PubMed Health⌕ Search

Biomedical subjects

M C Johnston

Publications and source records attributed to M C Johnston.

At least 19 recordsLinked to original sources
PubMed1992

Foodhandling practices of Dunedin caterers: a cause for concern.

AIM: Foodhandling practices in the Dunedin catering industry were assessed to determine if they were correct, preventing the transmission of foodborne disease to the public. METHOD: A random sample of 300 foodservice outlets was selected. Information was collected during personal interviews with managers using a prepared questionnaire. Potentially dangerous practices were further analysed and summed to identify "at risk" operations. RESULTS: Response rate was 71%. Thirty-six percent of restaurants, 27% of takeaway bars and 25% of deli-bars and butchers could have been considered at risk operations. Few managers had any formal training in preparing and serving food, and less than 20% of managers and personnel had any food hygiene training. CONCLUSIONS: Current legislation and its enforcement is unable to adequately address incorrect food handling practices. It is recommended that revisions of the law emphasise the importance of correct practices and their enforcement. Food hygiene training should become compulsory for all who work in the catering industry.

Cooking↗
PubMed1990

Congenital malformations of the external, middle, and inner ear produced by isotretinoin exposure in mouse embryos.

Isotretinoin (Accutane), a widely used dermatologic drug, produces severe congenital malformations when used during pregnancy. The isotretinoin teratogen syndrome consists of multiple cardiovascular and craniofacial anomalies, most commonly involving the external ear. This study examined the pathogenesis of isotretinoin teratogenicity in a mouse model, using microdissection and histologic examination of fetal mouse ears after treatment with the drug at various stages of embryonic development. In this study, earlier treatment times frequently produced microtia similar to that seen in affected infants, as well as recognizable patterns of temporal bone and ossicular abnormalities; exposure at a later developmental stage resulted in facial tags with less severely affected ears. Possible teratogenic mechanisms of isotretinoin are discussed. Suitability of the mouse model for studying human congenital craniofacial malformations, such as Goldenhar's and Treacher Collins Syndrome, is also explored.

Abnormalities, Drug-Induced↗
PubMed1989

Pathogenesis of cleft palate in Treacher Collins, Nager, and Miller syndromes.

Abnormalities of the secondary palate were studied in an animal model in which features of Treacher Collins syndrome (TCS) and Nager or Miller syndromes (both of which are facially similar to Treacher Collins, but include limb malformations) were induced by acute maternal exposure to 13-cis-retinoic acid (13-cis-RA, isotretinoin, Accutane). Previous work in our laboratory has illustrated that excessive cell death in the proximal aspect of the maxillary and mandibular prominences of the first visceral arch and in the apical ectodermal ridge of the limb bud probably accounts for the characteristic craniofacial and limb abnormalities observed (Sulik et al, 1987; Sulik and Dehart, 1988). The current study shows that maternal treatment with 400 mg per kilogram 13-cis-RA at 8 days 14 hours (8d14hr) or 9d6hr post fertilization results in abnormalities of the secondary palate that vary in incidence and severity. Following the earlier treatment time, 82 percent (68 of 74) of the 18d fetuses were affected, with, severely hypoplastic, unfused palatal shelves present in 34 percent (25 of 74). The less severely affected fetuses had malformations that involved primarily the posterior aspect of the palatal shelves. This malformation (foreshortening of the posterior portion of the palate) constituted the major developmental alteration that resulted from treatment at the later time, at which time a 52 percent (26 of 50) malformation incidence was seen. The change in pattern of malformations with treatment time is consistent with the changing pattern of programmed cell death, which was observed to occur in the first visceral arch.

Animals↗
PubMed1987

Mandibulofacial dysostosis (Treacher Collins syndrome): a new proposal for its pathogenesis.

Acute exposure to 400 mg/kg 13-cis retinoic acid (13-cis RA, isotretinoin, Accutane) on the ninth day postfertilization in mice (a time that corresponds to the fourth week postfertilization in humans) results in malformations that characterize mandibulofacial dysostosis (MFD, Treacher Collins syndrome). Deficiencies in the infraorbital region and in the mandibular ramus and condyle, abnormalities of the secondary palate, and external ear malformations were observed. Light and scanning electron microscopic analyses of affected embryos illustrate that within 12 hours of maternal 13-cis RA treatment, markedly excessive (possibly premature) cell death occurs in regions where some of the cells are normally destined to undergo programmed cell death. Previous studies with retinoids have shown that they labilize lysosomal membranes and expand and strengthen regions of programmed cell death. Of particular interest for this study was cell death occurring in the dorsal (proximal) aspects of the maxillary and mandibular prominences of the first visceral arch, the second visceral arch, and the first visceral cleft, areas that correspond to the locations of the first and second arch ectodermal ("ganglionic") placodes and first closing membrane, respectively. The derivatives of this region are those that are severely affected in MFD. As described in previous reports from this laboratory, 13-cis RA is known to interfere with neural crest cells, resulting in major craniofacial malformations. However, the exposure times involved were earlier than those described herein. It is hypothesized that effects on the first and second arch ectodermal placodal cells at a time following the release from the neural folds of neural crest cells into the developing cranial region are of great significance in the pathogenesis of MFD. This is in contrast to the prevailing hypothesis that these malformations are the direct result of a primary interference with neural crest cells.

Animals↗
PubMed1986

Fetal alcohol syndrome and DiGeorge anomaly: critical ethanol exposure periods for craniofacial malformations as illustrated in an animal model.

Acute maternal ethanl (alcohol) administration induces different craniofacial anomalies in the offspring of experimental animals, depending on the gestational day of teratogen exposure. Previous studies in our laboratories have illustrated the sequence of developmental changes leading to the "typical" fetal alcohol syndrome (FAS) craniofacial phenotype which results from teratogen exposure during gastrulation. These facial features are accompanied by deficiencies in median forebrain derivatives. Ethanol teratogenesis at this time apparently results in a loss of midline territory of the embryonic disc with little effects on neural crest-dependent laterally derived structures including the visceral arches. Acute ethanol exposure in mice 1 1/2 days later, at a time when neural crest cells are populating the frontonasal prominence and the visceral arches, results in a craniofacial phenotype that is similar to that noted in the DiGeorge anomaly or sequence. Sequential scanning electron microscopic analysis in our laboratory of embryos exposed on day 8 1/2 have illustrated deficiencies in the developing facial prominences and the visceral arches. The developing forebrain and midbrain appear hypoplastic. We have also observed heart, great vessel, and thymus abnormalities in these fetuses. Histologic analyses indicate that a common pathogenetic basis for the above-mentioned (day 8 1/2-induced) fetal alcohol effects appears to be an interference with the integrity of the cranial (including occipital) neural crest. Other discrete cell populations may also be involved since we have observed abnormalities in other regions, including placodal and closing membrane tissues. This animal model provides evidence linking maternal ethanol abuse during the 3rd or 4th weeks of human gestation to the development in the conceptus of FAS or DiGeorge anomally craniofacial characteristics, respectively. As the DiGeorge anomaly has been noted in the offspring of alcoholic women, this animal model indicates that ethanol and/or its metabolites is, in these cases, the causative agent.

Animals↗
PubMed1986

Abnormal heart and great vessel development following acute ethanol exposure in mice.

Two maternal intraperitoneal doses of ethanol (2.9 g/kg) administered on gestational day (GD) 8, 12 hours (8 d, 12 h) and 8 d, 16 h result in abnormal heart and great vessel development in C57B1/6J mice. Heparinized hearts from GD 9 to 18 conceptuses were dissected to expose the forming or already completed ventricular septum and great vessels and then routinely processed for scanning electron microscopy. As early as GD 9 (12 hours post-treatment), size deficiency and abnormal external contour of the cardiac tube were notable. By GD 12, deficiencies in the size of the conal and atrioventricular (A-V) endocardial cushions, as well as abnormal positioning of the A-V canal, were demonstrable. On GD 13, when the ventricular septum should be complete, a range of deficiencies in the conal tissue was observed. Deficiencies observed were a lack of closure of the ventricular septum in the region of the membranous septum, and lack of septation of the conal portion of the developing heart. These deficiencies persist and have been documented through GD 18. Other abnormalities noted on GD 18 include double-outlet right ventricle, as well as distal defects of the great vessels including interrupted aortic arch, right aortic arch, and a vascular ring. While these defects are comparable to those seen in the fetal alcohol syndrome, they also overlap considerably with cardiac defects that are characteristic of those in the DiGeorge Syndrome as well as in the CHARGE Association. Recent work by others as well as the fact that acute ethanol exposure in this animal model corresponds to a time of neural crest cell migration has led to the speculation that this cell population is involved in the cardiovascular pathogenesis described.

Abnormalities, Drug-Induced↗
PubMed1986

Isotretinoin embryopathy and the cranial neural crest: an in vivo and in vitro study.

Severe congenital malformations have been associated with the inadvertant use in early pregnancy of a new dermatological drug, isotretinoin. We present proposals for the pathogenesis of this embryopathy based on the study of animal models. The characteristic malformations of the face, thymus, and great vessels were induced in mice by prenatal exposure to the drug during the early somite stages of development. From histological examination of mouse embryos it was shown that the drug directly interferes with the development of cranial neural crest cells. Subsequent deficiency of crest cell-derived mesenchyme adequately explains most of the observed malformations. Rat embryo culture studies showed that, when used at concentrations of 500 ng/ml, both isotretinoin and its main metabolite in the human, 4-oxo-isotretinoin, induce malformations similar to those seen in vivo. Since during normal repetitive dosing in the human the mean trough blood concentration of isotretinoin ranges from 132 to 196 ng/ml, while 4-oxo-isotretinoin ranges from 610 to 791 ng/ml, it is likely that the metabolite plays a major role in the induction of the isotretinoin embryopathy.

Abnormalities, Drug-Induced↗
PubMed1986

Morphogenesis of hypoxia-induced cleft lip in CL/Fr mice.

Cleft lip with or without associated cleft palate [CL(P)], one of the most common human malformations, is in most cases, believed to be caused by a combination of genetic and environmental factors. Previous studies have shown that maternal respiratory hypoxia (10% O2) increases the incidence of CL(P) from the spontaneous level of 36% to 89% in CL/Fr mice. The current investigation was designed to study, morphologically, the developmental alterations of the primary palate primordia in CL/Fr embryos, following a reduction in maternal respiratory oxygen levels. Scanning electron microscopy was utilized to compare the development of 35-43 somite hypoxia and control (normoxia) embryos. Hypoxia increased the incidence of resorptions and increased the incidence of CL(P) in viable embryos, compared to normoxia. Debris, most of which was limited to the deeper aspects of the invaginating nasal placode, was present in hypoxia embryos at stages prior to primary palate fusion and was absent in comparably staged normoxia embryos. It is believed that this debris is cellular in nature and that associated retardation of placodal invagination is primarily responsible for the increased incidence of CL(P). Other effects on morphogenesis and/or growth retardation may also be contributing factors.

Animals↗
PubMed1985

Normal and abnormal development of the lip and palate.

Largely because fusion of the lip and the palate are developmental weak points, common facial clefts may arise in a great many ways, both experimentally and in man. However, we believe that the vast majority of human clefts have similar origins with minor variations. One must always question the appropriateness of animal models. Apparently appropriate animal models are giving us considerable insight into the manner in which genetic and environmental factors alter development and how they interact with one another in the developing embryo. These studies help us understand the nature of the multifactorial threshold concept as it applies to cleft lip and cleft palate, and they emphasize the potential importance of even "minor" environmental factors in determining on which side of the threshold for clefting an individual embryo may fall.

Animals↗
PubMed1979

Phenytoin (dilantin)-induced cleft lip and palate in A/J mice: a scanning and transmission electron microscopic study.

High incidences of cleft lip and palate (CLP) produced by maternal intraperitoneal administration of 75 mg/kg phenytoin on gestational day 10 to A/J mice are associated with a severe size reduction in the lateral nasal process. Scanning and transmission EM analyses of this region demonstrate a marked change in the morphology of the mesenchymal cells underlying the surface epithelium in treated versus control day 11 (7-tail somite) embryos: long, branching cellular processes, which form a dense meshwork that appears to interact with the epithelial basement lamina in control embryos are undeveloped or absent in phenytoin-treated embryos. The ultrastructural morphology of these cell processes is described and their possible importance in normal development is discussed. Scanning EM observations of incomplete clefts of the lip which frequently result from phenytoin treatment indicate that Simonart's bands form from fusion of the lateral and medial nasal processes in association with a lack of fusion of the maxillary process with the medial nasal process.

Animals↗
PubMed1979

Scanning electron microscopy (SEM) of cranial neural crest migration in chick embryos.

This study describes migrating cranial neural crest cells and the microenvironment through which they migrate in chick embryos. Just prior to and during cell migration, an extensive fibrillar meshwork is observed, particularly on the outer surface of the neural tube and the inner surface of the ectoderm. This meshwork in general had a random orientation. This suggested to us that the meshwork does not provide a directive vector for cell migration but rather a substratum to promote or enhance crest cell filopodial attachment as the cells migrate. Much remains to be done in characterizing the composition of this meshwork. Based on other studies in which a smiliar meshwork has been observed, it is not unreasonable to consider it to be partly collagenous. Another major component in the relatively cell-free space through which avian crest cells migrate is hyaluronic acid. The migrating crest cells are characteristically bipolar and are generally oriented in the direction of migration, although little is known about the actual mechanism of motility. Alterations in the migrating cell or in the environment through which it migrates may interfere with normal craniofacial morphogenesis, as discussed elsewhere in this volume by Johnston and Sulik.

Animals↗