Biomedical subjects

Yoshihiro Takahashi

Publications and source records attributed to Yoshihiro Takahashi.

At least 19 recordsLinked to original sources

PubMed2026

Digenic HNF1A and ABCC8 variants provide mechanistic insight into early-onset diabetes.

CONTEXT: Oligogenic inheritance in maturity-onset diabetes of the young (MODY) remains poorly characterized, and the contribution of multiple candidate variants to disease pathogenesis is incompletely understood. OBJECTIVE: To investigate the pathogenicity and mechanistic contribution of multiple MODY gene variants identified in a MODY-like family and determine their role in early-onset diabetes. METHODS: Comprehensive genetic analysis of known MODY genes was performed in a MODY-like family. Functional effects of HNF1A and HNF1B variants were assessed using luciferase reporter assays in HEK293T cells. Functional characterization of ABCC8 variants included Kir6.2-dependent thallium (Tl+) flux assays, sulfonylurea responsiveness, and channel stability. RESULTS: Four variants in 3 MODY genes were identified in the proband: novel HNF1A p.Ser551Lysfs*2, HNF1B p.Glu102Ala, and ABCC8 p.Arg298Cys and p.Arg521Gln. Functional analysis showed that HNF1A p.Ser551Lysfs*2 retained approximately 5% of wild-type transactivation activity, consistent with loss-of-function, whereas HNF1B p.Glu102Ala and ABCC8 p.Arg521Gln exhibited wild-type-like function. In contrast, ABCC8 p.Arg298Cys reduced channel activity to 77% of wild-type levels while preserving sulfonylurea responsiveness. Segregation analysis identified HNF1A p.Ser551Lysfs*2 and ABCC8 p.Arg298Cys in affected parents. The proband, who inherited both pathogenic variants, developed diabetes earlier than either parent and was exposed to maternal hyperglycemia in utero, which may also have contributed to this early onset. CONCLUSION: Functional characterization distinguishes pathogenic from variants of unknown significance and supports digenic inheritance of HNF1A and ABCC8. Their additive effects, together with intrauterine hyperglycemia, likely accelerated disease onset. This study provides mechanistic evidence for oligogenic contributions to MODY and expands the genetic architecture of early-onset diabetes.

Humans↗

PubMed2007

Large-scale DNA polymorphism study of Oryza sativa and O. rufipogon reveals the origin and divergence of Asian rice.

Polymorphism over approximately 26 kb of DNA sequence spanning 22 loci and one region distributed on chromosomes 1, 2, 3 and 4 was studied in 30 accessions of cultivated rice, Oryza sativa, and its wild relatives. Phylogenetic analysis using all the DNA sequences suggested that O. sativa ssp. indica and ssp. japonica were independently domesticated from a wild species O. rufipogon. O. sativa ssp. indica contained substantial genetic diversity (pi = 0.0024), whereas ssp. japonica exhibited extremely low nucleotide diversity (pi = 0.0001) suggesting the origin of the latter from a small number of founders. O. sativa ssp. japonica contained a larger number of derived and fixed non-synonymous substitutions as compared to ssp. indica. Nucleotide diversity and genealogical history substantially varied across the 22 loci. A locus, RLD15 on chromosome 2, showed a distinct genealogy with ssp. japonica sequences distantly separated from those of O. rufipogon and O. sativa ssp. indica. Linkage disequilibrium (LD) was analyzed in two different regions. LD in O. rufipogon decays within 5 kb, whereas it extends to approximately 50 kb in O. sativa ssp. indica.

Base Sequence↗

PubMed2006

The polyamine spermine protects against high salt stress in Arabidopsis thaliana.

It is well known that changes in abiotic conditions such as the concentration of ions, temperature and humidity lead to modulation of polyamine contents in plants. However, little is known about the relevant parts these polyamines play in abiotic stress responses. Here we addressed a specific role of spermine during high salt stress using an Arabidopsis double knockout-mutant plant (acl5/spms) which cannot produce spermine. The mutant showed higher sensitivity to high salt than wild type plants. This phenotype was cured by exogenous spermine but not by the other polyamines putrescine and spermidine, suggesting a strong link between spermine-deficiency and NaCl-hypersensitivity. The mutant was also hypersensitive to high levels of KCl but not to MgCl(2) or to high osmoticum. NaCl-hypersensitivity of the mutant was compromised by treatment with Ca(2+) channel blockers. Moreover, the mutant showed poor growth on Ca(2+)-depleted Murashige-Skoog agar media. The data suggest that the absence of spermine causes an imbalance in Ca(2+) homeostasis in the mutant plant. Based on the data obtained, we propose a model for a role of spermine in high salt stress responses.

Arabidopsis↗

PubMed2006

A protective role for the polyamine spermine against drought stress in Arabidopsis.

Cellular polyamine content often changes in response to abiotic stresses. However, its physiological relevance is unknown. We found that an Arabidopsis mutant plant (acl5/spms), which cannot produce spermine, is hypersensitive to high salt. Examination of drought sensitivity of the mutant and comparison with wild type plants indicated hypersensitivity to drought. This phenotype was cured by spermine pretreatment but not by the other polyamines putrescine and spermidine, suggesting that drought-hypersensitivity exhibited by the mutant is due to spermine deficiency. The water loss rate of wild type and mutant plants were similar until 20 min after onset of dehydration stress, but after a longer exposure the rate in mutant plants was higher than in wild type plants. Consistent with this result, the stomata of the mutant leaves remained open while in wild type leaves they closed. Based on the collected data, we discuss a role for spermine in response to drought stress.

Arabidopsis↗

PubMed2006

Identification of a novel Cys2/His2-type zinc-finger protein as a component of a spermine-signaling pathway in tobacco.

In a previous work, we identified a Cys(2)/His(2)-type zinc-finger transcription repressor, (ZFT1), that functions in a spermine-mediated signal transduction pathway in tobacco plants. Database search disclosed the presence of another Cys(2)/His(2)-type zinc-finger protein ZFP1 (accession number AAC06243) in tobacco plants. In this work, we characterized ZFP1 and investigated whether this protein is also involved in a Spm-signaling pathway. This factor showed the highest identity to petunia ZPT2-2 and higher similarity to petunia ZPT2-3, Arabidopsis STZ/ZAT10, soybean SCOF-1, red pepper CAZFP1/CaPIF1 as well as to tobacco ZFT1. ZFP1 localized to the nucleus and had a specific DNA-binding activity, supportive to be a transcription factor. Furthermore, the protein had a mild repression activity on transcription in plant cells. The expression of ZFP1, encoding ZFP1, was upregulated during tobacco mosaic virus-induced hypersensitive response. ZFP1 expression was also induced by exogenously applied spermine and its induction was repressed by inhibitors of amine oxidase/polyamine oxidase. Collectively, our data indicate that ZFP1 is a new transcription factor which functions in a spermine-signaling pathway in tobacco.

Amino Acid Sequence↗

PubMed2006

Nitric oxide modulates elicitation of reflex swallowing from the pharynx in rats.

The pharynx is very important for elicitation of reflex swallowing. The region of the pharynx is innervated by the pharyngeal branch of the glossopharyngeal nerve (GPN-ph). Nitric oxide (NO) plays an important role in various physiological functions. The purpose of this study is to investigate the contribution of NO to reflex swallowing evoked by electrical stimulation of the GPN-ph. Swallowing was evoked in urethane-anesthetized rats by application of repetitive electrical stimulation (10- to 20-microA amplitude, 10- to 20-Hz frequency, 1.0-ms duration) to the central cut end of the GPN-ph or superior laryngeal nerve. Swallowing was identified by electromyographic activity of the mylohyoid muscle. Latency to the first swallow and the interval between swallows were measured. Intravenous administration of N(G)-nitro-L-arginine (L-NNA, 0.6 mg/kg), a nonselective inhibitor of NO synthase (NOS), extremely prolonged latency to the first swallow and the interval between swallows evoked by the GPN-ph. Intraperitoneal administration of 7-nitroindazole (5.0 mg/kg), a selective inhibitor of neuronal NOS, significantly prolonged latency to the first swallow and the interval between swallows evoked by the GPN-ph. Administration of L-arginine (an NO donor, 500 mg/kg) and sodium nitroprusside (an NO releaser, 0.6 mg/kg) restored the suppression of swallowing induced by the NOS inhibitor. Superior laryngeal nerve-evoked swallowing was suppressed by administration of a higher dose of L-NNA (6.0 mg/kg). Swallowing evoked by water stimulation of the pharynx was also suppressed by L-NNA (0.6 mg/kg). These results suggest that NO plays an important role in signal processing for initiation of reflex swallowing from the pharynx.

Animals↗

PubMed2006

Density dependences of long-range fluctuations and short-range correlation lengths of CHF3 and CH2F2 in supercritical states.

Small-angle x-ray scattering (SAXS) measurements are carried out for supercritical polar fluorocarbons, CHF3 and CH2F2, along the isotherm of 1.04 in reduced temperatures with the density range from 0.3 to 1.5 in reduced units. A novel apparatus for determination of absorption factors of the sample fluids is used in the present measurements. The apparatus enables us to detect simultaneously the accurate factors during the observation of the SAXS signals. Long-range fluctuations such as density fluctuations and correlation lengths are evaluated from the obtained SAXS data. The reduced correlation lengths are obtained by normalization by each molecular size, in order to discuss the fluctuations independent of the difference of the individual molecular size. The density fluctuations and the reduced correlation lengths of CHF3 and CH2F2 are compared with those of CO2 and H2O. The results are as follows: H2O>CH2F2>CHF3 approximately CO2 in the order of magnitude. The fluctuations of CH2F2 are significantly distinguishable from those of CHF3 and show intermediate aspect between H2O and a group of CO2 and CHF3. In addition, the short-range correlation lengths, i.e., the Ornstein-Zernike direct correlation lengths, are firstly discussed from both viewpoints of density and substance dependences. The reduced short-range correlation lengths normalized by individual molecular size are found to trace a universal curve as a function of the reduced density.

Journal Article↗

PubMed2006

Infants with acute lymphoblastic leukemia and a germline MLL gene are highly curable with use of chemotherapy alone: results from the Japan Infant Leukemia Study Group.

Although infants with acute lymphoblastic leukemia (ALL) and a germline MLL gene have a better prognosis than comparable infants with a rearranged MLL gene, their optimal therapy is controversial. In 2 consecutive studies, conducted between 1996 and 2002, we treated 22 cases of infant ALL with germline MLL using chemotherapy alone. The 5-year event-free survival rate was 95.5% with a 95% confidence interval of 86.9 to 100%. All 21 infants with precursor B-cell ALL have been in first complete remission for 3.5 to 8.8 years. Most treatment-related toxicities were predictable and well tolerated, and neither secondary malignancies nor physical growth impairments have been observed. These results indicate that chemotherapy of the type described here is both safe and highly effective against infant precursor B-cell ALL with MLL in the germline configuration.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Development of acute megakaryoblastic leukemia from a minor clone in a Down syndrome patient with clinically overt transient myeloproliferative disorder.

A Down syndrome male showed leukocytosis from birth and was diagnosed as transient myeloproliferative disorder (TMD). Eight months later, his condition had progressed to myelodysplastic syndrome after spontaneous resolution, and it then evolved to acute megakaryoblastic leukemia (AMKL) at the age of 20 months. Sequencing analysis showed that the predominant TMD and AMKL clones had different GATA1 mutations, although a minor TMD clone identical to the AMKL clone was present at birth. These observations suggest that a minor clone rather than the predominant clone at the time of TMD may give rise to AMKL later on.

Cell Lineage↗

PubMed2005

Incidence and burden of rotavirus gastroenteritis in Japan, as estimated from a prospective sentinel hospital study.

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.

Child, Preschool↗

PubMed2005

Genesis of the decrement of intraluminal pressure in the UES during swallowing in rabbits.

The intraluminal pressure in the upper esophageal sphincter (UES) briefly decreases during swallowing. This decrement in pressure plays an important role in smooth transport of the ingested bolus from the pharynx to the esophagus. It is known that the decrement is caused by cessation of tonic activity of the cricopharyngeus (CP) muscle and also by elevation of the larynx. On the other hand, it is suspected that the recurrent laryngeal nerve (RLN) also contributes to the decrement, since our preliminary study showed for the first time that the decrement in UES pressure was much reduced after the RLN was sectioned. In the present study, we examined the genesis of the decrement of the UES pressure in anesthetized rabbits. When swallowing was elicited by repetitive electrical stimulation of the superior laryngeal nerve, the UES pressure briefly decreased and then abruptly increased. After bilateral sectioning of the RLN, the decrement of the pressure was significantly reduced, whereas the increment was little altered. Sectioning of the pharyngeal branch of the vagus nerve (X-ph) and the RLN mostly eliminated both the decrement and increment of the pressure, and abolished tonic and burst activities of the CP muscle. Electrical stimulation of peripheral end of the RLN decreased the pressure. These results indicate that the RLN and X-ph are involved in the decrement of the UES pressure during swallowing. The RLN generates the decrement by adducting the arytenoid cartilage and closing the glottis. The X-ph contributes to the decrement both by suppressing the tonic activity of the CP muscle and by regulating the laryngeal elevation.

Animals↗

PubMed2005

Tobacco ZFT1, a transcriptional repressor with a Cys2/His2 type zinc finger motif that functions in spermine-signaling pathway.

We previously proposed that a spermine (Spm)-mediated signal transduction pathway is involved in the hypersensitive response induced by Tobacco mosaic virus (TMV) in tobacco plants. To identify regulatory component(s) of this pathway, we surveyed a tobacco cDNA library and found that the ZFT1 gene, which encodes a Cys2/His2 type zinc-finger protein, is Spm-responsive. ZFT1 was not induced by two other polyamines, putrescine and spermidine, or by salicylic acid (SA), jasmonic acid or ethylene. Furthermore, ZFT1 was upregulated in TMV- inoculated tobacco plants in an N gene-dependent manner. Notably, induction of ZFT1 by Spm and by TMV infection was unimpaired in NahG-transgenic tobacco plants, indicating that cross-talk with an SA signaling pathway is not involved in this response. Within the Spm-signaling pathway, we found that ZFT1 functioned downstream of both mitochondrial dysfunction and mitogen-activated protein kinase activation. The ZFT1 protein has two zinc finger motifs and shows a high degree of similarity to ZPT2-3 in petunia and SCOF1 in soybean. However, unlike the latter two proteins, ZFT1 binds to the EP1S sequence and functions as a transcription repressor. Moreover, interestingly, ZFT1 overexpression rendered tobacco plants more tolerant to TMV. Based on the results presented here, we propose that ZFT1 functions as a transcription repressor in a Spm signaling pathway, thereby accelerating necrotic local region formation in tobacco leaves.

Amino Acid Sequence↗

PubMed2005

HLA-B polymorphism in Japanese HIV-1-infected long-term surviving hemophiliacs.

Approximately 30% of patients with hemophilia in Japan were infected with human immunodeficiency virus (HIV) in early 1980s through contaminated blood products. In 1995, a cohort of HIV-infected, asymptomatic patients with hemophilia was set up for follow-up study. Although the patients met the criteria for long-term non-progressor (LTNP) at the entry to the cohort, some of them later developed lymphopenia during five more years of observation. We collected blood samples from 80 long-term survivors; 42 of them did not require antiviral therapy, but the rest were under treatment. Analysis of HLA-B genotype revealed that carriers of known HIV-resistant alleles such as HLA-B*5701, B*5801, and alleles of B27 antigenic group were not increased in frequency, but that HLA-B*1507 was increased in the cohort (6.25% vs. 1.03%, OR = 6.40, p = 0.039). We also observed the decrease in carriers of HLA-B*5401 (3.75% vs. 14.95%, OR = 0.22, p = 0.016). HLAB* 5401 is a relatively common allele in East Asian populations and belongs to the same B22 antigenic group as B55 and B56 which were reported to associate with rapid progression. Our data indicated that HLA class I is one of the host factors involved in the retardation of HIV disease progression as also reported in the previous studies; however, the alleles associated with this resistance were not the same because of divergent host genetic background.

Alleles↗

PubMed2005

High-throughput in planta expression screening identifies a class II ethylene-responsive element binding factor-like protein that regulates plant cell death and non-host resistance.

We performed high-throughput screening using the potato virus X (PVX) system to overexpress Nicotiana benthamiana genes in planta and identify positive regulators of cell death. This screening identified NbCD1, a novel class II ethylene-responsive element binding factor (ERF), as a potent inducer of the hypersensitive response (HR)-like cell death. NbCD1 expression was induced by treatments with INF1 elicitor and a non-host pathogen Pseudomonas cichorii. NbCD1 exhibited transcriptional repressor activity through its EAR motif, and this motif was necessary for NbCD1 to cause cell death. We identified 58 genes that displayed altered transcription following NbCD1 overexpression. NbCD1 overexpression downregulated the expression of HSR203, a negative regulator of hypersensitive death. Conditional expression of NbCD1 in Arabidopsis also caused cell death, indicating that NbCD1 downstream cascades are conserved in dicot plants. To further confirm the role of NbCD1 in defense, we used virus-induced gene silencing to demonstrate that NbCD1 is required for non-host resistance of N. benthamiana to the bacterial pathogen P. cichorii. Our data point to a model of transcriptional regulatory cascades. NbCD1 positively regulates cell death and contributes to non-host resistance, possibly by downregulating the expression of other defense response genes.

Amino Acid Sequence↗

PubMed2005

Menaquinone-specific prenyl reductase from the hyperthermophilic archaeon Archaeoglobus fulgidus.

Four genes that encode the homologues of plant geranylgeranyl reductase were isolated from a hyperthermophilic archaeon Archaeoglobus fulgidus, which produces menaquinone with a fully saturated heptaprenyl side chain, menaquinone-7(14H). The recombinant expression of one of the homologues in Escherichia coli led to a distinct change in the quinone profile of the host cells, although the homologue is the most distantly related to the geranylgeranyl reductase. The new compounds found in the profile had successively longer elution times than those of ordinary quinones from E. coli, i.e., menaquinone-8 and ubiquinone-8, in high-performance liquid chromatography on a reversed-phase column. Structural analyses of the new compounds by electron impact-mass spectrometry indicated that their molecular masses progressively increase relative to the ordinary quinones at a rate of 2 U but that they still contain quinone head structures, strongly suggesting that the compounds are quinones with partially saturated prenyl side chains. In vitro assays with dithionite as the reducing agent showed that the prenyl reductase is highly specific for menaquinone-7, rather than ubiquinone-8 and prenyl diphosphates. This novel enzyme noncovalently binds flavin adenine dinucleotide, similar to geranylgeranyl reductase, but was not able to utilize NAD(P)H as the electron donor, unlike the plant homologue.

Amino Acid Sequence↗

PubMed2004

(S)-2,3-Di-O-geranylgeranylglyceryl phosphate synthase from the thermoacidophilic archaeon Sulfolobus solfataricus. Molecular cloning and characterization of a membrane-intrinsic prenyltransferase involved in the biosynthesis of archaeal ether-linked membrane lipids.

The core structure of membrane lipids of archaea have some unique properties that permit archaea to be distinguished from the others, i.e. bacteria and eukaryotes. (S)-2,3-Di-O-geranylgeranylglyceryl phosphate synthase, which catalyzes the transfer of a geranylgeranyl group from geranylgeranyl diphosphate to (S)-3-O-geranylgeranylglyceryl phosphate, is involved in the biosynthesis of archaeal membrane lipids. Enzymes of the UbiA prenyltransferase family are known to catalyze the transfer of a prenyl group to various acceptors with hydrophobic ring structures in the biosynthesis of respiratory quinones, hemes, chlorophylls, vitamin E, and shikonin. The thermoacidophilic archaeon Sulfolobus solfataricus was found to encode three homologues of UbiA prenyltransferase in its genome. One of the homologues encoded by SSO0583 was expressed in Escherichia coli, purified, and characterized. Radio-assay and mass spectrometry analysis data indicated that the enzyme specifically catalyzes the biosynthesis of (S)-2,3-di-O-geranylgeranylglyceryl phosphate. The fact that the orthologues of the enzyme are encoded in almost all archaeal genomes clearly indicates the importance of their functions. A phylogenetic tree constructed using the amino acid sequences of some typical members of the UbiA prenyltransferase family and their homologues from S. solfataricus suggests that the two other S. solfataricus homologues, excluding the (S)-2,3-di-O-geranylgeranylglyceryl phosphate synthase, are involved in the production of respiratory quinone and heme, respectively. We propose here that archaeal prenyltransferases involved in membrane lipid biosynthesis might be prototypes of the protein family and that archaea might have played an important role in the molecular evolution of prenyltransferases.

Alkyl and Aryl Transferases↗

PubMed2004

Pravastatin has an additional depressor effect in patients undergoing long-term treatment with antihypertensive drugs.

BACKGROUND: Statins have been reported to have direct vascular effects independent of cholesterol reduction. To assess the antihypertensive effect of statins, a crossover study was designed to compare the depressor effect of pravastatin and probucol in hypertensive patients undergoing long-term treatment with antihypertensive drugs. METHODS: The subjects enrolled in this study were 52 hypertensive patients (22 men and 30 women, mean age 62.8 +/- 9.3 years) who were treated with the same antihypertensive drugs for more than 1 year and had serum cholesterol levels of more than 5.69 mmol/L. In 26 subjects, pravastatin at a dose of 10 mg/d was given first for 6 months followed by treatment with probucol at a dose of 500 mg/d, and vice versa in the remaining 26 subjects. Serum lipids, apolipoproteins, glucose, and insulin were measured on the final day of the control period, and pravastatin and probucol treatments. The homeostatic model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance. RESULTS: The blood pressure decreased after pravastatin treatment (141.2 +/- 4.7/81.3 +/- 4.9 to 136.5 +/- 5.3/80.6 +/- 5.1 mm Hg, P <.001/.499), but did not decrease after probucol treatment (141.2 +/- 4.7/81.3 +/- 4.9 to 141.4 +/- 4.9/80.8 +/- 4.9 mm Hg, P =.832/.634). Total cholesterol decreased significantly after pravastatin (6.69 +/- 0.69 to 5.23 +/- 0.77 mmol/L, P <.001) and probucol treatment (6.69 +/- 0.69 to 5.53 +/- 0.64 mmol/L, P <.001). The HOMA-IR was decreased by probucol (1.92 +/- 0.78 to 1.57 +/- 0.59, P =.029), whereas pravastatin had no effect on HOMA-IR. CONCLUSIONS: It can be concluded that the depressor effect of pravastatin may have an additional benefit in the treatment of hypertensive patients with hyperlipidemia without any adverse effect on insulin sensitivity.

Adult↗

PubMed2004

Identification of tobacco HIN1 and two closely related genes as spermine-responsive genes and their differential expression during the Tobacco mosaic virus -induced hypersensitive response and during leaf- and flower-senescence.

Previously we showed that the polyamine spermine (Spm) specifically leads to mitochondrial dysfunction in tobacco that is followed by the activation of salicylic acid-induced protein kinase and wound-induced protein kinase. To identify the possible downstream components of the Spm signalling pathway, we isolated Spm-responsive genes by a differential hybridization approach. This showed that the harpin-induced 1 (HIN1) gene is responsive to Spm. Genomic Southern analysis showed that HIN1 constitutes a multi-gene family and this led to the isolation of two novel HIN1 -like tobacco cDNAs that we designated as HIN9 and HIN18. Both genes are also responsive to Spm, albeit HIN18 is induced weakly compared to HIN1 and HIN9. As HIN1 is up-regulated both during the hypersensitive response (HR) generated by an incompatible plant-pathogen interaction and during senescence, we compared the expression of the three HIN1 family genes in these situations. All three were responsive to HR due to Tobacco mosaic virus infection, although HIN18 was less efficiently induced, and HIN1 and HIN18 were both strongly up-regulated during leaf- and flower-senescence. This suggests that the signalling pathways in the HR and senescence overlap somehow but are distinct. That HIN1 and its closely related genes are Spm-responsive genes also supports the idea that Spm plays a role as a signal transmitter in the HR process.

Amino Acid Sequence↗