Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated - an open-label pilot study.

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules. Methods: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months. Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported. Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.

Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy.

A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at performing mutational analysis of the gene and characterizing the associated immunohistochemical features. Sixty-five unrelated patients (55 fulfilling Task Force criteria and 10 borderline cases) were screened for mutations in TMEM43. Immunohistochemistry with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c.1073C> T; in two related patients) and one novel variant (c.705+ 7G> A; in one patient) of unknown significance. All three patients fulfilled Task Force criteria and did not carry mutations in any other ARVC-related gene. Immunostaining with TMEM43 antibody showed intense staining of the sarcolemma. The signal level was reduced in all the three TMEM43-positive patients. Immunostaining with plakoglobin-specific antibody also showed reduced signal levels in the three carriers. All patients displayed a similar immunoreactive signal for plakophilin-2, connexin-43, and emerin. In conclusion, two TMEM43 sequence variants were identified in this Danish ARVC cohort. Evaluation of the expression of TMEM43 showed a unique cardiac localization. The immunoreactive signal for the desmosomal protein plakoglobin was reduced in mutation carriers. The TMEM43 gene underlies a distinctive form of ARVC which may share a final common pathway with desmosome-associated ARVC.

Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a lethal condition characterised by ventricular tachyarrhythmias, right and/or left ventricular involvement and fibrofatty infiltrations in the myocardium. The disease has been associated with mutations in genes encoding desmosomal proteins. OBJECTIVE: To thoroughly evaluate an ARVC cohort for desmosomal mutations and large genomic rearrangements and characterise the phenotype associated with double-mutation carrier status. METHODS: 65 unrelated patients (55 fulfilling current criteria and 10 borderline cases) were screened for mutations in all known desmosome genes (desmocollin-2 (DSC2), desmoglein-2 (DSG2), desmoplakin (DSP), plakoglobin (JUP) and plakophilin-2 (PKP2)) and TGFb3. Presence of genomic rearrangements was assessed by multiplex ligation-dependent probe amplification. Results The screening identified 19 different mutations: two mutations in DSG2, four in DSC2, two in DSP (one heterozygous and one homozygous), four in JUP (one patient with compound heterozygous) and seven in PKP2. No genomic rearrangements or mutations in TGFb3 were identified. Ten of the mutations were novel. Seven families carried more than one mutation. Clinical evaluation of these families showed a variable phenotype associated with the double-mutation carrier status. The homozygous desmoplakin mutation (DSP p.G2056R+p.G2056R) carrier came from a consanguineous Danish family and had left ventricular involvement, palmar keratoderma and curly hair consistent with a Carvajal-like syndrome. CONCLUSIONS: 33% of patients in this Danish cohort with ARVC carried desmosomal mutations with a surprisingly wide mutation spectrum. A substantial proportion of patients carried more than one mutation. Our study supports comprehensive desmosomal mutation screening beyond the first encountered mutation, whereas routine screening for genomic rearrangements does not seem indicated.

Ubiquitin promoter-based vectors for high-level expression of selectable and/or screenable marker genes in monocotyledonous plants.

A set of plasmids has been constructed utilizing the promoter, 5' untranslated exon, and first intron of the maize ubiquitin (Ubi-1) gene to drive expression of protein coding sequences of choice. Plasmids containing chimaeric genes for ubiquitin-luciferase (Ubi-Luc), ubiquitin-beta-glucuronidase (Ubi-GUS), and ubiquitin-phosphinothricin acetyl transferase (Ubi-bar) have been generated, as well as a construct containing chimaeric genes for both Ubi-GUS and Ubi-bar in a single plasmid. Another construct was generated to allow cloning of protein coding sequences of choice on Bam HI and Bam HI-compatible restriction fragments downstream of the Ubi-1 gene fragment. Because the Ubi-1 promoter has been shown to be highly active in monocots, these constructs may be useful for generating high-level gene expression of selectable markers to facilitate efficient transformation of monocots, to drive expression of reference reporter genes in studies of gene expression, and to provide expression of biotechnologically important protein products in transgenic plants.

The Helicobacter pylori theory and duodenal ulcer disease. A case study of the research process.

OBJECTIVES: To describe the medical research process from the time of the generation of a new theory to its implementation in clinical practice. The Helicobacter pylori (H. pylori) theory, i.e. the theory that H. pylori plays a significant causal role in duodenal ulcer disease was chosen as a case. MATERIAL: Abstracts from 1984 to 1993, identified in the CD-Rom, Medline system, ("Silverplatter"), using the search terms Campylobacter pylori and Helicobacter pylori, and reviews and editorials about H. pylori in some of the most widespread clinical journals. RESULTS: 2204 papers on H. pylori were published, of which 64% (1,403) were original articles. Of these, 30% (415/1,403) were descriptive clinical studies, 5% (64) were epidemiological studies, 33% (459) were laboratory studies of disease mechanisms, 8% (112) were therapeutic intervention studies, and 24% (336) concerned diagnostic and therapeutic techniques. A total of 204 of the clinical studies addressed duodenal ulcer disease. Of these, 72% (147) were cross-sectional studies, 3% (7) were observational cohort studies and 25% (50) were therapeutic intervention studies. Thirty-one editorials and reviews concerning the etiological role of H. pylori in duodenal ulcer disease had been published in some of the most widespread clinical journals. In half of the papers the authors were convinced of the causal role of H. pylori in duodenal ulcer disease, while in the remainder they were sceptical. In seven cases the authors stated which patients should be selected for H. pylori eradication treatment. CONCLUSION: Descriptive clinical studies and laboratory studies of disease mechanisms were the prevailing types of research about H. pylori. Comparatively few therapeutic intervention studies were done; this fact may have hampered the acceptance of the H. pylori theory and the introduction of eradication therapy in clinical practice.

Non-systemic expression of a stress-responsive maize polyubiquitin gene (Ubi-1) in transgenic rice plants.

We have used the promoter, 1st exon and 1st intron of the maize polyubiquitin gene (Ubi-1) for rice transformation experiments and revealed the characteristic expression of Ubi-1 gene: (1) Ubi-1 gene is not regulated systemically but rather individual cells respond independently to the heat or physical stress; (2) Ubi-1 gene changes its tissue-specific expression in response to stress treatment; (3) the expression of Ubi-1 gene is dependent on cell cycle.

Do clinicians accept the role of Helicobacter pylori in duodenal ulcer disease: a survey of European gastroenterologists and general practitioners.

OBJECTIVES: To examine to what extent clinicians in Europe accepted the theory of the casual role of Helicobacter pylori (H.pylori) in duodenal ulcer disease in the year 1992, and to what extent the theory had influenced their diagnostic and therapeutic habits in the management of duodenal ulcer patients at that time. DESIGN: Postal questionnaire. SETTING: Three European countries: the UK, the Netherlands, and Denmark. SUBJECTS: Three hundred and three gastroenterologists, 250 general practitioners, 83 junior hospital doctors. MAIN OUTCOME MEASURES: Number of doctors believing H. pylori to be a significant cause of duodenal ulcer disease, use of diagnostic tests for detection of H. pylori and therapeutic regimens for eradicating H. pylori. RESULTS: Four hundred and forty-two doctors replied. Eighty-four per cent of the British doctors, 73% of the Dutch doctors, and 47% of the Danish doctors accepted the role of H. pylori in duodenal ulcer disease. The rates were higher among gastroenterologists than among general practitioners. Eighty-four per cent of the British doctors, 80% of the Dutch doctors, and 48% of the Danish doctors used diagnostic tests for H. pylori, most frequently histological examination (64%). In patients with duodenal ulcer disease, H. pylori eradication was undertaken by 93% of the British doctors, 89% of the Dutch doctors, and 60% of the Danish doctors. A triple therapy (a bismuth salt, metronidazole, and either amoxicillin or tetracycline) was used by 57% (181/315) of the doctors. CONCLUSIONS: H.pylori treatment is frequently used in some countries. However, the role of H. pylori in duodenal ulcer disease has not been accepted to the same extent in different European countries.

Opinions in Denmark on the causes of peptic ulcer disease. A survey among Danish physicians and patients.

The aim of the study was to investigate opinions among Danish patients and physicians on causes of peptic ulcer disease. Fifty-nine patients with an ulcer history and 77 physicians with a special interest in gastroenterology participated. They were given a questionnaire listing 16 possible causes of peptic ulcer and indicated for each whether they believed it was a contributory cause of the disease. The patients stated 0-10 causes each (median, 4), and the physicians 3-12 causes (median, 6) (p < 0.01). Younger physicians stated more causes than did the older ones (p < 0.01), and female physicians stated more causes than did their male colleagues (p < 0.01). Seventy-five per cent of the patients indicated that psychologic factors, such as grief, anxiety, and stress, were contributory causes of peptic ulcer disease, whereas only around 40% believed that coffee/tea, alcohol, smoking, side effects of medicine, and working conditions played a causal role. Around 95% of the physicians indicated that medical drugs and smoking were contributory causes of peptic ulcer disease, and around 80% that alcohol and psychologic factors were so. Only 30-40% of the physicians believed that coffee/tea, food habits, infection, and working conditions could play a causal role in ulcer disease. It is concluded that the opinion on causal agents in peptic ulcer disease differ considerably among both patients and physicians. Opinions on causes of diseases may influence the way we treat and advise our patients, and attempts should thus be made to unify our knowledge and interpretations of causes of diseases to reach more solid ground in counselling our patients.

Observer homogeneity in the histologic diagnosis of Helicobacter pylori. Latent class analysis, kappa coefficient, and repeat frequency.

Four pathologists independently examined 82 antral mucosal biopsy specimens for the presence of Helicobacter pylori and indicated whether their assessments were certain. The pathologists made a positive diagnosis in from 56% to 84% of the specimens (significant heterogeneity, p < 0.01). The frequency of uncertain diagnoses was from 4% to 20% (p < 0.01). Uncertain statements occurred more frequently among negative than among positive diagnoses. For the six pairs of observers the kappa coefficients were between 0.39 and 0.82. By a latent class analysis measures of diagnostic accuracy were calculated comparing the observers' assessments with an estimated consensus diagnosis. The predictive values of a positive diagnosis ranged from 0.70 to 1.00. By calculation of repeat frequencies--that is, the probability that an observer's statement was confirmed by another observer--it became evident that uncertain statements were less frequently (61%) confirmed than were certain ones (85%). It is concluded that observer homogeneity is only moderate with regard to the histologic diagnosis of H. pylori, which should be considered both in daily clinical routine and in scientific studies. Disagreement between observers was associated with negative diagnoses, presumably because the pathologists felt more uncertain in these cases.

Expression of a Maize Ubiquitin Gene Promoter-bar Chimeric Gene in Transgenic Rice Plants.

We have constructed a chimeric gene consisting of the promoter, first exon, and first intron of a maize ubiquitin gene (Ubi-1) and the coding sequence of the bar gene from Streptomyces hygroscopicus. This construct was transferred into rice (Oryza sativa L.) protoplasts via electroporation, and 10 plants were regenerated from calli that had been selected for resistance to exogenously supplied bialaphos. Transgenic plants grown in a greenhouse were resistant to both bialaphos and phosphinothricine at a dosage lethal to untransformed control plants. Evidence of stable integration of the transferred gene into the genome of the regenerated primary transformant plants was obtained from Southern blot analysis. In addition, northern blot analysis indicated expression and proper splicing of the maize ubiquitin gene first intron from the primary chimeric transcript in these transgenic rice plants, and western blot analysis and enzymic assays verified expression of the active bar gene product. Apparent mendelian segregation for bialaphos resistance in T(1) progeny of primary transformants was confirmed.

Maize polyubiquitin genes: structure, thermal perturbation of expression and transcript splicing, and promoter activity following transfer to protoplasts by electroporation.

Two genomic clones (lambda Ubi-1 and lambda Ubi-2) encoding the highly conserved 76 amino acid protein ubiquitin have been isolated from maize. Sequence analysis shows that both genes contain seven contiguous direct repeats of the protein coding region in a polyprotein conformation. The deduced amino acid sequence of all 14 repeats is identical and is the same as for other plant ubiquitins. The use of transcript-specific oligonucleotide probes shows that Ubi-1 and Ubi-2 are expressed constitutively at 25 degrees C but are inducible to higher levels at elevated temperatures in maize seedlings. Both genes contain an intron in the 5' untranslated region which is inefficiently processed following a brief, severe heat shock. The transcription start site of Ubi-1 has been determined and a transcriptional fusion of 0.9 kb of the 5' flanking region and the entire 5' untranslated sequence of Ubi-1 with the coding sequence of the gene encoding the reporter molecule chloramphenicol acetyl transferase (CAT) has been constructed (pUBI-CAT). CAT assays of extracts of protoplasts electroporated with this construct show that the ubiquitin gene fragment confers a high level of CAT expression in maize and other monocot protoplasts but not in protoplasts of the dicot tobacco. Expression from the Ubi-1 promoter of pUBI-CAT yields more than a 10-fold higher level of CAT activity in maize protoplasts than expression from the widely used cauliflower mosaic virus 35S promoter of a 35S-CAT construct. Conversely, in tobacco protoplasts CAT activity from transcription of pUBI-CAT is less than one tenth of the level from p35S-CAT.

[Duodenal ulcer in systemic mastocytosis]. / Ulcus duodeni ved systemisk mastocytose.

Two cases of systemic mastocytosis are presented. Both patients had peptic ulceration. Greatly raised values on investigation of gastric acid secretion in patients with therapy-resistant peptic ulceration and normal serum gastrin should raise the suspicion of systemic mastocytosis.

phyB is evolutionarily conserved and constitutively expressed in rice seedling shoots.

Southern blot analysis indicates that the rice genome contains single copies of genes encoding type A (phyA) and type B (phyB) phytochromes. We have isolated overlapping cDNA and genomic clones encoding the entire phyB polypeptide. This monocot sequence is more closely related to phyB from the dicot, Arabidopsis (73% amino acid sequence identity), than it is to the phyA gene in the rice genome (50% identity). These data support the proposal that phyA and phyB subfamilies diverged early in plant evolution and that subsequent divergence accompanied the evolution of monocots and dicots. Moreover, since rice and Arabidopsis phyB polypeptides are more closely related to one another (73% identity) than are monocot and dicot phyA sequences (63-65% identity), it appears that phyB has evolved more slowly than phyA. Sequence conservation between phyA and phyB is greatest in a central core region surrounding the chromophore attachment site, and least toward the amino-terminal and carboxy-terminal ends of the polypeptides, although hydropathy analysis suggests that the overall structure of the two phytochromes has been conserved. Gene-specific Northern blot analysis indicates that, whereas phyA is negatively regulated by phytochrome in rice seedling shoots in the manner typical of monocots, phyB is constitutively expressed irrespective of light treatment. In consequence, phyA and phyB transcripts are equally abundant in fully green tissue. Since Arabidopsis phyB mRNA levels are also unaffected by light, the present results suggest that this mode of regulation is evolutionarily conserved among phyB genes, perhaps reflecting differences in the functional roles of the different phytochrome subfamilies.

[False negative mammography]. / Falsk negativ mammografi.

During the period 1.1.1984-31.12.1986, primary surgical treatment of 423 women with palpaple, invasively progressing cancer of the breast was performed. All of these had been examined mammographically prior to operation. The uncorrected nosographical sensitivity of the mammographic investigation was 0.93, decreasing to 0.83 prior to the age of 50 years. It is emphasized that patients in whom there is a disproportion between the mammographic and palpatory findings must be referred for surgical assessment without delay.

Photoregulation of a phytochrome gene promoter from oat transferred into rice by particle bombardment.

The regulatory photoreceptor phytochrome controls the transcription of its own phy genes in a negative feedback fashion. We have exploited microprojectile-mediated gene transfer to develop a rapid transient expression assay system for the study of DNA sequences involved in the phytochrome-regulated expression of these genes. The 5'-flanking sequence and part of the structural region of an oat phy gene have been fused to a reporter coding sequence (chloramphenicol acetyltransferase, CAT) and introduced into intact darkgrown seedlings by using high-velocity microprojectiles. Expression is assayable in less than 24 hr from bombardment. The introduced oat phy-CAT fusion gene is expressed and down-regulated by white light in barley, rice, and oat, whereas no expression is detected in three dicots tested, tobacco, cucumber, and Arabidopsis thaliana. In bombarded rice shoots, red/far-red light-reversible repression of expression of the heterologous oat phy-CAT gene shows that it is regulated by phytochrome in a manner parallel to that of the endogenous rice phy genes. These data indicate that the transduction pathway components and promoter sequences involved in autoregulation of phy expression have been evolutionarily conserved between oat and rice. The experiments show the feasibility of using high-velocity microprojectile-mediated gene transfer for the rapid analysis of light-controlled monocot gene promoters in monocot tissues that until now have been recalcitrant to such studies.

Structure and expression of a maize phytochrome-encoding gene.

We have isolated genomic clones for three loci encoding the phytochrome polypeptide of Zea mays, and have determined the entire sequence of one of them (phyA1) together with approximately 1 kb of 5' flanking DNA. The structure of this gene is highly conserved in comparison with other phytochrome-encoding genes (phy). The deduced amino acid (aa) sequence indicates that the maize phytochrome protein is 1130 aa long (125 kDa). Overall aa sequence identity is 88% with Avena and rice type A phytochromes and 65% with the type A phytochromes of the dicots, pea, zucchini and Arabidopsis. Northern analysis indicates that maize phy transcripts are down-regulated only two- to threefold in etiolated seedlings 3 h after a red light pulse, in contrast to Avena where a ten- to 20-fold decrease is observed. On the other hand, a more than tenfold reduction in maize phy mRNA abundance occurs in seedlings transferred to white light for 24 h. Several conserved sequence elements have been identified by comparison of the maize phyA1 and other monocot phy promoters, suggesting that these common regions may be regulatory elements involved in phy expression.

[Non-palpable tumors of the breast demonstrated by mammography]. / Ikke-palpable mammatumorer påvist ved mammografi.

During the period 1.1.1985-28.2.1987, 114 mammographic markings with needles were undertaken on cancer-suspect, non-palpable tumours of the breast in 106 patients. In 27.2% of the cases, carcinomata were found and, in 16.7%, carcinoma in situ. Mammographic examination combined with needle marking is recommended as a diagnostic supplement to clinical examination.

Isolation and characterization of a maize chlorophyll a/b binding protein gene that produces high levels of mRNA in the dark.

A cDNA library prepared using mRNA isolated from red-light irradiated maize seedlings was screened by a difference procedure for clones that represent red-light regulated mRNA. Two such clones were found to represent mRNA for a chlorophyll a/b binding protein (CAB), and one of these (pAB1084) was used to screen a maize genomic library. One positive genomic clone (lambda AB1084) was isolated and sequenced. The gene represented by lambda AB1084, which we designate maize cab-1, contains extensive nucleotide homology within its protein coding region to CAB genes from other species. The boundaries of the transcribed region of the cab-1 gene were determined by S1 nuclease mapping. The 5' terminus of cab-1 mRNA is located 52-54 nucleotides (nt) upstream of the translation start site and 34 nt downstream of a TATA box. As in the case of petunia CAB genes, several poly(A) addition sites are present in mRNA from the cab-1 gene. The 5' flanking DNA of cab-1 contains sequences related to elements that have been implicated in the light-regulated expression of CAB and rbcS genes in other plant systems. Quantitative Northern blot hybridization analysis using a gene specific probe for cab-1 indicates that the mRNA for this gene is present at 0.4% of the total mRNA and up to 80% of the total CAB mRNA in the leaves of dark-grown seedlings. In consequence, although the degree of up-regulation by white light is only moderate (3- to 6-fold), cab-1 transcripts account for approximately 2% of the mRNA in the leaves of light-grown seedlings.

Sequence analysis and transcriptional regulation by heat shock of polyubiquitin transcripts from maize.

We have isolated a maize ubiquitin cDNA clone which encodes one partial and three full-length, identical 76 amino acid repeats, in a polyprotein conformation. The deduced amino acid sequence of the mature monomeric polypeptide is identical to that determined for three other plants, barley, oat, and Arabidopsis, and differs from yeast and animal ubiquitin by only two and three amino acids, respectively. Hybridization of the cDNA clone to restriction endonuclease-digested genomic DNA revealed that ubiquitin is encoded by a small multigene family in maize. Northern blot analysis of poly(A)(+) RNA indicated that multiple ubiquitin mRNAs of 2.1, 1.6 and 0.8 kb are produced in maize shoots and roots. The abundance of the largest (2.1 kb) of these transcripts increased transiently 3- to 4-fold over the first 1 to 3 h in seedlings that were subjected to heat shock, and then returned dramatically within 1 h almost to the preshocked level. In contrast, the two smaller transcripts showed little or no change following heat shock. Run-on transcription assays in isolated maize nuclei showed a heat shock-induced increase in ubiquitin run-on transcripts that paralleled the increase in mature 2.1 kb mRNA levels over the first 3 h following the heat shock treatment. This result indicates that heat shock regulates ubiquitin gene expression at least in part at the transcriptional level. The subsequent rapid decline in steady-state mRNA levels, on the other hand, was not preceded by decreased ubiquitin gene transcription, raising the possibility of both transcriptional and posttranscriptional regulation. The run-on transcription assays also revealed a transient 5-fold reduction in rRNA gene transcription following heat shock, indicating that the transcriptional machinery for these genes is selectively sensitive to this stress.

Phytochrome and the regulation of the expression of its genes.

In attempting to understand the mechanism of phytochrome action we are studying structural properties of the photoreceptor molecule and the autoregulation of expression of phytochrome genes. Run-off transcription assays in isolated nuclei from Avena indicate that phytochrome decreases the transcription of its own genes threefold in less than 15 min form Pfr formation. The extent of this decrease is insufficient to account for the observed 10- to 50-fold decrease in mature phytochrome mRNA levels, suggesting that enhanced degradation may also play a significant role in determining the level of this mRNA. Structural analysis of native phytochrome from Avena indicates that the molecule is an elongated dimer of 124 kDa monomers, each consisting of a globular, 74 kDa, NH2-terminal domain bearing the single chromophore at Cys-321, and a more open COOH-terminal domain that bears the dimerization site. Controlled proteolysis and binding of monoclonal antibodies to mapped epitopes has identified two regions, one in the 6-10 kDa NH2-terminal segment and the other ca. 70 kDa from the NH2-terminus, that undergo photoconversion-induced conformational changes and are therefore candidates for involvement in the molecule's regulatory function. Comparison of the full-length amino acid sequences of Avena and Cucurbita phytochromes, derived from nucleotide sequence analysis, indicates overall homology of 65%. The most highly conserved regions are those immediately surrounding the chromophore attachment site, where 29 residues are invariant, and a hydrophobic region between residues 150 and 300, postulated to form a cavity containing the chromophore. In contrast, a strikingly lower level of homology exists at the COOH-terminus of the polypeptide between residues 800 and 1128, indicating a possible lack of involvement of this region in phytochrome function.