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Biomedical subjects

H Schipper

Publications and source records attributed to H Schipper.

At least 37 records · Page 2Linked to original sources

Expression of Hoxb-1 during gastrulation and segmentation stages of carp (Cyprinus carpio).

This report describes the cDNA sequence and embryonic RNA expression pattern of carp Hoxb-1. Carp Hoxb-1 is a labial-like, homeobox-containing gene of the 3' end of the Hox gene cluster. The expression pattern in carp is compared to that of homologs in other vertebrates. As holds for other Hox genes, carp Hoxb-1 is expressed with highest intensity at a sharp anterior boundary, and expression fades out towards posterior. At later stages, gaps were found in the domain. The gene is expressed from late gastrulation onwards, first mainly in the hypoblast but later in all germ layers. Its most prominent expression area is rhombomere 4 (r4) of the hindbrain. Transcripts were also found in the neural tube, mesoderm (lateral, head and presomite), epidermis and neural crest. At 30 hours post fertilization, Hoxb-1 was still expressed in r4, in the anterior trunk neural tube and in the branchial arches posterior to r4. Hox genes are thought to be involved in the specification of positional values along the embryonic anterior-posterior axis, and Hoxb-1 expression in r4 is supposed to be important for specifying the unique identity of this hindbrain segment. The conserved expression in r4 suggests that this is also true for carp Hoxb-1.

Amino Acid Sequence↗

Measuring quality of life in different cultures: translation of the Functional Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.

Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.

Activities of Daily Living↗

Epithelial cell invasion and survival of Bordetella bronchiseptica.

Wild-type Bordetella bronchiseptica and a bvg mutant strain were used for invasion and survival experiments in human Caco-2 and A549 epithelial cells. Both bacterial strains were able to enter and persist within the host cells for at least a week. A significant proportion of the bacteria from both B. bronchiseptica strains but not from Bordetella pertussis were found free in the cytoplasm, suggesting different invasion and survival strategies of the two species in epithelial cells.

Bordetella bronchiseptica↗

Treating cancer: is kill cure?

For more than fifty years, the paradigm which has formed the basis of cancer research and treatment has been that of irreversibly deranged cells, which would inevitably kill their host unless they were totally eradicated. Experimentation procedures, evaluation criteria, and therapies are all based on cell killing. Yet there is substantial evidence that the kill/cure paradigm has reached its limit, and may be blinding us to other mechanisms to control this family of diseases. Both old and new data lead to the conclusion that the derangements in cellular function, while profound, are in large measure derivatives of normal mechanisms for organ growth, repair and renewal. Further, these are dynamic processes, potentially capable of reversal. If one views cancer as a community of cells in which signalling and communication is deranged, but functional, it becomes clear that cytotoxic approaches may serve to exacerbate the very control and communication defects which permit growth, invasion and metastasis. A new model is proposed, in which the cancer cell is seen as largely normal, but aberrantly regulated. Viewed from this perspective, the "cures" we have achieved may not be the result to total kill, but instead may result from a reassertion of control. This conceptualization offers an explanation for many laboratory and clinical observations, such as the induction of drug resistance medicated by pre-existing detoxification mechanisms, the cyclic progression of many tumours, and the compelling relationship between graft-versus-host disease and the long-term disease-free survival of transplanted leukaemia patients. Further, it opens conceptual avenues to new therapies and evaluation procedures.

Cell Communication↗

The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer.

The therapeutic efficacy of gemcitabine, a new nucleoside analogue, was assessed in a variety of well-established human soft tissue sarcoma and ovarian cancer xenografts grown s.c. in nude mice. Tumour lines selected had different histological subtypes, growth rates and sensitivities to conventional cytostatic agents. The three different doses and schedules designed on the basis of a mean weight loss between 5% and 15% were i.p. injections of daily 3.5 mg kg-1 x 4, every 3 days 120 mg kg-1 x 4, and weekly 240 mg kg-1 x 2, which ultimately resulted in 19%, 10% and 4% toxic deaths, respectively. The weekly schedule induced > or = 50% growth inhibition in 2/4 soft tissue sarcoma and 4/6 ovarian cancer lines, while in three ovarian cancer lines > or = 75% growth inhibition was obtained. The anti-tumour effects of gemcitabine appeared to be similar or even better than previous data with conventional drugs tested in the same tumour lines. In comparison with the every 3 days schedule, the weekly and the daily schedule were less effective in 5/7 and 3/3 tumour lines (P < 0.001), respectively. In another experiment in three human tumour lines selected for their differential sensitivity to gemcitabine, weekly injections of 240 mg kg-1 x 6 did not result in a significant increase in the percentages of growth inhibition when compared to lower doses of 120 mg kg-1 or 60 mg kg-1 in the same schedule. However, the 240 mg kg-1 weekly x 6 schedule showed superior effects in 2/3 tumour lines in comparison with the same dose given every 2 weeks x 3 (P < 0.05). The preclinical activity of gemcitabine suggests that the drug can induce responses in soft tissue sarcoma and ovarian cancer patients. Our results further indicate that clinical trials of gemcitabine in solid tumour types should be designed on the basis of a schedule rather than a dose dependence.

Animals↗

Proliferative activity of colonic mucosa at different distances from primary adenocarcinoma as determined by the presence of statin: a nonproliferation-specific nuclear protein.

The field change is one hypothesis concerning the development of colorectal carcinoma. Removal of a carcinoma without its entire surrounding altered mucosa may result in the development of a recurrence. S44, a monoclonal antibody directed against statin, a nuclear protein expressed in nonproliferating cells in either a quiescent or senescent state, was used to determine the rate of cell growth in colorectal mucosa at different distances from carcinomas. The specimens of 18 patients undergoing resection of a colorectal carcinoma were immediately opened after operation, and strips of mucosa were taken at distances of 1 cm, 5 cm, and 10 cm from the carcinoma. For each location, 10 longitudinally oriented crypts were evaluated for statin-positive cells identified by the presence of a dark brown peroxidase-conjugated antibody reaction product. The average percentage of statin-positive cells per crypt was significantly lower at a 1-cm distance from the carcinoma compared with the mucosa located 5 and 10 cm from the carcinoma (20.89 +/- 4.33 at 1 cm, 32.41 +/- 5.27 at 5 cm, and 34.23 +/- 6.45 at 10 cm). None of the calculated parameters showed any significant difference between the 5-cm and 10-cm locations. The fact that the proliferation rate of the mucosal cells returns to the normal level at 5 cm from the margin of the carcinoma suggests that cells located within this distance still retain proliferative potential even though they are morphologically indistinguishable from their normal counterparts. We conclude that failure to remove this transitional, potentially proliferative mucosa may result in subsequent development of anastomotic or perianastomotic recurrences.

Antibodies, Monoclonal↗

Origin of primordial germ cells, as characterized by the presence of nuage, in embryos of the teleost fish Barbus conchonius.

The presence, location and morphology of cells containing nuage, an ultrastructural characteristic of primordial germ cells (PGCs), is described from the moment of first morphological recognition of PGC (around 100% epiboly) in embryos of the teleost fish Barbus conchonius. Thus characterized cells were studied in relation to their cellular contacts with somatic germ layer cells, possibly involved in the determination of PGCs. The results show that from the very moment that cells, likely to be PGCs, can be light microscopically identified with morphological and positional criteria (from 10 h post fertilization (p.f.) onwards), they contain nuage near the nuclear envelope, which is a strong indication of their PGC-identity. During the studied period (9-12 h and 24 h p.f.) nuage-containing cells seem to translocate from the mesoderm towards the yolk syncytial layer (YSL). These PGCs usually appear not to be directly connected with the YSL but to remain separated from the YSL by one or more endodermal extensions, at least up to 12 h p.f. Also at 24 h p.f. somatic cells separate the PGCs from the YSL.

Animals↗