Biomedical subjects

T H Ho

Publications and source records attributed to T H Ho.

At least 37 records · Page 2Linked to original sources

PubMed1999

An abscisic acid-induced protein kinase, PKABA1, mediates abscisic acid-suppressed gene expression in barley aleurone layers.

The phytohormone abscisic acid (ABA) induces genes-encoding proteins involved in desiccation tolerance and dormancy in seeds, but ABA also suppresses gibberellin (GA)-responsive genes encoding hydrolytic enzymes essential for postgermination growth. A unique serine/threonine protein kinase, PKABA1 mRNA, up-regulated by ABA in seeds, has been identified. In this report, the effect of PKABA1 on the signal transduction pathway mediating ABA induction and suppression of genes has been determined in aleurone layers of barley seeds. Two groups of gene constructs were introduced to barley aleurone layers by using particle bombardment: the reporter constructs containing the coding sequence of beta-glucuronidase gene linked to hormone-responsive promoters and the effector constructs containing the coding region of protein kinases linked to a constitutive promoter. Constitutive expression of PKABA1 drastically suppressed expression of low- and high-pI alpha-amylase and protease genes induced by GA. However, the presence of PKABA1 had only a small effect on the ABA induction of a gene encoding a late embryogenesis abundant protein, HVA1. Our results indicate that PKABA1 acts as a key intermediate in the signal transduction pathway leading to the suppression of GA-inducible gene expression in cereal aleurone layers.

Journal Article↗

PubMed1999

Management of adenocarcinoma in situ (ACIS) of the uteri cervix--a clinical dilemma.

OBJECTIVE: We retrospectively reviewed 24 cases of adenocarcinoma in-situ (ACIS) of the cervix, managed at KK Hospital, with the objective of determining our local approach to its treatment, the consequent clinical outcome and problems encountered. METHODS: Except for one case, all patients were treated between 1991-1996. Nineteen cone biopsies (17 laser and 2 cold knife) and eleven hysterectomies were performed. The mean follow-up duration was 20.5 months (range: 1-75 months). RESULTS: The mean age was 44.2 years (range: 32-68) with 80% of the cohort being more than 35 years old and the mean parity was 2.2. Six (25%) patients were symptomatic. Majority (21/23) had an abnormal initial Pap smear. Glandular lesions were found in 39% (9/23) of Pap smear, 28% (6/21) of colposcopy, 58% (8/14) of cervical biopsies and in 3 of 4 endocervical curettage. Of the 17 laser cone biopsy specimens, lesion involved the surgical margin in 6 patients (35%). ACIS was found in conjunction with CIN in 14 patients (58%). Five hysterectomies were performed for involved surgical margin and one for dubious surgical margin of the prior cone biopsy, of which 3 had residual ACIS. At the time of the study, there was no case of recurrent ACIS or overt adenocarcinoma developing following cone biopsy. CONCLUSION: Preconisation diagnosis of ACIS using Pap smear, colposcopy and cervical biopsy was found to be difficult in our series. Concurrent CIN occurred in a sizeable portion of patients. Laser cone biopsy was the preferred method employed. Total hysterectomy was frequently employed following cone biopsy for treating possible residual disease. We recommend greater vigilance for this condition especially in patients with CIN and the need for regular endocervical sampling in the follow-up of patients treated by cone biopsy.

Adenocarcinoma↗

PubMed1998

Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?

Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects.

Alleles↗

PubMed1998

Uterine papillary serous carcinoma--the KK Hospital experience.

A review of 355 cases of endometrial cancer treated at the KK Gynaecological Cancer Centre from June 1987 to June 1997 revealed 19 cases (5.3%) of uterine papillary serous carcinoma (UPSC), a clinically aggressive and pathologically distinct variant of adenocarcinoma which closely resembles ovarian papillary serous carcinoma. The majority of UPSC presented as late stage disease with 79% showing extrauterine disease. Twelve of 15 patients also had lymphovascular space invasion. Of the 19 cases, 15 had total hysterectomy and bilateral salpingo-oophorectomy with or without omentectomy and lymphadenectomy. Two had omental biopsy only and another 2 had dilatation and curettage only. The overall median survival in the series was 15 months. Twelve patients had died of disease (67%). Early stage disease seemed to confer a better prognosis. The poor prognosis is frequently ascribed to its tendency to present at a late stage.

Combined Modality Therapy↗

PubMed1997

Endometrial hyperplasia and the risk of endometrial carcinoma.

OBJECTIVES: To determine the incidence of endometrial carcinoma in endometrial hyperplasia and try to identify those patients at greatest risk. METHODS: We conducted a retrospective study of 116 patients who had simple, complex or mixed (simple with focal complex) endometrial hyperplasia with or without atypia, from January 1991 to December 1994. RESULTS: Twenty-nine patients had endometrial hyperplasia with atypia and 87 without atypia. Incidence of endometrial carcinoma was 27.6% in those with atypia; and 3.4% in those without atypia. All were stage I (A or B) adenocarcinomas. Polycystic Ovary Disease and subfertility were found significantly in the cases with cytological atypia; however, they were not significant in the cases with carcinoma. No significant historical differences that could predict carcinoma were found.

Adenocarcinoma↗

PubMed1997

A 5-year review of FIGO stage IB cervical cancer in an Asian population.

OBJECTIVE: We studied the clinical patterns and outcome of patients with FIGO (1985) Stage 1b cervical cancer. In particular, looking at the clinico-pathological characteristics in relation with disease recurrence. PATIENTS & METHODS: Ninety-nine Asian patients were managed at (the former) K K Hospital, Singapore, from 1987 to 1991. The mean and median follow-up periods were 67 and 60 months respectively. This study was performed in 1995. RESULTS: The majority of the patients (81%) was treated by radical hysterectomy with or without adjuvant radiotherapy/chemotherapy while 15% were treated by radical pelvic radiotherapy alone and 4% of patients had pelvic radiotherapy following the diagnosis of cervical cancer after a simple hysterectomy. Thirteen patients developed tumour recurrence (13.1%). In these patients, there was a greater proportion of adenocarcinomas (31% vs 13%, p = 0.1065), lymph node metastases (45% vs 20%, p = 0.09) and surgical margins involvement (45% vs 7%) 7%, p = 0.004) while there seemed to be no difference in histological sub-types, vascular space involvement and cytological grading. The relative risks of developing tumour recurrence in patients with adenocarcinoma was 2.5 times (95% CI: 0.88-7.05), lymph-node metastasis: 2.3 times (95% CI: 0.96-4.93) and involved surgical margins; 5.9 times (95% CI: 2.27-15.5). The mean time to recurrence were 21.7 months with all of them detected within 36 months following primary therapy. All of them had abnormal physical findings while routine follow-up Pap smear was positive in only one patient (8%). In general, the outcome of salvage treatment was poor. CONCLUSIONS: In our group of patients with FIGO Stage lb cervix cancer, majority had radical surgery performed initially. Thirteen percent had disease recurrence, in which there were greater proportions of patients with adenocarcinoma, lymph-node metastasis, and involved surgical margins. The mean time-to-recurrence was 21.7 months with all detected by 36 months. Routine follow-up Pap smear seemed to be a poor indicator of disease status.

Adenocarcinoma↗

PubMed1996

Two cases of primary retroperitoneal mucinous cystadenocarcinoma.

Two cases of primary retroperitoneal mucinous cystadenocarcinoma of the ovarian type in the presence of bilateral normal ovaries are reported. Benign, borderline, and malignant mucinous epithelium were present in both tumors; no separate ovarian tissue was identified. In addition to removal of the tumor, the uterus and both ovaries were removed and the patients are well with no evidence of disease at 30 and 15 months. Only 10 cases of primary retroperitoneal mucinous cystadenocarcinoma have been reported in the English literature and these are reviewed. The outcome of these limited number of cases suggests that removal of both ovaries and the uterus in addition to extirpation of the retroperitoneal tumor, even though the uterus and ovaries are normal, may improve the prognosis.

Cystadenocarcinoma, Mucinous↗

PubMed1996

A major cysteine proteinase, EPB, in germinating barley seeds: structure of two intronless genes and regulation of expression.

The barley cysteine proteinase B (EPB) is the main protease responsible for the degradation of endosperm storage proteins providing nitrogenous nutrients to support the growth of young seedlings. The expression of this enzyme is induced in the germinating seeds by the phytohormone, gibberellin, and suppressed by another phytohormone, abscisic acid. In situ hybridization experiments indicate that EPB is expressed in the scutellar epithelium within 24 h of seed germination, but the aleurone tissue surrounding the starchy endosperm eventually becomes the main tissue expressing this enzyme. The EPB gene family of barley consists of two very similar genes, EPB1 and EPB2, both of which have been mapped to chromosome 3. The sequences of EPB1 and EPB2 match with the two previously published cDNA clones indicating that both genes are expressed. Interestingly, neither of these genes contain any introns, a rare phenomenon in which all members of a small gene family are active intronless genes. Sequence comparison indicates that the barley EPB family can be classified as cathepsin L-like endopeptidases and is most closely related to two legume cysteine proteinases (Phaseolus vulgaris EP-C1 and Vigna mungo SHEP) which are also involved in seed storage protein degradation. The promoters of EPB1 and EPB2 have been linked to the coding sequence of a reporter gene, GUS, encoding beta-glucuronidase, and introduced into barley aleurone cells using the particle bombardment method. Transient expression studies indicate that EPB promoters are sufficient to confer the hormonal regulation of these genes.

Amino Acid Sequence↗

PubMed1996

Modular nature of abscisic acid (ABA) response complexes: composite promoter units that are necessary and sufficient for ABA induction of gene expression in barley.

The modular nature of the abscisic acid response complex (ABRC), the promoter unit necessary and sufficient for abscisic acid (ABA) induction of gene expression in barley, is defined in this study. We investigated ABA induction of a barley late embrogenesis abundant (Lea) gene, HVA1, and found that the ABRC of this gene consists of a 10-bp box with an ACGT core (ACGT-box) and the 11 bp directly upstream, named coupling element 3 (CE3). Only one copy of this ABRC is sufficient to confer ABA induction when linked to a minimal promoter. Because we previously reported another ABRC in the barley HVA22 gene, which consists of an ACGT-box with a distal coupling element (CE1), exchange experiments were conducted to study the interaction among modular elements in these ABRCs. We show that ACGT-boxes in these ABRCs are interchangeable, indicating that an ACGT-box can interact with either a distal or a proximal coupling element to confer ABA response. However, the two coupling elements are not fully exchangeable. Although CE3 can function either proximal or distal to the ACGT-box, CE1 is only functional at the distal position. The presence of both the distal and the proximal coupling elements has a synergistic effect on the absolute level of expression as well as on ABA induction. These ABRCs function in both seed and vegetative tissues. In seeds, ABA induction of the ABRC containing the proximal CE3, but not the ABRC with the distal CE1, is enhanced in the presence of the transcription regulator Viviparous1, indicating that these two ABRCs are mediated by different ABA signal transduction pathways.

Abscisic Acid↗

PubMed1996

Uterine cancer--the KK Hospital experience.

Kandang Kerbau Hospital saw 165 new cases of uterine cancers over the 4-year period from 1991 to 1994. The median age of presentation was 54.1 years and 10.9% of these cases occurred in those aged less than 40 years, unlike the corresponding figures of 61 years and less than 5%, respectively, which are often quoted for endometrial cancers in standard textbooks. Endometrioid adenocarcinoma was the commonest type of uterine cancer seen in our population (75.2%) as in other series. However, we had fewer cases of adenoacanthoma (1.4%) and adenosquamous carcinoma (1.4%) but more cases of uterine sarcoma (11.5%) than is usually reported. 6.7% of our patients had papillary serous adenocarcinoma and 3.0% had clear cell carcinoma. These 2 sub-types are associated with poorer prognosis and there is a need to increase awareness of their existence in our local population as their management differs from that for the usual endometrioid adenocarcinoma. We had fewer patients with stage I disease (53.3%) but more patients with stage III disease (22.4%). This is most likely due to the use of surgico-pathological staging currently as opposed to the clinical staging used previously which led to the under-staging of a proportion of patients.

Adenocarcinoma, Clear Cell↗

PubMed1995

Functional dissection of an abscisic acid (ABA)-inducible gene reveals two independent ABA-responsive complexes each containing a G-box and a novel cis-acting element.

To elucidate the mechanism by which abscisic acid (ABA) regulates gene expression, the promoter of the barley ABA-responsive HVA22 gene has been analyzed by both loss- and gain-of-function studies. Previous reports indicate that G-box sequences, which are present in genes responding to a variety of environmental and physiological cues, are involved in ABA response. However, our data suggest that G-box sequences are necessary but not sufficient for ABA response. Instead, an ABA response complex consisting of a G-box, namely, ABRE3 (GCCACGTACA), and a novel coupling element, CE1 (TGCCACCGG), is sufficient for high-level ABA induction, and replacement of either of these sequences abolishes ABA responsiveness. We suggest that the interaction between G-box sequences, such as ABRE3 in the HVA22 gene, and CE-type sequences determines the specificity in ABA-regulated gene expression. Our results also demonstrate that the ABA response complex is the minimal promoter unit governing high-level ABA induction; four copies of this 49-bp-long complex linked to a minimal promoter can confer more than 100-fold ABA-induced gene expression. In addition to ABA response complex 1, composed of ABRE3 and CE1, the HVA22 promoter contains another ABA response complex. The ABA responsiveness of this ABA response complex 2 relies on the interaction of G-box (ABRE2; CGCACGTGTC) with another yet unidentified coupling element. These two complexes contribute incrementally to the expression level of HVA22 in response to ABA.

Abscisic Acid↗

PubMed1995

Serum antibodies to Trichomonas vaginalis in invasive cervical cancer patients.

OBJECTIVE: To evaluate, by seroepidemiology, the possible role of the sexually-transmitted flagellate, Trichomonas vaginalis, in invasive cervical cancer. SUBJECTS AND METHOD: Sera from 121 invasive cervical cancer patients and 242 random age-matched female controls. Antibodies to T. vaginalis were detected by the western blot technique. RESULTS: Antibodies to T. vaginalis were detected in the sera of 41.3% (50/121) of invasive cervical cancer patients compared with only 5.0% (12/242) of female controls. All the reactive sera reacted strongly with the immunogenic surface membrane proteins of T. vaginalis of molecular weights of about 92 and 115 kDa, with variable reactivity to other immunogenic proteins of T. vaginalis. CONCLUSION: The significantly increased relative risk, RR = 3.42 (95% CI = 1.73-6.78), is comparable to the RRs derived in seroepidemiological studies of human papillomavirus, suggesting that T. vaginalis may be even more closely associated with invasive cervical cancer than previously realized.

Adult↗

PubMed1993

Hormone response complex in a novel abscisic acid and cycloheximide-inducible barley gene.

The phytohormone, abscisic acid (ABA), plays a variety of roles during seed development and in the plant's response to environmental stresses. To study the molecular action of ABA, we have isolated a single copy ABA-induced gene, HVA22, which is mapped to barley chromosome 1. The HVA22 gene can be induced by either ABA or the protein synthesis inhibitor, cycloheximide, and addition of both inducers to barley aleurone layers has a synergistic effect on the expression of this gene. Sequence comparison indicates that the HVA22 gene product is highly homologous to the product of human DP1 gene, which is likely to contribute to colorectal tumorigenesis. The hormonal regulation of HVA22 expression has been studied, and there appear to be at least three elements, two located in the promoter and one in the first intron, which are essential for the high level of ABA induction of HVA22 expression. Among the promoter elements is a homolog of ABA response element, which has been shown to be important in the expression of other ABA-induced genes in plants. We suggest that the barley HVA22 gene product is likely a regulatory protein, and the ABA induction of this gene requires the action of a complex set of hormone response elements.

Abscisic Acid↗

PubMed1993

Barley embryo globulin 1 gene, Beg1: characterization of cDNA, chromosome mapping and regulation of expression.

We report identification of a 2189 bp cDNA clone from barley corresponding to a single-copy gene, Beg1 (Barley embryo globulin), on chromosome 4, which encodes a storage globulin. In barley, the major protein reserve in the aleurone layer belongs to the 7S globulin class of proteins found in many seeds. Electrophoretically and antigenically similar proteins are present in the barley embryo. Accumulation of Beg1 mRNA was noted beginning 15-20 days post-anthesis in both the aleurone layer and embryo of the developing barley grain but not in the starchy endosperm. A high level of Beg1 mRNA is also present in the mature imbibed aleurones, which can be repressed by treatment with gibberellic acid. This repressive effect of gibberellin on the levels of Beg1 mRNA is confirmed in the gibberellin response-constitutive mutant, slender, whose aleurone layers do not accumulate Beg1 mRNA even in the absence of applied gibberellic acid. The deduced primary translation product of the Beg1 mRNA is a 63.7 amino acid (72 kDa) protein with homology to maize embryo globulin 1 (GLB1) and a partial sequence of a wheat 7S globulin. The internal amino acid sequence of BEG1 closely matches the N-terminal sequence of isolated barley aleurone globulin. Seven imperfect tandem repeats of 16 amino acids each are present near the N-terminus of BEG1, which conform to the consensus HGEGEREEEXGRGRGR, and contribute to the observed unusual amino acid composition of this protein. A second, distinct barley globulin gene, Beg2, which is homologous to maize Glb2, was detected by Northern and Southern analysis. Beg2 and Beg1 are regulated differently which may indicate variation in storage or utilization properties among the barley globulins.

Abscisic Acid↗

PubMed1993

Gibberellin treatment stimulates nuclear factor binding to the gibberellin response complex in a barley alpha-amylase promoter.

The promoters of a majority of cereal alpha-amylase genes contain three highly conserved sequences (gibberellin response element, box I, and pyrimidine box). Recent studies have demonstrated the functional importance of four regions that either coincide with or are immediately proximal to these three conserved elements as well as an upstream Opaque-2 binding sequence. In this study, we describe the characterization of nuclear protein factors from barley aleurone layers whose binding activity toward gibberellin response complex sequences from the barley low-pl alpha-amylase gene (Amy32b) promoter is stimulated by gibberellin A3 (GA3) treatment. Barley proteins isolated from crude nuclear extracts prepared from aleurone layers incubated with or without GA3 were fractionated by anion exchange fast protein liquid chromatography and studied using band shift assays, sequence-specific competitions, and DNase I footprinting. A GA3-dependent binding activity eluting at 210 mM KCl was shown to bind specifically to the gibberellin response element and the closely associated box I. DNase I footprinting with the proteins in this fraction indicated interactions with sequences in the gibberellin response element and box I. A second DNA binding activity eluting at 310 mM KCl was present constitutively in extracts prepared from tissues incubated both in the absence and in the presence of hormone. Proteins in this fraction were able to bind to many DNA sequences and, in general, were largely nonspecific. DNase I footprinting with the proteins in this fraction indicated a large area of protection with a single unoccupied region located at the 3' end of box I. The possible function of such an activity in hormone regulation of the alpha-amylase genes is discussed.

Base Sequence↗

PubMed1992

Developmental and organ-specific expression of an ABA- and stress-induced protein in barley.

An mRNA species, HVA1, has been shown to be rapidly induced by abscisic acid (ABA) in barley aleurone layers (Hong, Uknes and Ho, Plant Mol Biol 11: 495-506, 1988). In the current work we have investigated the expression of HVA1 in other organs of barley plants. In developing seeds, HVA1 mRNA is not detected in starchy endosperm cells, yet it accumulates in aleurone layers and embryo starting 25 days after anthesis, and its level remains high in these organs in dry seeds. Although the levels of HVA1 mRNA are equivalent in the dry embryos of dormant and nondormant barley seeds, upon imbibition HVA1 mRNA declines much slower in the dormant than in the nondormant embryos. The HVA1 mRNA and protein levels are highly induced by ABA treatment in all organs of 3-day-old seedlings. However, the induction in the leaf of 7-day-old seedlings is less than one tenth the level observed in the leaf of 3-day-old seedlings. In the leaf, HVA1 mRNA and protein are induced mainly at the base. These observations indicate that the expression of HVA1 is under developmental regulation. Besides the HVA1 protein, a smaller protein (p20) of approximately 20 kDa cross-reacting with anti-HVA1 polyclonal antibodies, is induced by ABA in barley seedlings but not in seeds. HVA1 mRNA is induced by drought, NaCl, cold or heat treatment. Similar to ABA treatment, the drought induction of HVA1 occurs in all the tissues of 3-day-old seedlings, but the induction decreases dramatically in the leaf of 7-day-old plants. The significance of organ-specific, developmentally regulated, and stress-induced expression of HVA1 is discussed.

Abscisic Acid↗

PubMed1992

A gibberellin response complex in cereal alpha-amylase gene promoters.

The Amy32b gene is a representative member of a closely related family of alpha-amylase genes expressed under hormonal control in aleurone layers of barley grains. Transcription of this gene is induced by gibberellin (GA) and suppressed by abscisic acid. In this study, we functionally defined the promoter elements of the Amy32b gene that govern the developmental and hormonal control of its expression in aleurone. Two functionally distinct yet physically associated elements are essential: a gibberellin response element mediates regulation by GA and abscisic acid, and an Opaque-2 binding sequence (O2S) is thought to interact with a barley homolog of the maize endosperm-specific transcriptional regulator Opaque-2. An additional element CCTTTT, which with the O2S forms part of a canonical "endosperm box," is important in modulating the absolute level of expression of the Amy32b promoter, as is another separate, highly conserved element TATCCATGCAGTG.

Abscisic Acid↗

PubMed1992

Combined chemotherapy using cisplatin, ifosfamide and bleomycin (PIB) in the treatment of advanced and recurrent cervical carcinoma.

Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial.

Adenocarcinoma↗