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Biomedical subjects

J B Upfold

Publications and source records attributed to J B Upfold.

7 recordsLinked to original sources

Neural tube defects in the parietal region of human embryos: failure to close or closure-reopening?

This is a follow-up study to earlier investigations on neural tube defects (NTD) in the Kyoto collection of human embryos. It includes an extensive examination of abnormal embryos which have been photographed and serially sectioned following routine histological preparation. Two new types of NTD are described in the parietal region (the roof of the third ventricle) which had previously been overlooked. These anomalies were found most commonly in embryos at the developmental period. Carnegie stage [CS] 16-23 (embryonic days 38-52). Hypotheses are advanced regarding the genesis of NTD and whether encephaloceles and NTD are part of a spectrum of malformation. This study also reinforces evidence that the occurrence of NTD is significantly higher in the embryonic period than at birth. Animal studies, using the guinea-pig are discussed with regard to the investigation of hypotheses put forward to explain the genesis of NTD.

Cerebral Ventricles↗

The induction of neural tube defects by maternal hyperthermia: a comparison of the guinea-pig and human.

In our recent studies on the effects of maternal hyperthermia on the embryonic guinea-pig, we have demonstrated two 'teratogenic windows' at embryonic days 13 and 21 (E13 and E21). E13 encompasses the period of the closure of the neural groove and anterior neuropore, and E21 the commencement of the cortical plate. The approximate equivalent developmental times in the human are E23-E25 and E49-E56 respectively. In the guinea-pig, maternal hyperthermia at E13 results in a high incidence of neural tube defects (NTD), many open, and associated with other defects such as microphthalmia, and scoliosis or kyphosis. The NTD were most common in the developing hindbrain and all demonstrated considerable infoldings of neural tissue, rosettes of neuroepithelial cells, outpocketings of neural tissue and large cystic cavities beneath the defect. In human examples from the Kyoto Human Embryo Collection, 16 had verified hyperthermic insults at E23-E25 and all had NTD which showed similar deformities to the guinea-pig. Most embryos with such gross defects are aborted in the early fetal period in both species.

Animals↗

Interference with neural crest migration by maternal hyperthermia as a cause of embryonic death due to heart failure.

Maternal hyperthermia has been demonstrated to be a teratogen in every animal species studied, and a minimum core temperature rise of 2.5 degrees C can produce a number of developmental defects. However, numerous embryos fail to survive to term. In the guinea-pig, heating the embryos prior to neural tube closure induces significant neural tube defects, but all embryos die within 20 days of heating. A number have aberrant cardiac development and many show spectacular pericardial effusions and congestion in the peripheral circulation. We suggest that maternal hyperthermia has interfered with neural crest migration which is a major component in the induction of these changes.

Animals↗

Quantitative study of the effects of maternal hyperthermia on cell death and proliferation in the guinea pig brain on day 21 of pregnancy.

On embryonic day 21, pregnant guinea pigs were exposed to a 44 degrees C environment for 1 hour. As a result, all brain ventricular zone cells in M phase of the mitotic cycle when heat-shock occurred became immediately pyknotic and all cell division was stopped for 4-8 hr. The pyknotic cells were removed at a definable rate until mitosis resumed, after which removal occurred in an apparently random manner. Long delays in the return to mitosis were related to increased destruction of S-phase cells deep within the ventricular zone and largely confined to the alar lamina. Upon recovery, a rostrocaudal delay in mitosis was apparent, and the number of mitotic figures was increased compared with control numbers for 1 hr, after which they returned to control numbers. It was evident that up to 40% of the cells within the ventricular zone were destroyed following brief maternal heat stress.

Animals↗

Maternal hyperthermia as a cause of "idiopathic" mental retardation.

Maternal hyperthermia of even short duration induces dramatic teratogenic (monster producing) effects in all experimental animals studied. In humans, several studies have reported cases analogous to some laboratory results in animal experiments, e.g., mental retardation, brain and nerve abnormalities and facial deformity. Recent computer-aided 3D reconstructions of pyramidal cells from guinea-pig brains subjected embryonically to a 1 hr stress at 44 degrees C environmental temperature, show that structural changes are induced in dendritic arbors. The alterations are greatest for dendritic segments closest to the cell body and are consistent with several reports linking topological and metrical anomalies with disturbances of brain function. We suggest that many cases of "idiopathic" subnormality are due to maternal hyperthermia during early pregnancy.

Animals↗

Three-dimensional reconstruction of tissue using computer-generated images.

In the study of brain ventricles for both teaching and research, it is often of considerable advantage to graphically display the reconstructed shape of the specimen. This paper describes the making of two-dimensional serial cross-sections and their storage for subsequent manipulation and display on a personal computer; the three-dimensional (3D) reconstructions may have hidden lines removed and various parts coloured for definition of areas of interest, for example the density and position of pyknotic (dead) nuclei. Current research involved the investigation of the effects of maternal hyperthermia on early embryonic brains. The 3D reconstructions were found ideal for understanding the temporal changes occurring in embryonic brains subjected to defined maternal heat stresses. The method involved 4 X 4 matrices using homogenous coordinate theory, being the most ideal and allowing a constant mechanism for all transformations. Total time from examination of sections to obtaining an accurate printed 3D reconstruction is approximately 1 h if 22 sections are used.

Animals↗