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M H Kaufman

Publications and source records attributed to M H Kaufman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Morphometric analysis of myelinated fibre composition in the optic nerve of adult C57BL and CBA strain mice and (C57BL x CBA) F1 hybrid: a comparison of interstrain variation.

In a study involving 50 optic nerves isolated from 3 different strains of adult male mice, C57BL, CBA and (C57BL x CBA) F1 hybrids, and from adult female CBA strain mice, we observed that the mouse had a lower mean total myelinated nerve fibre count than other mammals such as the rat, cat, rabbit, monkey and man where similar information was available from the literature. The nerve fibre spectrum, however, which mostly consisted of small diameter fibres, was similar to the distribution seen in these other species. The largest myelinated nerve fibres observed in any of the strains of mice investigated had a diameter of not more than 1.92 microns. The C57BL optic nerve had the largest population of large diameter fibres, while the F1 had the largest population of small diameter fibres. In all the strains of mice investigated, the distribution of nerve fibres was unimodal, with a modal diameter of 0.48 microns. The mean nerve fibre diameter was 0.62 +/- 0.02 microns (S.E.M.), 0.57 +/- 0.03 microns and 0.55 +/- 0.01 microns for C57BL, F1 and CBA, respectively. The F1 had the lowest population of fibres around the modal diameter. The myelinated nerve fibres were most densely packed in the CBA strain of mice, whereas the C57BL was the least densely populated. There was a significant interstrain difference in the parameters measured between the 3 strains of mice studied, whereas there was no significant intrastrain difference.

Animals↗
PubMed1994

An early caesarean operation (1800) performed by John and Charles Bell.

An articulated skeleton in the Bell Collection in the Museum of the Edinburgh College of Surgeons is of a woman who died shortly after a Caesarean section, believed to be the 18th recorded case of such an operation performed in the UK and Ireland. The fact that John and Charles Bell were the surgeons involved is of particular interest, due to their importance in the practice of surgery and surgical anatomy in Edinburgh during the early part of the 19th century. The woman had a restricted pelvic inlet and outlet resulting from puerperal osteomalacia, the commonest indication for carrying out this operation during the 18th and 19th centuries. Evidence from the examination of contemporary parish baptism and burial records, as well as meteorological records, established that the Caesarean operation was performed on 29 January 1800. The surviving child was subsequently baptized 'Caesar', in accordance with the common practice at that time.

Cesarean Section↗
PubMed1994

Morphometric study of the optic nerve of adult normal mice and mice heterozygous for the Small eye mutation (Sey/+).

The Small eye (Sey) gene, which has been mapped to chromosome 2 in the mouse, is known to cause variable malformations of the eye and nose. The effect of the gene in the heterozygous state is mainly on the eye. A combined electron microscopy and morphometric analysis of the optic nerve in adult littermates with a normal (+/+) and heterozygous mutant (Sey/+) genotype was carried out. The optic nerve could be dissected from the posterior pole of the eyeball to the optic chiasma in all the mice examined. The results of morphometric analyses carried out in this study show that the Sey gene indirectly affects the normal morphogenesis of the optic nerve in the heterozygous mutant Sey male mouse to a significant degree compared with its male normal littermate. The heterozygous mutant Sey female mouse is also affected, but not significantly so when compared with its normal female littermate. The mean nerve cross-sectional area and mean nerve fibre counts for the Sey strain are lower than those observed in other strains of mice that have been studied. The nerve fibre densities and the spectrum of nerve fibre sizes encountered are, however, similar to those seen in other strains of mice. We believe that the findings indicate that the smaller mean nerve fibre counts observed in the heterozygous mutant (Sey/+) mice compared to their normal (+/+) siblings is unlikely to have resulted from primary retinal dysgenesis, but is a consequence of the reduced size of their neural retina, and total retinal ganglion cell population.

Animals↗
PubMed1993

The cleavage rate of digynic triploid mouse embryos during the preimplantation period.

Triploidy is a lethal condition in mammals, with most dying at some stage between implantation and term. In humans, however, a very small proportion of triploids are liveborn but display a wide range of congenital abnormalities. In particular, the placentas of human diandric triploid embryos consistently display "partial" hydatidiform molar degeneration, while those of digynic triploids generally do not show these histopathological features. In mice, the postimplantation development of diandric and digynic triploid embryos also differs. While both classes are capable of developing to the forelimb bud stage, no specific degenerative features of their placentas have been reported. Diandric triploid mouse embryos are morphologically normal while digynic triploid mouse embryos consistently display neural tube and occasionally cardiac abnormalities. Previously it was shown that the preimplantation development of micromanipulated diandric triploid mouse embryos was similar to developmentally matched diploid control embryos. In this study, the preimplantation development of micromanipulated digynic triploid mouse embryos is analysed and compared with that of diandric triploid mouse embryos in order to determine whether there is any difference in cleavage rate between these two classes of triploids. Standard micromanipulatory procedures were used to insert a female or a male pronucleus into a recipient diploid 1-cell stage embryo. The karyoplast was fused to the cytoplasm of the embryo by electrofusion. These tripronucleate 1-cell stage embryos were then transferred to pseudopregnant recipients and, at specific times after the HCG injection to induce ovulation, the embryos were recovered and total cell counts made. These results were plotted and regression lines drawn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The incidence of aneuploidy after single pulse electroactivation of mouse oocytes.

A brief electric pulse often produces a high rate of activation of recently ovulated oocytes. Some other efficient parthenogenetic stimuli, such as alcohol, however, disrupt the spindle apparatus and increase the incidence of aneuploidy. In this paper, we have determined whether electroactivation per se increases the incidence of chromosomal segregation errors in haploid parthenogenones as evidenced at first cleavage mitosis. Superovulated F1 hybrid female mice were killed at 15.5, 18.5, 22.5, and 25 h after the HCG injection. Batches of 10-12 cumulus-denuded oocytes were transferred to an electroactivation chamber containing mannitol which was connected to a high voltage pulse stimulator and the pulse was triggered once. A high proportion of oocytes activated following this treatment, but only the single-pronuclear haploid parthenogenones were incubated overnight in medium containing colcemid, to determine the incidence of aneuploidy as evidenced at first cleavage mitosis. "Sham" electroactivation groups were also examined for evidence of activation and aneuploidy as described above. In these cases, cumulus-denuded oocytes were put through the electroactivation chamber but the pulse was not triggered. A further group of oocytes was studied to determine the effect of handling and exposure to hyaluronidase on activation frequency and parthenogenetic pathways. Finally, the spontaneous rate of aneuploidy was examined in fertilised embryos of F1 hybrid female mice x Rb(1.3)1Bnr male mice at first cleavage mitosis. The results show that single pulse electroactivation does not increase the level of aneuploidy in single-pronuclear parthenogenous compared to the "sham" group or the spontaneous rate observed in 1-cell fertilised embryos, nor does aneuploidy appear to increase with postovulatory age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1993

Inheritance of a meiotic abnormality that causes the ovulation of primary oocytes and the production of digynic triploid mice.

Previous studies have demonstrated that the LT/SvKau strain of mice ovulates a high proportion of oocytes as diploid primary oocytes rather than secondary oocytes. These ovulated primary oocytes are arrested at meiotic metaphase I but may be fertilized to produce digynic triploid embryos. In the present study, 40.4% of eggs analysed from LT/SvKau females were ovulated as primary oocytes, compared to 1.2% from control C57BL/Ws strain mothers. These two inbred strains were intercrossed to produce eight sets of F1, F2 and backcross females and the frequency of triploidy was investigated. The results are compatible with segregation of a co-dominant, autosomal gene that has a major influence on the incidence of triploidy. We suggest that the provisional gene symbol Poo (primary oocyte ovulation) be assigned to this gene, with alleles Poo(l) (the 'mutant' allele present in the LT/SvKau strain) and Poo(b) (the normal allele present in C57BL/Ws mice). Poo is incompletely penetrant and has variable expressivity because the proportion of oocytes ovulated as primary oocytes by LT/SvKau mice was variable and, in some cases, nil. In putative Poo(l)/Poo(b) heterozygotes the frequency of ovulated primary oocytes was increased only marginally (from 1.2% to 6.6%) by the presence of one copy of the Poo(l) allele, but this increase was found consistently (in two reciprocal F1 crosses) and was statistically significant. No evidence was found for tight genetic linkage between Poo and two Mendelian loci (brown on chromosome 4 and glucose phosphate isomerase on chromosome 7), that were segregating in the crosses. The Poo(l) mutant in the LT/SvKau strain of mice provides a valuable resource to study the cell and molecular biology of mammalian oocyte maturation and the control of meiosis.

Alleles↗
PubMed1993

Reflections on Dr Henderson of Perth's case of impracticable labour: an early case (1820) in which the caesarean operation was performed.

The rediscovery of a female pelvis with features characteristic of osteomalacia stimulated an enquiry into the clinical history of the woman involved. It was established that she died in 1820, aged 30. Despite being severely debilitated and confined to bed for some years with increasing skeletal deformities, she became pregnant, and in due course laboured unsuccessfully for about 102 hours. An elective caesarean section was performed, but she died some hours later, though her daughter survived and was appropriately christened Caesar Anna. This represents one of the earliest cases in which the caesarean operation was performed where the full obstetric history was carefully recorded by the obstetrician involved, Dr. Henderson of Perth. The case was clearly considered important, and in 1836 engravings of this pelvis were used to illustrate Professor Hamilton's "Practical Observations of Various Subjects Related to Midwifery". Such cases are now of great rarity in the developed world.

Cesarean Section↗
PubMed1993

Cellular and nuclear volume of primitive red blood cells in digynic and diandric triploid and control diploid mouse embryos.

It has long been known that a relationship exists between ploidy and cellular and nuclear volume. This has been observed in amphibia and plants, and more recently in postimplantation tetraploid mouse embryos. We wished to establish whether a similar relationship exists in digynic and diandric triploid mouse embryos, as well as establishing whether the cellular or nuclear volume of primitive nucleated red blood cells of these two classes of triploids were the same. Spontaneously occurring digynic triploid embryos isolated from LT/Sv strain female mice result from the fertilisation of primary oocytes. These embryos develop to the forelimb-bud stage but invariably possess neural tube and cardiac abnormalities. Diandric triploid embryos were also analysed, and were produced experimentally by standard micromanipulatory techniques. They have a relatively normal morphology, and can survive up to the forelimb--bud stage. Primitive red blood cellular and nuclear volume was analysed in serially sectioned digynic and diandric triploid and in developmentally matched diploid control embryos isolated both as littermates of triploid embryos from LT/Sv strain mice, and from other genetically dissimilar diploid controls. The triploid and diploid embryos were analysed between 8-8.5 and 10-10.5 days of gestation, respectively. The cellular and nuclear volumes of the primitive red blood cells in the digynic and diandric triploid embryos were not significantly different, though they were significantly greater than comparable measurements for diploid embryos. We have therefore confirmed that a predictable relationship exists between cellular and nuclear volume and ploidy in the material analysed. The red blood cellular volume in triploid and diploid embryos increased in a predictable way over time, while their nuclear volume decreased in a predictable way over the same time period. A similar relationship has previously been observed when the nucleated red blood cells of diploid and tetraploid embryos were analysed morphometrically.

Animals↗
PubMed1993

Eyelid development, fusion and subsequent reopening in the mouse.

The process of eyelid development was studied in the mouse. The critical events occur between about 15.5 d postcoitum (p.c.) and 12 d after birth, and were studied by conventional histology and by scanning electron microscopy. At about 15.5 d p.c. the cornea of the eye is clearly visible with the primitive eyelids being represented by protruding ridges of epithelium at its periphery. Over the next 24 h, eyelid development proceeds to the stage when the cornea is completely covered by the fused eyelids. Periderm cells stream in to fill the gap between the developing eyelids. Their proliferative activity is such that they produce a cellular excrescence on the outer surface of the line of fusion of the eyelids. This excrescence had almost disappeared by about 17.5 d p.c. Keratinisation is first evident at this stage on the surface of the eyelids and passes continuously from one eyelid to the other. Evidence of epidermal differentiation is more clearly seen in the newborn, where a distinctive stratum granulosum now occupies about one third of its entire thickness. Within the subjacent dermis, hair follicles are differentiating. By about 5 d after birth, a thick layer of keratin extends without interruption across the junctional region. While a noticeable surface indentation overlies the latter, a similar depression is only seen on the conjunctival surface by about 10 d after birth. Keratinisation is also observed to extend in from the epidermal surface to involve the entire region between the 2 eyelids at about this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Relationship between cell size and nuclear volume in nucleated red blood cells of developmentally matched diploid and tetraploid mouse embryos.

Analysis of control diploid and polyploid amphibia indicated that cell and nuclear volumes were closely related to their ploidy, so that an increase in ploidy was generally associated with an increase in cell size. This relationship is also believed to occur in mammalian polyploids. However, since the latter are only rarely encountered spontaneously, or only occasionally following experimental manipulation, no detailed morphometric studies have been carried out to date to confirm whether such a relationship exists. In this study, the cellular and nuclear volume of primitive red blood cells was analyzed in carefully developmentally matched control diploid mouse embryos and tetraploid embryos produced by the technique of electrofusion. All of the cells and/or nuclei studied had a characteristic spherical shape which greatly simplified the morphometric analysis. A defined and predictable relationship between ploidy and cellular and/or nuclear volume was observed in the red blood cells between 8.25 and 14.5 days of gestation. During this period the primitive red blood cells are gradually replaced by the definitive erythrocytes. The ratio of control values to tetraploid values was found to be close to the theoretical value of 1:2 when comparable cells and/or their nuclei were analyzed in carefully developmentally matched material.

Animals↗
PubMed1992

Cleavage rate of haploid and diploid parthenogenetic mouse embryos during the preimplantation period.

The lack of a paternal genome in parthenogenetic embryos clearly limits their postimplantation development, but apparently not their preimplantation development, since morphologically normal blastocysts can be formed. The cleavage rate of these embryos during the preimplantation period gives a better indication of the influence of their genetic constitution than blastocyst formation. Conflicting results from previous studies prompted us to use a more suitable method of following the development of haploid and diploid parthenogenetic embryos during this period. Two classes of parthenogenetic embryos were analysed following the activation of oocytes in vitro with 7% ethanol: 1) single pronuclear (haploid) embryos and 2) two pronuclear (diploid) embryos. Each group was then transferred separately during the afternoon to the oviducts of recipients on the 1st day of pseudopregnancy. Control (diploid) 1-cell fertilised embryos were isolated in the morning of finding a vaginal plug, and transferred to pseudopregnant recipients at approximately the same time of the day as the parthenogenones. Embryos were isolated at various times after the HCG injection to induce ovulation, from each of the three groups studied. Total cell counts were made of each embryo, and the log mean values were plotted against time. The gradient of the lines indicated that 1) the cell doubling time of the diploid parthenogenones was 12.25 +/- 0.34 h, and was not significantly different from the value obtained for the control group (12.74 +/- 1.17 h), and that 2) the cell doubling time of the haploid parthenogenones (15.25 +/- 0.99 h) was slower than that of the diploid parthenogenones and the control diploid group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cleavage rate of diandric triploid mouse embryos during the preimplantation period.

The postimplantation development of human and animal triploid embryos is well documented, but there is little informative data on their preimplantation development. An analysis of cell number at appropriate times during this period and thus their cleavage rate would give an indication of the potential triploids have for further development and may explain some problems associated with their postimplantation development. To rule out any effects of technical procedures on cleavage rate, appropriate controls were used. Diandric triploid embryos were produced using standard micromanipulatory techniques, which involved the injection of a male pronucleus into a recipient one-cell-stage embryo. The karyoplast was fused to the cytoplasm by electrofusion, and the resulting tripronucleate diandric triploid embryos were transferred to appropriate pseudopregnant recipients. At specific times after the transfer, the embryos were recovered and cell numbers established. The results were plotted and regression lines drawn. Three controls were used 1) micromanipulated diploid embryos from which the male pronucleus had been removed and immediately reinserted and fused to restore diploidy, 2) diploid embryos that had been briefly incubated in cytochalasin D and colcemid to find out the effects these agents had on development, and 3) diploid embryos that had been isolated and briefly incubated in tissue culture medium. All embryos were subsequently transferred to recipients. After isolation at specific times during the preimplantation period, cell numbers were also established and the results plotted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tetraploidy in mice, embryonic cell number, and the grain of the developmental map.

Tetraploid mice prepared by electrofusion develop for up to 14 days in utero. The embryos are essentially normal save that the forebrain and its associated tissues fail to develop properly. Here, we report measurements of cell counts in tissues and volume measurements of tetraploid and control embryos together with observations on the morphology of tetraploid embryos. The results show that the tetraploid embryos are about 85% normal size, but have only a little under half the number of cells of control embryos, with their nuclei being about twice the size of those of diploid cells. Close examination of sectioned material, in contrast, showed that tetraploid morphology and morphogenesis were indistinguishable from those of controls, except in forebrain-associated material. This conclusion gives some insight into an important developmental question, how fine can the developmental map be for normal cellular differentiation to proceed? As tetraploids have only about half the expected number of cells, the ability of these embryos to develop normally in all regions except the forebrain and its derivatives argues that pattern formation mechanisms can cope with the abnormally small number of cells in all regions except the forebrain. The results as a whole argue for size regulation in mammalian embryos being achieved by assaying absolute size rather than counting cell numbers.

Animals↗
PubMed1992

The differential staining pattern of the X chromosome in the embryonic and extraembryonic tissues of postimplantation homozygous tetraploid mouse embryos.

(C57BL x CBA)F1 hybrid female mice were mated with hemizygous Rb(X.2)2Ad males to distinguish the paternal X chromosome. Homozygous tetraploids were produced by blastomere fusion at the 2-cell stage, and 161 of these were transferred to recipients and analysed on the 10th day of gestation. 59 implants contained resorptions and 76 contained either an embryo and/or extraembryonic membranes. 38 (20, XXXX and 18, XXYY) were analysed to investigate their X-inactivation pattern. Embryonic and yolk sac endodermally- and mesodermally-derived samples were analysed by G-banding and by Kanda analysis. In the XX and XY controls, the predicted pattern of X-inactivation was observed, though 12.2% of metaphases in the XX series displayed no X-inactivation. In the XY series the Y chromosome was seen in a high proportion of metaphases. In the XXXX tetraploids, 8 cell lineages were recognized with regard to their X-inactivation pattern, though most belonged to the following 3 categories: (XmXm)XpXp, Xm(XmXp)Xp and XmXm(XpXp). The other categories were only rarely encountered. In the embryonic and mesodermally-derived tissue the ratio of these groups was close to 1:2:1, whereas in the endodermally-derived tissue it was 1:4.11:4.88, due to preferential paternal X-inactivation. A significant but small proportion of all 3 tissues analysed displayed no evidence of X-inactivation. Indirect evidence suggests that this represents a genuine group because of the high efficiency of the Kanda staining. The presence of the Xm(XmXp)Xp category is consistent with the expectation that X-inactivation occurs randomly in 2 of the 4 X chromosomes present. The presence of small numbers of preparations with no evidence of X-inactivation and other unexpected categories suggests that these are probably selected against during development.

Animals↗
PubMed1992

Electrofusion of mouse embryos results in uniform tetraploidy and not tetraploid/diploid mosaicism.

Some previous attempts to produce tetraploids experimentally have resulted in a proportion of treated embryos becoming 2n/4n mosaics at a frequency which may be as high as 20%, when using cytochalasin B as a fusigenic stimulus and cytogenetic techniques to identify putative tetraploid embryos. To investigate the possible occurrence of 4n/2n mosaicism, tetraploid embryos were produced by electrofusion, a process which allows adjacent blastomeres at the 2-cell stage to fuse following exposure to electric field pulses. Embryos used for electrofusion were hemizygous for a transgene consisting of approximately 1000 copies of the mouse beta-globin gene. After in situ hybridization, one hybridization signal is expected per diploid genome. Tetraploid cells in 7.5-, 8.5-, 9.5- and 10.5-day-old conceptuses were distinguished from diploid cells by performing in situ hybridization on histological sections. The frequency of nuclei with two hybridization signals in the 'hemizygous' tetraploid embryos was compared to diploid embryos which were either hemizygous or homozygous for the beta-globin transgene. Comparison of the frequency of nuclei with two hybridization signals between tissues of 'hemizygous' tetraploid conceptuses and homozygous diploid conceptuses showed no significant difference, which implies that the tissues in the tetraploid conceptuses were uniformly tetraploid. No evidence was found to suggest that electrofusion results in 2n/4n mosaicism.

Animals↗
PubMed1992

The prion protein gene: a role in mouse embryogenesis?

The neural membrane glycoprotein PrP (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. During pathogenesis, PrP accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. Although the involvement of PrP in the pathology of these diseases has long been known, the normal function of PrP remains unknown. Previous studies have shown that the PrP gene is expressed tissue specifically in adult animals, the highest levels in the brain, with intermediate levels in heart and lung and low levels in spleen. Prenatally, PrP mRNA has been detected in the brain of rat and hamster just prior to birth. In this study we have examined the expression of the PrP gene during mouse embryonic development by in situ hybridisation and observed dramatic regional and temporal gene expression in the embryo. Transcripts were detected in developing brain and spinal cord by 13.5 days. In addition, PrP gene expression was detected in the peripheral nervous system, in ganglia and nerve trunks of the sympathetic nervous system and neural cell populations of sensory organs. Expression of the PrP gene was not limited to neuronal cells, but was also detected in specific non-neuronal cell populations of the 13.5 and 16.5 day embryos and in extra-embryonic tissues from 6.5 days. This cell-specific expression suggests a pleiotropic role for PrP during development.

Animals↗
PubMed1992

Postcranial morphological features of homozygous tetraploid mouse embryos.

The postcranial morphological features of 22 homozygous tetraploid mouse embryos were studied. The latter were produced by electrofusion of blastomeres at the 2-cell stage in vitro, and were transferred to appropriate recipients that were autopsied on d 12-16 of gestation. Seven embryos were isolated on d 15 or d 16 of gestation and were developmentally equivalent to control diploid embryos of 13-14.5 d p.c. In each of these embryos, their sex could be determined from the histological analysis of their gonads. A further 15 embryos were isolated on d 12-14 of gestation and most were developmentally equivalent to controls of between 11-11.5 and 12-12.5 d p.c. The sex of these embryos could not be determined from the analysis of their gonads, as these were all at the 'indifferent' stage. Twelve of the 22 embryos had a normal postcranial axial morphology, while 10 had an abnormal postcranial axial morphology associated with an enormous omphalocele which contained most of the abdominal viscera and often, particularly in the more advanced specimens, the heart as well. In each of the 7 developmentally most advanced embryos studied, a major congenital abnormality involving at least one organ system was present, but none of these was believed to be life-threatening. The most interesting finding was that 3 of these embryos had abnormalities of the aortic arch arterial system; in 2 embryos the arch of the aorta was retro-oesophageal and retrotracheal, while a 3rd embryo had transposition of the great vessels associated with a right-sided descending aorta. In a 4th embryo, an aneurysmal dilatation of the posterior cardinal vein was present, and this was associated with the anomalous persistence of the left subcardinal/supracardinal venous system. These abnormalities represent a degree of mirror imaging of the normal vascular arrangement. Analysis of the gonads revealed that all of the embryos with vascular abnormalities in this group were male (XXYY), and no vascular abnormalities were present in the females (XXXX). The histological features of the viscera were normal. In 5 of the 15 developmentally less advanced embryos, the distal part of the bulbus cordis region of the heart was displaced medially, and consequently the outflow tract was located on the left part of the pericardial cavity rather than on the right where it is normally found. This may represent an early stage in the differentiation of the aortic arch arterial vascular anomalies indicated above. In 2 additional embryos, abnormally located (i.e. retro-oesophageal) innominate vessels were present.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗