Limb reduction defects in fetuses with homozygous alpha-thalassaemia-1

Limb reduction defect is a rare event. Its exact pathogenesis is unknown. We retrospectively reviewed the outcome of 130 fetuses affected by homozygous alpha-thalassaemia-1 and found that 11 of them (8 per cent; 95 per cent confidence interval: 4-13 per cent) had terminal transverse limb reduction defects. Chromosome study was available in ten fetuses with limb defects and the results were normal. We postulate that the strong association between homozygous alpha-thalassaemia-1 and limb reduction is related to the hypoxic insult in early gestation. This may be the final common pathway in the pathogenesis of other forms of limb reduction defects.     

Bone loss associated with a high fibre weight reduction diet in postmenopausal women

OBJECTIVE: To examine the effect of high fibre weight reduction on bone density in postmenopausal women. DESIGN: Case-control study. SETTING: Hospital outpatient dietetic clinic and Osteoporosis Screening Unit. SUBJECTS AND INTERVENTIONS: Sixteen overweight volunteers who followed a high fibre reducing diet for 6 months, to lose 20% of excess body weight (above body mass index 25 kg/m2), and returned to their starting weight by the end of a further 6 months. Forty-six non-dieting controls, matched for age and years postmenopause, selected from screening unit volunteer register. RESULTS: Annual percentage changes in lumbar spine bone mineral density, measured by dual energy X-ray absorptiometry were: controls -2.5% (SE 0.5), dieters -4.8% (0.9), 95% confidence interval of difference between groups -0.2 to -4.3% (P = 0.03); femoral neck bone density controls -2.5% (0.5), dieters -2.1% (0.9), 95% confidence interval of difference -1.7 to 2.5% (P = 0.69). CONCLUSIONS: High fibre weight reduction in postmenopausal women significantly increased annual bone loss from the lumbar spine. This loss was not reversed by weight regain in the second 6 months. Repeated cycles of high fibre weight loss and weight gain may increase the risk of spinal osteoporosis.     

Plasticity of auditory cortex associated with sensorineural hearing loss in adult C57BL/6J mice

The representation of frequency was mapped in the primary auditory cortex (AI) of C57BL/6J (C57) mice during young adulthood (1.5-2 months) when hearing is optimal, and at 3, 6, and 12 months of age, a period during which progressive, high frequency, sensorineural hearing loss occurs in this strain. Maps were also obtained from CBA/CaJ mice which retain good hearing as they age. In AI of young adult C57 mice and CBA mice, characteristic frequencies (CFs) of multiple-unit clusters were easily identified with extracellular recordings, and a general tonotopic organization was observed from dorsal (high frequency) to ventral and caudal (low frequency). In individual cases there appeared to be deviations from the above tonotopic organization, despite the fact that inbred mice are genetically invariant. As progressive loss of high frequency sensitivity ensued peripherally, a substantially increased representation of middle frequencies was observed in AI. There was no apparent change in the surface area of the auditory cortex despite the elimination of high frequencies, and virtually the entire auditory cortex became devoted to the middle frequencies (especially 10-13 kHz) for which sensitivity remained high. Similar age-related changes were not observed in normal-hearing CBA mice. These findings indicate that plasticity in the representation of frequency in AI is associated with high frequency hearing loss in C57 mice.     

Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and mutations in the Ki-ras oncogene

The polycyclic aromatic hydrocarbon benzo[b]fluoranthene (B[b]F) is a pervasive constituent of environmental combustion products. We sought to examine the lung tumorigenic activity of B[b]F in strain A/J mice, to study the relationship between formation and decay of B[b]F-DNA adducts and to examine mutations in the Ki-ras proto-oncogene in DNA from B[b]F-induced tumors. Mice were given i.p. injections of 0, 10, 50, 100 or 200 mg/kg body wt and lung adenomas were scored after 8 months. B[b]F induced significant numbers of mouse lung adenomas in a dose-related fashion, with the highest dose (200 mg/kg) yielding 6.95 adenomas/ mouse, with 100% of the mice exhibiting an adenoma. In mice given tricaprylin, the vehicle control, there were 0.60 adenomas/mouse, with 55% of the mice exhibiting an adenoma. Based on dose, B[b]F was less active than benzo[a]pyrene. DNA adducts were analyzed qualitatively and quantitatively by 32P-post-labeling in lungs of strain A/J mice 1, 3, 5, 7, 14 and 21 days after i.p. injection. Maximal levels of adduction occurred 5 days after treatment with the 200 mg/kg dose group, producing 1230 amol B[b]F-DNA adducts/microgram DNA. The major B[b]F-DNA adduct was identified by co-chromatography as trans-9, 10-dihydroxy-anti-11, 12-epoxy-5-hydroxy-9, 10, 11, 12-tetra-hydro-B[b]F-deoxyguanosine. Approximately 86% of the tumors had a mutation in codon 12 of the Ki-ras oncogene, as determined by direct DNA sequencing of PCR-amplified exon 1 and single-stranded conformation polymorphism analysis. Analysis of the Ki-ras mutation spectrum in 25 of 29 B[b]F-induced tumors revealed the predominant mutation to be a G-->T transversion in the first or second base of codon 12, congruous with the DNA adduct data. Our data are consistent with previous reports in mouse skin implicating a phenolic diol epoxide as the proximate carcinogenic form of B[b]F that binds to guanine.     

A low incidence of histiocytic sarcomatosis associated with infection of chickens with the HPRS-103 strain of subgroup J avian leukosis virus

Ten cases of histiocytic proliferative lesions in meat-type chickens associated in low incidence with infection by subgroup J avian leukosis virus (ALV) are described. Six were field cases in adult chickens from naturally infected flocks and four were from younger birds from transmission experiments with HPRS-103 ALV or the related acutely transforming ALV strains 17 and 879. The lesions were observed mostly in the spleen and in some cases in other organs. Microscopically, the lesions were comprised mainly of pleomorphic histiocyte-like cells admixed with variable numbers of lymphoid cells. More detailed studies were carried out on two birds at 4 and 7 wk of age following infection with HPRS-103 at 1 day of age. These birds had multiple small nodular lesions in the spleen, liver, and kidney that appeared similar cytologically to the more extensive lesions in older birds. Monoclonal antibodies specific for various lymphoid and nonlymphoid accessory cells were used in immunohistochemical studies to identify a predominance of cells of monocyte/macrophage lineage, and CD4- and CD8-positive lymphocytes, in the splenic nodules. Ultrastructural studies also revealed a similar mixed population of cells. Expression of ALV group-specific antigen, and gag and ALV-J env RNA, was not a marked feature of the histiocytic lesions. The proliferative histiocytic lesion is designated a histiocytic sarcomatosis.     

Changes in maternal middle cerebral artery blood flow velocity associated with general anesthesia in severe preeclampsia

In women with severe preeclampsia, significant increases in mean arterial pressures (MAP) are common after rapid induction of general anesthesia (GA) and tracheal intubation. The objectives of this prospective study were to assess the effects of the rapid induction-intubation technique on middle cerebral artery (MCA) flow velocity in severe preeclampsia and to examine the correlation between mean MCA flow velocity (Vm) and MAP. Eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean section under GA were studied. Before induction, patients in the study group received i.v. labetalol in divided doses to lower diastolic pressures to <100 mm Hg. Anesthesia was induced with pentothal 4-5 mg/kg, followed by succinylcholine 1.5 mg/kg to facilitate tracheal intubation. A transcranial Doppler was used to measure Vm. Both Vm and MAP were recorded before induction and every minute for 6 min after intubation. In the study group, after the administration of labetalol, MAP decreased from 129 +/- 9 to 113 +/- 9 mm Hg (P < 0.05), and Vm decreased from 59 +/- 11 to 54 +/- 10 cm/s (P < 0.05). After intubation, MAP increased from 113 +/- 9 to 134 +/- 5 mm Hg (P < 0.001), and Vm increased from 54 +/- 10 to 70 +/- 10 cm/s (P < 0.001). In the control group, while MAP increased significantly from 89 +/- 6 to 96 +/- 4 mm Hg (P < 0.05) after intubation, the concurrent increase in Vm from 49 +/- 5 to 54 +/- 7 cm/s was not significant. There was a significant positive pooled correlation between Vm and MAP (r = 0.5, P < 0.0006) in the study group but not in the control group (r = 0.24). After induction and intubation, both Vm and MAP values were significantly increased in the study group patients at all observation points compared with the control group patients. The findings indicate that Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia, and there seems to be a direct relationship between MAP and Vm. Implications: In women with severe preeclampsia, rapid-sequence induction of general anesthesia and tracheal intubation can cause severe hypertension. Our results indicate that the increase in blood pressure is associated with a significant increase in maternal cerebral blood flow velocity and that there is a significant correlation between these two variables.     

Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke

OBJECTIVE: To determine variations among hospitals in use of intensive care units (ICUs) for patients with low severity of illness. DESIGN: Retrospective cohort study. SETTING: Twenty-eight hospitals with 44 ICUs in a large metropolitan region. PATIENTS: Consecutive eligible patients (N=104,487) admitted to medical, surgical, neurological, or mixed medical-surgical ICUs from March 1, 1991, to March 31, 1995. OUTCOME MEASURES: The predicted risk of in-hospital death for each patient was assessed using a validated method that is based on age, ICU admission source, diagnosis, severe comorbid conditions, and abnormalities in 17 physiologic variables. Admissions were classified as low severity if the patient's predicted risk of death was less than 1%. In a subset of 12,929 consecutive patients, use of 19 specific interventions typically delivered in ICUs was examined. RESULTS: Twenty thousand four hundred fifty-one admissions (19.6%) were categorized as low severity, including 23.6% of postoperative and 16.9% of nonoperative admissions. Alcohol and other drug overdoses accounted for 40.2% of nonoperative low-severity admissions; laminectomy and carotid endarterectomy accounted for 52.3% of postoperative low-severity admissions. Mortality among patients with low-severity illness was 0.3%, and only 28.6% received an ICU-specific intervention during the first ICU day. Although mean ICU length of stay was shorter (P<.001) in low-severity admissions (2.2 vs 4.7 days in nonoperative and 2.4 vs 4.2 days in postoperative admissions), low-severity admissions accounted for 11.1% of total ICU bed days. Rates of low-severity admissions varied (P<.001) across hospitals, ranging from 5% to 27% for nonoperative and 9% to 68% for postoperative admissions. CONCLUSIONS: A large proportion of patients admitted to the ICU have a low probability of death and do not receive ICU-specific interventions. Rates of low-severity admissions varied among hospitals. The development and implementation of protocols to target ICU care to patients most likely to benefit may decrease the number of low-severity ICU admissions and improve the cost-effectiveness of ICU care.     

Limb blood flow in treated hyperlipoproteinaemic patients with peripheral vascular disease. A preliminary report

Fourteen patients with hyperlipoproteinaemia and peripheral vascular disease have been investigated to determine the effect on limb blood flow of hypolipidaemic therapy. Satisfactory lowering of serum lipoprotein levels was achieved in the treated group. There was a significant deterioration in peak reactive blood flow measurements in the placebo group compared with the treated group. Treatment of hyperlipoproteinaemia may, therefore, be of value in preventing the progression of peripheral atherosclerosis.     

A major gene affecting age-related hearing loss in C57BL/6J mice

A major gene responsible for age-related hearing loss (AHL) in C57BL/6J mice was mapped by analyses of a (C57BL/6J x CAST/Ei) x C57BL/6J backcross. AHL, as measured by elevated auditory-evoked brainstem response (ABR) thresholds, segregated among backcross mice as expected for a recessive, primarily single-gene trait. Both qualitative and quantitative linkage analyses gave the same genetic map position for the AHL gene (Ahl on chromosome 10, near D10Mit5. Marker assisted selection was then used to produce congenic lines of C57BL/6J that contain different CAST-derived segments of chromosome 10. ABR test results and cochlear histopathology of aged progenitors of these congenic lines are presented. Ahl is the first gene causing late-onset, non-syndromic hearing loss that has been reported in the mouse.     

Identification of a unique form of p53 in human cord blood associated with the development of maternal autoantibodies

PROBLEM: The possible link between p53-reactive antibodies in multiparous women and exposure to a unique p53 protein during pregnancy was examined. METHOD OF STUDY: p53-reactive antibodies were evaluated in sera from nulligravid and multiparous women and patients with ovarian cancer by Western immunoblot. Furthermore, the presence of p53 protein was assayed in cord blood by enzyme-linked immunosorbent assay. Cord blood-derived p53 was compared structurally by protein fingerprinting and functionally by gel mobility shift assay to other isolates of p53. RESULTS: Antibodies reactive with wild-type p53 were observed in 92% of multiparous women and 42% were reactive with one tumor-derived p53 protein. p53 protein was detected in 27 of 154 samples of cord blood. Structural analysis indicated that the fetal p53 resembled the UL-1 p53. Functionally, the fetal and UL-1 protein failed to bind DNA. CONCLUSIONS: Fetal p53 protein seems to be distinct from wild-type p53, characterized by enhanced stability, structural differences and inability to bind DNA, analogous to alternatively spliced variants. Exposure to fetal p53 protein may form the basis for immunologic protection against cancer induced by multiparity.     

Regionalization defects in the weaver mouse cerebellum

The mammalian cerebellum consists of parasagittal bands and transverse zones that are laid down early in development. When the adult cerebellum is immunostained for the Purkinje cell-specific antigen zebrin II (i.e., aldolase C), compartmentation is reflected in alternating zebrin II+ (P+) and zebrin II- bands (P ). The zebrin II phenotype is Purkinje cell autonomous; thus, disruptions in the zebrin pattern may reflect early problems in pattern formation. Zebrin II expression has been examined in the weaver (wv) mouse cerebellum. Both zebrin II- and zebrin II Purkinje cells are present in the homozygous weaver (wv/wv) mouse, but they are not distributed normally. In the posterior vermis, although the zebrin II+ bands are wider and multilaminate, the standard compartmentation is present. However, a large zebrin II+ cell mass is absent from the central vermis, and analysis of the anterior lobe reveals several missing zebrin II- bands. The cytoarchitectonic defects in wv mice are not simply related to the Purkinje cell abnormalities. Instead, serial reconstruction reveals two transverse boundaries-one rostrally in lobule VI and the other caudally in lobule IX-that delineate cytoarchitectonic transverse zones important in cerebellar development. The abnormal zebrin expression pattern in wv/wv mice may be secondary to the deletion of a transverse zone. This is the first demonstration that Purkinje cell compartmentation can be altered by mutation; therefore, the wv mutation should prove valuable in understanding cerebellar regionalization.     

A simulation of the NiO/Ag interface with point defects

The NiO/Ag interface has been modelled using established simulation techniques, which have been modified to include the image interactions between the oxide ions and the induced charge in the metal. The energies of point defects near the interface were calculated and it was found that the surface rumpling was such that defects with a negative net charge were favoured. This will result in a space charge layer with excess cation vacancies which will cancel the interfacial potential. A low energy interface was modelled in which the cation sub-lattice of the second oxide plane was saturated with vacancies and Ni³⁺ ions. Such a structure may be responsible for the observed excess of oxygen near the NiO/Ni interface, and also for the low wetting angles of metals on NiO, compared with MgO.     

A neuroanatomical correlate of paternal and maternal behavior in the biparental California mouse (Peromyscus californicus).

The medial preoptic area (MOPA) is important in the control of maternal behavior in rodents, and it is sexually dimorphic. This study demonstrates that the MPOA of 10 nonparental virgin male Peromyscus californicus was larger than that of 9 virgin females because of a significantly greater number of neurons in the MPOA of virgin males. However, this sex difference in MPOA volume disappeared when males and females became parents. Soma size increased significantly when females became mothers. These data suggest that maternal behavior may require a structural change in the MPOA, whereas paternal responsivity, which is normally inhibited in virgin males, may require a change in neuronal activity. Furthermore, these results underscore the importance of reproductive status in examination of sexually dimorphic nuclear structures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental researches in infections with associated myxoviruses in the mouse

Infections with influenza virus, A/Beijing 353/89 (H3N2) strain, to which there were associated parainfluenza virus type 3, 739-2D strain, adenovirus type 3, and respiratory syncytial virus Long strain, were experimentally induced in white mice. The experimental models were set up so as to permit the obtaining of an associated infection with three viruses, in which the influenza virus should be inoculated the first, the participation of the others being variable, according to their presence by alternation. The infections were detected by means of the presence of homologous serum antibodies, of positive immunofluorescence reactions in the pulmonary tissue, of the histological, histochemical and histoenzymatic lesions at the level of the respiratory system, as well as of pathomorphological changes in other organs. The severity of lesions varied from one to another infection produced by a viral association. At the level of the pulmonary parenchyma, the inflammatory lesion had a frequency of 100%. The severest pathomorphological picture characterized the diffuse interstitial lymphohistio-macrophagocytic bronchopneumonia. The bronchopulmonary block was marked by cytoinfiltrative processes, with a prevalence of lymphocytes in the infection with influenza virus + adenovirus + respiratory syncytial virus, but with a proportionality between lymphocytes and histiocytes in the other infections. The lesion of the highest incidence was the thickening of interalveolar septa, as a consequence of stasis hyperemia, oedema and lymphohistio-macrophagocytic cytoinfiltrate, sometimes associated with hyalinosis of tunica media of the blood vessels and of the Reisseisen's muscle. In other organs, particularly in the liver and kidney, vascular lesions, stasis hyperemia, inflammatory and dystrophico-inflammatory lesions were present; in the spleen, megakaryocyte hyperplasia was recorded at a significant rate in associated infections in which the adenovirus was present.     

Hepatocellular dysfunction after severe hypotension in the absence of blood loss is associated with the increased IL-6 and PGE2

Activation of ATP-sensitive K+ channels is involved in the coronary vascular response to decreases in perfusion pressure and ischemia. Since activation of ATP-sensitive K+ channels in collateral vessels may be important in determining flow to collateral-dependent myocardium, the ability of collaterals to respond to activation of the channel was tested. In the beating heart of dogs, we compared responses of non-collaterals less than 100 microns in diameter to collaterals of similar size using computer-controlled stroboscopic epi-illumination of the left ventricle coupled to a microscope-video system. Aprikalim, a selective activator of ATP-sensitive K+ channels (0.1-10 microM) produced similar dose-dependent dilation of non-collaterals and collaterals. Relaxation was decreased by inhibition of ATP-sensitive K+ channels with glibenclamide, but not by inhibition of nitric oxide synthase with nitro-L-arginine. Bradykinin (10-100 microM) produced similar dilation of non-collaterals and collaterals which was decreased by nitro-L-arginine but not glibenclamide. Thus, in microvascular collaterals, relaxation to both nitric oxide and activation of ATP-sensitive K+ channels is similar to non-collaterals.     

Genetic defects in Chediak-Higashi syndrome and the beige mouse

Nine spouses of people who had suffered from acute leukemia or highly malignant lymphoma were interviewed about their everyday life experiences throughout their partner's illness and treatment, and concerning their view of the professional care provided. The transcribed texts were subjected to phenomenological-hermeneutic analysis. The spouses felt they were in a situation of overall severe crisis (i.e., experiencing feelings of distress, restrictions, and limited or lack of support). The analysis revealed three family types: the couple acting as a unit, the couple acting independently on equal terms, and the couple acting separately with the spouse in a subordinate position. The spouses' evaluation of the entire experience varied according to the family type and the spouses' personal resources, which influenced the availability and utilization of their social network as well as the support of health-care staff. Contentment was related to the couple acting as a unit or the couple acting independently on equal terms and taking control over the situation, actively asking for support and requiring the staff to meet their needs. Discontentment was related to subordination of the spouse to the partner or to health-care staff, and failure of the couple to obtain support between them or from others. Empowering the spouses may mean helping them develop their skills, providing them with opportunities and authority, and assisting them in gaining access to resources based on knowledge of the family type, the consent of the partner, and the spouse's freedom to make choices. This may well lead to increased efficiency and have positive effects for the patient, for the spouse, and for them both as a couple.     

Plant tumor reversal associated with the loss of foreign DNA

Transformation of plant tissues into crown gall tumors has been associated with the transfer of a portion of a tumor-inducing plasmid (Ti-plasmid) into plant DNA. Various laboratories have regenerated normal-appearing plants from a number of crown gall tumors. This study investigates the fate of the foreign DNA in a series of tissues derived from various parts of a plant regenerated from the tumor BT-37 by Braum and his coworkers. It was found that all the foreign DNA sequences were lost from tissues that had lost all their tumorous traits; whereas the plasmid DNA sequences were still present in tissues that appeared normal but still exhibited tumorous traits when returned to tissue culture media. From these studies it would appear that the presence of the Ti-plasmid sequences in the plant DNA is required for the maintenance of the transformed state.