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M Blum

Publications and source records attributed to M Blum.

At least 19 recordsLinked to original sources
PubMed1992

Gastrulation in the mouse: the role of the homeobox gene goosecoid.

Mouse goosecoid is a homeobox gene expressed briefly during early gastrulation. Its mRNA accumulates as a patch on the side of the epiblast at the site where the primitive streak is first formed. goosecoid-expressing cells are then found at the anterior end of the developing primitive streak, and finally in the anteriormost mesoderm at the tip of the early mouse gastrula, a region that gives rise to the head process. Treatment of early mouse embryos with activin results in goosecoid mRNA accumulation in the entire epiblast, suggesting that a localized signal induces goosecoid expression during development. Transplantation experiments indicate that the tip of the murine early gastrula is the equivalent of the organizer of the amphibian gastrula.

Activins↗
PubMed1992

The possible relationship between menorrhagia and occult hypothyroidism in IUD-wearing women.

A high incidence of occult hypothyroidism in menorrhagic women has been reported and emphasized in recent studies. In order to verify this statement, we have evaluated the functional status of the thyroid gland in intrauterine device (IUD) wearers suffering from increased menstrual bleeding. The study group consisted of 40 IUD-wearing women, aged 26-46 years, suffering from metrorrhagia. The control group consisted of 38 IUD-fitted women, 22-44 years old, in whom menstrual bleeding was not significantly increased. Menorrhagia was defined as excessive vaginal bleeding lasting for 6 days or more, and/or containing a significant amount of blood clots. Free thyroxine (FT) and thyroid-stimulating hormone (TSH) levels were assessed. FT levels were identical in both groups and within the normal range (1.31 +/- 0.28 ng/dl). TSH levels were significantly higher in the study group than in the controls, although they remained within the normal range (2.75 +/- 2.06 vs. 1.45 +/- 0.45 microU/ml, p < 0.01). A thyrotropin-releasing hormone (TRH) test was performed in 10 women having the highest TSH levels. All the results of TRH tests were consistent with occult hypothyroidism. These women were treated with L-thyroxine and all had a significant improvement in their bleeding within 3 months of treatment. We concluded that any IUD-wearing woman suffering from menorrhagia may have occult hypothyroidism. Should FT and TSH be within normal limits, a TRH test should be performed as the definitive diagnostic test. A frequent side-effect of intrauterine contraception is menometrorrhagia. The intrauterine device (IUD) has to be removed in 5-15% of cases to prevent iron deficiency anemia.

Adult↗
PubMed1992

Transynaptic regulation of low-affinity p75 nerve growth factor receptor mRNA precedes and accompanies lesion-induced collateral neuronal sprouting.

The bilateral sympathetic innervation of the rat pineal gland from the two superior cervical ganglia (SCG) is a useful model system to investigate the mechanisms by which intact neurons compensate for neuronal losses. Cutting of the internal carotid nerve (ICN) on one side has been shown to result in the removal of approximately one-half of the innervation to the pineal gland within 2 days. This denervation is followed by the development of collateral neuronal sprouting from the contralateral "intact" SCG, most of which takes place during the next 2 days. Using a solution hybridization protection assay, levels of low-affinity NGF receptor p75NGFR mRNA (pg/microgram total RNA) were found to be increased 25%, with no change in cyclophilin mRNA, in the SCG contralateral to the lesion performed 1 or 3 days earlier. In situ hybridization with a 35S riboprobe complementary to p75NGFR mRNA demonstrated a large increase in this mRNA in some cells of this intact SCG at both 1 and 3 days after a contralateral ICN cut lesion. The clustering of these cells toward the rostral portion of the SCG suggests that they may overlap with the population of sympathetic neurons which provides innervation to bilaterally innervated structures such as the pineal gland. The nature of the signals involved in the regulation of NGF receptor mRNA levels and their role in initiating and maintaining collateral sprouting remain to be fully established. Nevertheless, the time course of the changes in mRNA levels suggests that regulation of the low-affinity NGF receptor gene may be involved in the sequence of events associated with the collateral sprouting response by intact sympathetic nerve cells following partial denervation.

Amino Acid Isomerases↗
PubMed1992

Genomic structure of the locus associated with an insertional mutation in line 4 transgenic mice.

In line 4 transgenic mice, six to eight copies of a 50-kb lambda recombinant clone are arranged in a head-to-tail tandem array on chromosome 3. Embryos homozygous for the transgene become arrested in their development on Day 5 of gestation shortly after implantation. The insertion site was cloned using a small segment of the transgene as a probe. Comparison of the insertion site with the wildtype locus indicates that a 22-kb deletion of host DNA has occurred in line 4 mice. Restriction enzyme analyses showed that neither the tandem array nor the flanking chromosomal DNA had any detectable rearrangements. Sequencing of the junctions between host and foreign DNA, however, revealed insertions of small fragments of DNA of unknown origin as well as an insertion of a DNA segment derived from another region of the transgene. Therefore, disruption of an essential gene in the line 4 transgenic mouse may have been caused by the insertion of 300-400 kb of foreign DNA or a deletion of sequences in the host genome.

Animals↗
PubMed1992

A Hox 3.3-lacZ transgene expressed in developing limbs.

We describe transgenic mouse lines that express lacZ under the control of the Hox 3.3 Promoter II. The correct anterior boundary can be fixed by 3.6 kb of promoter DNA (plus 1.6 kb of 5' transcribed sequences), both in tissues of ectodermal and mesodermal origin. The posterior border, however, is not respected, and lacZ expression continues into the tail region. One line has particularly strong graded expression in the anterior proximal limb bud. Other lines, containing a shorter promoter fragment (0.6 kb), have ectopic expression in the head region, including one line that has expression in the anterior half of the retina. Such mouse lines make it possible to molecularly distinguish cells in regions of the embryo that look otherwise identical and may be useful in studying the establishment of molecular differences in the mouse embryo.

Animals↗
PubMed1992

Severe defect in clearing postprandial chylomicron remnants in dialysis patients.

Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridemia using the vitamin A loading test. This method investigates specifically postprandial lipoprotein metabolism. The determination of vitamin A ester level retinyl palmitate (RP) differentiates the circulating plasma chylomicron and chylomicron remnant fractions from the endogenous VLDL and IDL. Subjects with normal renal function with or without fasting hypertriglyceridemia served as control groups. Dialysis patients have significantly higher level of chylomicron remnants for a more prolonged period of time than controls, irrespective of their fasting triglyceride levels. The area below retinyl palmitate chylomicron remnants curve was 26308 +/- 12422 micrograms/liter.hr in the normolipidemic dialysis patients, significantly higher than (6393 +/- 2098 micrograms/liter.hr; P < 0.0001) in the normolipidemic controls. The retinyl palmitate chylomicron remnants curve of the hypertriglyceridemic dialysis patients was 21021 +/- 4560 micrograms/liter.hr, which was higher than 12969 +/- 2215 micrograms/liter.hr (P < 0.0001) in the hypertriglyceridemic controls. Moreover, the hypertriglyceridemic dialysis patients had an additional defect in the lipolysis metabolic step, that is, accumulation of chylomicrons in circulation. These findings show a severe defect in postprandial lipoprotein metabolism in chronic renal failure patients. The prolonged exposure of the vascular wall to high chylomicron remnant concentrations might be an important pathogenetic factor in the accelerated atherosclerosis seen in chronic dialysis patients.

Adult↗
PubMed1992

The role of the human acetylation polymorphism in the metabolic activation of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

The metabolic activation of the heterocyclic food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by two human cytochrome P450 monoxygenases (P4501A1 and P4501A2) and two human N-acetyltransferases (NAT1 and NAT2) was investigated. Various combinations of these enzymes were functionally expressed in COS-1 cells. DNA adducts resulting from the activation of IQ were assayed quantitatively by the 32P-postlabeling procedure. The highest adduct frequency was observed in cells expressing both CYP1A2 and NAT2. CYP1A2 in combination with NAT1 was 3-6 times less active. When expressed alone these enzymes gave rise to low adduct frequencies. Experiments with N-acetyl-IQ as substrate suggest that NAT1 and NAT2 in addition to their known role in N-acetylation display arylhydroxamic acid N, O-acetyltransferase (AHAT) activity. Quantitative differences in adduct formation between IQ and N-acetyl-IQ indicated that metabolic activation of these arylamines preferentially occurs by P4501A2-catalyzed N-hydroxylation followed by O-acetylation mediated through NAT1 and/or NAT2. These data, in combination with the known genetic polymorphism of NAT2, may explain the clinical observation that the acetylation polymorphism constitutes a risk factor in the carcinogenic activation of environmental mutagens.

Acetylation↗
PubMed1992

Early diagnosis of gram-negative peritonitis in continuous ambulatory peritoneal dialysis patients with the Lymulus amebocyte lysate assay.

The treatment of peritonitis in continuous ambulatory peritoneal dialysis patients is empiric until the bacteriological results are available. The Lymulus amebocyte lysate assay (LAL) is a very sensitive method for the detection of endotoxin, a structural component of gram-negative bacteria. We performed the LAL assay in a prospective study in 36 consecutive episodes of peritonitis. The LAL assay was positive in all 10 episodes of gram-negative peritonitis (100% specificity). Treatment directed specifically against gram-negative or -positive infection was started based on the LAL assay result. In 26 episodes with LAL-negative test, a gram-positive bacterium was cultured in 23 episodes, in 1 there was fungal infection and 2 were sterile. In summary: the LAL assay is a rapid (1 h) and sensitive method for the differentiation of gram-positive or -negative peritonitis and enables starting an immediate and more appropriate antibiotic therapy.

Endotoxins↗
PubMed1992

Clinical and laboratory work-up prior to hormone replacement therapy in postmenopausal women.

In a retrospective study on 100 female patients (mean age 52 years), with a menopause lasting for 3.5 years, referred to the Menopausal Clinic of Beilinson Medical Center, we studied the pretreatment, clinical and laboratory work-up before administration of hormone replacement therapy (HRT). The work-up consisted of clinical and medical examination and history. Mammography is a necessary test for malignancy exclusion, and also the assessment of lipid metabolism. Pap smear is not so important since cervical cancer is a rare event in Jewish women and pelvic sonography cannot be a decisive diagnostic tool for ruling out malignancy. We conclude that HRT for prevention of osteoporosis and cardiovascular disease should be administered in a menopausal clinic by a gynecologist, after performing a few tests: confirmation of menopause by follicle-stimulation hormone (FSH) and E2, excluding malignancy by mammography, and confirmation of normal lipid metabolism.

Clinical Protocols↗
PubMed1992

Goosecoid and the organizer.

The molecular nature of Spemann's organizer phenomenon has long attracted the attention of embryologists. goosecoid is a homeobox gene with a DNA-binding specificity similar to that of Drosophila bicoid. Xenopus goosecoid is expressed on the dorsal side of the embryo before the dorsal lip is formed. Cells expressing goosecoid are fated to become pharyngeal endoderm, head mesoderm and notochord. Transplantation of goosecoid mRNA to the ventral side of Xenopus embryos by microinjection mimics the properties of Spemann's organizer, leading to the formation of twinned body axes, goosecoid is activated by dorsal inducers and not affected by ventral inducers. In the mouse, goosecoid is expressed in the anterior tip of the primitive streak. The availability of two early markers, goosecoid and Brachyury, opens the way for the comparative analysis of the vertebrate gastrula. The results suggest that the goosecoid homeodomain protein is an integral component of the biochemical pathway leading to Spemman's organizer phenomenon.

Animals↗
PubMed1992

[Intrauterine device, the best method for spacing births in breastfeeding mothers].

Twenty-nine breastfeeding women, with a mean age of 36.5 years, were fitted with an IUD, Nova T or Multi load 375, at an average time of 3.6 months after delivery. Insertion at this time was easy, without dilatation, pain or bleeding. During a follow up of 18 months, the IUD has to be discontinued in one woman (3.4%) because of excessive menstrual bleeding, at a time when she was no more fully breastfeeding. The continuation rate was 96.56%, as compared to only 82% for a general population of 216 women fitted with IUD at the same period after delivery and followed up for the same period of time. The IUD is in our opinion the birthspacing method of choice for breastfeeding mothers.

Adult↗
PubMed1992

Regional distribution and developmental expression of epidermal growth factor and transforming growth factor-alpha mRNA in mouse brain by a quantitative nuclease protection assay.

A solution-hybridization ribonuclease-protection assay was used to identify epidermal growth factor (EGF) mRNA in mouse brain and to compare the regional and developmental levels of EGF gene expression in the CNS with those of its structural homolog, transforming growth factor-alpha (TGF-alpha). Adult brain regions examined included brainstem, cerebellum, cerebral cortex, hippocampus, basal hypothalamus, olfactory bulb, olfactory tubercle, striatum, and thalamus. While both EGF and TGF-alpha mRNAs were detected in all regions, TGF-alpha mRNA levels were 15-170 times higher, ranging from 0.39 (cerebellum and cerebral cortex) to 2.93 (striatum) pg TGF-alpha mRNA/micrograms total cytoplasmic RNA. In contrast, EGF mRNA levels ranged from 11 to 36 fg EGF mRNA/micrograms, with the highest regional concentrations observed in olfactory bulb, basal hypothalamus, and cerebellum. In our comparison between sexes, no significant male-female differences in EGF or TGF-alpha mRNA levels were observed for any region of adult brain. However, in the pituitary gland, consisting of both endocrine and neural elements, EGF and TGF-alpha mRNA levels were significantly higher in males (234 and 215 fg/micrograms, respectively) than in females (172 and 118 fg/micrograms, respectively). An examination of growth factor gene expression in the developing CNS revealed EGF and TGF-alpha mRNAs detectable as early as embryonic day 14 (earliest time point studied). While gene expression for both peptides continued into the postnatal period, EGF and TGF-alpha mRNA levels were nearly equal to adult concentrations by postnatal day 10. Taken together, our findings provide evidence for the synthesis of EGF in brain and suggest a role for both EGF and TGF-alpha in the development and support of the mammalian CNS.

Aging↗
PubMed1992

The bone sparing effect of oral contraceptive use in non-smoking women.

In a group of 30 women, mean age 23.7 years, we have examined the urinary calcium: creatinine ratio (Ca:Cr) as an indicator of bone resorption, before and 6.8 months after oral contraceptive (OC) use. Fasting Ca:Cr decreased significantly during OC use, being more pronounced in nonsmokers. We agree with those who propose the use of OC in women also after 35 years of age, in view of their good effect on bone density.

Adolescent↗
PubMed1991

[Oral contraceptive lowers serum magnesium].

The effect of an oral contraceptive on serum magnesium was assessed in a group of 32 women, mean age 24.2 years, attending a family planning clinic. The pill contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg. As in pregnancy and during estrogen replacement in postmenopausal women, the contraceptive pill lowered serum magnesium (from a mean of 0.82 mmol/l, to 0.61 mmol/l in 6 months). Larger studies may determine whether routine dietary magnesium supplementation is necessary in oral contraception.

Adult↗
PubMed1991

Molecular mechanism of slow acetylation of drugs and carcinogens in humans.

The acetylation polymorphism is one of the most common genetic variations in the transformation of drugs and chemicals. More than 50% of individuals in Caucasian populations are homozygous for a recessive trait and are of the "slow acetylator" phenotype. They are less efficient than "rapid acetylators" in the metabolism of numerous drugs and environmental and industrial chemicals. The acetylation polymorphism is associated with an increased risk of drug toxicity and with an increased frequency of certain cancers. We report the identification of the primary mutations in two alleles of the gene for the N-acetyltransferase (NAT; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) isozyme NAT2 associated with slow acetylation. These alleles, M1 and M2, account for more than 90% of slow acetylator alleles in the European population we have studied. M1 and M2 were identified by restriction fragment length polymorphisms with Kpn I and Msp I and subsequently cloned and sequenced. M1 and M2 each are characterized by a combination of two different point mutations, one causing an amino acid substitution (Ile-113----Thr in M1, Arg-197----Gln in M2), the other being silent (C 481----T in M1, C 282----T in M2). Functional expression of M1 and M2 and of chimeric gene constructs between mutant and wild-type NAT2 in COS-1 cells suggests that M1 causes a decrease of NAT2 protein in the liver by defective translation, whereas M2 produces an unstable enzyme. On the basis of the mutations described here and a rare mutant allele (M3) reported recently, we have developed a simple DNA amplification assay that allows the predictive genotyping of more than 95% of slow and rapid acetylator alleles and the identification of individuals at risk.

Acetylation↗
PubMed1991

Basic proline-rich proteins from human parotid saliva: relationships of the covalent structures of ten proteins from a single individual.

Eleven basic proline-rich proteins were purified from the parotid saliva of a single individual. The complete amino acid sequences of six of these were determined by conventional protein sequence methodology, bringing to nine the number of known primary structures of nonglycosylated basic proline-rich proteins from the same individual. The partial sequence of one additional protein is also reported. All of the basic proline-rich proteins studied contain segments with identical or very similar sequences, but with two possible exceptions, none of the proteins is derived from another secreted proline-rich protein. The amino acid sequences of nine nonglycosylated basic proline-rich proteins were compared with primary structures deduced from published nucleotide sequences of DNA coding for human parotid proline-rich proteins. The sequences align well, in general, but differences also exist pointing to the complexity of the genetics of these proteins. Seven secretory basic proline-rich proteins appear to be formed from three larger precursors by selective posttranslational proteolyses of arginyl bonds. One of the basic proline-rich proteins appears to derive from human acidic proline-rich proteins. The remaining two proteins studied do not conform to any DNA structure as yet reported. Two of the basic proline-rich proteins studied are phosphoproteins and exhibit abilities to inhibit hydroxyapatite formation in vitro.

Amino Acid Sequence↗
PubMed1991

EGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture.

Epidermal growth factor (EGF) immunoreactive material has been demonstrated to be present in the basal ganglia. In this study, we investigated the effect of EGF on cells cultured from 16-day embryonic rat mesencephalon, which included dopamine neurons that project to the striatum in vivo. EGF receptors were detected in untreated cultures by [125I]-EGF binding. Treatment of the cultures with EGF resulted in up to 50-fold increases in neuronal high-affinity dopamine uptake. Scatchard analysis of uptake kinetics and counting of tyrosine hydroxylase-immunoreactive cells suggest that the effect of EGF on uptake is due to increased survival and maturation of dopaminergic neurons. By contrast, the high-affinity uptake for serotonin was increased only threefold over its controls. There was no significant effect on high-affinity gamma-aminobutyric acid (GABA) uptake. These results suggest that EGF is acting as a neurotrophic agent preferential for dopaminergic neurons in E16 mesencephalic cultures. Immunocytochemistry for glial fibrillary acidic protein demonstrated an increase in astroglia with EGF treatment. Fluorodeoxyuridine, an agent that is toxic to proliferating cells was able to eliminate the effect of EGF on dopamine uptake, suggesting that EGF may be increasing dopaminergic cell survival largely through a population of dividing cells.

Animals↗