts.

OBJECTIVES: This study sought to assess the flow dynamics of internal mammary artery grafts (IMAGs) in no-flow situations by use of a Doppler guide wire. BACKGROUND: Functionally no-flow and anatomically patent IMAGs have been reported by angiography in patients with a patent recipient coronary artery. METHODS: The study included 12 patients with an IMAG to the left anterior descending coronary artery (LAD) in whom no-flow patency of the graft was suspected angiographically. Thirteen patients with a normally functioning IMAG whose LAD was occluded in the proximal portion and was supplied only from the graft served as control patients. Phasic flow velocities were recorded in the distal portion of the graft and the recipient LAD using a 0.014-in., 15-MHz Doppler guide wire at rest and during hyperemia (0.14-mg/kg body weight per min intravenous adenosine infusion). RESULTS: There were no significant differences in systolic (15+/-3 vs. 19+/-6 cm/s, p = NS), diastolic (35+/-11 vs. 37+/-7 cm/s, p = NS) and time-averaged peak velocities at rest (20+/-5 vs. 21+/-5 cm/s, p = NS), during hyperemia (51+/-12 vs. 54+/-8 cm/s, p = NS) and in coronary flow velocity reserve (2.8+/-0.9 vs. 2.7+/-0.3, NS) in the native LAD in patients with a no-flow patent graft versus control patients. Within the graft, to and fro signals with systolic reversal and diastolic anterograde flow were seen in the no-flow patent grafts, although anterograde flow signals were recorded in systole and diastole in control patients. Systolic (-28+/-19 vs. 22+/-9 cm/s, p < 0.01), diastolic (18+/-17 vs. 44+/-14 cm/s, p < 0.01) and time-averaged (-2+/-6 vs. 26+/-9 cm/s, p < 0.01) peak velocities at rest were significantly smaller in the no-flow patent grafts than in control grafts. During hyperemia, anterograde flow became predominant, with a reduction in retrograde systolic flow signal and an increase in diastolic flow velocity and time-averaged peak velocity in the no-flow patent grafts, and no-flow situations disappeared temporarily. CONCLUSIONS: Functionally no-flow situations of IMAGs manifesting to and fro signals with systolic flow reversal and diastolic antegrade low flow velocity are temporary conditions in certain hemodynamic circumstances, and these grafts function as conduits during hyperemic states.

Adolescent↗

PubMed1998

Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique.

OBJECTIVES: The purpose of this study was to evaluate whether transthoracic Doppler echocardiography (TTDE) can reliably measure coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) in the clinical setting. BACKGROUND: Coronary flow velocity measurement has provided useful clinical and physiologic information. Advancement in TTDE provides noninvasive measurement of CFV and CFVR in the distal LAD. METHODS: In 23 patients, CFV in the distal LAD was measured by TTDE (5 or 3.5 MHz) under the guidance of color Doppler flow mapping at the time of Doppler guide wire (DGW) examination. Coronary flow velocity in the distal LAD were measured at baseline and hyperemic conditions (intravenous administration of adenosine 0.14 mg/kg/min) by both TTDE and DGW techniques. Coronary flow velocity reserve was defined as the ratio of peak hyperemic to basal averaged peak velocity in the distal LAD. RESULTS: Clear envelopes of basal and hyperemic CFV in the distal LAD were obtained in 18 (78%) of 23 study patients by TTDE. There were excellent correlations between TTDE and DGW methods for the measurements of CFV (averaged peak velocity: r=0.97, y=0.94x + 0.40; averaged diastolic peak velocity: r=0.97, y=0.94x + 0.69; systolic peak velocities: r=0.97, y=0.91x + 0.87; diastolic peak velocity: r=0.98, y=0.95x + 1.10). Coronary flow velocity reserve from TTDE correlated highly with those from DGW examinations (r=0.94, y=0.95x + 0.21). CONCLUSIONS: Noninvasive measurement of CFV and CFVR in the distal LAD using TTDE accurately reflects invasive measurement of CFV and CFVR by DGW method.

Adenosine↗

PubMed1998

Restricted coronary flow reserve in patients with mitral regurgitation improves after mitral reconstructive surgery.

OBJECTIVES: The purpose of this study was to assess coronary flow characteristics in patients with chronic mitral regurgitation (MR). BACKGROUND: Coronary flow reserve (CFR) has been reported to be restricted in cases with left ventricular (LV) volume overload caused by aortic regurgitation and increased LV preload. METHODS: The study populations consisted of 31 patients with nonrheumatic chronic MR. Eleven with chest pain and normal coronary arteries served as control subjects. Phasic coronary flow velocities were obtained in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg/min adenosine infusion intravenously) using a 0.014-in. (0.036 cm), 15-MHz Doppler guide wire. Coronary flow reserve was obtained from the ratio of hyperemic/baseline time-averaged peak velocity (APV). Thirteen cases who underwent mitral valve reconstructive surgery were also studied 1 month after surgery. RESULTS: Compared with control subjects, CFR was significantly reduced in cases with MR (2.1+/-0.5 vs. 33+/-0.6, respectively, p < 0.01) because baseline APV was significantly greater (28+/-8 vs. 19+/-6 cm/s, respectively, p < 0.01), although maximal hyperemic APV was not significantly different (56+/-14 vs. 61+/-16 cm/s, respectively, p = NS). Significant correlations were obtained between CFR and LV end-diastolic pressure (LVEDP) (r = 0.70, p < 0.01), LV mass index (r = 0.42, p < 0.01), LV end-diastolic volume (r = 038, p = 0.04) and MR volume (r = 0.39, p = 0.03), and stepwise regression analysis showed LVEDP was the most important determinant of CFR in MR (r2 = 0.49, p < 0.0001). This restricted CFR improved significantly after mitral valve reconstructive surgery (2.1+/-0.5 vs. 3.1+/-0.6, respectively, p < 0.01) because of reduction of baseline APV (28+/-8 vs. 21+/-8 cm/s, respectively, p < 0.01). CONCLUSIONS: Coronary flow reserve is limited in cases with MR because of elevation of baseline resting flow velocity. This reduction of CFR correlates well with increase in LV preload, mass and volume overload, especially with increase in LV preload, and this restricted CFR improves after mitral valve surgery.

Adult↗

PubMed1998

Synthesis and evaluation of nitro 5-deazaflavin-pyrrolecarboxamide(s) hybrid molecules as novel DNA targeted bioreductive antitumor agents.

A series of 6-nitro-5-deazaflavins bearing at N(3) or N(10) position the pyrrolecarboxamide(s) group as DNA minor groove binder has been synthesized. These hybrid molecules show similar redox properties to those of 6-nitro-5-deazaflavins with no pyrrolecarboxamide(s) group, suggesting that they generate stable one- and two-electron reduction product(s). Electrolytic reductions of the hybrid molecules were carried out at a controlled potential under anaerobic conditions in the presence of plasmid pBR322 DNA. Significant conversions of the supercoiled circular pBR322 DNA (form I) to the open circular DNA (form II) have been found by treatment with the reductively activated 6-nitro-5-deazaflavin derivatives. Their DNA damaging effects have been found to be enhanced as the number of pyrrolecarboxamide group as the DNA binder increases. Antitumor activities of the hybrid molecules towards KB and L1210 cells were evaluated in vitro. It has been found that the antitumor effects of the compounds on KB cells slightly change and those on L1210 cells decrease as the number of the pyrrolecarboxamide group increases. These results reveal that the combination of 6-nitro-5-deazaflavin molecule with the pyrrolecarboxamide(s) group increase the DNA binding properties of the compounds, giving rise to promoted DNA damaging effects, and also suggest that the combination would affect the capacity of the compounds to act as the substrate for intracellular reductases and/or the cellular uptake of the compounds.

Animals↗