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Biomedical subjects

M Melnick

Publications and source records attributed to M Melnick.

At least 37 records · Page 2Linked to original sources
PubMed1991

Neural tube and neural crest: a new view with time-lapse high-definition photomicroscopy.

The dynamic process of neural tube formation and neural crest migration in live, unstained cultured avian embryos at Hamburger-Hamilton (H.H.) stages 8-11 was investigated by time-lapse cinematography using a high-definition microscope. These studies have demonstrated that neural tube closure in the trunk region differs from that observed in the head. The cephalic neural folds elevate slowly, then make contact rapidly. Following this initial apposition, they gradually "zip-up" in the rostrad and caudad direction. In the trunk region where the neuroepithelium bulges adjacent to the somites, the edges of the folds pulsate and forcefully touch-retract-touch in these bulging regions; the intersomitic epithelia retract, remain open even after more posterior somitic regions have apposed, and then close slowly. Epithelial blebs and N-CAM antibody were observed at the leading edges of the neuroepithelia. Between the open folds only a few bridging cells were seen; they probably represent the sites of initial cell adhesion following epithelial retraction. Focusing into the developing embryo shows that neuroepithelial fusion occurs prior to surface epithelial fusion. A meshwork of synchronously pulsating neural crest cells was identified below the surface epithelium and a preliminary investigation of their initial migration was conducted.

Animals↗
PubMed1991

Mouse major histocompatibility complex and lung development: haplotype variation, H-2 immunolocalization, and progressive maturation.

The association of the mouse major histocompatibility complex (H-2), lung maturation, and corticosteroid responsiveness has recently been demonstrated in congenic B10 (H-2b) and B10.A (H-2a) mice (Hu et al.: American Journal of Medical Genetics 35:126-131, 1990). We have investigated additional haplotypes [B10.BR (H-2k) and B10.D2 (H-2d)] to confirm that there is a strong association between H-2 haplotype variation and the degree of pulmonary maturation. Lungs of B10.D2, B10.BR, B10, and B10.A congenic mice achieve haplotypic specific maturation: B10.D2 lungs greater than B10 lungs = B10.BR lung greater than B10.A lungs. It appears that the expression of these developmental potentials is under corticosteroid regulation. Further, to test the hypothesis that H-2 antigens would be expressed earlier in embryonic lungs with the H-2b (B10) or H-2k (B10.BR) haplotype than with the H-2a (B10.A) haplotype, we investigated the spatiotemporal patterns of H-2 antigen localization in B10, B10.BR, and B10.A congenic mouse strains with and without corticosteroid treatment. The spatial patterns of H-2 antigen localization was similar in the B10, B10.BR, and B10.A mouse lungs; however, these patterns appeared earlier in both untreated and treated B10 and B10.BR mice as compared with untreated B10.A mice, suggesting an H-2 haplotype associated rate of pulmonary maturation. Following corticosteroid treatment, all congenic strains had a temporally comparable spatial distribution of H-2 antigens. Our results provide preliminary evidence suggesting that both a lung "developmental gene(s)" and a "glucocorticoid responsiveness gene(s)" are most likely outside the K-D subregions of the H-2 complex. A model of the H-2 regulation of lung maturation and corticosteroid responsiveness is discussed.

Animals↗
PubMed1991

Bone remodeling in W/Wv mast cell deficient mice.

Strong experimental evidence exists for a relationship between mast cells and bone disease, but the role of mast cells in the regulation of bone remodeling is unknown. In order to address this question, mast cell deficient mice (W/Wv) were paired with their mast cell sufficient (+/+) littermates and evaluated for differences in response to an induced cycle of bone remodeling. This was achieved using a tooth egression protocol, in which a synchronous cycle of bone remodeling was induced in the mandibular buccal alveolar periosteum by extraction of the opposing dentition. Quantitative histomorphometric changes during the activation, resorption, reversal, and formation phases of bone remodeling were documented using standard techniques. Most cell deficient mutants exhibited the following defects in response to an induced cycle of bone remodeling: (a) the onset of the remodeling cycle was delayed by a prolonged activation phase, (b) the duration and extent of the active formation phase was decreased, and (c) the amount of new bone matrix synthesized was diminished while mineralization rates were found to be normal. These results suggest that mast cells and their mediators provide a paracrine mechanism which influences the recruitment of osteoclast and osteoblast progenitors and their participation in bone remodeling. Nonetheless, since bone remodeling occurs in mast cell deficient mice, albeit less efficiently, this mechanism is most likely one of several redundant mechanisms that provide for adequate skeletal homeostasis.

Animals↗
PubMed1990

CD44 is the principal cell surface receptor for hyaluronate.

CD44 is a broadly distributed cell surface protein thought to mediate cell attachment to extracelular matrix components or specific cell surface ligands. We have created soluble CD44-immunoglobulin fusion proteins and characterized their reactivity with tissue sections and lymph node high endothelial cells in primary culture. The CD44 target on high endothelial cells is sensitive to enzymes that degrade hyaluronate, and binding of soluble CD44 is blocked by low concentrations of hyaluronate or high concentrations of chondroitin 4- and 6-sulfates. A mouse anti-hamster hyaluonate receptor antibody reacts with COS cells expressing hamster CD44 cDNA. In sections of all tissues examined, including lymph nodes and Peyer's patches, predigestion with hyaluronidase eliminated CD44 binding.

Amino Acid Sequence↗
PubMed1990

Mouse major histocompatibility complex (H-2) and fetal lung development: implications for human pulmonary maturation.

Using C57/10Sn (B10, H-2b) and B10.A/SgSn (B10.A,H-2a) congenic mice, we measured 1) the level of endogenous pulmonary corticosterone during mouse development; 2) the degree of lung morphological maturation on gestation day 17, with or without corticosteroid treatment; and 3) the maternal influence on normal lung development and fetal response to corticosteroids. The results of our study indicate that there was a progressive increase in the level of endogenous hormone with time in fetal B10 (H-2b) and B10.A (H-2a) mice; throughout mid- to late gestation, the detectable amount of hormone was almost identical in lungs of both strains. Evaluating the degree of lung maturation by morphometry, B10.A mouse lungs were found to be less mature than B10 mouse lungs. Following corticosteroid treatment on day 12 of gestation, H-2a lungs were equal to or more mature than H-2b lungs. We also compared heterozygous mouse lungs from reciprocal crosses (B10.B10.A, b/a and B10.A.B10, a/b). Mice with a maternally derived H-2a haplotype had less mature lungs than those with a maternally derived H-2b haplotype, suggesting a maternal effect. When exogenous hormone was administered, all heterozygous mouse lungs increased in maturity regardless of the origin of the H-2a haplotype. The treated a/b or b/a lungs were more mature than homozygous b/b and less mature than homozygous a/a lungs. We conclude that progressive lung maturation is associated with a gene(s) at or near the H-2 complex, as is the ability to respond to corticosteroids.

Adrenal Cortex Hormones↗
PubMed1988

Cleft lip and handedness: a study of laterality.

Research on the malformation cleft lip with or without cleft of the palate is complex and may involve studies of etiology, pathogenesis, natural history, and other disease associations. One of the more intriguing areas of study is developmental lateralization. The 3 extant reports of the relationship between laterality of cleft lip and handedness are in conflict. The purpose of the present study is an attempt to resolve the confusion and to explore possible hypotheses that could explain the data. A random sample of 149 probands with unilateral cleft lip +/- palate was ascertained from 2 Los Angeles area hospitals. Laterality of clefting and handedness was determined for each, the former by inspection and the latter by the method of Oldfield [1971]. Information was also obtained on the nuclear family about the number of sibs, presence of clefting, and handedness of the probands' parents. The probability of non-right-handedness (NRH) was much greater for probands with left-sided cleft lip than those with right-sided cleft lips; this was independent of the proband's sex. The cleft lip laterality in probands was independent of parental handedness, suggesting that the significantly increased frequency of left-sided clefting and NRH is embryologic in origin and may have a common etiology and/or pathogenesis. Several explanations are proposed and discussed.

Biometry↗
PubMed1988

Corticosteroid-induced cleft palate in short-ear mice.

Corticosteroid-induced facial clefting was examined in short-ear mice (inbred strain SEA/GnJ from Jackson Laboratory). They were found to be gentle, prolific breeders (average litter size 7.3 +/- 2.6), with no increased fetal loss due to treatment. Although they have the most "resistant" H-2 haplotype (H-2d), they were found to be highly susceptible to corticosteroid-induced clefting, demonstrating that loci other than H-2 are involved in susceptibility. The short-ear locus itself is a plausible candidate, given that this gene on chromosome 9 leads to defective mesenchymal condensation, which in turn may render these mice extremely sensitive to teratogen exposure. Another gene or genes on chromosome 9 are also possibilities.

Animals↗
PubMed1987

Studies in neural tube defects. I. Epidemiologic and etiologic aspects.

In the NIH Collaborative Perinatal Project, a prospective study of over 53,000 pregnant women and their offspring, 71 single-born children (13.33/10,000) were found to have a non-syndromal neural tube defect (NTD). A family history was present in only one case. The group of individuals with NTD was compared to a group of 400 randomly selected non-malformed control infants. Of over 50 maternal factors studied the following showed significant association with NTD in the offspring: diabetes mellitus; organic heart disease; lung disease; and diuretic, antihistamine, and sulfonamide use. The interval between the termination of the immediately previous pregnancy and the start of the proband pregnancy was significantly shorter in mothers of NTD children than in mothers of control infants. The risk for NTD was also significantly increased if the immediately previous pregnancy was a spontaneous abortion. There was no increased risk for NTDs among sibs of children with major malformations such as tracheo-esophageal "dysraphism," cleft lip/palate, or renal agenesis. NTDs are apparently etiologically heterogeneous.

Anencephaly↗
PubMed1987

Studies in neural tube defects. II. Pathologic findings in a prospectively collected series of anencephalics.

This report presents the pathologic anatomy of a prospectively collected series of 36 anencephalic infants. This series provides an opportunity to investigate the epidemiology of organ system pathology in anencephaly (AN) as well as other facets of its natural history. AN infants had a mean gestational age 2.5 weeks younger than normal controls, though birthweight was normal for gestational age. Nearly 1/3 of the liveborn infants with AN died within 15 minutes, 2/3 within 3 hours; 3 AN infants survived to 48 hours. Details and discussions of the pathologic findings and their physiologic significance are presented. Regarding those AN infants who received detailed neurologic examinations, correlations are made between the brain pathology and neurologic function prior to death.

Abnormalities, Multiple↗
PubMed1986

Genetic analysis of cleft lip with or without cleft palate in Chinese kindreds.

Cleft lip with or without cleft palate (CL +/- P) affects 1 in 500-1,000 newborns worldwide; the cause remains unclear. For CL +/- P, Asians are at higher risk than Caucasians or Blacks. This report presents the results of a genetic analysis of 163 CL +/- P proband families ascertained in Shanghai, China. Based on statistical tests of several predictions from the classical multifactorial/threshold model, no evidence could be found to support it. Further, goodness-of-fit (PGOODFIT) tests of this model were also unsupportive, there being more families with two or more affected sibs than expected. Classical segregation analysis for Mendelian inheritance showed a maximum likelihood estimate of the segregation ratio of 0.187 +/- 0.068. This value was not significantly less than 0.25 (recessive inheritance) but was significantly less than 0.50 (dominant inheritance). Sex ratio data from these Chinese families suggest that manifestation of the putative single major gene is sex influenced. The apparent reduced penetrance is likewise to be expected if manifestation of CL +/- P also depends on in utero exposure to deleterious environmental agents, as demonstrated in a variety of human and animal model studies.

California↗
PubMed1986

Major gene determination of liability to cleft lip with or without cleft palate: a multiracial view.

Despite nearly half a century of intensive investigation, the etiology of non-syndromic cleft lip with or without cleft palate (CL +/- P) remains unknown because most studies have been descriptive rather than analytic. This study summarizes rigorous analyses of CL +/- P in the families of non-syndromic, CL +/- P surgical probands from three populations: Denmark, London, England, and Shanghai, China. Three main conclusions could be drawn from the results. The data provide no support for the multifactorial threshold model summarized by Carter (1976) and most often proposed to explain the etiology of CL +/- P. Each dataset provides evidence that there may be a major gene for liability to CL +/- P in at least a portion of cases. The data are consistent with possible genetic heterogeneity in CL +/- P.

China↗
PubMed1985

Multiwell chamber chemotaxis assays: improved experimental design and data analysis.

The chemotaxis assay using the Boyden transfilter technique has become widely used in recent years for assessing migratory responses of a wide variety of cell types. In the study reported here we examined the migratory responses of mouse peritoneal macrophages using a multiwell chamber. The experiments were designed to analyze the components of variance in the assay method, to optimize the experimental design, and to develop objective statistical criteria for choosing among experiments with disparate results. Cell counts were obtained with the aid of an image analyzer coupled to a light microscope. Microcomputer software was developed to drive the image analyzer, collect data and conduct statistical analyses. Nested analysis of variance (ANOVA, either 2- or 3-level) was employed to partition the components of variance and F-tests were used to determine their significance. Significant sources of experimental error were identified both within and among wells and were attributed mostly to variability in the chamber/filter assembly and counting procedure. Statistical analyses demonstrated that there was significant variation among assays conducted in different multiwell chambers on the same day, among assays where the same agent was tested on different days in the same chamber, and among replicate counts of the same assay. The following recommendations were made: use ANOVA to distinguish differences due to biological effects from those due to experimental error, design experiments so that all relevant comparisons are included in the same chamber and the same assay, avoid pooling data from different assays unless ANOVA treatment variances are comparable, and when replicate assays yield disparate results choose the assay with the lowest percentage of variation due to experimental error.

Animals↗