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Biomedical subjects

M Placzek

Publications and source records attributed to M Placzek.

52 records · Page 3Linked to original sources

The mouse homolog of the hst/k-FGF gene is adjacent to int-2 and is activated by proviral insertion in some virally induced mammary tumors.

The fibroblast growth factor-related protooncogenes, int-2 and hst/k-FGF, are within 17 kilobase pairs of one another on mouse chromosome 7 and are in the same transcriptional orientation. Approximately 70% of tumors induced in BR6 mice by mouse mammary tumor virus have proviral insertions adjacent to the int-2 gene. We find that the murine homolog of the hst/k-FGF gene can also be transcriptionally activated by the insertion of mouse mammary tumor virus DNA either upstream or downstream of the gene. In most tumors, only one of these adjacent genes is activated, but in some cases both genes are expressed. One of the hst-expressing tumors also has a virally activated int-3 gene. At least five distinct cellular genes (int-1, -2, -3, -4, and hst/k-FGF) can therefore contribute, either singly or in concert, to the development of histologically indistinguishable mammary tumors in mice infected by mouse mammary tumor virus.

Animals↗

A putative int domain for mouse mammary tumor virus on mouse chromosome 7 is a 5' extension of int-2.

We extended the physical map of the mouse int-2 locus by demonstrating that the site of insertion for mouse mammary tumor virus DNA in plaque-type mammary tumors of GR mice is directly linked to int-2. An additional example of proviral integration is described in which a provirus in a presumed enhancer-insertion mode 15 kilobases upstream of the int-2 promoters is capable of activating expression of the gene at levels typical of other virally induced mammary tumors.

Animals↗

An unusual case of neonatal myasthenia.

An unusual case of neonatal myasthenia gravis is reported in an infant who had respiratory failure due to diaphragmatic weakness. Although power and tone in the limbs were normal, fatiguability of both diaphragm and peripheral muscles was demonstrated. Acetylcholine receptor antibodies were absent in the mother, which suggests that an alternative humoral mechanism may have been responsible for the transient (6-week) neonatal weakness.

Female↗

Insertion elements and transitions in cloned mouse mammary tumour virus DNA: further delineation of the poison sequences.

The provirus of mouse mammary tumour virus (MMTV) is reputed to contain sequences within the viral gag gene that prevent or inhibit its propagation as a recombinant DNA clone in Escherichia coli. Here we report the successful isolation of several lambda and plasmid clones comprising the 5' virus-host DNA junction fragments from integrated MMTV proviruses in BR6 mice. Although the lambda clones appeared intact, almost all of the plasmids were found to contain the bacterial insertion sequences IS1 or IS2 within a small region of the gag gene. One nondisrupted clone was recovered which had undergone multiple G to A transitions, some of which created stop codons in gag. These results have provided more precise information as to the location of the poison sequences and are discussed in relation to possible explanations for the phenomenon.

Amino Acid Sequence↗

Characterization, chromosome assignment, and segregation analysis of endogenous proviral units of mouse mammary tumor virus.

In the course of analyzing sites of proviral integration in tumors induced by mouse mammary tumor virus (MMTV), we have isolated recombinant DNA clones corresponding to the 5' and 3' ends of four endogenous MMTV proviruses present in BALB/c and BR6 mice. This has permitted the structural characterization of each locus by detailed restriction mapping and the preparation of DNA probes specific for the cellular sequences flanking each provirus. These probes have been used to trace the segregation patterns of the proviruses, designated Mtv-8, Mtv-9, Mtv-17, and Mtv-21, in a panel of inbred strains of laboratory mice and to map Mtv-17 and Mtv-21 to mouse chromosomes 4 and 8, respectively. The unambiguous resolution of these four proviruses on Southern blots has greatly facilitated the analysis of other endogenous MMTV proviruses in these inbred mice.

Animals↗

Maturation of the visual evoked response and its correlation with visual acuity in preterm infants.

Visual evoked responses (VERs) were elicited in 70 infants with postmenstrual ages between 30 and 39 weeks. On the basis of neurological and ultrasound examinations, 30 of the infants were classed as neurologically normal and 40 as abnormal: 26 of the latter had periventricular haemorrhage. Initially the VER consisted of a negative deflection only, and the appearance of a positive wave immediately preceding the negative deflection was taken to indicate maturation of the VER. Maturation was significantly delayed in the neurologically abnormal infants, and the delay was related to the degree of neurological insult. The visual acuity of 32 infants was estimated within seven days of the VER recording. There was a correlation of 79 per cent between the VER and the data for visual acuity.

Birth Weight↗

Comparison of two feeding regimens following acute gastroenteritis in infancy.

Forty-eight children below 18 months of age suffering from acute gastroenteritis were given a glucose-electrolyte mixture (GEM) for the first 24 h following hospital admission. They were then allocated alternately to the study group which immediately went back to full-strength cow's milk feeds, or to the control group to which milk was reintroduced gradually over a 4-day period. The majority of infants in both groups had an uncomplicated recovery (70 and 96%, respectively). A complicated recovery, however, occurred more commonly in the study group. Seven patients in this group, compared with only one in the control group, had an immediate recurrence of symptoms of such severity that a return to intravenous fluids or the GEM was necessary. These complications were confined to those less than 9 months of age. It is concluded that children over 9 months of age with acute gastroenteritis may be given full-strength milk immediately after 24 h of treatment with a glucose-electrolyte solution, but for children under 9 months the conventional regrading over several days should be retained.

Acute Disease↗

Small intestinal mucosal fat in childhood enteropathies.

A sequential series of 100 small bowel mucosal biopsies from children was studied to assess the frequency and pattern of mucosal fat staining, and to compare patterns of fat distribution with mucosal structure and clinical diagnosis. Deep mucosal fat was commonly associated with those clinical groups showing normal mucosal structure. While fine granular surface epithelial fat was common in normal and abnormal biopsies, the presence of large fat globules in the surface epithelium was almost entirely limited to biopsies showing villous shortening. Large fat globules in the surface epithelium in coeliac disease and cow's milk sensitive enteropathy were probably related to the more severe degrees of villous abnormality encountered in these clinical groups. However, large fat globules in surface epithelium were also found in a few cases of cow's milk sensitive enteropathy with normal or minimal villous blunting. Fat staining may be a useful additional histological marker to aid in the interpretation of small intestinal mucosal biopsies.

Adolescent↗

Phenobarbitone for prevention of periventricular haemorrhage in very low birth-weight infants. A randomised double-blind trial.

A double-blind randomised trial was carried out in 60 infants with a birth-weight of less than 1500 g or a gestational age below 31 weeks. 30 infants received phenobarbitone (20 mg/kg) within 4 h of birth and 30 infants received a placebo. The two groups of infants were similar in birth-weight, gestational age, frequency of vaginal delivery, sex, Apgar scores, ventilator dependence before the injection, pneumothorax, hypercapnia, and acidosis. Cranial ultrasound scans were carried out daily for 14 days. 12 out of 30 phenobarbitone-treated infants and 11 out of 30 placebo-treated infants had PVH, with parenchymal haemorrhages in 2 of the placebo group. Plasma phenobarbitone was over 15 micrograms/ml in 28 out of 30 of the phenobarbitone-treated infants during the first 72 h. 7 out of 17 spontaneously breathing infants became ventilator-dependent within 12 h of the phenobarbitone injection, whereas only 1 of 18 spontaneously breathing placebo-treated infants became ventilator-dependent within 12 h of injection. Although the possibility of protection against parenchymal haemorrhages may justify further investigation, there is no justification for administration of 20 mg/kg of phenobarbitone to all infants below 1500 g.

Cerebral Hemorrhage↗

The maturation of visual acuity in neurologically normal and abnormal newborn infants.

The maturation of visual acuity was studied in 162 neurologically normal and 96 neurologically abnormal newborn infants. Ninety-five percent of the neurologically normal infants developed an acuity of 80 min arc by 35 weeks postmenstrual age (PMA) but only 50% developed an acuity of 40 min arc by 40 weeks PMA. Neurologically abnormal infants, and in particular those with periventricular haemorrhage (PVH), had a delay in the development of acuity. There was a close correlation between the development of 80 min arc acuity and the appearance of the first positivity of the flash visually evoked potential (VEP).

Cerebral Hemorrhage↗

Selective placement of bronchial suction catheters in intubated neonates.

Flexible suction catheters were passed through the endotracheal tubes of infants undergoing mechanical ventilation, just before chest radiographic examination for clinical purposes. With the head straight, 7 of 10 straight catheters entered the right main bronchus but with the head turned, 17 of 20 straight catheters and 19 of 20 curved tip catheters entered the contralateral bronchus.

Catheterization↗

Piperacillin in early neonatal infection.

Seventy infants with suspected bacterial infection in the first 48 hours of life were treated either with piperacillin and flucloxacillin or with penicillin and gentamicin. Infection was confirmed and successfully eradicated in 6 of the 35 infants receiving piperacillin and flucloxacillin. Four infants treated with penicillin and gentamicin had confirmed infection and one deteriorated initially but then recovered when treated with piperacillin. Serum piperacillin concentrations above 100 mg/l and cerebrospinal fluid piperacillin concentrations of 2.6-6 mg/l were noted for up to four hours and 7 hours respectively, even in the absence of inflamed meninges, after administration of piperacillin 100 mg/kg body weight intravenously. Median half life of piperacillin was 6.5 hours and was prolonged in renal impairment. Piperacillin is considered to be a safe and effective first line single agent treatment for early neonatal infection but because some Escherichia coli are resistant to it we recommend that a second agent be used in critically ill infants with neutropenia or meningitis.

Bacterial Infections↗

Chemotropic guidance of developing axons in the mammalian central nervous system.

In the developing nervous system, axons project considerable distances along stereotyped pathways to reach their targets. Axon guidance depends partly on the recognition of cell-surface and extracellular matrix cues derived from cells along the pathways. It has also been proposed that neuronal growth cones are guided by gradients of chemoattractant molecules emanating from their intermediate or final cellular targets. Although there is evidence that the axons of some peripheral neurons in vertebrates are guided by chemotropism and the directed growth of some central axons to their targets is consistent with such a mechanism, it remains to be determined whether chemotropism operates in the central nervous system. During development of the spinal cord, commissural axons are deflected towards a specialized set of midline neural epithelial cells, termed the floor plate, which could reflect guidance by substrate cues or by diffusible chemoattractant molecules. Here we provide evidence in support of chemotropic guidance by demonstrating that the rat floor-plate cells secrete a diffusible factor(s) that influences the pattern and orientation of commissural axon growth in vitro without affecting other embryonic spinal cord axons. These findings support the hypothesis that chemotropic mechanisms guide developing axons to their intermediate targets in the vertebrate CNS.

Animals↗

Phototoxic lysis of erythrocytes from humans is reduced after oral intake of ascorbic acid and d-alpha-tocopherol.

Ultraviolet (UV) radiation causes hemolysis of human erythrocytes in the presence of photosensitizers. This can be used as an in vitro model for evaluating photosensitizing properties of substances. Antioxidants such as ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E) have been found to be photoprotective in such test systems. We assessed the effect of combined systemic intake of both ascorbic acid and d-alpha-tocopherol by human volunteers on phototoxic in vitro lysis of their erythrocytes. In a double-blind placebo-controlled study, 10 subjects took daily 2 g ascorbic acid combined with 1000 IU d-alpha-tocopherol, and 10 took a placebo. Blood was taken before and after 7 days of treatment, erythrocytes were prepared and then incubated with 10(-3) mol/l fenofibrate, a photosensitizer acting in the UVA and UVB region. The suspensions were exposed to radiation rich in UVA (up to 40 J/cm2 UVA) or to radiation rich in UVB (up to 1.6 J/cm2). Photohemolysis of the samples was calculated as a percentage of complete hemolysis. At the end of the treatment phase, in the placebo group photohemolysis was not significantly reduced compared with the initial values at all irradiation doses except for 1.6 J/cm2 UVB (96% vs 79%; P < 0.01). In the group taking vitamins, photohemolysis was significantly reduced at nearly all UV doses, most impressively after moderate UVA irradiation (20 J/cm2 UVA: 86.5% vs 14.5%; P < 0.01). It is concluded that the results of the photohemolysis test are influenced by the antioxidative status of the cell donor and that ascorbic acid and d-alpha-tocopherol also may protect against phototoxic damage in vivo.

Administration, Oral↗