Craniofacial growth modified by blood supply. 8. Discussion of normal cranial growth of the rat

The dimensions of the skull and the dry weight of the skull bones show definite sexual dimorphism. The dynamics of the growth in the skull dimensions and their vectorial presentation show that skull growth in Rattus norvegicus BERKENHOUT is most rapid between the 42nd d and the 4th month of life. This phase is followed by a phase of localized bone growth, which persists up to an age of 300 d. The faster growth of the viscerocranium leads to changes in the proportions of the skull. The relative positions of viscerocranium and mandible and the higher relative position of the dentures are similar to principle to those seen in man. Finally, the morphogenetic effect of the temporalis muscle together with that of the brain in the shaping of the skull are discussed.     

Craniofacial growth modified by the blood supply. 7. Dry weight of the skull and growth of the mandible

The dry weight of the skull and jaw bone increases faster in operated rats than in the controls during the fourth and 12 months, but their rates of growth do not differ in the 8th month. The distances measured on the mandible reveal definite sexual dimorphism in the development of the different lengths and heights, these distance being greater in the male rats. Growth in the length of the processes predominated over the growth of the body of the mandible. Local changes in the bone were observed at the points of origin and attachment of muscles.     

Craniofacial growth modified by blood supply. 2. Changes in arterial cross sections and arterial blood supply

The cross sectional areas of arteries were calculated from their measured thicknesses. The monthly increase in size of the cross sectional area of the aorta is higher in both the controls and the operated animals between the 6th week and 4th month of life than during the subsequent period. The rate at which the cross sectional area of the aorta increased in operated animals was about twice that observed in the controls. The left common carotid artery increased its cross section in the operated animals most rapidly up to the fourth month. The cross sectional areas of all anastomoses increased five-fold by the 12th month of life. The quantities of blood flowing correlated closely with the angiometric values.     

Craniofacial growth under the influence of the blood supply. 6. Metric studies of the skull

Cephalometric data show that the distances spanning several skull bones also have the highest growth rates. No sexual dimorphism can be observed in the skulls of animals that are six weeks old; such differences do not appear until after the fourth month of life. Allometric studies reveal a relative narrowing of the neurocranium and a relative broadening of the rostrum and zygomatic arch. The broadening of the zygomatic arch complex is related to the postnatal development of the masseter muscle. Vector analysis is used to demonstrate the growth activities of the different parts of the skull. Local changes in the bone during growth was observed in the regions of muscle origin and attachment.     

Prenatal growth of the human tympanic membrane.

The questions connected with the morphology of developing tympanic membrane are rather inadequately dealt with in the relevant literature. The aim of this article has been the morphometric analysis of the prenatal growth of human tympanic membrane. The experiment was conducted on 33 fetuses aged from the 4th to 8th month of gestation. Significant individual variability of the tympanic membrane measurements was revealed in the material studied. The growth of the structure discussed was bilaterally symmetric during the whole period investigated. The fourth and 7th month of gestation seem to be the crucial stages for the tympanic membrane development. The measurements of the membrane exhibited the highest variability, simultaneously being negatively correlated with the fetal age in that periods. Relatively more intensive growth of the vertical diameter of the membrane was noted in the 5th and 8th months of gestation. In the 8th month of gestation the tympanic membrane reached a vertically elongated shape, typical of the postnatal period. On the basis of our results it is possible to conclude that the quantitative developmental process takes place in the tympanic membrane till the end of the prenatal period, determining the final functional capacity of the structure discussed.     

Craniofacial growth under the influence of the blood supply. II. Skull scoliosis

After unilateral ligature of the common carotid artery in young rats, the rostrum was observed to shift towards the ligated side. The scoliosis was combined with arthropathic changes in the temporomandibular joint. The deflection of the rostrum is situated in the region of the right premaxillar bone. It is assumed that the scoliosis is caused by reduction of the blood flow to the frontonasal sutures because the terminal branches of the infraorbital artery have no collaterals. Moreover, the reduction in the blood supply also leads to disturbance of the muscular function and thus to a reduction in growth stimuli to the frontonasal sutures.     

The influence of blood supply on craniofacial growth. 4. Reactions of the jaw musculature

The dry weight of the chewing muscles differ distinctly between male and female. In rats aged 8 to 12 months the dry weight of the chewing muscles after ligature of the carotid artery was lower on the side of the ligature. Necrotic fibres were occasionally found in the masseter muscle on the ligature side. Morphometric investigation of the masseter muscle fibres revealed no significant differences between the 2 sides in the operated rats. Since the rats were relatively young when the commune carotid artery was ligatured unilaterally, the consequences of the initially reduced blood supply to the chewing muscles on the right side could be compensated for rather well, mainly by the enlargement of previously existing anastomoses. Our quantitative and histological studies nevertheless show that muscular dysbalance of the masticatory apparatus was severe.     

Animal experiment studies on the effect of unilateral tooth extraction on the growth of the skull and masticatory muscles. III. The masticatory muscles

All continuous teeth were unilaterally extracted on the right side of the upper and lower jaws of 57 male and female Vietnamese belly pig. The animals were slaughtered 6, 7, 8, 9, 10, 11 and 12 after the extraction. Our investigations into quantitative changes in the masticatory musculature after unilateral extraction showed the dry weight of the musculature on the extraction side was reduced. This reduction was greatest in the case of the M. temporalis. The findings relating to the muscles are consistent with the results of the skull evaluations reported in the first 2 publications, with indicated that tooth extraction leads to only local changes in the jaw during postnatal development. The findings published in the 3 publications of this series relating to the bones and muscles are discussed.     

Prenatal growth stages show the development of the ruminant bony labyrinth and petrosal bone

Foetuses are a source of scientific information to understand the development and evolution of anatomical structures. The bony labyrinth, surrounding the organ of balance and hearing, is a phylogenetically and ecologically informative structure for which still little concerning growth and shape variability is known in many groups of vertebrates. Except in humans, it is poorly known in many other placentals and its prenatal growth has almost never been studied. Ruminants are a diversified group of placentals and represent an interesting case study to understand the prenatal growth of the ear region. We computed tomography ‐scanned five cow foetuses and an adult petrosal bone (Bos taurus, Artiodactyla, Mammalia), and describe the bony labyrinth when already ossified. The foetuses encompass the second half of the 9.3‐month‐long gestation period of the cow. They were sampled at different ontogenetic stages to understand how and when the petrosal bone and bony labyrinth ossify in ruminants. The petrosal bone and bony labyrinth ossify within about 20 days in the fourth month of gestation. The bony labyrinth is already fully ossified at least in the 6th month, while only the cochlea, most of the vestibule and the common crus are already ossified at the beginning of the 4th month. The pars canalicularis of the petrosal thus ossifies at last. The size and volume of the bony labyrinth stay similar from the 6th month (possibly even from the 5th). From the end of the 4th month of gestation, a progressive lengthening of the cochlear aqueduct and endolymphatic sac occurs, culminating in the adult form and partly explaining the larger volume of the later. The inner ear in the cow ossifies quickly during the gestation period, being fully ossified around mid‐gestation time, as in humans. The adult size and most of its volume are reached by mid‐gestation time while the petrosal bone and skull still grow. A negative ontogenetic allometry between the bony labyrinth and the petrosal bone and skull is thus observed. It matches the evolutionary negative allometry of the structure observed in earlier studies. Few changes occur after ossification is achieved; only open structures (i.e. cochlear aqueduct and endolymphatic sac) continue to grow after birth and reflect size increase of the petrosal bone.     

Phrenoblysis: special brain and mind growth periods. II. Human mental development

Spurts in the mental age of humans are shown to be recoverable from data giving the average mental age as a function of chronological age. Data from 13 independent studies are shown to give a highly consistent spectrum of ages at which spurts are found; these are 2-4, 6-8, 10-12, and 14-16, with an especially clear low rate of growth at 12-14 yr. These ages correlate very well with those found for spurts in brain and skull sizes so that an obvious working hypothesis is that mutations for increased brain weight were selected for by virtue of the greater mental ability thus afforded to humans.     

Effect of brain growth stages on T-maze acquisition in mice

Recently, it has been shown that brain growth is characterized by periods of especially large increases in growth, with “plateaus” in growth between these “spurt” periods. In humans, these spurts in brain growth are correlated with spurts in mind growth, collectively termed phrenoblysis. Brain growth spurts in rodents occur at 0–6, 8–12, and 17–23 days of age with plateaus in-between. We examined two questions. First, are there differences in learning ability associated with spurts and plateaus in brain growth? Second, can learning during these stages be altered through genetic and environmental manipulations? We employed the high and low lines of the Fuller brain weight selection mice, which are known to have different developmental patterns, and early handling procedures, known to alter growth rates. The results showed that animals tested during a proposed brain growth spurt were superior to animals tested during a brain growth plateau in learning a shock-escape T-maze.     

Craniofacial growth influenced by blood supply. 1. Collaterals and anastomoses following unilateral ligation of the common carotid artery

The influence of the blood supply on craniofacial growth was investigated in 396 albino rats (Rattus norvegicus Berkenhout). This was done by blocking the right common carotid artery of animals aged 42 d. The rats were slaughtered at previously specified intervals after the operation. The ligature led to dilation of the other major arteries of the neck. Numerous collaterals and anastomoses were also formed. These occurred on the ligature side in the flow region between the proximal and distal stumps of the right common carotid artery, between the flow regions of the right external carotid artery and the right vertebral artery and between the flow regions of the right subclavian artery and the right external carotid artery. Further anastomoses arose between the arteries of the other side, i.e. the rostral thyroid artery, lingual artery, submental artery and labial mandibular artery.     

1-year monitoring of the course of chronic renal insufficiency induced by subtotal nephrectomy in rats. Pharmacokinetic value

A subtotal nephrectomy is realized on 200 rats Wistar IOPS, producing a chronical renal failure (CRF). Evolution is studied during 12 months and compared to 100 normal rats of the same age. Biochemical criteria show an increased blood urea and creatinemia with a diminution of creatinin clearance and an appearance of important proteinuria. Morphological results show as soon as the third month, irreversible tubulo-interstitial lesions; afterwards glomerular lesions appear and become more and more visible and are accompagnied by membranous depots; then, a pan-nephritis is noted at the 10th month. These observations allow to class animals into three groups according to the CRF degree: low, medium or severe. As soon as the fifth month, all surviving animals present a medium CRF generally, or a severe CRF. Our work allows to create homogeneous lots used in pharmacokinetic applications.     

Phrenoblysis: special brain and mind growth periods. I. Human brain and skull development

Although gross brain properties averaged over many individuals are highly unlikely to exhibit possible special growth periods, the hypothetical spurts in brain growth can be recovered to some extent from averaged data by computing multiyear weight increments. And, since brain weight correlates very well with skull circumference, similar spurts may be found in that parameter. A review of the literature shows that, indeed, characteristic spurts in brain and skull occur, roughly, at ages 6-8, 10-12, 14-17, and possibly 2-4 yr. The spurts are, as expected, especially clear in data from longitudinal studies, although spurts are detectable in the data from every study thus far found in the literature.     

Craniofacial growth under the influence of the blood supply. 14. Theoretical deductions and clinical conclusion

After eliminating the masticatory muscles as a growth factor in our animal model is was possible to analyze the blood supply to the skull in sufficient detail. The animal organism and its parts may be regarded as self-regulating, self-optimizing and self-adapting systems. Open systems exchange energy and material with their surroundings. This is typical of all organisms and, since growth is one of their properties, to growth. The processes of ossification and growth of the rat skull are therefore comparable in principle with those taking place in the human. The specific features of the chewing mechanism, in contrast, are not comparable. The clinical conclusions drawn from our model studies illustrate the importance of the blood supply for craniofacial growth while simultaneously demonstrating the compensation ability and adaptability of arteries and bones.     

Quantification of 5-hydroxytryptamine1A receptors in the cerebellum of normal and X-irradiated rats during postnatal development.

5-Hydroxytryptamine1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [1251]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [3H]8-OH-DPAT specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine1A sites per mg membrane protein (Bmax) was higher in X-irradiated animals than in age-paired controls. However, on a "per cerebellum" basis, no significant difference could be detected between the total number of 5-hydroxytryptamine1A sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine1A receptors are not located on developing granule cells. The progressive decrease in 5-hydroxytryptamine1A receptor density during the first postnatal month did not reflect a transient expression of 5-hydroxytryptamine1A receptors in the cerebellum of newborn rats, but resulted from the progressive "dilution" of these sites in this growing structure. The higher density of 5-hydroxytryptamine1A sites in X-irradiated rats simply reflected a lower "dilution" due to the delayed growth of the cerebellum in these animals.     

Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice.

Transforming growth factor-alpha (TGF-alpha) expression is associated with hepatocyte DNA replication both in vivo and in culture. Our previous work using TGF-alpha transgenic mice showed that constitutive overexpression of this growth factor in the liver causes hepatic tumors in 75 to 80% of the animals at 12 to 15 months of age. To understand the cellular events by which TGF-alpha overexpression leads to abnormal liver growth, we examined hepatocyte proliferative activity in young and old TGF-alpha transgenic mice and hepatocyte ploidy in normal, dysplastic, and neoplastic livers of these animals. At 4 weeks of age, transgenic mice had higher liver weights and liver weight/body weight ratios than non-transgenic mice of the same age and hepatocyte proliferative activity, measured by 3H-thymidine incorporation after 3- and 7-day infusion, proliferating cell nuclear antigen staining, and mitotic index determination, was 2 to 3 times higher than in controls. In both transgenic and non-transgenic mice hepatocyte proliferation declined with age but the decrease was much more pronounced in control animals, so that at 8 months of age, hepatocyte replication was 8 to 10 times higher in transgenic animals. Surprisingly, however, transgenic and non-transgenic mice at this age had similar liver weight/body weight ratios. Labeling studies done in 3-month-old animals revealed that hepatocyte turnover was much faster in transgenic than in control animals, suggesting that a homeostatic compensatory mechanism involving cell death tended to restore normal liver weight/body weight ratios in older transgenic mice. Ploidy analyses showed that at 4 weeks of age transgenic mice had a higher proportion of diploid and tetraploid hepatocytes and that the hepatocellular tumors which developed in TGF-alpha transgenic mice at 13 months of age contained a higher fraction of diploid hepatocytes than that present in adjacent tissue or in dysplastic livers. The results demonstrate that constitutive overexpression of TGF-alpha causes increased hepatocyte proliferation and liver enlargement in young animals and is associated with a delay in the establishment of hepatic polyploidy. These findings as well as the response of transgenic mice to partial hepatectomy show that constitutive overexpression of TGF-alpha initially caused increased but regulated hepatocyte proliferation which in older animals was compensated in part by a faster cell turnover. At 8 to 10 months of age, proliferative activity may become constitutive in some TGF-alpha expressing hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Monthy growth increments from a longitudinal study of Canadian infants

Reference data for 1 month increments in weight, recumbent length, and head circumference, at ages 1 to 12 months, have been derived from serial data for 351 full-term Canadian infants. This derivation was achieved by (1) fitting a family of three parameter mathematical models to the data for each infant, (2) using these models to estimate values 1 month apart (3) calculating 1 month increments from the status values of 1 month intervals, (4) obtaining the distributions of these increments, and (5) presenting the percentiles of these increments in tables and in figures. The 1 month increments decreased with age during infancy in each sex, and these increments tended to be more rapid for boys than for girls. It is suggested that these reference data are suitable for the assessment of growth rates in infants born at term in Canada or in the United States. They can be used to assist the early identification of deviations from expected growth rates for individuals and to compare population samples.     

CD8 membrane expression is down-regulated by transforming growth factor (TGF)-beta 1, TGF-beta 2, and prostaglandin E2.

PROBLEM: CD8 T-cells are present at a lower frequency in human decidua than in peripheral blood. Because transforming growth factor (TGF)-beta 2 down-regulates CD4 membrane expression, its contribution, as well as the contribution of TGF-beta 1 and prostaglandin (PG) E2, to the modulation CD8 expression was studied using human peripheral blood lymphocytes (PBLs). METHOD OF STUDY: PBLs were cultured with TGF-beta 1, TGF-beta 2, PGE 2, PGI 2, or day-12 rabbit blastocoelic fluid (BF) that was or was not depleted of TGF-beta 2 and/or PGE 2. Quantum Simply Cellular Microbeads were then used to evaluate CD8 membrane expression levels. RESULTS: This study is the first demonstration that treatment of PBLs with TGF-beta 1, TGF-beta 2, and PGE 2 leads to a dose-dependent decrease in CD8 expression. A significant inhibition was observed at 2.5 mg/mL for TGF-beta 2, 5 ng/mL for TGF-beta 1, and 10 ng/mL for PGE 2. In contrast, PGI 2 had no effect. Treatment of PBLs with BF day-12 decreased CD8 expression. This effect, however, was not observed when BF was depleted of TGF-beta 2 and/or PGE 2. CONCLUSIONS: Our results suggest that TGF-beta s and PGE 2 are important modulators of CD8 membrane expression in human lymphocytes. Because TGF-beta 1, TGF-beta 2, and PGE 2 are produced by the conceptus and by uterine cells and because the effect is observed after only 3 days of treatment, the present data suggest that these substances can locally modulate the phenotype of lymphocytes at the fetomaternal interface. Such modulation may explain, at least partly, the changes observed in the population of decidual lymphocytes during pregnancy.