Biomedical subjects

Yasuhiro Yoshikawa

Publications and source records attributed to Yasuhiro Yoshikawa.

At least 55 records · Page 3Linked to original sources

PubMed2003

Inhibition of staurosporine-induced neuronal cell death by bisphenol A and nonylphenol in primary cultured rat hippocampal and cortical neurons.

We examined whether bisphenol A (BPA) and 4-nonylphenol (NP) influenced staurosporine-induced neuronal cell death in primary cultured rat hippocampal and cortical neurons. In hippocampal neurons, 17beta-estradiol (E2) (1 nM and 10 microM) and BPA (10 microM) significantly inhibited the staurosporine-induced release of lactate dehydrogenase (LDH). In cortical neurons, BPA significantly inhibited the LDH release, while E2 did not. In hippocampal neurons, E2 and BPA significantly inhibited the staurosporine-induced increase in caspase-3 activity. In cortical neurons, BPA and NP significantly inhibited the increase in caspase-3 activity, while E2 did not. Furthermore, low-dose BPA (10 nM) also significantly inhibited the increase in caspase-3 activity in both hippocampal and cortical neurons. BPA and NP might impede normal brain development by inhibiting even desirable neuronal cell death, interfering with caspase-3 activation.

Animals↗

PubMed2003

Age-related changes of Alzheimer's disease-associated proteins in cynomolgus monkey brains.

We characterized senile plaques (SPs) immunohistochemically in cynomolgus monkey brains and also examined age-related biochemical changes of Alzheimer's disease (AD)-associated proteins in these brains from monkeys of various ages. In the neocortex of aged monkeys (>20 years old), we found SPs but no neurofibrillary tangles (NFTs). Antibodies against beta-amyloid precursor protein (APP) or apolipoprotein E (ApoE) stained SPs; however, the pattern of immunostaining was different for the two antigens. APP was present only in swollen neurites, but ApoE was present throughout all parts of SPs. Western blot analysis revealed that the pattern of APP expression changed with age. Although full-length APP695 protein was mainly expressed in brains from young monkeys (4-years-old), the expression of full-length APP751 protein was increased in brains from older monkeys (>20 years old). Biochemical analyses also showed that levels of various AD-associated proteins increased significantly with age in nerve ending fractions. Both SP-associated (APP) and NFT-associated proteins (tau, activated glycogen synthase kinase 3beta, cyclin dependent kinase 5, p35, and p25) accumulated in the nerve ending fraction with increasing age; however, we found no NFTs or paired helical filaments of tau in aged cynomolgus monkey brains. This age-related accumulation of these proteins in the nerve ending fraction was similar to that observed in our laboratory previously for presenilin-1 (PS-1). The accumulation of these SP-associated proteins in this fraction may be a causal event in the spontaneous formation of SPs; thus, SPs may be formed initially in nerve endings. Taken together, these results suggest that intensive investigation of age-related changes in the nerve ending and in axonal transport will contribute to a better understanding of the pathogenesis of neurodegenerative disorders such as AD.

Aging↗

PubMed2003

Familial early onset macular degeneration in cynomolgus monkeys (Macaca fascicularis).

The mode of inheritance of macular degeneration was determined with 45 cynomolgus monkeys (18 females and 27 males) who were the offspring of one breeding male with typical macular degeneration. In the first generation, 27 offspring (10 females and 17 males) were born from mating between the macular degeneration-affected founder male and 5 normal female breeders. Among them, 18 monkeys (9 females and 9 males) were judged as having macular degeneration (affected). Next, the distribution of affected offspring was examined with 18 offspring who were born from 3 different mating pairs, normal vs normal, affected vs normal and affected vs affected, when they became 2 years old. All of the 9 monkeys (4 females and 5 males) obtained from the 2 pairs of normal vs normal were normal. On the other hand, 6 affected monkeys (3 females and 3 males) were detected in 8 offspring from the mating pair of affected vs normal, and the single offspring produced by the mating pair of affected vs affected was affected. These results showed that this degeneration must be early onset familial macular degeneration controlled by autosomal dominant gene(s).

Age of Onset↗

PubMed2003

Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice.

The Jackson shaker (js) mouse carries a recessive mutation causing phenotypes such as deafness, abnormal behavior (circling and/or head-tossing) and degeneration of inner ear neuroepithelia. Two alleles have been identified so far, the original js and js(seal). A contig of three BAC clones was isolated by positional cloning. Two of the clones rescue the js phenotype by BAC transgenesis. Analysis of transcripts in an overlapping region of the two clones revealed a gene encoding a new scaffold-like protein, Sans, that showed mutations in the two js mutants. One was a guanine nucleotide insertion in the original js allele and the other a 7-base insertion in the js(seal) allele. Both insertions are predicted to inactivate the Sans protein by frameshift mutations resulting in a truncated protein lacking the C-terminal SAM domain. Cochlear hair cells in the js mutants show disorganized stereocilia bundles, and Sans were highly expressed in inner and outer hair cells of cochlea. The existence of major motifs, ankyrin repeats and a SAM domain suggests that Sans may have an important role in the development and maintenance of the stereocilia bundles through protein-protein interaction.

Amino Acid Sequence↗

PubMed2003

Collection and analysis of hematopoietic progenitor cells from cynomolgus macaques (Macaca fascicularis): assessment of cross-reacting monoclonal antibodies.

Previous studies have shown that hematopoietic progenitor cells can be isolated from human or nonhuman primate bone marrow (BM) cells. In the present study, we studied the cross-reactivity of 13 anti-human CD34, two anti-human c-Kit, and one anti-human CD133 monoclonal antibodies (mAbs) with cynomolgus macaque (Macaca fascicularis) BM cells, using flow cytometric analysis, cell enrichment, and clonogenic assay. Among the 13 anti-human CD34 mAbs assessed, six cross-reacted as previously reported by other groups. However, only three of these six mAbs (clones 561, 563, and 12.8) recognized cynomolgus CD34+ cells that formed progenitor colonies when grown in methylcellulose culture. Similarly, of the two anti-human c-Kit mAbs (clones NU-c-kit and 95C3) that were previously reported to cross-react with cynomolgus BM cells, only one (clone NU-c-kit) resulted in a similar outcome. The anti-human CD133 mAb (clone AC133) also cross-reacted with cynomolgus BM cells, although these cells did not give rise to colonies when grown in culture. These results suggest that antibodies that cross-react with nonhuman primate cells may not identify the hematopoietic cells of interest. In addition, while the CD34 mAb (clone 561) results in the selection of hematopoietic progenitor cells of all lineages when assessed in methylcellulose culture, the c-Kit(high) fraction (NU-c-kit) exclusively identifies erythroid-specific progenitor cells after growth in culture. It is important to consider these findings when selecting cross-reacting mAbs to identify cells of hematopoietic lineages in macaque species.

AC133 Antigen↗

PubMed2003

Modification of the leukapheresis procedure for use in rhesus monkeys (Macaca mulata).

One of the most serious problems in applying leukapheresis to human infants is the large extracorporeal blood volume (ECV), resulting in substantial loss of platelets and red blood cells (RBCs). In this study, we developed a safe and effective modified procedure to collect peripheral blood stem cells (PBSCs) from rhesus monkeys (Macaca mulata) using a Baxter CS3000+ Blood Cell Separator (Baxter, Deerfield, IL) with several devices that reduced chamber size and shortened the standard apheresis kit to decrease ECV from 130 to 70 ml. Pump speed was controlled by monitoring hematocrit values and platelet counts during leukapheresis. This system makes it possible to perform safe and effective leukapheresis in rhesus monkeys whose body weight is similar to that of human infants. A total of 12 leukapheresis procedures were performed in nine monkeys and resulted in the collection of sufficient numbers of white blood cells (mean, 1.38 x 10(9) cells/kg), CD34(+) cells (mean, 17.80 x 10(6) cells/kg), mononuclear cells (mean, 3.67 x 10(8) cells/kg), and colony forming units (mean, 75.02 x 10(6) cells/kg) in all cases. In addition, no complications, such as anemia or thrombocytopenia, occurred after leukapheresis. This modified leukapheresis procedure will be useful to test new approaches in gene therapy, perform organ transplantation using nonhuman primates, and collect PBSCs from human infants in a noninvasive manner. Our nonhuman primate model provides an important framework for such future clinical studies.

Animals↗

PubMed2003

Locking of the thumb in a patient with de Quervain's disease: a case report.

We report a patient with a locked left thumb in association with de Quervain's disease. While bathing her baby 1 month after giving birth a 32-year-old woman suddenly noticed that she could not radially abduct her left thumb. Magnetic resonance imaging showed thickening of the abductor pollicis longus tendon with a heterogeneous signal intensity on T2-weighted images. Bandage fixation for 4 weeks did not improve her thumb movement, and she was subsequently treated by surgery. Operative findings revealed inhibition of the tendon gliding proximally as a result of nodule formation in the abductor pollicis longus tendon distal to the first dorsal compartment. This condition, locking of the thumb, was improved by excising the extensor retinaculum of the first dorsal compartment and tenosynovium around the abductor pollicis longus and extensor pollicis brevis tendon. At the 1-year follow-up examination the patient had no limitations or pain during active radial abduction of the left thumb.

Adult↗

PubMed2003

Molecular cloning, functional characterization, and enzyme-linked immunosorbent assay of cynomolgus monkey Fas ligand.

Fas ligand (FasL) cDNAs were cloned and sequenced from cynomolgus, rhesus, and pig-tailed monkeys. The 840-bp cDNAs were identical among these three species of monkeys except for one nucleotide. The deduced 280 amino acids were completely identical and displayed 97% homology with human FasL (hFasL). Recombinant soluble FasL obtained from COS cells transfected with cynomolgus monkey FasL (cm-FasL) cDNA induced apoptosis in cells displaying human or cynomolgus monkey Fas-expressing cells. Several anti-human FasL monoclonal antibodies (mAbs) were able to neutralize the cytotoxic activity of monkey FasL, and a combination of mAbs was selected to obtain the most sensitive detection of monkey soluble FasL (sFasL) under sandwich enzyme-linked immunosorbent assay (ELISA). Plasma from normal monkey did not contain detectable levels of sFasL, whereas plasma from monkeys acutely infected with simian immunodeficiency virus (SIV) displayed increased levels of sFasL.

Amino Acid Sequence↗

PubMed2003

Age-related increase of peripheral CD4+ CD8+ double-positive T lymphocytes in cynomolgus monkeys: longitudinal study in relation to thymic involution.

The age-related increase of peripheral CD4+ CD8+ double-positive (DP) T cells in cynomolgus monkeys has been reported previously. Because the percentage of DP T cells in cynomolgus monkeys increases abruptly in parallel with the thymic involution occurring at around 11 years of age, it was suggested that thymic involution was associated with this increase. Therefore, a longitudinal study was carried out over 5 years to clarify the exact time when DP T lymphocytes start to increase in relation to the thymic involution. Twelve cynomolgus monkeys at 6 years of age were classified into three groups, based on their percentage of DP T cells, as follows: DP-High (>5% DP T cells); DP-Middle (1-5% DP T cells); and DP-Low (<1% DP T cells). In the DP-High group, the percentage of DP T cells showed an abrupt increase, of >10%, in monkeys at 7 years of age, and the prevalence of this subset correlated with a distinctive increase in the percentage of memory T cells (CD4+ CD29(high), CD8+ CD28-), indicating an association with the maturation of immune function, including thymic involution. To assess the thymic function, the coding joint of T-cell receptor excision circles (cjTREC) levels in sorted T cells were analysed by polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA). The cjTREC in the T cells of the DP-High group (4362 +/- 3139 copies/105 T cells) was significantly lower than that (22 722 +/- 4928 copies/105 T cells) of the DP-Low group. Moreover, the mean copy number of cjTREC in naive T cells was also significantly different between the DP-High and the DP-Low group (0.457 +/- 0.181 and 1.141 +/- 0.107, respectively). These findings suggest that thymic involution has an influence on the age-related increase of DP T cells in cynomolgus monkeys.

Aging↗

PubMed2003

A small deletion hotspot in the type II keratin gene mK6irs1/Krt2-6g on mouse chromosome 15, a candidate for causing the wavy hair of the caracul (Ca) mutation.

A new mutation has arisen in a colony of mice transgenic for human alpha-galactosidase. The mutation is independent of the transgenic insertion, autosomal dominant, and morphologically very similar to the classical wavy coat mutation, caracul (Ca), on chromosome 15. Therefore, we designated this locus the caracul Rinshoken (Ca(Rin)). Applying a positional cloning approach, we identified the mK6irs1/Krt2-6g gene as a strong candidate for Ca(Rin) because among five Ca alleles examined mutations always occurred in the highly conserved positions of the alpha-helical rod domain (1A and 2B subdomain) of this putative gene product. The most striking finding is that four independently discovered alleles, the three preexistent alleles Ca(J), Ca(9J), Ca(10J), and our allele Ca(Rin), all share one identical amino acid deletion (N 140 del) and the fifth, Ca(medJ), has an amino acid substitution (A 431 D). These findings indicate that a mutation hotspot exists in the Ca locus. Additionally, we describe a Ca mutant allele induced by ENU mutagenesis, which also possesses an amino acid substitution (L 424 W) in the mK6irs1/Krt2-6g gene. The identification of the Ca candidate gene enables us to further define the nature of the genetic pathway required for hair formation and provides an important new candidate that may be implicated in human hair and skin diseases.

Amino Acid Sequence↗

PubMed2003

Antigen capture enzyme-linked immunosorbent assay for specific detection of Reston Ebola virus nucleoprotein.

Antigen capture enzyme-linked immunosorbent assay (ELISA) is one of the most useful methods to detect Ebola virus rapidly. We previously developed an antigen capture ELISA using a monoclonal antibody (MAb), 3-3D, which reacted not only to the nucleoprotein (NP) of Zaire Ebola virus (EBO-Z) but also to the NPs of Sudan (EBO-S) and Reston Ebola (EBO-R) viruses. In this study, we developed antigen capture ELISAs using two novel MAbs, Res2-6C8 and Res2-1D8, specific to the NP of EBO-R. Res2-6C8 and Res2-1D8 recognized epitopes consisting of 4 and 8 amino acid residues, respectively, near the C-terminal region of the EBO-R NP. The antigen capture ELISAs using these two MAbs detected the EBO-R NP in the tissues from EBO-R-infected cynomolgus macaques. The antigen capture ELISAs using Res2-6C8 and Res2-1D8 are useful for the rapid detection of the NP in EBO-R-infected cynomolgus macaques.

Animals↗

PubMed2003

nef gene is required for robust productive infection by simian immunodeficiency virus of T-cell-rich paracortex in lymph nodes.

The pathogenesis of AIDS virus infection in a nonhuman primate AIDS model was studied by comparing plasma viral loads, CD4(+) T-cell subpopulations in peripheral blood mononuclear cells, and simian immunodeficiency virus (SIV) infection in lymph nodes for rhesus macaques infected with a pathogenic molecularly cloned SIVmac239 strain and those infected with its nef deletion mutant (Deltanef). In agreement with many reports, whereas SIVmac239 infection induced AIDS and depletion of memory CD4(+) T cells in 2 to 3 years postinfection (p.i.), Deltanef infection did not induce any manifestation associated with AIDS up to 6.5 years p.i. To explore the difference in SIV infection in lymphoid tissues, we biopsied lymph nodes at 2, 8, 72, and 82 weeks p.i. and analyzed them by pathological techniques. Maximal numbers of SIV-infected cells (SIV Gag(+), Env(+), and RNA(+)) were detected at 2 weeks p.i. in both the SIVmac239-infected animals and the Deltanef-infected animals. In the SIVmac239-infected animals, most of the infected cells were localized in the T-cell-rich paracortex, whereas in the Deltanef-infected animals, most were localized in B-cell-rich follicles and in the border region between the paracortex and the follicles. Analyses by double staining of CD68(+) macrophages and SIV Gag(+) cells and by double staining of CD3(+) T cells and SIV Env(+) cells revealed that SIV-infected cells were identified as CD4(+) T cells in either the SIVmac239 or the Deltanef infection. Whereas the many functions of Nef protein were reported from in vitro studies, our finding of SIVmac239 replication in the T-cell-rich paracortex in the lymph nodes supports the reported roles of Nef protein in T-cell activation and enhancement of viral infectivity. Furthermore, the abundance of SIVmac239 infection and the paucity of Deltanef infection in the T-cell-rich paracortex accounted for the differences in viral replication and pathogenicity between SIVmac239 and the Deltanef mutant. Thus, our in vivo study indicated that the nef gene enhances SIV replication by robust productive infection in memory CD4(+) T cells in the T-cell-rich region in lymphoid tissues.

Animals↗

PubMed2003

Characterization of the testis in congenitally ubiquitin carboxy-terminal hydrolase-1 (Uch-L1) defective (gad) mice.

The gracile axonal dystrophy (gad) mice are known to have a deletion within the gene encoding ubiquitin carboxy-terminal hydrolase-1 (Uch-L1) and show hereditary sensory deterioration and motor paresis. Expression of Uch-L1 is reported to be almost limited to the nervous system and testis. To understand whether Uch-L1, one of the major ubiquitin carboxy-terminal hydrolase (UCH) isozymes in the testis, affects spermatogenesis and other UCH isozymes (Uch-L3, L4 and L5) expression in the testis, we compared the testis between gad, hetero and wild type mice by histological, immunohistochemical analyses and RT-PCR. Histological analysis in 25-week-old gad mice showed shrinking of seminiferous tubules, decreasing total number of cells and enlargement of remaining cells in seminiferous tubules. By immunohistochemistry, a significant decrease (p < 0.05) in the number of proliferating cell nuclear antigen (PCNA) positive cells was observed. Expression of other UCH isozyme mRNAs was not apparently affected by Uch-L1 deficiency in 25-week-old gad mice. This study is the first report on the testis of gad mutant mouse.

Animals↗

PubMed2003

Sendai virus vector-mediated gene transfer of glial cell line-derived neurotrophic factor prevents delayed neuronal death after transient global ischemia in gerbils.

We have developed a cytoplasmic replicating virus vector of Sendai virus (SeV) that infects and replicates in most mammalian cells, including neurons, and directs high-level gene expression. To investigate the protective effect of SeV vector-mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) on the delayed neuronal death caused by transient global ischemia in gerbils, SeV vectors carrying either GDNF (SeV/GDNF) or enhanced green fluorescent protein gene (SeV/GFP) were stereotaxically microinjected into the lateral ventricle. Four days after injection, occlusion of the bilateral common carotid arteries for 5 min produced transient global forebrain ischemia. Treatment with SeV/GDNF significantly decreased the delayed neuronal death of the hippocampal CA1 pyramidal neurons observed 6 days after the operation. TUNEL staining demonstrated that SeV/GDNF treatment markedly reduced the number of apoptotic cells in the hippocampal CA1 neurons, indicating that SeV/GDNF treatment prevented apoptosis. Furthermore, delayed neuronal death on the contralateral side of the hippocampal CA1 was also prevented to a similar extent as that on the ipsilateral side. These results suggest that SeV/GDNF prevents the delayed neuronal death induced by ischemia and is potentially useful for gene therapy for stroke.

Animals↗

PubMed2003

Molecular cloning of ELOVL4 gene from cynomolgus monkey (Macaca fascicularis).

ELOVL4, elongation factor of very long chain fatty acids-4, is known to be responsible for autosomal dominant macular degeneration and Stargardt-like macular degeneration. In this study, we cloned the monkey homologue of ELOVL4 and determined the cellular and tissue distribution of the gene product. Sequence analysis of the monkey ELOVL4 gene revealed a high degree of homology between human and monkey. The cloned full-length cDNA of monkey ELOVL4 encoded 314 amino acids, the same length as human and two amino acids longer than mouse. The monkey ELOVL4 conserved the characteristics typical of the super family of ELO enzymes involved in the metabolism of membrane-bound fatty acid elongation. Real-time quantitative PCR demonstrated that the monkey ELOVL4 gene was highly expressed in restricted tissue-specific fashion, not only in the retina but also in the skin (90% of retina) and thymus (111% of retina). Immunohistochemical analysis detected signals predominantly in the photoreceptor layer of the monkey retina.

Amino Acid Sequence↗

PubMed2003

Ratio of leptin to adiponectin as an obesity index of cynomolgus monkeys (Macaca fascicularis).

Obesity is responsible for inducing various metabolic diseases. Laboratory-bred cynomolgus monkeys exhibit spontaneous onset of obesity. However, to date, no blood chemistry index to identify the state of obesity in cynomolgus monkeys has been determined. In the present study, to determine such an index, we measured the serum levels of two adipocyte-derived hormones, leptin and adiponectin, and evaluated the relationship between these hormones and other serum energy metabolic factors (i.e. insulin, total protein, glucose, total cholesterol and triglyceride) as well as the percentage of body fat (%Fat) in mature cynomolgus monkeys. Both in females and males, leptin was positively correlated with insulin and %Fat, and adiponectin was negatively correlated with insulin and %Fat. In female cynomolgus monkeys, leptin, adiponectin, and glucose were selected as the most important determinants for %Fat in multiple regression analysis, and in male cynomolgus monkeys, leptin was selected. The ratio of leptin to adiponectin (L/A ratio) was significantly elevated in the animals with %Fat over 40 (P < 0.01). The results indicate that L/A ratio is a potential index for comprehensively identifying obesity in cynomolgus monkeys.

Absorptiometry, Photon↗

PubMed2003

Possible role of genetic factor(s) on age-related increase of peripheral CD4+CD8+ double positive T cells in cynomolgus monkeys.

Mature TCR alpha beta T cells in peripheral blood are generally classified into either CD4 single positive (sp) T cells or CD8sp T cells. Several studies demonstrated that considerable amounts of CD4+CD8+ double positive (DP) T cells exist in peripheral blood of human and several animals. In particular, we previously reported that peripheral DP T cells increase in an age-related manner in cynomolgus monkeys (Macaca fascicularis), but the finding that DP T cells in some aged monkeys were maintained at a low proportion (under 5%), suggests that the increase in peripheral DP T cells might be genetically controlled in cynomolgus monkeys. To test this hypothesis, 24 families were randomly selected and used in a formal genetic analysis of the proportion of DP T cells. Parents and offspring in selected families were classified into DP-High and DP-Low groups based on a 5% cutoff level of DP T cells. The cutoff value was set by analysis of the distribution of the proportion of DP T cells. Nine out of 13 offspring (69.2%) with DP-High x DP-High parents belonged to the DP-High group, whereas three out of nine offspring (33.3%) belonged to DP-High group in the case of DP-High x DP-Low mating pairs. No offspring (0%) of two offspring with DP-Low x DP-Low parents belonged to the DP-High group. In addition, heritability (h2: narrow sense) obtained from the regression coefficient of offspring on mid-parent values was 0.54 +/- 0.19. Both findings suggest that increases in DP T cells in cynomolgus monkeys may be genetically controlled.

Aging↗

PubMed2003

Protective effects of probucol treatment on pancreatic beta-cell function of SZ-induced diabetic APA hamsters.

To clarify whether oxidative stress is involved in the pathogenesis of islet lesions of diabetic animals, the effects of probucol (PB), an antioxidant and anti-hyperlipidemia agent, on the islets in streptozotocin (SZ)-induced diabetic APA hamsters in the acute and chronic phases of diabetes were examined. The control (CB group) and diabetic (SZ group) hamsters were treated with PB (1% in the diet) for 4 weeks from several days after SZ injection as the acute diabetic group, or 8 weeks from 6 weeks after SZ injection as the chronic diabetic group. Glucose tolerance test revealed that PB treatment decreased the high serum glucose level after glucose injection in the diabetic APA hamsters in the acute diabetic phase. Immunohistochemistry revealed that PB treatment significantly increased the percentage of the insulin positive area in the diabetic hamsters pancreata in both the acute and chronic phases. In addition, 4-hydroxy-2-nonenal (4HNE; an oxidative stress marker) positive cells were slightly reduced by PB treatment in the acute diabetic phase. Double-immunostaining for insulin and PCNA (proliferating cell nuclear antigen) revealed that elevation of the percentage of insulin and PCNA double-positive cells against insulin-positive cells was seen in the islets of PB-treated diabetic hamsters, but the difference was not significant compared with untreated diabetic hamsters (p = 0.07). In semi-quantitative RT-PCR, the expression of two genes, Reg (Regenerating gene) and INGAP (islet neogenesis associated protein), in the diabetic APA hamsters was significantly increased compared to the control groups in both diabetic phases. PB treatment significantly reduced Reg expression in the chronic diabetic phase. These data suggest that PB treatment in SZ-injected diabetic hamsters partially restored beta-cell function through acting as an antioxidant and induced higher expression of Reg and INGAP genes in the pancreas of hamsters.

Aldehydes↗